Kanker payudara adalah kanker pada jaringan payudara

Kanker payudara adalah kanker pada jaringan payudara. Ini adalah jenis kanker paling umum yang
diderita kaum wanita. Kaum pria juga dapat terserang kanker payudara, walaupun kemungkinannya
lebih kecil dari 1 di antara 1000. Pengobatan yang paling lazim adalah dengan pembedahan dan jika
perlu dilanjutkan dengan kemoterapi maupun radiasi.
1.1. Definisi 1.1.1. Kanker adalah suatu kondisi dimana sel telah kehilangan pengendalian dan
mekanisme normalnya, sehingga mengalami pertumbuhan yang tidak normal, cepat dan tidak
terkendali. (http://www.mediasehat.com/utama07.php) 1.1.2. Kanker payudara (Carcinoma mammae)
adalah suatu penyakit neoplasma yang ganas yang berasal dari parenchyma. Penyakit ini oleh Word
Health Organization (WHO) dimasukkan ke dalam International Classification of Diseases (ICD)
dengan kode nomor 17 (http://www.tempo.co.id/medika/arsip/082002/pus-3.htm)
1.2. Patofisiologi 1.2.1. Transformasi Sel-sel kanker dibentuk dari sel-sel normal dalam suatu proses
rumit yang disebut transformasi, yang terdiri dari tahap inisiasi dan promosi. 1.2.1.1. pada tahap inisiasi
terjadi suatu perubahan dalam bahan genetik sel yang memancing sel menjadi ganas. Perubahan dalam
bahan genetik sel ini disebabkan oleh suatu agen yang disebut karsinogen, yang bisa berupa bahan
kimia, virus, radiasi (penyinaran) atau sinar matahari. tetapi tidak semua sel memiliki kepekaan yang
sama terhadap suatu karsinogen. kelainan genetik dalam sel atau bahan lainnya yang disebut promotor,
menyebabkan sel lebih rentan terhadap suatu karsinogen. bahkan gangguan fisik menahunpun bisa
membuat sel menjadi lebih peka untuk mengalami suatu keganasan. 1.2.1.2. pada tahap promosi, suatu
sel yang telah mengalami inisiasi akan berubah menjadi ganas. Sel yang belum melewati tahap inisiasi
tidak akan terpengaruh oleh promosi. karena itu diperlukan beberapa faktor untuk terjadinya keganasan
(gabungan dari sel yang peka dan suatu karsinogen). 1.2.2. Stadium Stadium penyakit kanker adalah
suatu keadaan dari hasil penilaian dokter saat mendiagnosis suatu penyakit kanker yang diderita
pasiennya, sudah sejauh manakah tingkat penyebaran kanker tersebut baik ke organ atau jaringan
sekitar maupun penyebaran ketempat jauh Stadium hanya dikenal pada tumor ganas atau kanker dan
tidak ada pada tumor jinak. Untuk menentukan suatu stadium, harus dilakukan pemeriksaan klinis dan
ditunjang dengan pemeriksaan penunjang lainnya yaitu histopatologi atau PA, rontgen , USG, dan bila
memungkinkan dengan CT Scan, scintigrafi dll. Banyak sekali cara untuk menentukan stadium, namun
yang paling banyak dianut saat ini adalah stadium kanker berdasarkan klasifikasi sistim TNM yang
direkomendasikan oleh UICC(International Union Against Cancer dari WHO atau World Health
Organization) / AJCC(American Joint Committee On cancer yang disponsori oleh American Cancer
Society dan American College of Surgeons). 1.2.2.1. Pada sistim TNM dinilai tiga faktor utama yaitu
"T" yaitu Tumor size atau ukuran tumor , "N" yaitu Node atau kelenjar getah bening regional dan "M"
yaitu metastasis atau penyebaran jauh. Ketiga faktor T,N,M dinilai baik secara klinis sebelum
dilakukan operasi , juga sesudah operasi dan dilakukan pemeriksaan histopatologi (PA) . Pada kanker
payudara, penilaian TNM sebagai berikut :
• T (Tumor size), ukuran tumor :
•
•
•
•
•
T 0 : tidak ditemukan tumor primer
T 1 : ukuran tumor diameter 2 cm atau kurang
T 2 : ukuran tumor diameter antara 2-5 cm
T 3 : ukuran tumor diameter > 5 cm
T 4 : ukuran tumor berapa saja, tetapi sudah ada penyebaran ke kulit atau dinding dada atau
pada keduanya , dapat berupa borok, edema atau bengkak, kulit payudara kemerahan atau ada
benjolan kecil di kulit di luar tumor utama
• N (Node), kelenjar getah bening regional (kgb) :
•
•
•
•
N 0 : tidak terdapat metastasis pada kgb regional di ketiak / aksilla
N 1 : ada metastasis ke kgb aksilla yang masih dapat digerakkan
N 2 : ada metastasis ke kgb aksilla yang sulit digerakkan
N 3 : ada metastasis ke kgb di atas tulang selangka (supraclavicula) atau pada kgb di mammary
interna di dekat tulang sternum
• M (Metastasis) , penyebaran jauh :
•
•
•
M x : metastasis jauh belum dapat dinilai
M 0 : tidak terdapat metastasis jauh
M 1 : terdapat metastasis jauh
1.2.2.2. Setelah masing-masing faktot T,.N,M didapatkan, ketiga faktor tersebut kemudian digabung
dan didapatkan stadium kanker sebagai berikut :
•
•
•
•
•
•
•
•
Stadium 0 : T0 N0 M0
Stadium 1 : T1 N0 M0
Stadium II A : T0 N1 M0 / T1 N1 M0 / T2 N0 M0
Stadium II B : T2 N1 M0 / T3 N0 M0
Stadium III A : T0 N2 M0 / T1 N2 M0 / T2 N2 M0 / T3 N1 M0 / T2 N2 M0
Stadium III B : T4 N0 M0 / T4 N1 M0 / T4 N2 M0
Stadium III C : Tiap T N3 M0
Stadium IV : Tiap T-Tiap N -M1
1.3. Gejala Klinis Gejala klinis kanker payudara dapat berupa • benjolan pada payudara Umumnya
berupa benjolan yang tidak nyeri pada payudara. Benjolan itu mula-mula kecil, makin lama makin
besar, lalu melekat pada kulit atau menimbulkan perubahan pada kulit payudara atau pada puting susu.
• erosi atau eksema puting susu Kulit atau puting susu tadi menjadi tertarik ke dalam (retraksi),
berwarna merah muda atau kecoklat-coklatan sampai menjadi oedema hingga kulit kelihatan seperti
kulit jeruk (peau d'orange), mengkerut, atau timbul borok (ulkus) pada payudara. Borok itu makin lama
makin besar dan mendalam sehingga dapat menghancurkan seluruh payudara, sering berbau busuk, dan
mudah berdarah. • pendarahan pada puting susu. • Rasa sakit atau nyeri pada umumnya baru timbul
kalau tumor sudah besar, sudah timbul borok, atau kalau sudah ada metastase ke tulang-tulang. •
Kemudian timbul pembesaran kelenjar getah bening di ketiak, bengkak (edema) pada lengan, dan
penyebaran kanker ke seluruh tubuh (Handoyo, 1990). Kanker payudara lanjut sangat mudah dikenali
dengan mengetahui kriteria operbilitas Heagensen sebagai berikut: • terdapat edema luas pada kulit
payudara (lebih 1/3 luas kulit payudara); • adanya nodul satelit pada kulit payudara; • kanker payudara
jenis mastitis karsinimatosa; • terdapat model parasternal; • terdapat nodul supraklavikula; • adanya
edema lengan; • adanya metastase jauh; • serta terdapat dua dari tanda-tanda locally advanced, yaitu
ulserasi kulit, edema kulit, kulit terfiksasi pada dinding toraks, kelenjar getah bening aksila berdiameter
lebih 2,5 cm, dan kelenjar getah bening aksila melekat satu sama lain
1.4. Faktor Resiko Menurut Moningkey dan KodimPenyebab spesifik kanker payudara masih belum
diketahui, tetapi terdapat banyak faktor yang diperkirakan mempunyai pengaruh terhadap terjadinya
kanker payudara diantaranya: 1.4.1. Faktor reproduksi Karakteristik reproduktif yang berhubungan
dengan risiko terjadinya kanker payudara adalah nuliparitas, menarche pada umur muda, menopause
pada umur lebih tua, dan kehamilan pertama pada umur tua. Risiko utama kanker payudara adalah
bertambahnya umur. Diperkirakan, periode antara terjadinya haid pertama dengan umur saat kehamilan
pertama merupakan window of initiation perkembangan kanker payudara. Secara anatomi dan
fungsional, payudara akan mengalami atrofi dengan bertambahnya umur. Kurang dari 25% kanker
payudara terjadi pada masa sebelum menopause sehingga diperkirakan awal terjadinya tumor terjadi
jauh sebelum terjadinya perubahan klinis. 1.4.2. Penggunaan hormon Hormon eksogen berhubungan
dengan terjadinya kanker payudara. Laporan dari Harvard School of Public Health menyatakan bahwa
terdapat peningkatan kanker payudara yang bermakna pada para pengguna terapi estrogen replacement.
Suatu metaanalisis menyatakan bahwa walaupun tidak terdapat risiko kanker payudara pada pengguna
kontrasepsi oral, wanita yang menggunakan obat ini untuk waktu yang lama mempunyai risiko tinggi
untuk mengalami kanker ini sebelum menopause. 1.4.3. Penyakit fibrokistik Pada wanita dengan
adenosis, fibroadenoma, dan fibrosis, tidak ada peningkatan risiko terjadinya kanker payudara. Pada
hiperplasis dan papiloma, risiko sedikit meningkat 1,5 sampai 2 kali. Sedangkan pada hiperplasia
atipik, risiko meningkat hingga 5 kali. 1.4.4. Obesitas Terdapat hubungan yang positif antara berat
badan dan bentuk tubuh dengan kanker payudara pada wanita pasca menopause. Variasi terhadap
kekerapan kanker ini di negara-negara Barat dan bukan Barat serta perubahan kekerapan sesudah
migrasi menunjukkan bahwa terdapat pengaruh diet terhadap terjadinya keganasan ini. 1.4.5. Konsumsi
lemak Konsumsi lemak diperkirakan sebagai suatu faktor risiko terjadinya kanker payudara. Willet
dkk., melakukan studi prospektif selama 8 tahun tentang konsumsi lemak dan serat dalam hubungannya
dengan risiko kanker payudara pada wanita umur 34 sampai 59 tahun. 1.4.6. Radiasi Eksposur dengan
radiasi ionisasi selama atau sesudah pubertas meningkatkan terjadinya risiko kanker payudara. Dari
beberapa penelitian yang dilakukan disimpulkan bahwa risiko kanker radiasi berhubungan secara linier
dengan dosis dan umur saat terjadinya eksposur. 1.4.7. Riwayat keluarga dan faktor genetik Riwayat
keluarga merupakan komponen yang penting dalam riwayat penderita yang akan dilaksanakan skrining
untuk kanker payudara. Terdapat peningkatan risiko keganasan ini pada wanita yang keluarganya
menderita kanker payudara. Pada studi genetik ditemukan bahwa kanker payudara berhubungan dengan
gen tertentu. Apabila terdapat BRCA 1, yaitu suatu gen suseptibilitas kanker payudara, probabilitas
untuk terjadi kanker payudara sebesar 60% pada umur 50 tahun dan sebesar 85% pada umur 70 tahun.
1.5. Pengobatan Kanker Ada beberapa pengobatan kanker payudara yang penerapannya banyak
tergantung pada stadium klinik penyakit (Tjindarbumi, 1994), yaitu: 1.5.1. Mastektomi Mastektomi
adalah operasi pengangkatan payudara. Ada 3 jenis mastektomi (Hirshaut & Pressman, 1992): 1.5.1.1.
Modified Radical Mastectomy, yaitu operasi pengangkatan seluruh payudara, jaringan payudara di
tulang dada, tulang selangka dan tulang iga, serta benjolan di sekitar ketiak. 1.5.1.2. Total (Simple)
Mastectomy, yaitu operasi pengangkatan seluruh payudara saja, tetapi bukan kelenjar di ketiak. 1.5.1.3.
Radical Mastectomy, yaitu operasi pengangkatan sebagian dari payudara. Biasanya disebut
lumpectomy, yaitu pengangkatan hanya pada jaringan yang mengandung sel kanker, bukan seluruh
payudara. Operasi ini selalu diikuti dengan pemberian radioterapi. Biasanya lumpectomy
direkomendasikan pada pasien yang besar tumornya kurang dari 2 cm dan letaknya di pinggir
payudara. 1.5.2. Penyinaran/radiasi Yang dimaksud radiasi adalah proses penyinaran pada daerah yang
terkena kanker dengan menggunakan sinar X dan sinar gamma yang bertujuan membunuh sel kanker
yang masih tersisa di payudara setelah operasi (Denton, 1996). Efek pengobatan ini tubuh menjadi
lemah, nafsu makan berkurang, warna kulit di sekitar payudara menjadi hitam, serta Hb dan leukosit
cenderung menurun sebagai akibat dari radiasi. 1.5.3. Kemoterapi Kemoterapi adalah proses pemberian
obat-obatan anti kanker dalam bentuk pil cair atau kapsul atau melalui infus yang bertujuan membunuh
sel kanker. Tidak hanya sel kanker pada payudara, tapi juga di seluruh tubuh (Denton, 1996). Efek dari
kemoterapi adalah pasien mengalami mual dan muntah serta rambut rontok karena pengaruh obatobatan yang diberikan pada saat kemoterapi.
1.6. Strategi Pencegahan Pada prinsipnya, strategi pencegahan dikelompokkan dalam tiga kelompok
besar, yaitu pencegahan pada lingkungan, pada pejamu, dan milestone. Hampir setiap epidemiolog
sepakat bahwa pencegahan yang paling efektif bagi kejadian penyakit tidak menular adalah promosi
kesehatan dan deteksi dini. Begitu pula pada kanker payudara, pencegahan yang dilakukan antara lain
berupa: 1.6.1. Pencegahan primer Pencegahan primer pada kanker payudara merupakan salah satu
bentuk promosi kesehatan karena dilakukan pada orang yang "sehat" melalui upaya menghindarkan diri
dari keterpaparan pada berbagai faktor risiko dan melaksanakan pola hidup sehat. 1.6.2. Pencegahan
sekunder Pencegahan sekunder dilakukan terhadap individu yang memiliki risiko untuk terkena kanker
payudara. Setiap wanita yang normal dan memiliki siklus haid normal merupakan populasi at risk dari
kanker payudara. Pencegahan sekunder dilakukan dengan melakukan deteksi dini. Beberapa metode
deteksi dini terus mengalami perkembangan. Skrining melalui mammografi diklaim memiliki akurasi
90% dari semua penderita kanker payudara, tetapi keterpaparan terus-menerus pada mammografi pada
wanita yang sehat merupakan salah satu faktor risiko terjadinya kanker payudara. Karena itu, skrining
dengan mammografi tetap dapat dilaksanakan dengan beberapa pertimbangan antara lain: • Wanita
yang sudah mencapai usia 40 tahun dianjurkan melakukan cancer risk assessement survey. • Pada
wanita dengan faktor risiko mendapat rujukan untuk dilakukan mammografi setiap tahun. • Wanita
normal mendapat rujukan mammografi setiap 2 tahun sampai mencapai usia 50 tahun. Foster dan
Constanta menemukan bahwa kematian oleh kanker payudara lebih sedikit pada wanita yang
melakukan pemeriksaan SADARI (Pemeriksaan Payudara Sendiri) dibandingkan yang tidak. Walaupun
sensitivitas SADARI untuk mendeteksi kanker payudara hanya 26%, bila dikombinasikan dengan
mammografi maka sensitivitas mendeteksi secara dini menjadi 75%. 1.6.3. Pencegahan Tertier
Pencegahan tertier biasanya diarahkan pada individu yang telah positif menderita kanker payudara.
Penanganan yang tepat penderita kanker payudara sesuai dengan stadiumnya akan dapat mengurangi
kecatatan dan memperpanjang harapan hidup penderita. Pencegahan tertier ini penting untuk
meningkatkan kualitas hidup penderita serta mencegah komplikasi penyakit dan meneruskan
pengobatan. Tindakan pengobatan dapat berupa operasi walaupun tidak berpengaruh banyak terhadap
ketahanan hidup penderita. Bila kanker telah jauh bermetastasis, dilakukan tindakan kemoterapi dengan
sitostatika. Pada stadium tertentu, pengobatan diberikan hanya berupa simptomatik dan dianjurkan
untuk mencari pengobatan alternatif.
KANKER PAYUDARA
Fakta dan Angka
Menurut WHO 8-9% wanita akan mengalami kanker payudara. Ini menjadikan
kanker payudara sebagai jenis kanker yang paling banyak ditemui pada wanita. Setiap
tahun lebih dari 250,000 kasus baru kanker payudara terdiagnosa di Eropa dan kurang
lebih 175,000 di Amerika Serikat. Masih menurut WHO, tahun 2000 diperkirakan 1,2
juta wanita terdiagnosis kanker payudara dan lebih dari 700,000 meninggal karenanya.
Belum ada data statistik yang akurat di Indonesia, namun data yang terkumpul dari
rumah sakit menunjukkan bahwa kanker payudara menduduki ranking pertama
diantara kanker lainnya pada wanita.
Kanker payudara merupakan penyebab utama kematian pada wanita akibat kanker.
Setiap tahunnya, di Amerika Serikat 44,000 pasien meninggal karena penyakit ini
sedangkan di Eropa lebih dari 165,000. Setelah menjalani perawatan, sekitar 50%
pasien mengalami kanker payudara stadium akhir dan hanya bertahan hidup 18 – 30
bulan.
Penyebab dan Faktor Resiko
Penyebab pasti kanker payudara tidak diketahui. Meskipun demikian, riset
mengidentifikasi sejumlah faktor yang dapat meningkatkan risiko pada individu
tertentu, yang meliputi:
• Keluarga yang memiliki riwayat penyakit serupa
• Usia yang makin bertambah
• Tidak memiliki anak
• Kehamilan pertama pada usia di atas 30 tahun
• Periode menstruasi yang lebih lama (menstruasi pertama lebih awal atau
menopause lebih lambat)
• Faktor hormonal (baik estrogen maupun androgen).
Dari faktor risiko tersebut di atas, riwayat keluarga serta usia menjadi faktor
terpenting. Riwayat keluarga yang pernah mengalami kanker payudara meningkatkan
resiko berkembangnya penyakit ini. Para peneliti juga menemukan bahwa kerusakan
dua gen yaitu BRCA1 dan BRCA2 dapat meningkatkan risiko wanita terkena kanker
sampai 85%. Hal yang menarik, faktor genetik hanya berdampak 5-10% dari
terjadinya kanker payudara dan ini menunjukkan bahwa faktor risiko lainnya
memainkan peranan penting.
Pentingnya faktor usia sebagai faktor risiko diperkuat oleh data bahwa 78% kanker
payudara terjadi pada pasien yang berusia lebih dari 50 tahun dan hanya 6% pada
pasien yang kurang dari 40 tahun. Rata-rata usia pada saat ditemukannya kanker
adalah 64 tahun.
Studi juga mengevaluasi peranan faktor gaya hidup dalam perkembangan kanker
payudara yang meliputi pestisida, konsumsi alkohol, kegemukan, asupan lemak serta
kurangnya olah fisik.
Diagnosis dan Skrining
Sejumlah studi memperlihatkan bahwa deteksi kanker payudara dan serta terapi dini
dapat meningkatkan harapan hidup dan memberikan pilihan terapi lebih banyak pada
pasien.
Diperkirakan 95% wanita yang terdiagnosis pada tahap awal kanker payudara dapat
bertahan hidup lebih dari lima tahun setelah diagnosis sehingga banyak dokter yang
merekomendasikan agar para wanita menjalani ‘sadari’ (periksa payudara sendiri –
saat menstruasi) di rumah secara rutin dan menyarankan dilakukannya pemeriksaan
rutin tahunan untuk mendeteksi benjolan pada payudara. Pada umumnya, kanker
payudara dideteksi oleh penderita sendiri dan biasanya berupa benjolan yang keras
dan kecil. Pada banyak kasus benjolan ini tidak sakit, tapi beberapa wanita mengalami
kanker yang menimbulkan rasa sakit.
Selain tes fisik, mamografi tahunan atau dua kali setahun dan USG khusus payudara
disarankan untuk mendeteksi adanya kelainan pada wanita berusia lanjut dan wanita
berisiko tinggi kanker payudara, sebelum terjadi kanker. Jika benjolan bisa teraba atau
kelainan terdeteksi saat mamografi, biopsi perlu dilakukan untuk mendapatkan
contoh jaringan guna dilakukan tes di bawah mikroskop dan meneliti kemungkinan
adanya tumor.
Jika terdiagnosis kanker, maka perlu dilakukan serangkaian tes seperti status reseptor
hormon pada jaringan yang terkena.
Jenis tes yang baru menyertakan juga tes gen HER2 (human epidermal growth factor
receptor-2) untuk tumor. Gen ini berhubungan dengan pertumbuhan sel kanker yang
agresif. Pasien dikatakan HER2-positif jika pada tumor ditemukan HER2 dalam
jumlah besar. Kanker dengan HER2-positif dikenal sebagai bentuk agresif dari kanker
payudara dan memiliki perkiraan perjalanan penyakit yang lebih buruk daripada
pasien dengan HER2-negatif. Diperkirakan satu dari empat sampai lima pasien
dengan kanker payudara tahap akhir memiliki HER2-positif.
Penatalaksanaan Kanker Payudara
Penatalaksanaan kanker payudara dilakukan dengan serangkaian pengobatan meliputi
pembedahan, kemoterapi, terapi hormon, terapi radiasi dan yang terbaru adalah
terapi imunologi (antibodi). Pengobatan ini ditujukan untuk memusnahkan kanker
atau membatasi perkembangan penyakit serta menghilangkan gejala-gejalanya.
Keberagaman jenis terapi ini mengharuskan terapi dilakukan secara individual.
Pembedahan
Tumor primer biasanya dihilangkan dengan pembedahan. Prosedur pembedahan
yang dilakukan pada pasien kanker payudara tergantung pada tahapan penyakit, jenis
tumor, umur dan kondisi kesehatan pasien secara umum. Ahli bedah dapat
mengangkat tumor (lumpectomy), mengangkat sebagian payudara yang mengandung
sel kanker atau pengangkatan seluruh payudara (mastectomy). Untuk meningkatkan
harapan hidup, pembedahan biasanya diikuti dengan terapi tambahan seperti radiasi,
hormon atau kemoterapi.
Terapi Radiasi
Terapi radiasi dilakukan dengan sinar-X dengan intensitas tinggi untuk membunuh
sel kanker yang tidak terangkat saat pembedahan.
Terapi Hormon
Terapi hormonal dapat menghambat pertumbuhan tumor yang peka hormon dan
dapat dipakai sebagai terapi pendamping setelah pembedahan atau pada stadium
akhir.
Kemoterapi
Obat kemoterapi digunakan baik pada tahap awal ataupun tahap lanjut penyakit
(tidak dapat lagi dilakukan pembedahan). Obat kemoterapi bisa digunakan secara
tunggal atau dikombinasikan. Salah satu diantaranya adalah Capecitabine dari Roche,
obat anti kanker oral yang diaktivasi oleh enzim yang ada pada sel kanker, sehingga
hanya menyerang sel kanker saja.
Terapi Imunologik
Sekitar 15-25% tumor payudara menunjukkan adanya protein pemicu pertumbuhan
atau HER2 secara berlebihan dan untuk pasien seperti ini, trastuzumab, antibodi yang
secara khusus dirancang untuk menyerang HER2 dan menghambat pertumbuhan
tumor, bisa menjadi pilihan terapi. Pasien sebaiknya juga menjalani tes HER2 untuk
menentukan kelayakan terapi dengan trastuzumab.
Mengobati Pasien Pada Tahap Akhir Penyakit
Banyak obat anti kanker yang telah diteliti untuk membantu 50% pasien yang
mengalami kanker tahap akhir dengan tujuan memperbaiki harapan hidup. Meskipun
demikian, hanya sedikit yang terbukti mampu memperpanjang harapan hidup pada
pasien, diantaranya adalah kombinasi trastuzumab dengan capecitabine. Fokus terapi
pada kanker tahap akhir bersifat paliatif (mengurangi rasa sakit). Dokter berupaya
untuk memperpanjang serta memperbaiki kualitas hidup pasien melalui terapi
hormon, terapi radiasi dan kemoterapi. Pada pasien kanker payudara dengan HER2positif, trastuzumab memberikan harapan untuk pengobatan kanker payudara yang
dipicu oleh HER2.
=====http://www.hompedin.org/download/kankerpayudara.pdf
INTRODUCTION
Breast Cancer constitutes a major public health issue globally with over 1 million new cases diagnosed
annually, resulting in over 400,000 annual deaths and about 4.4 million women living with the disease. It is
the commonest site specific malignancy affecting women and the most common cause of cancer mortality
in women worldwide.(1;2)
There is an international/geographical variation in the incidence of Breast Cancer.
Incidence rates are higher in the developed countries than in the developing countries and Japan.
Incidence rates are also higher in urban areas than in the rural areas.
In Africa, Breast Cancer has overtaken cervical cancer as the commonest malignancy affecting women
and the incidence rates appear to be rising. (3;4) In Nigeria for example, incidence rate has increased
from 13.8–15.3 per 100,000 in the 1980s, to 33.6 per 100,000 in 1992 and 116 per 100,000 in 2001. (5)
These increases in incidence are due to changes in the demography, socio-economic parameters,
epidemiologic risk factors, better reporting and awareness of the disease. While mortality rates are
declining in the developed world (Americas, Australia and Western Europe) as a result of early
diagnosis, screening, and improved cancer treatment programs, the converse is true in the developing
world as well as in eastern and central Europe.(6-8)
Breast cancer and its treatment constitute a great physical, psychosocial and economic challenge in
resource limited societies as found in Africa. The hallmarks of the disease in Africa are patients
presenting at advanced stage, lack of adequate mammography screening programs, preponderance of
younger pre-menopausal patients, and a high morbidity and mortality. (3;6)
This Review is meant to provide practical guidance for the surgeon working in the developing world.
We have relied on the Chapter on Breast Cancer by Bland et al in Schwartz’s Principles of Surgery, 8th
Edition. (9)
Material which is of interest but not immediately applicable has been placed in smaller print. In the
Recommendations we have followed the principles developed in the Breast Health Global Initiative.
(10-12)
2. HISTORY
Breast cancer is one of the oldest known forms of malignancies. The earliest known documentation on
breast cancer was the Smith Surgical Papyrus (3000-2500 B.C.) written in Africa (Egypt). It described
8 cases of tumors or ulcers of the breast that were treated by cauterization, with a tool called "the fire
drill." The writing says about the disease, "There is no treatment." At least one of the described cases is
male. There were few other historical references to breast cancer until the first century when Celsus
recognized the relevance of operations for early breast cancer.
In the second century, Galen inscribed his classical clinical observation: "We have often seen in the
breast a tumor exactly resembling the animal the crab. Just as the crab has legs on both sides of his
body, so in this disease the veins extending out from the unnatural growth take the shape of a crab's
legs. We have often cured this disease in its early stages, but after it has reached a large size, no one has
cured it. In all operations we attempt to excise the tumor in a circle where it borders on the healthy
tissue."(13)
Halsted and Meyer reported their operations for the local treatment of breast cancer in 1894. Both
Halsted and Meyer advocated complete dissection of axillary lymph node levels I to III and removal of
pectoral muscle along with the breast. By demonstrating locoregional control rates after radical
resection and providing the first opportunity for cure, these surgeons established radical mastectomy as
state-of-the-art treatment in the early part of the 20th century. Later in the century, there was a
transition from the Halsted radical mastectomy to the modified radical mastectomy (MRM) as the
surgical procedure most frequently used for breast cancer. This procedure maintained the en bloc
dissection of the breast and lymph nodes, but left the pectoralis major muscle intact.
The recognition in the 1950s that breast cancer was often a systemic disease at presentation shifted the
management of primary breast cancer away from a purely surgical approach to a multidisciplinary one
that uses systemic therapy, surgery and radiation. As a result surgery for breast cancer may now be
managed with more conservative and less locally ablative procedures such as lumpectomy. The past
three decades has witnessed an enormous growth in the knowledge and understanding of the basic
science of the disease especially the genetic and molecular basis of the disease.
3. ANATOMY OF THE BREAST
The breast is a modified sweat gland and therefore ectodermal in origin. It is present in all mammals
and becomes particularly prominent in females as the hallmark of pubertal development. It lies
cushioned in adipose tissue between the subcutaneous fat layer and the superficial pectoral fascia. It
extends from the clavicle above to the upper border of the rectus sheath below and from the midline to
the posterior axillary line. It overlies the second to the sixth ribs, the pectoralis major, serratus anterior
and the upper part of the rectus sheath. The area covered is wider than the visible protuberant breast.
An axillary extension of the breast (axillary tail of Spence) always exists and its size is proportional to
the total volume of the main breast mass. The innervation of the breast is derived from the anterior
branches of the intercostal nerves 2 through 6 with the nipple receiving its innervation from the 4th
intercostal nerve. The major blood supply, in order of importance, are the internal mammary branches,
the lateral thoracic, and the thoracodorsal perforating vessels from the pectoral branch of the
throacoacrominal branch of the axillary artery, and small intercostals branches. The venous and
lymphatic drainage parallel the blood supply.
The glandular tissue consists mainly of epithelium, fibrous stroma, and fat. The breast is organized into
roughly 20 lobular units made up of terminal ducts surrounded by fat and fibrous tissues and efferent
ductules. These terminal ducts coalesce and drain towards the areola forming the 15-20 ducts of the
nipple areolar complex.
The lymphatic drainage is primarily to the axillary nodes (75%), divided into three levels by the
Pectoralis minor muscle (level I nodes lie lateral, level II nodes behind and level III nodes medial to the
muscle). Usually, but with some exceptions, lymphatic drainage is progressive through these levels.
Drainage also occurs to the internal mammary chain of lymph nodes which lie in the intercostal spaces,
the supraclavicular nodes, the opposite breast and axilla, and to the liver via the rectus abdominis
muscle.
4. EPIDEMIOLOGIC RISK FACTORS/ETIOLOGY
The precise etiology of breast cancer is largely unknown, but several risk factors have been identified.
Table 1 lists the known risk factors.(14)
The risk factors include:
Age: The incidence of breast cancer increases with age and is rare before the age of 20 years. The
breast cancer incidence in Caucasians is highest at age 50-59, after menopause, dropping after age 70.
In Africa and African-Americans the peak age incidence is about one decade less, so that the majority
of the patients are pre- menopausal. While numerous theories have been proposed to explain this
difference, including age at menarche, time of first delivery, parity, socio-demographic factors, body
mass index, and underlying genetic difference, none are completely satisfactory and more research is
needed in this area.(3-5;15-17)
Sex: Breast Cancer is 100 times more common in women than in men with male breast cancer
accounting for <1% of all breast cancer cases in the United States and 0.1% of cancer mortality in men
(18-20).However in Africa this situation may be different as from 5-15% of breast cancer in Uganda
and Zambia may occur in males.(18;21-24)
Geographic variation: A wide difference in age adjusted incidence and mortality for breast cancer
exists between different countries (up to five fold). Figure 1 shows the difference which may be
explained by environmental and genetic factors.(25-28)
Hormone/Pregnancy related factors: The role of estrogen in the causation of breast cancer has been
extensively studied and the general opinion is that estrogen is the primary stimulant for breast epithelial
proliferation. Factors that increase exposure to high or prolonged level of estrogen are therefore
associated with an increased risk of developing breast cancer (29-33). These include early menarche,
late menopause, use of contraceptives and exogenous estrogen, nulliparity and increased age at first
term pregnancy. Induced abortion and spontaneous abortion do not increase the risk. Prolonged
lactation and breast feeding reduce the risk. As the living standard and health care facilities in Africa
improve, it is probable that age at menarche will decrease while that of menopause increases. The
demands for education and a career may increase the number of women who delay childbearing, have
fewer children, use contraceptives and breast feed for a shorter time. These will likely impact on the
increase in the incidence of breast cancer as African countries meet the minimum development goals.
Previous Breast Disease: Individuals who have a prior history of invasive carcinoma or ductal
carcinoma in situ have a 0.5%-1% per year risk of developing a new invasive breast carcinoma.
Women with atypical ductal or lobular hyperplasia have a four to five times higher risk of developing
breast cancer. Proliferative lesions without atypia, such as moderate hyperplasia and sclerosing
adenosis, are associated with a slightly increased risk (1.5-2%). Other common non-proliferative
changes such as palpable cysts, fibroadenomas and duct papillomas are not associated with a
significantly increased risk. (34)
Enviromental Exposures: Exposure to ionizing irradiation increases the risk of developing breast
cancer. Excess breast cancer has been observed in patients given multiple fluoroscopies, radiotherapy
for ankylosing spondylitis, Hodgkin’s disease, or enlargement of the thymus gland and in survivors of
the atomic bombings, painters of radium watch faces and X-ray technicians (28). Environmental
exposures to organic chlorines and other environmental/synthetic estrogens like cosmetics and
phytoestrogens found in food have also been postulated to increase the risk, but so far there are no
conclusive evidence linking organic chlorines to breast cancer. (31;35;36)
LIFESTYLE RISKS
Anthropometric indices and physical activity: Height, obesity and high body mass
index are risk factors especially in post menopausal women. In pre-menopausal women, obesity and
high body mass index has an insignificant but inverse relationship to breast cancer risk that is reduced
by physical activity. (37-39)
Diet, Alcohol and Smoking: Alcohol and Diets rich in fat especially saturated fat raises the risk while
smoking does not appear to affect the risk. (40-42)
FAMILY HISTORY AND GENETICS
A family history of breast cancer increases a woman's risk of developing the disease. A woman is
considered to be at increased risk if the family member is a first degree relation with early age of onset
(< age 50), if both breasts are involved, or if she has multiple primary cancers (such as breast and
ovarian cancer). Women with one, two, and three or more first-degree affected relatives have an
increased breast cancer risk when compared with women who do not have an affected relative (risk
ratios 1.8, 2.9 and 3.9, respectively) (43) Such women are recommended to begin breast cancer
screening at an age 10 years younger than the age at which the affected relative was diagnosed.
Hereditary breast cancer caused by an underlying inherited gene mutation accounts for a small
proportion (5-10%) of all breast cancers. The majority is accounted for by 2 germline mutations
BRCA-1 (50%) and BRCA-2 (32%), which are inherited in an autosomal dominant fashion with
varying penetrance. These tumor suppressor genes are important in the processing of DNA damage and
preservation of genomic integrity. BRCA-1 is located on chromosome 17q while BRCA-2 is located on
chromosome 13q. (44) They are most commonly found in the European Ashkenazi Jewish population
and their descendants, accounting for their relatively high prevalence in the developed world. In Europe
and North America, BRCA1 is found in 0.1% of the general population, compared with 20% in the
Ashkenazi Jewish population and is found in 3% of the unselected breast cancer population and in 70%
of women with inherited early-onset breast cancer. (9) Up to 50-87% of women carrying a mutated
BRCA1 gene develop breast cancer during their lifetime. Risks for ovarian and prostate cancers are
also increased in carriers of this mutation. BRCA2 mutations are identified in 10-20% of families at
high risk for breast and ovarian cancers and in only 2.7% of women with early-onset breast cancer. The
lifetime risk of developing breast cancer in female carriers is 25-30%. BRCA2 is also a risk factor for
male breast cancer; male carriers have a lifetime risk of 6% for developing the cancer. BRCA2
mutations are associated with other types of cancers, such as prostate, pancreatic, fallopian tube,
bladder, non-Hodgkin lymphoma, and basal cell carcinoma.
Risk management strategies for BRCA-1 and BRCA-2 carriers include:
• Prophylactic mastectomy and reconstruction;
• Prophylactic oophorectomy and hormone replacement therapy;
• Intensive surveillance for breast and ovarian cancer; and
• Chemoprevention using Tamoxifen or raloxifene (post-menopausal women)
In contrast, less is known about genetic mutations as a cause of breast cancer in the non-Caucasian
population. Studies that have been done of African-Americans, whose genetic history includes
Caucasians, have identified BRCA-1 and -2 mutations but of a different pattern.(17;45;46) In native
Africans, a wide range of BRCA-1 and BRCA-2 mutations and sequence variations have been found
which are unique. This suggests that there may be significant differences in the genetics of hereditary
breast cancer in Africa.
A screening of 206 black South African women with breast cancer revealed 3 common BRCA1 mutations: 185delAG in exon
2, 4184del4 in exon 11, and 5382insC in exon 2022. A second study of the coding regions of BRCA1 and BRCA2 genes from
70 Nigerian patients diagnosed with breast cancer before the age of 40 years revealed 2 novel BRCA1 truncating
mutations, Q1090X and 1742insG; four BRCA1 missense variations; one BRCA2 truncating mutation, 3034del4, previously
unreported in anyone of African descent; and 20 nontruncating variants were detected in BRCA2.45 BRCA1 and BRCA2
mutations and sequence variations are potentially significant in cases of early-onset breast cancer within Africa. However,
only a small portion of the mutations were protein truncating, fewer than those observed among white women.( 47)
Other rare genetic changes that account for predisposition to breast cancer include Li Fraumeni syndrome (TP53 gene
mutation), Cowdens syndrome, Peutz-Jeghers and Muir-Torre syndromes, Ataxia Telangiectasia syndrome (caused by the
ATM gene). (48-51) New breast cancer susceptibility genes are being reported and they include the CHEK2 or CHK2
gene, cytochrome P450 genes (CYP1A1, CYP2D6, CYP19), glutathione S-transferase family (GSTM1, GSTP1), alcohol and
one-carbon metabolism genes (ADH1C and MTHFR), DNA repair genes (XRCC1, XRCC3, ERCC4/XPF) and genes
encoding cell signaling molecules (PR, ER, TNFalpha or HSP70). All these factors contribute to a better understanding of
breast cancer risk but the degree of penetrance of these genes are far less than the BRCA1 and BRCA2 genes (43;51)
RISK ASSESSMENT
Several statistical models are currently in use in North America to predict the risk of breast cancer,
based on the above risk factors identified in the American Caucasian population. The universal
applicability of these models can not, however be taken for granted as the data on which they rely on
were generated from predominantly American Caucasian population and have not been tested for
African women (43;52;53)
The most prominent statistical models are the Gail and the Claus models. Gail and colleagues developed the most
frequently used model, which incorporates age at menarche, the number of breast biopsies, age at first live birth, and the
number of first-degree relatives with breast cancer. It predicts the cumulative risk of breast cancer according to decade of
life. To calculate breast cancer risk with the Gail model, a woman's risk factors are translated into an overall risk score by
multiplying her relative risks from several categories. This risk score is then compared to an adjusted population risk of
breast cancer to determine a woman's individual risk. A software program incorporating the Gail model is available from
the National Cancer Institute at http://bcra.nci.nih.gov/brc.
Claus and colleagues, using data from the Cancer and Steroid Hormone Study, a case-control study of breast cancer,
developed the other frequently used risk-assessment model, which is based on assumptions about the prevalence of highpenetrance breast cancer susceptibility genes. Compared with the Gail model, the Claus model incorporates more
information about family history, but excludes other risk factors. The Claus model provides individual estimates of breast
cancer risk according to decade of life based on knowledge of first- and second-degree relatives with breast cancer and
their age at diagnosis. Risk factors that are less-consistently associated with breast cancer (diet, use of oral contraceptives,
lactation), or are rare in the general population (radiation exposure), are not included in either the Gail or Claus riskassessment models.(54)
5. PATHOLOGY
Breast cancers are derived from the epithelial cells that line the terminal duct lobular unit. Cancer cells
that remain within the basement membrane of the elements of the terminal duct lobular unit and the
draining duct are classified as in situ or non-invasive. An invasive breast cancer is one in which there is
dissemination of cancer cells outside the basement membrane of the ducts and lobules into the
surrounding adjacent normal tissue.
Classification of Primary Breast Cancer
Noninvasive Epithelial Cancers
Lobular Carcinoma in situ (LCIS)
Ductal Carcinoma in situ (DCIS) or intraductal carcinoma: Papillary, cribriform, solid and
comedo types
Invasive Epithelial Cancers (percentage of total)
Invasive lobular carcinoma (10-15)
Invasive ductal carcinoma
Invasive ductal carcinoma, (NOS) Not Otherwise Specified (50-70)
Tubular carcinoma (2-3)
Mucinous or colloid carcinoma (2-3)
Medullary carcinoma (5)
Invasive cribriform (1-3)
Invasive papillary (1-2)
Adenoid cystic carcinoma (1)
Metaplastic carcinoma (1)
Pagets disease (<1)
Mixed Connective and Epithelial Tumors
Phylloides tumors, benign and malignant
Carcinosarcoma
Angiosarcoma
Paget’s disease of the breast is a rare manifestation of breast cancer characterized by neoplastic cells in
the epidermis of the nipple areolar complex. It most commonly presents with eczema of the areola,
bleeding, ulceration, and itching of the nipple. The diagnosis is often delayed because of the rare nature
of the condition and confusion with other dermatologic conditions. Because of this, it is recommended
that any ulcerated or irritated lesion on the nipple areolar complex undergo a punch biopsy under local
anesthesia. There is an associated cancer elsewhere in the breast in up to 80% of cases.
LCIS originates from the terminal duct lobular units and only develops in the female breast. It is 12
times more frequent in white women than in African American women. Invasive breast cancer
subsequently may develop in 25 to 35% of women with LCIS over their lifetime, and may develop in
either breast, regardless of which breast harbored the initial focus of LCIS
DCIS: predominantly seen in the female breast, it accounts for 5% of male breast cancers. The risk for
invasive breast cancer is increased nearly fivefold in women with DCIS. The invasive cancers are
observed in the ipsilateral breast, usually in the same quadrant as the DCIS that was originally detected,
suggesting that DCIS is an anatomic precursor of invasive ductal carcinoma.
Tumor Grade
The degree of differentiation of the tumor can be graded by these parameters: tubule formation, nuclear
pleomorphism, and frequency of mitoses. These are scored from 1 to 3. For example, a tumor with
many tubules (the cells are more differentiated, closer to normal breast tissue and therefore less
aggressive) would score 1 whereas a tumor with no tubules would score 3. These values are combined
and converted into three groups: grade I (score 3-5), grade II (scores 6 and 7), and grade III (scores 8
and 9). This derived histological grade—often known as the Bloom and Richardson grade or the Scarff,
Bloom, and Richardson grade after the originators of this system—is an important predictor of both
disease free and overall survival. (See Prognosis)
Staging
Staging of Cancer is an attempt to define characteristics that would reliably define tumors based on the
extent of the disease. It is useful for choosing treatment options, selection of patients and comparing the
outcome of treatment and clinical trials and for prognosticating. In Africa, where over 70% of breast
cancer patients present late, staging of breast cancer patients can provide revealing epidemiological
information about opportunities for improving breast cancer screening and management.
The first staging method for Breast Cancer was proposed by Steinthal, a German Physician in 1904,
and since then staging method has been evolving, with the TNM (Tumor, Node, Metastasis) method
being universally adopted by the UICC (The International Union Against Cancer) and the American
Joint Committee on Cancer (AJCC). Tables 2 and 3 show the latest TNM staging for Breast Cancer
(AJCC classification (6th edition or revision) (55), which incorporates both clinical information and
changes related to the growing use of new technology (e.g., sentinel lymph node biopsy,
immunohistochemical staining, reverse transcriptase-polymerase chain reaction). Patients with bilateral
or multicentric breast cancer are staged according to the size of the largest tumor.
6. DIAGNOSIS
1. Examination: Early breast cancer causes no symptoms and is usually painless. The
commonest symptom is a painless lump in the breast. Examination of the breast should be
done in such a way to show respect for the privacy and comfort of the patient. A systematic
approach to breast examination is important. Initial examination should start with the
patient in an upright position with careful visual inspection of masses, skin and nipple
changes, and asymmetries. Palpation should be done to include all the breast quadrants, the
nipple-areola complex, the axillary tail and the axilla. Simple maneuvers like stretching the
arms high above the head, tensing the pectoralis muscles may help accentuate asymmetries
and dimpling.
Other less frequent presenting signs and symptoms of breast cancer include (1) breast
enlargement or asymmetry; (2) nipple changes, retraction, or discharge, including Paget’s
disease; (3) ulceration or erythema of the skin of the breast including inflammatory
carcinoma; (4) an axillary mass; and (5) systemic symptoms such as fatigue, cough, ascites
or new musculoskeletal discomfort.
2. Imaging: Mammography, Ductography, Ultrasonography, MRI are imaging techniques
useful in the screening and diagnosis of breast cancer.
Mammography is the most useful test to differentiate between benign and malignant
lesions and is the one that is recommended for breast cancer screening. Specific
mammography features that suggest a diagnosis of a breast cancer include a solid mass with
or without stellate features, asymmetric thickening of breast tissues, and clustered
microcalcifications Mammography may also be used to guide interventional procedures,
including needle localization and needle biopsy.
Xeromammography techniques are identical to those of mammography with the exception that the image is
recorded on a xerography plate, which provides a positive rather than a negative image Details of the entire
breast and the soft tissues of the chest wall may be recorded with one exposure.
Ductography and Ductoscopy
Mammary ductoscopy (MD) is a newly developed endoscopic technique that allows direct visualization and
biopsy examination of the mammary ductal epithelium where most cancers originate. When combined with
ductal lavage and cytology , it may reveal early carcinoma.( 56-59) The primary indication for ductography
is nipple discharge, particularly when the fluid contains blood. Radiopaque contrast media is injected into
one or more of the major ducts and mammography is performed. Intraductal papillomas are seen as small
filling defects surrounded by contrast media .Cancers may appear as irregular masses or as multiple
intraluminal filling defects.
Ultrasonography is an important method of resolving equivocal mammography findings,
defining cystic masses, and demonstrating the echogenic qualities of specific solid
abnormalities. Ultrasonography is used to guide fine-needle aspiration biopsy, core-needle
biopsy, and needle localization of breast lesions. It is highly reproducible and has a high
patient acceptance rate, but does not reliably detect lesions that are 1 cm or less in diameter
and when used alone is a poor screening test (60;61)
Magnetic Resonance Imaging is a non invasive, non radiating imaging technique. In the process of
evaluating MRI as a means of characterizing mammography abnormalities, additional breast lesions have
been detected. However, in the circumstance of both a negative mammogram and a negative physical
examination, the probability of a breast cancer being diagnosed by MRI is extremely low. There is current
interest in using MRI to screen the breasts of high-risk women and of women with a newly diagnosed breast
cancer. In the first case, women with a strong family history of breast cancer or who carry known genetic
mutations require screening at an early age, but mammography evaluation is limited because of the increased
breast density in younger women. In the second case, a study of MRI of the contralateral breast in women
with a known breast cancer showed a contralateral breast cancer in 5.7% of these women. ( 62-64)
Plain X-rays and Bone Scan are useful in the detection and diagnosis of metastasis
especially to the bones.
MRI, PET, CT Scans and bone scans are not readily available in most centers in the
developing world, and when available, the cost of these procedures makes them virtually
unrealistic for many of the patients. Ultrasonography and X-rays are however readily
available and many patients will end up with these minimal investigations and the standard
history and physical examination.
3. Biopsy
Pathologic diagnosis of a breast lesion can be achieved using a number of biopsy
techniques. With a larger biopsy sample, greater accuracy and more information are
obtained, but this is at the expense of increased invasiveness. Ideally, needle biopsies
should be performed after imaging to help prevent distortions of imaging due to hematoma.
The various needle biopsy techniques can be divided into two groups
1. Fine needle aspiration will provide cytology which will allow a diagnosis of malignant
cells but will not differentiate between in situ or invasive disease.
2. Tissue biopsy for histology which include Tru cut biopsy, Biopty cut, Mammotome.
These relatively larger tissue samples will allow the diagnosis of invasive versus in situ
cancer.
Table 4 compares the accuracy of needle biopsy techniques.
Open Biopsy (Excision or Incision biopsy) The ultimate diagnostic biopsy is open biopsy of a lesion,
normally performed under general or local anesthetic. Open excisional biopsy should be reserved for
lesions for which some doubt remains regarding diagnosis after less invasive assessment or for benign
lesions that the patient wants removed. A wide clearance of the lesion is usually not the goal in
diagnostic biopsies, thus avoiding unnecessary distortion of the breast. It is also useful for excision of
mammographic lesions when percutaneous biopsy has failed or is equivocal. Where frozen section is
available, open excisional biopsy may be performed at the same time the as definitive breast cancer
surgery. Incisional biopsy is used only in cases where the lesion is very large and a percutaneous biopsy
has been unsuccessful.
7. SCREENING
Annual screening mammography has been demonstrated to reduce breast cancer mortality among
women older than 50 years by 20 -39%. The benefit in younger women is not yet established. For
Caucasian women aged 40–49, the results of RCTs are consistent in showing no benefits at 5–7 years
after entry, a marginal benefit at 10–12 years, and unknown benefit thereafter. This is primarily because
when used as a screening tool, the detection rate per screened individual is lower because of denser
breasts and an overall lower incidence. The controversy over the effectiveness of screening
mammography among younger women (i.e., 40–49 years) has led to varying recommendations about
its use for this age group. In patients with high risk factors a yearly mammography assessment from the
age of 40 years is advisable.(65-67). Considering the younger demographic pattern of Breast Cancer in
Africa, it is not clear what role screening mammography should have in Africa.
Other methods of early breast cancer screening like Self Breast Examination and Clinical Breast
Examination have not been demonstrated to improve mortality in patients; rather SBE has resulted in
more breast biopsies due to false positive results, more physician visits and apprehension in patients
(68). It is pertinent to state that most of the studies that evaluated the role of SBE and CBE have been
done in developed societies where cancers are small at diagnosis and this may not be relevant in Africa
where the majority of patients present late. Incorporation of Breast Awareness programs and health
education into the Primary Health Care of African countries may very well be a useful option to allow
for a diagnosis at an earlier stage. Cultural attitudes play important roles in the acceptance of screening
programs.(69)
8. TREATMENT
Treatment strategy will depend on the stage of the disease.
In situ Breast Cancer (DCIS and LCIS)
LCIS: Observation alone with or without tamoxifen is the preferred option for women diagnosed with
LCIS because their risk of developing invasive carcinoma is relatively low (approximately 21% over
15 years) and is equal in both breast..(70) Follow-up of patients with LCIS includes physical
examinations every 6 to 12 months for 5 years and then annually. Annual diagnostic mammography is
recommended in patients being followed with clinical observation.
DCIS: Treatment options for DCIS are mastectomy, breast-conserving surgery (BCS) plus radiotherapy
or BCS alone. The goal of treatment for DCIS is to reduce local recurrence, because 50% of the time
that DCIS recurs it recurs as an invasive cancer. Factors that may modify treatment are (1) the grade of
the lesion, with higher-grade lesions more likely to recur in a short time; (2) the youth of the patient,
with many more years at risk for recurrence and (3) the size of the lesion. For years the traditional
surgical management of DCIS was mastectomy, with or without axillary dissection. Breast
conservation technique and irradiation is now a preferred alternative where local breast radiation is
available. Only small, low grade DCIS that has been excised with a large margin may be considered for
BCS alone. Axillary lymph node staging is discouraged in women with apparent pure DCIS. However,
a small proportion of patients with apparent pure DCIS will be found to have invasive cancer at the
time of their definitive surgical procedure which will require a further axillary dissection. (71) Addition
of Tamoxifen reduces the risk of developing contralateral breast cancer.(72;73). Follow-up of women
with DCIS includes a physical examination every 6 months for 5 years and then annually, as well as
yearly diagnostic mammography.
Early Breast Cancer (Stages I and II or T1-3N0-1 M0):
Staging for metastatic disease is standard for most patients diagnosed with early breast cancer and
include a chest X-ray, bone scan and ultrasound of the abdomen. If negative, treatment intent is
curative, and involve modalities that fight the cancer locally (surgery and radiation) and systemically
(chemotherapy and endocrine therapy).
Loco-regional Treatment:
Local treatment requires the treatment of the entire breast and the axillary lymph nodes with surgery,
radiation, or a combination of both. Surgery can be breast conservation therapy (BCT) and axillary
staging (SLNB or axillary dissection) or simple or total mastectomy with axillary staging (modified
radical mastectomy).
The surgical procedure for the excision of the breast in BCT goes by several names (Partial
mastectomy, tylectomy, segmental resection, quadrantectomy or lumpectomy).
The goal of breast-conserving surgery is to minimize the risk of local recurrence while leaving the
patient with a cosmetically acceptable breast. The selection of BCT versus mastectomy depends on the
size of the tumor relative to the rest of the breast and the availability of radiation. BCT and breast
radiation together offers equivalent survival to total mastectomy provided the BCT removes the entire
tumor with negative margins.
Generally a tumor less that 1/4 of the breast is amenable to BCT; anything much larger will result in
significant breast distortion after surgery and radiation.
The procedure can be done safely with local anesthesia and sedation unless axillary dissection is part of
the procedure. A curvilinear incision lying parallel to the nipple-areola complex is made in the skin
overlying the breast cancer. Radial scars are avoided because of poor cosmetic results. Skin
encompassing any prior biopsy site is excised, but skin excision is not otherwise necessary. The breast
cancer is removed with an envelope of normal-appearing breast tissue. Meticulous hemostasis is
important because a large hematoma distorts the appearance of the breast and makes re-excision and
follow-up more difficult.
The excised specimen is orientated for the pathologist using sutures, clips, or dyes. Additional margins
(superior, inferior, medial, lateral, superficial, and deep) can be taken from the surgical bed to confirm
complete excision of the tumor. These six margins are marked with titanic clips as this may help the
Radiotherapist in planning the boost. In addition, it helps the surgeon to do an adequate re-resection if
the margins are not free of cancer cells at definitive paraffin-embedded histology sections.
Attempts to re-approximate the cavity in the breast should be avoided, because this will usually distort
the breast contour, which may not be apparent when the patient is supine on the operating table.
Similarly, drains are not used. Allowing the cavity to fill with serum and fibrin maintains contour in the
early postoperative period and helps to avoid deformity. The procedure is completed with two-layer
closure of the deep dermis and the subcuticular layer, and a light dressing is used.
There is no firm consensus on the extent of the excision or margins required. The main benefit of BCT
is preservation of body image for the woman, which greatly improves her quality of life. Several
randomized controlled trials have shown that BCT and radiation has a similar survival advantage as
mastectomy as there were no significant differences in the two groups in disease-free survival, distantdisease-free survival, or overall survival and even in loco regional control.(74-80)
Contraindications to breast conservation therapy (BCT) can be divided into absolute or relative.
Absolute contraindications include lack of mammography facilities to ensure all tumors have been
removed, adequate pathology facilities to ensure tumor- free resection margins and/or lack of
radiotherapy facilities.(10;11) Other contraindications include pregnancy (first or second trimester
because of the risk of radiotherapy to the fetus), patient’s preference, diffuse suspicious calcifications,
inflammatory breast carcinoma, previous radiation to the region, and inability to achieve negative
margins particularly with extensive intraductal carcinoma (EIC). Relative contraindications also
include two or more gross tumors (multicentric disease) in different quadrants, tumor greater than 5 cm
initially or after neoadjuvant chemotherapy, large tumor-breast ratio for cosmesis, and collagen
vascular disease.(74)
In Africa, many of the factors above make the practice of BCT difficult and these include lack of
adequate diagnostic oncology services like mammography and surgical pathology, lack of adequate
therapeutic oncology services like radiotherapy, advanced stage disease and poor follow up culture.(5)
Thus the majority of the patients with early breast cancer in Africa should still undergo total
mastectomy and axillary clearance.
In a total or simple mastectomy, the patient is placed in the supine position with the ipsilateral arm
extended horizontally. General anesthesia is used. The incision is in the form of an ellipse is designed
to include the skin overlying the tumor or biopsy scar and the nipple–areola complex. Superior and
inferior skin flaps are then raised. The plane between the subcutaneous tissue and breast tissue is not
always obvious and is most easily identified at the medial superior flap; it is therefore easiest to begin
here. The skin flaps must be thin, to ensure that all the breast tissue is removed, and yet enough
subcutaneous fat to ensure adequate blood supply to the skin. Superiorly the dissection must include the
tail of Spence laterally. Inferiorly, the dissection ends at the inframammary fold. The entire breast, the
skin ellipse, nipple-areola complex are then dissected off the pectoralis fascia. The procedure is
completed with an en bloc excision of the axillary lymph nodes level I and II (see description below).
The mastectomy site and axillary nodal basin are then irrigated with saline solution, and meticulous
hemostasis is achieved. The wound is closed with a closed suction drainage bottle fixed to a catheter
brought out through a separate stab incision.
Modified radical mastectomy can be done alone or in association with breast reconstruction. Reconstruction, using
implants or myocutaneous flaps, provides many women with an enhanced body image and self-esteem, and better
psychosocial adjustment, but it does not impact on the probability of disease recurrence or survival. ( 81;82) One method
becoming widely used is the skin-sparing mastectomy (SSM) that conserves an extensive section of skin, as well as the more
recent skin and nipple-sparing mastectomy that preserves the nipple-areolar complex. ( 83-85). SSM is clearly
contraindicated in patients with direct involvement of the skin by the underlying tumor. Nicotine, previous radiotherapy,
diabetes and obesity increase the risk of skin envelope ischemia, skin necrosis and infection.
However, the additional cost of reconstruction is an issue especially in resource poor countries.
Treatment of the Axilla
Axillary lymph node dissection (ALND)
The status of axillary and internal mammary lymph nodes is the most significant prognostic factor for
survival in patients with breast cancer. In breast cancer, the status of axillary and internal mammary
lymph nodes is the most significant prognostic factor for survival. The axillary nodal basin has been the
main target in lymphatic staging in breast cancer because over 75% of the lymphatic flow from the
breast is directed to the ipsilateral axilla. Axillary clearance (ALND) has been the gold standard in
axillary staging in breast cancer, providing valuable information about the planning of adjuvant
therapy, prognosis and an excellent regional disease control as well. Removal of 10 or more nodes as
assessed by the pathologist provides accurate information about the axillary nodal status of the patient.
The most accepted surgical axillary clearance procedure is a level I and II axillary dissection, detecting
98.5% of cases with positive axillary nodes. (86) Either at the time of mastectomy, or through a
separate incision (if BCT), the lateral border of pectoralis major muscle is identified. The clavipectoral
fascia, extending laterally from the edge of this muscle, is divided parallel to the edge of the muscle to
allow entry into the axilla. The superior border of the dissection is the lower border of the axillary vein;
dissection above the vein runs the risk of damage to the brachial plexus. The nerves to latissimus dorsi
(thoracodorsal) and to serratus (long thoracic) are identified and are the posterior border of the
dissection. The lateral border is the floor of the axilla, consisting of skin and subcutaneous tissue.
Retraction of the pectoralis minor muscle medially allows for the removal of level II nodes. All the
fatty tissue within these borders is removed. The sensory intercostal brachial nerve runs through the
axilla and may or may not be preserved.
Sentinel node biopsy
Although long considered the standard management of the axilla for breast cancer, ANLD is associated
with significant arm morbidity (20-25% risk of lymphedema) and risk of damage to the axillary vein,
nerve to the latissimus dorsi and serratus anterior and hypoesthesia of the arm and the thorax. For these
reasons, other less invasive but accurate methods have been sought for axillary staging in breast cancer,
especially in the developed world, where ¾ of patients present with early node negative disease .
Clinical examination of the axilla and available diagnostic imaging techniques like US, CT and PDGPET are manifestly inaccurate for axillary staging.
Less invasive than ALND, sentinel lymph node biopsy (SLNB) is now accepted as an alternative to
routine ALND for the detection of occult lymph node metastases in patients with clinically nodenegative breast cancer. (87;88) SNLD is based on the observation that specific areas of the breast drain
by way of afferent lymphatics to a specific ‘sentinel’ node. This node can be detected by injecting vital
blue dye (isosulfan blue dye, methylene blue or patent blue V dye) or a radioactive suspension (Tc99m
radioisotope labeled colloids). The route of injections include intra parenchymal (peri-tumorally),
intradermal or subareolar.(88;89). The use of vital dye is resource efficient (cheaper and less time
consuming) and safer, but may miss non axillary sites and also carries the risk of anaphylactic reactions
while radioactive agents are more expensive, carries the risk of exposure to staff, and requires that the
hospital have a nuclear medicine department.
There are five principal aims for the excision and histopathological analysis of the SN: (1) minimally
invasive assessment of the nodal status; (2) selection of patients with positive SNs for elective lymph
node dissection (ELND) or adjuvant therapy; (3) prevention of lymph node dissection and associated
morbidity in SN negative patients; (4) detection of aberrant or alternative lymphatic drainage; (5)
improvement of sensitivity of histopathological detection of lymph node metastasis.(90)
Further surgery of the axillary nodes now depends on the results of the sentinel lymph-node biopsy—if
negative, ALND is avoided. While SLNB is becoming widely used in the developed world as a method
to assess the axilla, ALND remains the recommended management for treatment in any hospital that
does not have access to a nuclear medicine department or a dedicated breast pathologist able to use
specialized immunohistochemistry markers.
Radiotherapy in early breast cancer: The aim of radiotherapy to the whole breast after BCT is to
establish local control. Numerous studies have shown reductions in local recurrences from 12-35% to
2-10% at 5-10 years. This compares to local recurrence rates after mastectomy of 5%.(91) In most
developed countries, the current standard of care for patients with early-stage breast cancer consists of
breast-conserving surgery, followed by 5–6 weeks’ postoperative radiotherapy used on the whole
breast. Probabilities of adequate local control rates and good cosmetic results are high with the use of
conventional fractionation. Patients who cannot receive radiation are treated with mastectomy. Some
recent papers suggest a small survival advantage which was rather offset by the long term toxicity from
radiotherapy resulting in deaths from vascular and cardiac injuries.(92).
Some data support the effectiveness of an additional dose applied to the tumor bed (i.e., boost irradiation) to reduce local
recurrence. However, delivery of the boosting dose raises the rate of morbidity, which reduces cosmetic outcome.
Recent advances in radiotherapy includes partial breast irradiation using various techniques such as such as low or highdose rate brachytherapy (interstitially or with an intracavitary balloon), conformal external-beam irradiation (including
intensity modulated radiotherapy), and intraoperative radiotherapy (Electron Intra Operative Therapy-ELIOT).(93;94)
Most reports of partial breast irradiation have provided results much the same as those achieved with conventional external
beam, even though some caution is needed until the safety and efficacy of such irradiation have been shown in appropriate
patients and analysis of long-term treatment outcomes.(95-97)
Systemic Treatment
More than half the women with operable breast cancer who receive only locoregional treatment die
from metastatic disease. This indicates that breast cancer is a systemic disease and that the
micrometastatic process can occur early even independently from lymphatic spread. (76;98) The way to
improve survival is to give these women systemic medical treatment, including endocrine therapy,
chemotherapy, or targeted therapy with trastuzumab along with surgery/radiotherapy.
Systemic treatment may be given after (adjuvant) or before (neoadjuvant, primary, or preoperative)
locoregional treatment. Adjuvant treatment has been shown to be effective in randomized clinical trials,
whereas the evaluation of neoadjuvant systemic therapy is ongoing.
It is important to realize, especially in the African context, that any systemic therapy including
hormonal therapies, will at least temporarily interrupt child bearing. The current recommendations of at
least 5 years of Tamoxifen after diagnosis will significantly impact on the ability of a woman to bear
many children. Chemotherapy will cause most women to stop menstruating and permanent premature
menopause is common. These recommendations listed below, based on the culture of the developed
world, may not be acceptable or applicable to African women.
The choice of systemic adjuvant therapy in early breast cancer will depend on the following factors;
estrogen (ER)/progesterone (PR) receptor status, menopausal status and over-expression of HER2. It
will also depend significantly on the risk of recurrence and therefore the potential benefit of the
treatment. Any systemic therapy carries with it a risk of toxicity, and can be quite expensive. A woman
at high risk of recurrence will benefit significantly from treatment while for a woman at low risk the
benefit will be small yet she will be exposed to the same toxicity. For example, a 20% reduction with
chemotherapy for a patient with a baseline 50% risk of recurrence will result in an absolute reduction to
10% (from 50% to 40%) where as a woman with a 10% recurrence risk reduces her risk of recurrence
to 8%, only a 2 % absolute reduction. Some women would not choose chemotherapy for a 2% risk
reduction and others might. The decision to take systemic therapy therefore is therefore very much
dependent on the woman and her understanding of these risks. (99)
Adjuvant endocrine therapy is effective in ER and/ or PR positive tumors. The most commonly used
endocrine therapy is the Selective Estrogen Receptor Modulator (SERM) Tamoxifen, used in
premenopausal women. Other SERM agents like Toremifene and Raloxifene are equally effective.
There is strong evidence to support the superiority of a 5 year Tamoxifen therapy over shorter
durations. Tamoxifen in addition helps to maintain bone mineral density in post menopausal women
and reduces the risk of developing cancer in the contralateral breast. The side effects of Tamoxifen
include hot flashes, risk of thrombo-embolic disease, endometrial carcinoma and cataracts.
For post-menopausal women, third generation selective aromatase inhibitors have been shown in recent
trials to be more effective than Tamoxifen and have become the standard of care. Examples include non
steroidal type (anastrozole and letrozole) and the steroidal type exemestane. Patients using aromatase
inhibitors have less gynecological symptoms such as endometrial cancer, vaginal bleeding, and vaginal
discharges. Fewer cerebrovascular events and venous thromboembolic events were also observed with
patients receiving aromatase inhibitors. However, musculoskeletal effects (arthritis, arthralgia, and/or
myalgia) and bone toxicity (bone fractures) are associated with aromatase inhibitors.
The combination of endocrine therapy and cytotoxic chemotherapy provides benefits greater than the
benefits from either therapy alone. They are therefore usually offered sequentially, with chemotherapy
given right after surgery, local radiation therapy is then given, and endocrine therapy commenced.
Premenopausal women are given Tamoxifen for five years. The optimal duration of the aromatase
inhibitors has not yet been determined and postmenopausal women remain on them indefinitely.
Ovarian ablation (e.g., surgical oophorectomy or radiation ablation) or suppression (e.g., use of the
gonadotropin- releasing hormone or luteinizing hormone-releasing hormone analogues) is another
effective way to reduce estrogen in premenopausal women. It can be used as an adjuvant treatment
alone or to induce menopause in very high risk premenopausal women to allow the use of adjuvant
aromatase inhibitors.
Chemotherapy: Chemotherapy has been shown to substantially improve the long-term, relapse-free,
and overall survival in both premenopausal and postmenopausal women up to age 70 years with lymph
node-positive and lymph node-negative disease irrespective of the hormone receptor status.
The administration of polychemotherapy (two or more agents) is superior to the administration of
single agents. Four to six courses of treatment (3–6 months) appear to provide optimal benefit, with the
administration of additional courses adding to toxicity without substantially improving overall
outcome. Popular regimes include CMF (cyclophosphamide, methotrexate,fluorouracil) , CAF, AC,
FEC. Anthracycline based adjuvant therapy (with doxorubicin or epirubicin) result in a small(4-5%) but
statistically significant improvement in survival compared with non-anthracycline-containing regimens.
(100).
Trials using accelerated or dose dense chemotherapy (two weekly interval instead of the standard three weeks) with
granulocyte colony stimulating factor (GCSF) support to overcome the risk of neutropenic sepsis has been demonstrated to
improve both disease free survival and overall survival with fewer neutropenic crises.
Trials using high dose chemotherapy with haemopoietic stem cell rescue on the other hand showed high morbidity and no
benefit from this approach.
Around 20% of breast cancers over express HER2, and this is associated with an adverse prognosis. Trastuzumab is a
humanised monoclonal antibody directed against the external domain of the receptor with clinical activity as a single agent
inpatients whose cancers over express HER2.
Trastuzumab in combination with Taxanes and other drugs have shown considerable improvement in metastastic breast
cancer. Its role in the adjuvant setting in early breast cancer has been so successful in HER2 positive breast cancer showing
significant DFS and OS. Unfortunately, the cost implication is a drawback to its use in countries with limited resources.
Bisphosphonates are drugs that inhibit osteoclast mediated bone resorption induced by tumors. Some adjuvant trials
indicate that two years of oral clodronate reduces the incidence of bone metastases. One trial showed a small, but
significant, improvement in overall survival. Further trials are underway with clodronate and the newer, more potent
bisphosphonate zoledronate to define their long term effectiveness.
They are very useful in patients taking Aromatase inhibitors because of the risk of bone loss and fractures.
Advanced Breast Cancer (Stages III and IV):
This includes Locally Advanced Breast Cancer (LABC), metastastic cancer and recurrent cancer. (see
photos)
Photo 1
Photo 2
Photo 3
Photo 4
Photo 5
LABC:
LABC refers to Stage III tumors according to the TNM staging. Locally advanced breast cancer
(LABC) accounts for at least half of all breast cancers in countries with limited resources and has a
poor prognosis (12). Locally advanced tumors include tumours that present with palpable lymph node
metastases, ulcerations, tumors greater than 5 cm etc.
A subtype of LABC that deserves some further discussion is Inflammatory Breast Cancer (IBC).
Inflammatory breast cancer is a rare but aggressive subtype of breast cancer, which historically was
considered uniformly fatal. Clinically, inflammatory breast cancer is characterized by the rapid onset of
breast warmth, erythema, and edema (peau d’orange) often without a well-defined mass.
Along with extensive breast involvement, women with inflammatory carcinoma often have early
involvement of the axillary lymph nodes. In general, women with inflammatory breast cancer present at
a younger age are more likely to have metastatic disease at diagnosis, and have shorter survival than
women with non-inflammatory breast
cancer.(101-103)
The management of LABC requires a combined modality treatment approach involving surgery,
radiotherapy and systemic therapy.
Radiotherapy in LABC:
Radiotherapy after MRM or mastectomy to the chest wall or axilla is restricted to patients with high
risk of recurrence. These include tumors larger than 5 cm in maximum diameter and those with four or
more involved axillary lymph nodes, those with positive surgical margins on resection, and those with
involvement of the skin or underlying chest wall. (12) It can also be a very effective local modality in
controlling or shrinking tumors that are not amenable to surgical therapy.
Preoperative and locoregional treatment:
The initial management should be neoadjuvant chemotherapy with Doxorubicin- or
Epirubicin-based or Paclitaxel- or Docetaxel based chemotherapy. Patients with HER2 positive tumors
should be considered for preoperative chemotherapy incorporating Trastuzumab.
The advantages of neoadjuvant therapy include down staging of the tumor, improving operability of
tumors and increasing the chances of BCT
For patients that respond to neoadjuvant chemotherapy, the following options are recommended
(71;104-108): modified radical mastectomy, radiotherapy to the chest wall and supraclavicular nodes
(plus internal mammary nodes if involved) with or without delayed breast reconstruction. In those
women with LABC who do not have access to neoadjuvant chemotherapy because of economic
constraints or radiotherapy, mastectomy with node dissection, when feasible, may still be considered in
an attempt to achieve local-regional control. (12) The second option is BCT with surgical axillary
staging, radiotherapy to the breast, supraclavicular nodes (plus internal mammary nodes if involved).
However, for patients who fail to respond to preoperative chemotherapy, recommended treatment is to
consider additional systemic chemotherapy and/or preoperative
radiation.
Adjuvant treatment:
Chemotherapy should contain an anthracycline. Acceptable regimens are 6 cycles of 5 Fluorouracil,
Doxorubicin, Cyclophosphamide (FAC) or Cyclophosphamide, Epirubicin, 5Fluorouracil (CEF).
Sequential addition of Taxanes has also proven very effective.
Tamoxifen for 5 years should be recommended to pre- and postmenopausal women whose tumours are
hormone responsive.
Aromatase inhibitors like Letrozole, Anastozole and Examestane can be used in post menopausal
patients.
Surgical oophorectomy causing ovarian ablation is a very effective therapy in the treatment of locally
advanced and metastatic ER positive breast cancer in premenopausal women. This therapy is one that
would be very feasibly applied in Africa provided that it was acceptable to the woman.
Metastastic and Recurrent Cancer
The standard evaluation procedure for this group of patients includes history and clinical examination,
full blood count, liver function test, platelet count , chest X-ray, limited skeletal survey especially of
any long or weight bearing bones that are painful, biopsy of recurrence, evaluation of hormone receptor
status, ultrasound of the abdomen or CT where available.
Others include bone scans, MRI, PET, and determination of HER2 status of the tumor. These are
however tall orders in countries with limited resources and where there are no medical insurances to
cover the cost of these investigations. Pragmatism is required in this setting.
Treatment of Local Recurrence
Local recurrence can occur in two settings; post BCT or MRM.
Post MRM local recurrence should undergo local resection of the recurrence where feasible without
unnecessarily endangering the lives of the patients. In addition, radiotherapy of the involved area
should be done if the chest wall was not previously irradiated or if it could be done safely.
Post BCT patients should undergo a total mastectomy. Systemic therapy for local recurrence could be
adjuvant chemotherapy or endocrine therapy as in LABC.
Addition of Hyperthermia to radiotherapy has been shown in some trials to cause a statistically significant increase in local
tumor response and greater duration of local control. This is however technically demanding and resource intensive.
Systemic disease
Systemic recurrence and metastatic cancers are incurable, so the goals of therapy are to prolong
survival, improve quality of life with minimal morbidity or toxicity from the therapy.
Minimally toxic endocrine therapy is therefore preferred to the use of cytotoxic therapy whenever
indicated. Endocrine therapies are indicated in women with hormone receptor status, bone or soft tissue
disease only and those with limited asymptomatic visceral disease. For post menopausal women, the
choice is between Tamoxifen and aromatase inhibitors, with aromatase inhibitors having a slight edge
especially in those who have taken anti-estrogen previously.
For premenopausal women who are anti-estrogen naïve, anti-estrogen with or without LHRH agonist is
the preferred choice. Oophorectomy is an excellent cheap alternative where drugs are not available.
Since the majority of African women with breast cancer are hormone receptor negative, few will
benefit from endocrine therapy, chemotherapy will be the option in most cases.
Premenopausal patients who have taken anti-estrogen previously have a choice of either surgical or
radiotherapeutic oophorectomy or luteinizing hormone-releasing hormone (LHRH) agonists with or
without an antiestrogen.
Endocrine therapies in postmenopausal women include selective, nonsteroidal aromatase inhibitors (anastrozole and
letrozole); steroidal aromatase inhibitors (exemestane); pure antiestrogens (fulvestrant); progestin (megestrol acetate);
androgens (fluoxymesterone); and high-dose estrogen (ethinyl estradiol). In premenopausal women, therapies include
LHRH agonists (goserelin and luprolide); surgical or radiotherapeutic oophorectomy; progestin (megestrol acetate);
androgens (fluoxymesterone); and high-dose estrogen (ethinyl estradiol).
Chemotherapy is the best option in women with estrogen and progesterone receptor-negative tumors, symptomatic visceral
metastasis, or endocrine therapy refractory disease.
The higher rates of objective response and longer time to progression of combination chemotherapy are at the expense of
increased toxicity with little survival benefit.
Therefore, there is no significant advantage of combination chemotherapy over sequential single agents.
Preferred first-line chemotherapies include sequential single agents or combination chemotherapy. Among preferred firstline single agents, are doxorubicin, epirubicin, pegylated liposomal doxorubicin, paclitaxel, docetaxel, capecitabine,
vinorelbine (all
category 2A), and gemcitabine (category 2B). Among preferred first-line
combination regimens are cyclophosphamide, doxorubicin, and fluorouracil (FAC/CAF); fluorouracil, epirubicin,
cyclophosphamide (FEC); doxorubicin, cyclophosphamide (AC);
epirubicin, cyclophosphamide (EC); doxorubicin in combination with either docetaxel or paclitaxel (AT);
cyclophosphamide, methotrexate, fluorouracil (CMF); docetaxel, capecitabine; gemcitabine, paclitaxel.
Patients with tumors that are HER2-positive may derive benefit from treatment with trastuzumab as a single agent or in
combination with selected chemotherapeutic agents. 27% of patients treated with a combination of Trastuzumab and
doxorubicin/cyclophosphamide chemotherapy develop significant cardiac dysfunction making this regime unsafe and
unpopular. (71)
Treatment of Complications
In Africa, a good number of women present with fungating/ ulcerating masses and many of them are so
ill that they can not undergo surgery or radiotherapy immediately. The following are some useful
supportive measures:
1. Dressing of the wound with honey and metronidazole cleanses and remove the odor. This
measure in addition to the use of neoadjuvant chemotherapy has largely reduced the need
for toilet mastectomy.
2. Clean malignant ulcers are prone to secondary hemorrhage; topical formalin is effective
in this setting.
3. Pain is another significant problem and this may be due to the disease, therapy or
depression. Optimal pain management is very crucial to improving the quality of life. If
pain occurs, there should be prompt oral administration of drugs in the following order:
non-opioids (aspirin and paracetamol); then, as necessary, mild opioids (codeine); then
strong opioids such as morphine, until the patient is free of pain. To calm fears and anxiety,
additional drugs – “adjuvants” – should be used. To maintain freedom from pain, drugs
should be given “by the clock”, that is every 3-6 hours, rather than “on demand” This threestep approach (see figure 2) of administering the right drug in the right dose at the right
time is inexpensive and 80-90% effective. Surgical intervention on appropriate nerves may
provide further pain relief if drugs are not wholly effective.(109)
4. Anemia as a result of the disease or chemotherapy is often under treated and
underestimated in patients. It has a negative impact on quality of life and survival. It will
require blood transfusion in some women. The introduction of recombinant human
erythropoietin (epoetin) has provided an effective and convenient treatment of anemia
without the risks of blood transfusion. Epoetin is also effective for the prevention of anemia
and reduction of transfusion requirements in patients with a high risk of developing anemia
during chemotherapy.(110-112)
5. Lymphedema of the arm is a very distressing complication which may occur as a result
of the disease itself or as a result of surgery or radiotherapy in the treatment
of breast cancer. Treatment options include compression treatments (using compression
bandage or garments and pneumatic compression devices),
therapeutic exercises and pharmacotherapy (antibiotics, flavonoids, hyaluronidase, and
selenium). Diuretics have not been found useful. (113;114)
6. Respiratory distress in advanced breast cancer may be as a result of pleural effusion or
deposits in the lungs. Closed thoracostomy tube drainage with
pleurodesis using Tetracycline or Bleomycin is an effective treatment. Lung metastasis can
be treated with steroids inhalers, bronchodilators, diuretics,
anxiolytics, chest physiotherapy and oxygen.(5)
7. Neurological complications include cerebral metastases, spinal, leptomeningeal, cranial
and peripheral nerve metastases.(115) Treatment includes steroids,
radiotherapy and surgery for localized metastases.
Younger women with breast cancer are more prone to physical and psychological distress which makes
them have poorer quality of life outcomes. These arise as a result of the disease and the complications
of treatment. Gonadal toxicity leading to irregular menses, amenorrhea and premature menopause is
especially disturbing for African patients, the majority of whom are in their reproductive age group.
Other problems like Alopecia, fertility problems and the cost of treatment may severely affect
relationship especially among young couples. In this context, a multi disciplinary approach is important
which will involve psychologists, social welfare/support groups and various advocacy groups where
survivors of breast cancer can share their experiences and support one another.(116-120)
9. PROGNOSIS
Natural History: The natural history of breast cancer in 250 untreated women revealed the following
statistics; Median survival of untreated breast cancer was 2.7 years after initial diagnosis. The 5- and
10-year survival rates were 18.0 and 3.6%, respectively. Only 0.8% survived for 15 years or longer.
Autopsy data confirmed that 95% of these women died of breast cancer, while the remaining 5% died
of other causes. Almost 75% of the women developed ulceration of the breast during the course of the
disease. The longest surviving patient died in the nineteenth year after diagnosis. (121)
With modern treatment, the 5-year survival rate for stage I patients is 94%; for stage IIa patients, 85%;
and for stage IIb patients, 70%, while for stage IIIa patients the 5-year survival rate is 52%; for stage
IIIb patients, 48%; and for stage IV patients, 18%.
Prognostic Iindicators:
Tumor size
Prognosis deteriorates with increasing tumor size, which is an independent predictor of survival in
node-negative patients and correlates with the incidence of nodal metastases.
Staging
The status of the axillary lymph nodes is one of the most useful prognostic indicators for breast cancer,
with average 10-year survival rates of 60-70% for node-negative patients, dropping to 20-30% in nodepositive patients.
Histopathology
• Histologic type
o Carcinoma in situ, because it is a preinvasive condition, is curable if completely removed,
although 16% of patients with carcinoma in situ develop invasive recurrence after local
excision of ductal carcinoma in situ, usually high grade. Similarly, 18% of patients develop
invasive recurrence after lobular carcinoma in situ excision.
o Well-differentiated invasive cancers have a relatively good prognosis if they are tubular,
mucinous, cribriform, or secretory.
o Medullary carcinoma is probably of intermediate prognosis, but different studies have
used different criteria for its definition.
o Invasive ductal and invasive lobular carcinomas have a less favorable prognosis but are
influenced heavily by other factors.
• Cytologic grade
o Cytologic grade is the best predictor of disease prognosis in carcinoma in situ but is
dependent on the grading system used, such as the Van Nuys classification (high-grade,
low-grade comedo, low-grade noncomedo).
o The grading of invasive carcinoma is also important as a prognostic indicator, with higher
grades indicating a worse prognosis. Microscopic criteria for grading are shown in Table 5.
• Lymphovascular: Lymphatic invasion, vascular invasion, microvessel quantification, and
lymphoplasmacytic infiltration are associated with a worse prognosis.
• Hormone receptor status: With the aid of gene expression studies using DNA microarrays
and immunohistochemistry, several distinct biologic breast cancer subtypes have been
identified. These subtypes differ markedly in prognosis and in the number of potential
therapeutic targets they express.
The intrinsic subtypes include 2 main subtypes of estrogen receptor (ER)–negative tumors (basal-likeand human epidermal
growth factor receptor-2 positive/ER- [HER2_/ER-] subtype) and at least 2 types of ER+ tumors (luminal A and luminal B).
The basal like subtype carries poor biologic (worse grade) and clinical prognostic indicators like positive axillary nodes.
This subtype was found to be more prevalent in pre-menopausal African –American women compared to post menopausal
African –American women and other races ( 122)This finding may be one of the reasons why African- American women
with breast cancer have high grade, late stage tumor and with poor prognosis and poor survival outcome.
The similar clinical outcome of native African women with breast cancer may tempt one to extrapolate these findings seen
in African-American women. To lend credence to this fact, the few studies on hormone receptor status of breast cancer in
native African women show that the majority of them are Estrogen or Progesterone negative (123-125).
There are also several other provocative parallels between African-American and native African breast cancer patients
which include a younger age distribution and a greater prevalence of high grade, estrogen-receptor-negative disease
among breast cancer patients in the Ghanaian and Nigerian populations of western Africa similar to the patterns of breast
cancer reported among African-American women. Western African populations served as the source for most of the slave
trade to colonial North America, and therefore share a common ancestry with present-generation African Americans. These
parallels suggest the possible contribution of founder effects.(16)
However, further research needs to be done in this area before reaching any conclusion is reached as the AfricanAmericans are a heterogeneous group with mixed genetic heritage consisting of Hispanics, Caucasians and Africans. In
addition other socioeconomic factors and environmental factors may contribute to the clinical outcome seen.( 126;127)
• Immunohistochemistry
o The most widely used tests are for the estrogen receptors (ER) and progesterone receptors
(PR). Immunohistochemistry analysis of heat-treated paraffin sections has largely
superseded the enzyme-linked immunosorbent assay (ELISA) ligand-binding assay. ERand PR-positive status (ie, >10 fmol on ELISA; >15 H-score on immunohistochemistry)
predict improved response to endocrine treatment, time to relapse, and overall survival.
o Immunohistochemical positivity for c-erb-B2 and p53 is associated with a worse
prognosis.
o HER-2 status: The human epidermal growth factor receptor-2 (HER-2/neu) is a wellcharacterized biomarker in the biology of breast carcinoma that has had immediate impact
on clinical medicine. The positive status of HER-2/neu is associated with a younger age
and several adverse prognostic factors, i.e., advanced stage, absence of estrogen and
progesterone receptors, metastasis to axillary lymph nodes, and high nuclear grade. In
addition, women diagnosed with positiveHER-2/neu breast carcinoma generally have
relative resistance to anthracycline-based chemotherapy, tamoxifen therapy, and have
shorter disease-free and overall survival. (128)
Other prognostic indicators
Advances, in the knowledge of the molecular mechanisms that influence normal and aberrant cell growth, have led to the
identification of an increasing number of surrogate biomarkers, which have been correlated with prognosis or used as
predictors of response to specific treatments. These novel prognostic markers can be classified as follows:
• Oncogene products
o Bcl-2
o p53
o HER-2/neu
o Cyclin D1
o Nm23
• Proteases
o uPA
o Cathepsin D
o Tenascin C
• Markers of proliferation - Ki-67
HER-2/neu identifies patients with a poor prognosis. These patients are likely to respond to treatment with trastuzumab
(Herceptin).
Tumors positive for Ki-67 have a high metastatic potential and warrant the possible use of early aggressive therapy.
uPA and cathepsin D identify poor prognosis node-negative tumors. In these cases, chemotherapy can be offered.
The use of gene expression profiling to detect breast carcinoma has already shown that the differential expression of
specific genes is a more powerful prognostic indicator than traditional determinants such as tumor size and lymph node
status. These molecular assays are awaiting clinical validation.
10. PREVENTION
Screening as currently practiced can reduce mortality but not incidence, and then only in a particular
age group. Advances in treatment have produced significant but modest survival benefits. A better
appreciation of factors important in the etiology of breast cancer would raise the possibility of disease
prevention. Currently, prevention strategies fall into two groups: chemoprevention and surgical
prophylaxis.
Chemoprevention is defined as the systemic use of natural or synthetic chemical agents to reverse or
suppress the progression of a premalignant lesion to an invasive carcinoma.(129). Tamoxifen is
currently the only agent that has been approved clinically for use in women with high risk of
developing cancer. Raloxifene, selenium, retinoids, aromatase inhibitors and cyclo-oxygenase 2
inhibitors require further clinical investigation before adoption in this context.
Surgical prophylaxis: by either a bilateral mastectomy or oophorectomy, is another avenue of
prevention. Some studies have demonstrated that women with definite BRCA1 or BRCA2 mutation
may have an overall reduction in their breast cancer risk profile after such operation.(130)
Dietary intervention If specific dietary factors are found to be associated with an increased risk of
breast cancer dietary intervention will be possible. However, reduction of dietary intake of such a factor
in whole communities may well be difficult to achieve without major social and cultural changes.
Dietary fat reduction and exercise decrease the circulating serum oestradiol level, but whether this in
turn leads to a reduction in the incidence of breast carcinoma has not been determined conclusively.
(131)
11. BREAST CANCER AND PREGNANCY
Pregnancy associated breast cancer is defined as breast cancer diagnosed during pregnancy or lactation
or one year post partum. Breast cancer and pregnancy can be classified into three main situations; these
are (a) breast cancer that is detected during the evolution of pregnancy, (b) breast cancer that is detected
during lactation or postpartum, and (c) pregnancy in patients who have had a previous breast cancer.
Cancer complicates approximately 1 per 1000 pregnancies and accounts for one-third of maternal
deaths during gestation. The prevalence of breast cancer during pregnancy is increasing due to delayed
onset of childbearing. Breast cancer is diagnosed in approximately 1 in 3000 pregnancies. The
incidence ranges from 0.76% to 3.8% of breast cancer cases. The median age of pregnant women
affected with breast cancer is 33 years. In a recent review in Nigeria, 12% of the patients with Breast
Cancer were pregnant or lactating and 74% were premenopausal , making it the most frequently
occurring malignancy during pregnancy, along with cancer of the uterine cervix.(5) Treatment
decisions for breast cancer patients during pregnancy become most difficult because not only the
mother but also the fetus is involved. The final advice should be based upon the following
considerations: (1) the parents’ decision whether or not to continue with the pregnancy, (2) the period
of pregnancy when the breast cancer is diagnosed, and (3) the stage of the breast cancer.
A detailed guideline on the management of breast cancer in pregnancy can be found in the NCCN
Clinical Practice Guidelines in Oncology™ Breast cancer V.1.2007 at www.nccn.org.
Early studies have indicated that the prognosis of breast cancer in pregnancy is very poor; however,
more recent studies with more careful consideration of age and the stage of the disease show no
significant differences. Evidence is lacking that termination of pregnancy changes the outcome of
breast cancer. Pregnancy after breast cancer does not alter the outcome of treatment. The ideal interval
between treatment for breast cancer and subsequent pregnancy is unknown. (132)
12. BREAST CANCER IN MALES
Male breast cancer is an uncommon disease although the incidence has increased over the past 25
years. Less than 1% of all breast cancer patients are male. Rates of male breast cancer vary widely
between countries: in Uganda and Zambia the annual incidence rates are 5% and 15%, respectively of
all breast cancer cases. These relatively high rates have been attributed to endemic infectious diseases
causing liver damage, leading to hyperestrogenism. By contrast, the annual incidence of male breast
cancer in Japan is less than five per million, in parallel with the lower than average incidence of female
breast cancer in that country. Jewish men are the only racial group with a higher than average incidence
(2•3/100 000 per year), irrespective of living in Israel or the USA.(133) Risk factors for Breast Cancer
include Genetic (BRCA2, Klinefelter’s syndrome), Lifestyle (Obesity, Alcohol, Estrogen intake), Work
(High ambient temperature, Exhaust emissions), and Disease (Testicular damage, Liver damage,
Radiotherapy to chest) The predominant histological type of disease is invasive ductal, which forms
more than 90% of all male breast tumors.
Much rarer tumour types include invasive papillomas and medullary lesions. Lobular carcinoma of the male breast has
been reported not only in men with Klinefelter’s syndrome, but also in genotypically normal men with no previous history of
oestrogen exposure or gynaecomastia. In large studies of male breast cancer, oestrogen receptor positivity has been
reported in more than 90% of tumours, with 92–96% being progesterone-receptor positive.
Some studies suggested that breast cancer has a worse prognosis in men than in women, but if agematched and stage-matched breast cancer is compared, there is no difference between the sexes
(18;134;135)
FUTURE TRENDS AND CONTROVERSIES
Diagnosis and early detection:
Several new technologies, apart from mammography are being evaluated to improve the early detection of breast cancer.
These include non ionizing imaging techniques like Ultrasonography and MRI. Other imaging tools being evaluated
include scintimammography, positron emission tomography, magnetic resonance spectroscopy, optical imaging, thermoacoustic computed tomography, microwave imaging, Hall effect imaging etc.
Molecular targets and new drugs
HER-2
Pertuzumab (also known as 2C4, Omnitarg) is a new recombinant humanised monoclonal antibody that also binds the
extracellular portion of HER2, which causes steric hindrance and impairs receptor dimerisation. Ongoing phase-I testing
has shown activity in patients with breast cancer that is either HER2-negative and trastuzumab-refractory HER2-positive.
Tyrosine kinase, cyclines, and proteosoma
Most tyrosine-kinase inhibitors are in preclinical investigations and only a few have been tested in patients with advanced
breast cancer. Gefitinib is an inhibitor of the tyrosine kinase of human epidermalgrowth-factor receptor (HER1) and has
shown some antitumour activity in preclinical studies and a phase II trial of patients heavily pretreated for metastatic breast
cancer.
Insulin-like growth factor (IGF)
IGF is an interesting therapeutic target in breast cancer because its ligands and receptors are often overexpressed and are
implicated in proliferation, transformation, and metastasis. The IGF system includes ligands IGF-I and IGF-II, receptors
IGF-IR and IGF-IIR, and six known IGF-binding proteins. These binding proteins are promising targets for the
manipulation of endocrine responsiveness and resistance to Trastuzumab.
Angiogenesis
Bevacizumab is a recombinant, humanised monoclonal antibody to vascular endothelial growth factor that has shown some
efficacy when used alone in phase II clinical trials.
Several anti-angiogenic drugs have been tested for efficacy, including thalidomide, endostatin, angiostatin, SU6668,
SU11248, and cyclo-oxygenase 2 (COX-2) inhibitors. COX-2 also improves the efficacy of
Receptors as targets for radionuclides
Efficacy of targeted therapy depends on the biologically relevant quality and quantity of the specific compound. This
treatment needs to reach the target efficiently and accurately and exert a selective therapeutic effect. The development of
biomarkers to assess in-vivo responses and the ability to use such biomarkers as targets for specific radionuclide treatment
represent great challenges in cancer medicine.
IN SITU ABLATION
In situ ablation of the primary tumour has been suggested as an alternative to surgery. There are preliminary reports on
methods using cryosurgery, or coagulating with heat,
delivered by a laser fiberoptic technique .
WHO WILL PERFORM BREAST SURGERY?
Within the next decade the number of patients undergoing axillary surgery will diminish as a result of improved staging by
sentinel node biopsy. A greater part of the patients will have only breast resection, and these operations can be performed
as day-case surgery, even under local anaesthesia. The surgical challenges during the next decade will be immediate breast
reconstruction and various oncoplastic procedures. Therefore breast surgery will increasingly be performed by plastic
surgeons. General surgeons will not be so interested in carrying out all the other rather undemanding breast procedures.
(136)
Controversies
1. Relevance.
2. The place of post mastectomy radiotherapy in early breast cancer especially in women with T1 ,T2 and one to three
positive lymph nodes.
3. Sequencing of post mastectomy radiotherapy and breast reconstruction(137)
4. The impact of mammographic screening in reduction of mortality in breast cancer
14. CONCLUSION
Management of breast cancer is a major challenge in resource limited countries.
Efforts should be geared towards early diagnosis, prompt and standardized treatment to reduce the
burden of advanced disease in African women, majority of who are worse hit in the most productive
part of their life time.
Our knowledge about breast cancer is evolving, but is still limited with respect to its etiology and
biology, and with respect to its features in individual countries and
cultures.
Further research is needed to understand the role of genetics and environment in the etiology of breast
cancer in Africa.
15. RECOMMENDATIONS
In high-resource countries, evidence-based guidelines outlining optimal approaches to early detection,
diagnosis, and treatment of breast cancer have been defined and
disseminated. These guidelines unfortunately are not applicable in countries with resource constraints
as they are not economically feasible or culturally appropriate.
The following recommendations might be considered appropriate in the resource-poor countries of
Africa. Following the Breast Health Global Initiative we have stratified the recommendations into
Basic, Limited, Enhanced and Maximal. (10-12;138)
Definition of Stratification terms
• Basic level—Core resources or fundamental services absolutely necessary for any breast health care
system to function. By definition, a health care system lacking any basic-level resource would be
unable to provide breast cancer care to its patient population. Basic-level services are typically applied
in a single clinical interaction.
• Limited level—Second-tier resources or services that produce major improvements in outcome, such
as increased survival, but which are attainable with limited financial means and modest infrastructure.
Limited-level services may involve single or multiple clinical interactions.
• Enhanced level—Third-tier resources or services that are optional but important. Enhanced-level
resources may produce minor improvements in outcome but increase the number and quality of
therapeutic options and patient choice.
• Maximal level—High-level resources or services that may be used in some high-resource countries,
but nonetheless should be considered lower priority than those in the basic, limited, or enhanced
categories on the basis of cost or impracticality for limited-resource environments. In order to be
useful, maximal-level resources typically depend on the existence and functionality of all lower-level
resources.
Recommendations are presented in tabular form and are reproduced with permission from the BHGI.
Our own recommendations include:
1.Early Detection and Diagnosis: Possible less resource-intensive methods for earlier diagnosis of
breast cancer like education in breast awareness, training in breast self-examination (BSE), regular
clinical breast examination (CBE) by experienced personnel and diagnostic ultrasound may be the
option in resource limited countries as mammography screening may be resource intensive. (69)
2. To improve breast pathological capacity and services in Africa, the following approaches may be
explored; including training pathologists, establishing pathology services in centralized facilities, and
organizing international pathology services. In particular it is important that estrogen and progesterone
receptor status of tumors be identified.
3. As staging is crucial to treatment decisions and prognosis, a thorough clinical evaluation after the
diagnosis of breast cancer to check for clinically obvious indications of metastases to the lymph nodes
and other areas is crucial. In addition, tests to assess the presence of metastases to the lungs, liver, and
bone provide valuable information, if available. Hormone receptor testing of pathology specimens
should be part of the pathology services
4. More training for surgeons in BCT and Sentinel node biopsy.
Adisa Adeyinka Charles MD,FWACS, FICS
Director, Residency Training Program
Abia State University Teaching Hospital
Aba, Nigeria
Alexandra M. Easson, MSc , MD , FRCSC, FACS
Assistant Professor, Department of Surgery
General Surgery and Surgical Oncology
Mount Sinai Hospital and Princess Margaret Hospital
610 University Avenue Toronto , Ontario M5G 2M9
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DR. Brian Ostrow
Surgery in Africa- Monthly Review
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Kanker Payudara, Momok bagi Setiap Wanita
Jumat, 29 Sep 2000 17:16:36
Pdpersi, Jakarta - Payudara indah dambaan wanita. Namun, tentu saja definisi indah ini menjadi sangat relatif.
Sebab, tak ada parameter yang menentukan indah atau tidaknya sepasang payudara. Nun atas segalanya,
Tuhan memang menciptakan tubuh wanita dengan segala keindahannya, serta fungsi-fungsinya yang hakiki.
Begitu pula dengan payudara. Disanalah setiap anak manusia menikmati detik-detik pertama “rasa” dunia. Rasa
yang dinikmati dari pancaran air susu ibu. Begitu tingginya penghargaan pada air susu ini, sehingga dalam
bahasa “sufi” kerap disebut sebagai “sungai kehidupan”.
Namun terkadang dibalik keindahan itu, Tuhan menyelipkan cobaan. Ironisnya, selain menjadikan tubuh wanita
tidak menarik, cobaan itu juga dapat mengakibatkan kematian, sehingga seringkali menjadi momok menakutkan
bagi wanita. Cobaan itu bernama Kanker Payudara. Dan tragisnya, pada wanita, frekuensi Kanker Payudara
ternyata menempati peringkat kedua setelah kanker leher rahim (serviks).
Menurut Dr Idral Darwis, Kepala Tim Kanker Payudara dan Kanker Kulit dari Rumah Sakit Kanker Dharmais,
Kanker Payudara adalah suatu penyakit neoplasma yang sifatnya ganas. Hal ini disebabkan pertumbuhan yang
tidak terkendali dari sel-sel kelenjar susu yang terdiri dari saluran kelenjar susu dan tempat produksi air susu.
Penyebabnya, perubahan struktur genetik dari sel tersebut, faktor lingkungan, prilaku, konsumsi makanan,
konsumsi obat-obatan, virus, sehingga pada akhirnya dapat mengakibatkan kematian bagi penderitanya.
“Penyakit itu berawal dari berubahnya sel normal menjadi abnormal. Untuk menjadi kanker, terdiri dari tiga
tahap. Tahap pertama inisiasi atau perubahan di dalam sel itu sendiri. Dalam tahap ini, terkadang sel bisa
kembali menjadi normal. Namun sel yang tidak kembali normal berlanjut ke tahap promosi. Di tahap promosi ini
ada faktor-faktor pencetus, misalnya lemak, sinar matahari, faktor lingkungan dan sebagainya. Proses di tahap
promosi hingga menjadi sel kanker memakan waktu yang cukup lama, inilah yang disebut tahap proliferasi”
papar Dr Idral yang di temui pdpersi.co.id di kediamannya bilangan Menteng, Jakarta, Senin (25/9).
Dr Idral menambahkan, sel kanker tersebut akan tumbuh terus dan melakukan penyebaran ke kelenjar getah
bening regional (ketiak), lalu menuju pembuluh darah. Dengan bantuan pembuluh darah, sel berhenti dan
menyebar di salah satu organ tubuh. Misalnya paru-paru, otak, tulang, lever atau hati. Akibatnya, jika fungsi
organ tubuh tadi berubah, dapat menimbulkan kematian.
Stadium dalam Kanker Payudara, menurut dokter kelahiran Padang 54 tahun silam ini, dilihat dari penilaian
tingkat klinis seperti besarnya tumor ganas (kanker), ada tidaknya kelenjar getah bening di ketiak, dan ada atau
tidaknya penyebaran di organ-organ tubuh yang lain. Stadium itu disebut dengan parameter TNM atau Tumor,
Nodus (kelenjar getah bening), dan Metastasis (penyebaran jauh).
Lemak Berkorelasi kuat
Berdasarkan penelitian Dr Idral dan rekan-rekan sejawatnya dari berbagai disiplin (Patologi Anatomi,
Epidemologi, Gizi) Fakultas Kedokteran Universitas Indonesia serta tim dari Jepang, diketahui, mengkonsumsi
lemak secara berlebihan ternyata punya korelasi kuat pada terjadinya kanker payudara. Hal ini diketahui setelah
melakukan penelitian terhadap 600 responden.
Faktor-faktor risiko tinggi kanker payudara lainnya ialah wanita umur di atas 40 tahun yang tidak mempunyai
anak, wanita yang mempunyai anak pertama pada umur 35 tahun, wanita yang tidak kawin, menarche lebih dini
(dibawah 14 tahun), menopause yang lambat, riwayat trauma pada payudara, berat badan rendah, cenderung
obesitas, hubungan keluarga dengan penderita kanker payudara (jalan ibu), jumlah kehamilan rendah, dan
masa menyusui yang singkat atau tidak menyusui.
“Berdasarkan penelitian kita, yang paling berpengaruh adalah masalah makanan tinggi lemak. Lalu masalah
hormonal orang yang tidak menyusui, serta orang yang tidak punya anak. Selain itu ada faktor keturunan jalan
ibu, entah kakak perempuan yang kena Kanker Payudara, atau adik perempuannya, ibu, saudara perempuan
ibu, nenek, sepupu, risiko mereka yang tumbuh pada keluarga yang punya riwayat Kanker Payudara ini adalah
10 persen,” kata Dr Idral.
Uniknya, ternyata pria pun dapat menderita kanker payudara. Hal ini berkaitan dengan faktor hormonal.
“Persentase Kanker Payudara pada pria adalah satu persen,” ujar Dr Idral. “Nah, untuk laki-laki hubungan
antara KPD dipengaruhi oleh adanya perubahan metabolisme hormonal yaitu esterogen, di mana didapatkan
penurunan estrone dan peningkatan estriol dalam darah,” ujar dokter yang juga menjadi Konsultan Senior
Bedah Onkologi (payudara, leher & kepala, kulit dan jaringan lunak di RSUPN Ciptomangunkusumo serta RS
Kanker Dharmais tersebut.
Hal lain yang juga unik adalah, faktor risiko Kanker Payudara di tiap-tiap negara sangat bervariasi dan
tergantung dari hasil penelitian yang telah dilakukan pada populasi di tempat tersebut. Misalnya, faktor lemak
tinggi ternyata juga menjadi penyebab signifikan Kanker Payudara bagi beberapa negara yang memang
mayoritas masyarakatnya mengkonsumsi makanan lemak tinggi. Misalnya Amerika Serikat, Australia dan
Belanda.
Sebaliknya, di Amerika Selatan dan Asia, Kanker Payudara mempunyai insidens yang rendah. Diperkirakan,
Jepang dan Indonesia mempunyai insidens yang rendah. Walau di Indonesia insidensnya termasuk rendah,
namun berdasarkan survei rumah tangga pada beberapa Rumah Sakit dan pencatatan hasil pemeriksaan
patologi, frekuensi Kanker Payudara menempati peringkat nomor dua setelah kanker leher rahim (serviks).
Dapat Disembuhkan
Dr Idral DarwisPada stadium dini, sebenarnya Kanker Payudara dapat disembuhkan. Sayangnya, di Indonesia,
biasanya penderita datang dalam kondisi stadium lanjut (50 persen). Akibatnya, penanganan Kanker Payudara
hanya berkisar pada tujuan valiatif atau meringankan gejalanya saja. Hal inilah yang menyebabkan insidens,
morbiditas serta angka kematian (mortalitas) masih tetap tinggi. Padahal jika sebelumnya ada upaya
pencegahan primer dan deteksi dini atau pencegahan sekunder, boleh jadi angka-angka itu dapat ditekan.
Berdasarkan penelitian yang dilakukan Dr Idral dan rekan-rekan, konsep dasar pencegahan primer ini meliputi:
* Mencegah terpaparnya substansi yang menyebabkan risiko terjadinya Kanker Payudara, misalnya merubah
kebiasaan hidup (lifestyle) konsumsi tinggi lemak.
* Menggunakan proteksi terhadap bahan karsinogenik (tumbuhan ganas yang berasal dari sel-sel epitel),
misalnya memakai proteksi terhadap radiasi.
* Menggunakan bahan yang dapat mencegah proses karsinogenik, misalnya memakai bahan antiproliferatif
untuk mencegah proses Kanker Payudara, contoh pemberian Tamoxifen (preparat antiesterogen). Pemberian
Tamoxifen ini pernah dilakukan pada 16 ribu wanita secara prospektif dan acak.
Sementara itu, pencegahan sekunder atau disebut juga skrining/deteksi dini, dianggap sebagai upaya paling
rasional untuk menurunkan angka kematian akibat Kanker Payudara. Penelitian skrining ini dilakukan pertama
kali oleh Health Insurance Plan of Greater New York tahun 1963, hasilnya mampu menurunkan angka kematian
antara 20 hingga 25 persen pada kelompok umur lebih dari 50 tahun.
Cara pemeriksaan untuk pelaksanaan skrining terdiri dari pemeriksaan klinis payudara oleh tenaga kesehatan,
misalnya spesialis bedah, dokter umum, perawat yang terlatih. Pemeriksaan payudara sendiri (SADARI).
Pemeriksaan penunjang atau mamografi.
Mendeteksi dini kanker payudara bisa dilakukan dengan cara:
* Pemeriksaan payudara sendiri (SADARI) sejak usia 20 tahun.
* Pemeriksaan berkala oleh dokter setiap dua hingga tiga tahun pada usia 20 hingga 40 tahun.
* Pemeriksaan berkala oleh dokter setiap tahun setelah berusia 35 tahun.
* Mamografi satu hingga dua kali pada usia 35 hingga 49 tahun. ( mamografi = pemeriksaan radiodiagnostik
khusus dengan mempergunakan teknik foto “soft tissue” pada payudara.).
* Mamografi setiap tahun setelah berusia 50 tahun.
Pemeriksaan Payudara Sendiri atau SADARI diangap sebagai cara termurah, aman, dan sederhana. Meski
demikian pemeriksaan ini haruslah berdasarkan petunjuk dan pedoman yang telah ada. Dengan SADARI, bukan
tidak mungkin akan lebih banyak Kanker Payudara stadium dini yang dapat dideteksi. Sayangnya, SADARI
diangap masih belum efektif. Hal ini dikarenakan ketakutan dan kecemasan dalam menghadapi kenyataan,
serta masih sedikitnya wanita yang memakai cara test ini (sekitar 15 hingga 30 persen). Selain itu pemahaman
SADARI secara teknis masih belum dikuasai.
Ada beberapa tanda kanker payudara dini yaitu:
* Benjolan dengan batas tidak tegas.
* Konsistensi keras.
* Tidak sakit.
* Ada cekungan pada kulit di atas tumor.
* Ada bagian kulit yang terlihat seperti kulit jeruk (pour d’ orange).
* Koreng dan kemerahan pada kulit.
* Pembesaran getah bening di ketiak dan di atas tulang selangka.
Andaipun Kanker Payudara sudah menyerang, berbagai pengobatan dapat ditempuh. Yaitu operasi, radiasi
(emisi gelombang elektromagnetik, seperti gelombang alfa, beta, gama) dan kemoterapi (mengobati penyakit
dengan zat-zat kimia).
Misteri Kanker Payudara
8 Januari 2007
Kanker payudara menduduki posisi kedua terbanyak sebagai penyebab kanker di Indonesia. Menurut WHO,
sebanyak 8 – 9 % wanita akan mengalami kanker payudara dalam hidupnya. Setiap tahun lebih dari 580.000
kasus baru ditemukan di berbagai negara berkembang dan kurang lebih 372.000 pasien meninggal karena
penyakit ini. Sayangnya sampai saat ini penyebab kanker payudara masih belum diketahui.
Siapa Saja yang Rentan Resiko?
Namun ada beberapa hal yang dapat meningkatkan resiko kanker payudara, antara lain usia, riwayat
kesehatan, faktor keturunan, faktor hormonal seperti menstruasi pertama terlalu cepat dan menopause dini.
Selain itu upaya menunda kehamilan atau kehamilan pertama terjadi di atas usia 30 tahun juga bisa
meningkatkan resiko. Gaya hidup yang tidak sehat, misalnya sering mengkonsumsi makanan yang mengandung
lemak jahat, atau kurang berolahraga, juga dapat memperbesar resiko terserang kanker payudara.
Data WHO menunjukkan bahwa 78% kanker payudara terjadi pada wanita usia 50 tahun ke atas. Hanya 6%-nya
terjadi pada mereka yang berusia kurang dari 40 tahun. Meski demikian, kian hari makin banyak penderita
kanker payudara yang berusia 30-an. Oleh karena itu jika Anda termasuk golongan yang beresiko tinggi, meski
baru berusia 30-an, tak ada salahnya untuk lebih bersikap waspada terhadap perubahan yang terjadi pada
payudara Anda.
Apa Saja Gejala-gejala Kanker Payudara?
Indonesia sudah cukup lama mengkampanyekan SADARI (periksa payudara sendiri). SADARI adalah tindakan
deteksi dini terhadap adanya gejala-gejala kanker payudara. Metode ini sangat sederhana, namun diharapkan
dapat menekan tingginya angka penderita kanker payudara, karena semakin awal terdeteksi maka semakin
cepat proses pengobatan yang diperlukan.
Dengan SADARI, Anda harus meraba ada/tidaknya benjolan, baik yang sakit maupun yang tidak. Benjolan
dapat menandakan adanya tumor. Walau tidak semua benjolan di payudara berbahaya, namun jika Anda
temukan sebaiknya segera konsultasikan ke dokter untuk mencegah hal-hal yang tidak diinginkan. Selain itu
perhatikan kulit payudara, apakah pembuluh vena-nya semakin terlihat? Apakah kulit di sekitar puting menjadi
berkerut? Kemudian cermati puting payudara bila ada cairan lengket atau darah yang keluar. Terakhir,
perhatikan ukuran dan posisi payudara. Bila ukurannya mengecil atau posisi yang satu lebih rendah daripada
yang lain, sebaiknya jangan dianggap remeh.
Tidak Semua Berupa Benjolan, Lho!
Hati-hati, ternyata ada sejumlah kecil kanker payudara muncul tanpa adanya benjolan sama sekali, dan gejala
ini bisa mengecohkan kita semua, bahkan para dokter. Jenis kanker payudara yang dikenal dengan
Inflammatory Breast Cancer (IBC) ini cukup jarang dan jenis yang sangat agresif. Jika tidak segera terdiagnosa
maka bisa menyebabkan kematian. Kenali gejala-gejalanya seperti :
1.
2.
3.
4.
5.
6.
7.
8.
9.
Pertumbuhan ukuran payudara yang cepat dan tidak normal
Timbul kemerahan, ruam atau bisul pada payudara
Rasa gatal berkepanjangan pada payudara atau puting
Adanya penebalan pada jaringan payudara
Timbul rasa sakit yang menusuk-nusuk dan/atau nyeri pada payudara
Timbul rasa panas (seperti demam) pada payudara
Adanya pembengkakan nodus limfe di ketiak atau di bawah tulang selangka
Adanya lesung pada payudara
Puting payudara menjadi rata atau melesak ke dalam
Inflammatory Breast Cancer ini sering disalahartikan sebagai infeksi. Jika Anda mengalami gejala-gejala di atas,
mintalah rujukan untuk melakukan mammogram. Jika ada perubahan warna pada payudara, minta pula rujukan
untuk biopsy. Jika gejala-gejala tetap ada tanpa adanya diagnosa penyebabnya, minta pendapat kedua atau
ketiga sampai ada dokter yang dapat menentukan penyebab gejala-gejala
tersebut.http://images.google.co.id/imgres?
imgurl=http://www.mediasehat.com/artikel/ibudanbalita/gambar/kanpay250.jpg&imgrefurl=http://www.mediasehat
.com/artikel.php%3Fkl%3D4%26no
%3D63&h=226&w=250&sz=7&hl=id&start=23&um=1&tbnid=3QvaMRsTaD11FM:&tbnh=100&tbnw=111&prev=/i
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%3Did%26sa%3DN
Kanker payudara adalah kanker pada jaringan payudara. Ini adalah jenis kanker paling umum yang
diderita kaum wanita. Kaum pria juga dapat terserang kanker payudara, walaupun kemungkinannya
lebih kecil dari 1 di antara 1000. Pengobatan yang paling lazim adalah dengan pembedahan dan jika
perlu dilanjutkan dengan kemoterapi maupun radiasi.
1.1. Definisi 1.1.1. Kanker adalah suatu kondisi dimana sel telah kehilangan pengendalian dan
mekanisme normalnya, sehingga mengalami pertumbuhan yang tidak normal, cepat dan tidak
terkendali. (http://www.mediasehat.com/utama07.php) 1.1.2. Kanker payudara (Carcinoma mammae)
adalah suatu penyakit neoplasma yang ganas yang berasal dari parenchyma. Penyakit ini oleh Word
Health Organization (WHO) dimasukkan ke dalam International Classification of Diseases (ICD)
dengan kode nomor 17 (http://www.tempo.co.id/medika/arsip/082002/pus-3.htm)
1.2. Patofisiologi 1.2.1. Transformasi Sel-sel kanker dibentuk dari sel-sel normal dalam suatu proses
rumit yang disebut transformasi, yang terdiri dari tahap inisiasi dan promosi. 1.2.1.1. pada tahap inisiasi
terjadi suatu perubahan dalam bahan genetik sel yang memancing sel menjadi ganas. Perubahan dalam
bahan genetik sel ini disebabkan oleh suatu agen yang disebut karsinogen, yang bisa berupa bahan
kimia, virus, radiasi (penyinaran) atau sinar matahari. tetapi tidak semua sel memiliki kepekaan yang
sama terhadap suatu karsinogen. kelainan genetik dalam sel atau bahan lainnya yang disebut promotor,
menyebabkan sel lebih rentan terhadap suatu karsinogen. bahkan gangguan fisik menahunpun bisa
membuat sel menjadi lebih peka untuk mengalami suatu keganasan. 1.2.1.2. pada tahap promosi, suatu
sel yang telah mengalami inisiasi akan berubah menjadi ganas. Sel yang belum melewati tahap inisiasi
tidak akan terpengaruh oleh promosi. karena itu diperlukan beberapa faktor untuk terjadinya keganasan
(gabungan dari sel yang peka dan suatu karsinogen). 1.2.2. Stadium Stadium penyakit kanker adalah
suatu keadaan dari hasil penilaian dokter saat mendiagnosis suatu penyakit kanker yang diderita
pasiennya, sudah sejauh manakah tingkat penyebaran kanker tersebut baik ke organ atau jaringan
sekitar maupun penyebaran ketempat jauh Stadium hanya dikenal pada tumor ganas atau kanker dan
tidak ada pada tumor jinak. Untuk menentukan suatu stadium, harus dilakukan pemeriksaan klinis dan
ditunjang dengan pemeriksaan penunjang lainnya yaitu histopatologi atau PA, rontgen , USG, dan bila
memungkinkan dengan CT Scan, scintigrafi dll. Banyak sekali cara untuk menentukan stadium, namun
yang paling banyak dianut saat ini adalah stadium kanker berdasarkan klasifikasi sistim TNM yang
direkomendasikan oleh UICC(International Union Against Cancer dari WHO atau World Health
Organization) / AJCC(American Joint Committee On cancer yang disponsori oleh American Cancer
Society dan American College of Surgeons). 1.2.2.1. Pada sistim TNM dinilai tiga faktor utama yaitu
"T" yaitu Tumor size atau ukuran tumor , "N" yaitu Node atau kelenjar getah bening regional dan "M"
yaitu metastasis atau penyebaran jauh. Ketiga faktor T,N,M dinilai baik secara klinis sebelum
dilakukan operasi , juga sesudah operasi dan dilakukan pemeriksaan histopatologi (PA) . Pada kanker
payudara, penilaian TNM sebagai berikut :
• T (Tumor size), ukuran tumor :
•
T 0 : tidak ditemukan tumor primer
•
T 1 : ukuran tumor diameter 2 cm atau kurang
•
T 2 : ukuran tumor diameter antara 2-5 cm
•
T 3 : ukuran tumor diameter > 5 cm
•
T 4 : ukuran tumor berapa saja, tetapi sudah ada penyebaran ke kulit atau dinding dada atau
pada keduanya , dapat berupa borok, edema atau bengkak, kulit payudara kemerahan atau ada
benjolan kecil di kulit di luar tumor utama
• N (Node), kelenjar getah bening regional (kgb) :
•
N 0 : tidak terdapat metastasis pada kgb regional di ketiak / aksilla
•
N 1 : ada metastasis ke kgb aksilla yang masih dapat digerakkan
•
N 2 : ada metastasis ke kgb aksilla yang sulit digerakkan
•
N 3 : ada metastasis ke kgb di atas tulang selangka (supraclavicula) atau pada kgb di mammary
interna di dekat tulang sternum
• M (Metastasis) , penyebaran jauh :
•
M x : metastasis jauh belum dapat dinilai
•
M 0 : tidak terdapat metastasis jauh
•
M 1 : terdapat metastasis jauh
1.2.2.2. Setelah masing-masing faktot T,.N,M didapatkan, ketiga faktor tersebut kemudian digabung
dan didapatkan stadium kanker sebagai berikut :
•
Stadium 0 : T0 N0 M0
•
Stadium 1 : T1 N0 M0
•
Stadium II A : T0 N1 M0 / T1 N1 M0 / T2 N0 M0
•
Stadium II B : T2 N1 M0 / T3 N0 M0
•
Stadium III A : T0 N2 M0 / T1 N2 M0 / T2 N2 M0 / T3 N1 M0 / T2 N2 M0
•
Stadium III B : T4 N0 M0 / T4 N1 M0 / T4 N2 M0
•
Stadium III C : Tiap T N3 M0
•
Stadium IV : Tiap T-Tiap N -M1
1.3. Gejala Klinis Gejala klinis kanker payudara dapat berupa • benjolan pada payudara Umumnya
berupa benjolan yang tidak nyeri pada payudara. Benjolan itu mula-mula kecil, makin lama makin
besar, lalu melekat pada kulit atau menimbulkan perubahan pada kulit payudara atau pada puting susu.
• erosi atau eksema puting susu Kulit atau puting susu tadi menjadi tertarik ke dalam (retraksi),
berwarna merah muda atau kecoklat-coklatan sampai menjadi oedema hingga kulit kelihatan seperti
kulit jeruk (peau d'orange), mengkerut, atau timbul borok (ulkus) pada payudara. Borok itu makin lama
makin besar dan mendalam sehingga dapat menghancurkan seluruh payudara, sering berbau busuk, dan
mudah berdarah. • pendarahan pada puting susu. • Rasa sakit atau nyeri pada umumnya baru timbul
kalau tumor sudah besar, sudah timbul borok, atau kalau sudah ada metastase ke tulang-tulang. •
Kemudian timbul pembesaran kelenjar getah bening di ketiak, bengkak (edema) pada lengan, dan
penyebaran kanker ke seluruh tubuh (Handoyo, 1990). Kanker payudara lanjut sangat mudah dikenali
dengan mengetahui kriteria operbilitas Heagensen sebagai berikut: • terdapat edema luas pada kulit
payudara (lebih 1/3 luas kulit payudara); • adanya nodul satelit pada kulit payudara; • kanker payudara
jenis mastitis karsinimatosa; • terdapat model parasternal; • terdapat nodul supraklavikula; • adanya
edema lengan; • adanya metastase jauh; • serta terdapat dua dari tanda-tanda locally advanced, yaitu
ulserasi kulit, edema kulit, kulit terfiksasi pada dinding toraks, kelenjar getah bening aksila berdiameter
lebih 2,5 cm, dan kelenjar getah bening aksila melekat satu sama lain
1.4. Faktor Resiko Menurut Moningkey dan KodimPenyebab spesifik kanker payudara masih belum
diketahui, tetapi terdapat banyak faktor yang diperkirakan mempunyai pengaruh terhadap terjadinya
kanker payudara diantaranya: 1.4.1. Faktor reproduksi Karakteristik reproduktif yang berhubungan
dengan risiko terjadinya kanker payudara adalah nuliparitas, menarche pada umur muda, menopause
pada umur lebih tua, dan kehamilan pertama pada umur tua. Risiko utama kanker payudara adalah
bertambahnya umur. Diperkirakan, periode antara terjadinya haid pertama dengan umur saat kehamilan
pertama merupakan window of initiation perkembangan kanker payudara. Secara anatomi dan
fungsional, payudara akan mengalami atrofi dengan bertambahnya umur. Kurang dari 25% kanker
payudara terjadi pada masa sebelum menopause sehingga diperkirakan awal terjadinya tumor terjadi
jauh sebelum terjadinya perubahan klinis. 1.4.2. Penggunaan hormon Hormon eksogen berhubungan
dengan terjadinya kanker payudara. Laporan dari Harvard School of Public Health menyatakan bahwa
terdapat peningkatan kanker payudara yang bermakna pada para pengguna terapi estrogen replacement.
Suatu metaanalisis menyatakan bahwa walaupun tidak terdapat risiko kanker payudara pada pengguna
kontrasepsi oral, wanita yang menggunakan obat ini untuk waktu yang lama mempunyai risiko tinggi
untuk mengalami kanker ini sebelum menopause. 1.4.3. Penyakit fibrokistik Pada wanita dengan
adenosis, fibroadenoma, dan fibrosis, tidak ada peningkatan risiko terjadinya kanker payudara. Pada
hiperplasis dan papiloma, risiko sedikit meningkat 1,5 sampai 2 kali. Sedangkan pada hiperplasia
atipik, risiko meningkat hingga 5 kali. 1.4.4. Obesitas Terdapat hubungan yang positif antara berat
badan dan bentuk tubuh dengan kanker payudara pada wanita pasca menopause. Variasi terhadap
kekerapan kanker ini di negara-negara Barat dan bukan Barat serta perubahan kekerapan sesudah
migrasi menunjukkan bahwa terdapat pengaruh diet terhadap terjadinya keganasan ini. 1.4.5. Konsumsi
lemak Konsumsi lemak diperkirakan sebagai suatu faktor risiko terjadinya kanker payudara. Willet
dkk., melakukan studi prospektif selama 8 tahun tentang konsumsi lemak dan serat dalam hubungannya
dengan risiko kanker payudara pada wanita umur 34 sampai 59 tahun. 1.4.6. Radiasi Eksposur dengan
radiasi ionisasi selama atau sesudah pubertas meningkatkan terjadinya risiko kanker payudara. Dari
beberapa penelitian yang dilakukan disimpulkan bahwa risiko kanker radiasi berhubungan secara linier
dengan dosis dan umur saat terjadinya eksposur. 1.4.7. Riwayat keluarga dan faktor genetik Riwayat
keluarga merupakan komponen yang penting dalam riwayat penderita yang akan dilaksanakan skrining
untuk kanker payudara. Terdapat peningkatan risiko keganasan ini pada wanita yang keluarganya
menderita kanker payudara. Pada studi genetik ditemukan bahwa kanker payudara berhubungan dengan
gen tertentu. Apabila terdapat BRCA 1, yaitu suatu gen suseptibilitas kanker payudara, probabilitas
untuk terjadi kanker payudara sebesar 60% pada umur 50 tahun dan sebesar 85% pada umur 70 tahun.
1.5. Pengobatan Kanker Ada beberapa pengobatan kanker payudara yang penerapannya banyak
tergantung pada stadium klinik penyakit (Tjindarbumi, 1994), yaitu: 1.5.1. Mastektomi Mastektomi
adalah operasi pengangkatan payudara. Ada 3 jenis mastektomi (Hirshaut & Pressman, 1992): 1.5.1.1.
Modified Radical Mastectomy, yaitu operasi pengangkatan seluruh payudara, jaringan payudara di
tulang dada, tulang selangka dan tulang iga, serta benjolan di sekitar ketiak. 1.5.1.2. Total (Simple)
Mastectomy, yaitu operasi pengangkatan seluruh payudara saja, tetapi bukan kelenjar di ketiak. 1.5.1.3.
Radical Mastectomy, yaitu operasi pengangkatan sebagian dari payudara. Biasanya disebut
lumpectomy, yaitu pengangkatan hanya pada jaringan yang mengandung sel kanker, bukan seluruh
payudara. Operasi ini selalu diikuti dengan pemberian radioterapi. Biasanya lumpectomy
direkomendasikan pada pasien yang besar tumornya kurang dari 2 cm dan letaknya di pinggir
payudara. 1.5.2. Penyinaran/radiasi Yang dimaksud radiasi adalah proses penyinaran pada daerah yang
terkena kanker dengan menggunakan sinar X dan sinar gamma yang bertujuan membunuh sel kanker
yang masih tersisa di payudara setelah operasi (Denton, 1996). Efek pengobatan ini tubuh menjadi
lemah, nafsu makan berkurang, warna kulit di sekitar payudara menjadi hitam, serta Hb dan leukosit
cenderung menurun sebagai akibat dari radiasi. 1.5.3. Kemoterapi Kemoterapi adalah proses pemberian
obat-obatan anti kanker dalam bentuk pil cair atau kapsul atau melalui infus yang bertujuan membunuh
sel kanker. Tidak hanya sel kanker pada payudara, tapi juga di seluruh tubuh (Denton, 1996). Efek dari
kemoterapi adalah pasien mengalami mual dan muntah serta rambut rontok karena pengaruh obatobatan yang diberikan pada saat kemoterapi.
1.6. Strategi Pencegahan Pada prinsipnya, strategi pencegahan dikelompokkan dalam tiga kelompok
besar, yaitu pencegahan pada lingkungan, pada pejamu, dan milestone. Hampir setiap epidemiolog
sepakat bahwa pencegahan yang paling efektif bagi kejadian penyakit tidak menular adalah promosi
kesehatan dan deteksi dini. Begitu pula pada kanker payudara, pencegahan yang dilakukan antara lain
berupa: 1.6.1. Pencegahan primer Pencegahan primer pada kanker payudara merupakan salah satu
bentuk promosi kesehatan karena dilakukan pada orang yang "sehat" melalui upaya menghindarkan diri
dari keterpaparan pada berbagai faktor risiko dan melaksanakan pola hidup sehat. 1.6.2. Pencegahan
sekunder Pencegahan sekunder dilakukan terhadap individu yang memiliki risiko untuk terkena kanker
payudara. Setiap wanita yang normal dan memiliki siklus haid normal merupakan populasi at risk dari
kanker payudara. Pencegahan sekunder dilakukan dengan melakukan deteksi dini. Beberapa metode
deteksi dini terus mengalami perkembangan. Skrining melalui mammografi diklaim memiliki akurasi
90% dari semua penderita kanker payudara, tetapi keterpaparan terus-menerus pada mammografi pada
wanita yang sehat merupakan salah satu faktor risiko terjadinya kanker payudara. Karena itu, skrining
dengan mammografi tetap dapat dilaksanakan dengan beberapa pertimbangan antara lain: • Wanita
yang sudah mencapai usia 40 tahun dianjurkan melakukan cancer risk assessement survey. • Pada
wanita dengan faktor risiko mendapat rujukan untuk dilakukan mammografi setiap tahun. • Wanita
normal mendapat rujukan mammografi setiap 2 tahun sampai mencapai usia 50 tahun. Foster dan
Constanta menemukan bahwa kematian oleh kanker payudara lebih sedikit pada wanita yang
melakukan pemeriksaan SADARI (Pemeriksaan Payudara Sendiri) dibandingkan yang tidak. Walaupun
sensitivitas SADARI untuk mendeteksi kanker payudara hanya 26%, bila dikombinasikan dengan
mammografi maka sensitivitas mendeteksi secara dini menjadi 75%. 1.6.3. Pencegahan Tertier
Pencegahan tertier biasanya diarahkan pada individu yang telah positif menderita kanker payudara.
Penanganan yang tepat penderita kanker payudara sesuai dengan stadiumnya akan dapat mengurangi
kecatatan dan memperpanjang harapan hidup penderita. Pencegahan tertier ini penting untuk
meningkatkan kualitas hidup penderita serta mencegah komplikasi penyakit dan meneruskan
pengobatan. Tindakan pengobatan dapat berupa operasi walaupun tidak berpengaruh banyak terhadap
ketahanan hidup penderita. Bila kanker telah jauh bermetastasis, dilakukan tindakan kemoterapi dengan
sitostatika. Pada stadium tertentu, pengobatan diberikan hanya berupa simptomatik dan dianjurkan
untuk mencari pengobatan alternatif.
http://id.wikipedia.org/wiki/Kanker_payudara