Male breast cancer and occult primary

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Male breast cancer and occult primary



2. MALE BREAST CANCER 3. EPIDEMIOLOGY In the US, app. 2140 new cases of breast cancer in menare diagnosed annually, and 450 deaths occur; thisrepresents less than 0.5 percent of all cancer deaths inmen annually. By contrast, in Tanzania and areas of central Africa,breast cancer accounts for up to 6 % of cancers in men. In the United States, the ratio of female to male breastcancer is approximately 100:1 in whites, but lower (70:1)in blacks. Blacks also have a poorer prognosis, even afteradjustment for clinical, demographic, and treatmentfactors. 4. The median age of onset of breast cancer in men is65 to 67, approximately 5 to 10 years older than inwomen Race:- Afro caraibbean men (6%)> white men (0.5%)(later and more advancerd disease) Incidence of breast cancer in men has beenincreasing, it has increased 26 %over the past 25years 5. RISK FACTORS 6. HORMONALTesticular abnormalities Undescended testes Congenital inguinal hernia Orchiectomy Orchitis Infertility Mumps affecting testes 7. Klinefelters syndrome (XXY ) Males with Klinefelters syndrome have a 50-foldgreater risk of breast cancer over the generalmale population. KS may be present in 3%7% of men with breastcancer. The syndrome consists of atrophic testes,gynecomastia, high serum concentrations ofgonadotropins ( FSH and LH)and low serumtestosterone levels; the net effect is a high ratio ofestrogen-to-testosterone. 8. GENETIC RISK FACTORS4-16% 9. BRCA-2 mutations More common in MBC.(4-16 % mutation carriers) Younger age Poorer survival Highest prevalence in Iceland where founder mutationis present in 40 % cases.Other possible mutations PALB2 Androgen receptor CYP17 CHEK2 PTEN hMLH1 10. Family history 2.5 times greater risk 15 to 20 percent of men with breast cancer have afamily history of the diseasePrior irradiation Chest wall radiation Mantle radiation for Hodgkins disease 11. Benign breast disease Gynecomastia Alcohal use Liver disease Electromagnetic fields Heat Volatile organic compounds (e.g.tetrachloroethylene,perchloroethylene,trichloroethylene, dichloroethylene, and benzene) 12. Painless subareolar mass (M C presentation)Nipple Retraction, ulcerationFixation to skin or underlying muscleNipple involvement is 40 to 50 percent, possibly because of the scarcity of breasttissue, and the central location of most tumors 13. WORKUP Mammogram(92 % sensitive and 90% specific)Spiculation,calcification, mass ecentric to nipple. USG is a useful adjunct (nodal) Biopsy from suspicious mass ER, PR and her-2 neu testing Metastatic workup(chest imaging , CT abdomenand bone scan) 14. PATHOLOGIC CHARACTERSTICS 90 % of breast cancers in men are invasive ductalcarcinomas. Lobular cancer :- 1.5 %The lack of a lobular histologic subtype is due to lack of aciniand lobules in the normal male breast, although these can beinduced in the context of estrogenic stimulation. DCIS more common in FBC (20 % v/s 7 to 11% ) DCIS in men tends to occur at a later age, presents morefrequently in an intraductal papillary form, and is more oftenlow-grade. Paget disease and inflammatory breast cancer are rare. 15. MOLECULAR CHARACTERSTICS High rates of hormone receptor (ER/PR) expresssion. ER- 90% + PR-81% + Her-2 neu expression is less likely- 5-15%Triple negative :- 4% Younger patients were more likely to be diagnosed witha HER2-positive tumor. Non-Hispanic black men were more likely to have triple-negativebreast cancer compared to non-Hispanic whiteor Hispanic men (9 versus 3 and 6 percent,respectively). 16. DIFFERENTIAL DIAGNOSIS Gynecomastia Breast abscess Metastases to the breast Sarcomas 17. DIFFERENCES FROM FEMALE CANCER Average age of presentation is late (5-10 yrs). Presents in more advanced stages with retroareolarlocation and chest wall involvment. BRCA-2 > >BRCA-1 Lobular histologies uncommon (15 % v/s 1.5%) High rates of hormone receptor expression 18. SURGERY MRM + ALND is standard approch. Extensive chest wall muscle involvment :- Radicalmastectomy BCS less appropriate Presentation in more advanced stage Retroareolar & chest wall inv Scarcity of breast tissue SLN :- data is limited but feasible.ASCO expert -acceptable 19. Reconstructive surgery 40% - stage III /IV Extensive resection, skin closure difficult Goal is adequate skin coverage in comparison tovolume replacement in FBC 20. HORMONAL THERAPY High expression of ER/ PR receptor Tamoxifen for 5 years recommended Based largely upon the benefits that have been observed inclinical trials performed in women Paucity of Prospective trials to confirm the validity of thisapproach in men. Retrospective comparisons support a survival benefit fromadjuvant tamoxifen in MBC (61 versus 44 percent) and disease-freesurvival (56 versus 28 percent) compared with a group ofhistorical controls who underwent mastectomy alone Low adherence:- VTE, Decrease libido, hot flushes,wt gain,social support 21. Aromatase inhibitors There are insufficient data to support the use of an AI inthe adjuvant setting for breast cancers in men. Unable to prevent testes derived estrogen synthesiswhich is the source of 20% of endogeneous estrogen inmen. The recommended choice is tamoxifen rather than anAI in the adjuvant setting for men with breast cancer. Her-2 Transtuzumab Insufficient data 22. CHEMOTHERAPY Chemo less frequently used than FBC Hormone unresponsive tumors (ER-) Retrospective studies revealed NS trend in menwith node + disease toward better outcome 23. METASTATIC DISEASE Hormonal manipulation :- Ist line therapy Origionally performed surgically via orchidectomy,adrenalectomy or hypophsectomy.(morbid) Tamoxifen:- as effective as Sx AI :- shown benefit in metastatic settingAI+ orchidectomy Complete estro supp.AI+ LHRH analoguesHormone refrectory :- chemo 24. CONTRALATERAL BREAST CANCER The risk of a C/L breast cancer appears to be higher for men than it isFBC. Compared to the general population, the standardized incidence ratio(SIR) for C/L breast cancer in male survivors was 30. However, formen diagnosed < 50 yrs the SIR was 110. Men with a h/o breast cancer had a 93-fold higher risk of developingc/l breast cancer than men without such a history. The absolute risk for an individual man with breast cancer developinga c/l breast cancer was 1.75 % Despite the significantly increased risk of a c/l cancer in men with ah/o breast cancer, the absolute risk of a c/l breast cancer is muchgreater in women because of the higher prevalence of the disease. The role of screening mammography for the c/l breast in men withMBC has not been explored. 25. SURVIVORSHIP ISSUES discontinue T/t Socially isolating for men, stigmatized by theirdiagnosis. Greater adjustment diff Poor physical and mental health Late age presentation :- more CV risks. 26. OCCULT BREAST CANCER 27. Cancer of unknown primary site (CUP), defined as thepresence of metastatic cancer with an undetectableprimary site at the time of presentation. 2 % of all cancer diagnoses. Occult breast cancer (OBC), which manifests as anaxillary lymph node metastasis without a detectableprimary breast tumor on clinical examination orradiography, is a rare presentation. OBC accounts for 0.3-1% of all breast cancers. 28. Occult primary breast cancer was first recognizedby William Halsted, who described three patientspresenting with axillary masses that wereeventually found to represent breast cancer. In modern series, occult breast cancer accounts for0.1 to 0.8 percent of all newly diagnosed breastcancers and the incidence has not decreased withimprovements in breast imaging 29. DIAGNOSTIC WORK-UP The first step in the diagnostic workup of a patientwith unexplained axillary adenopathy is a biopsy. Besides standard light microscopic examination ofH & E stained sections, other techniques such asIHC and sometimes electron microscopy can helpto narrow the differential diagnosis. 30. Histologies 70 % are adenocarcinomas 15 to 20 % are poorly differentiated carcinomas 10 % represent poorly differentiatedadenocarcinomas. The remainder are squamous cell, neuroendocrine,or poorly differentiated neoplasms. 31. DIFFERENTIAL DIAGNOSIS Lymphomas Melanomas Sarcomas Thyroid cancers Skin cancers Lung cancers Less often, uterine, ovarian, sweat gland, or gastriccancers.In approximately 30 percent of cases, the primarysite is never identified 32. IHC MARKERS CEA CK- 7 and CK-20 ER/PR Gross cystic disease fluid protein-15 (GCDFP) Mammaglobin Thyroid transcription factor (TTF-1) CA-125 In men :- Markers for prostste cancer 33. Advantages of MRI Breast MRI is more sensitive. Breast MRI can detect a primary breast cancer inapproximately 75 % of women who present with ALN metswith negative clinical exam & imaging. Identification of a primary breast cancer by MRI mayfacilitate BCS instead of mastectomy. Some lesions found on MRI can be identified onsubsequent, targeted "second-look ultrasound and maythen be biopsied under US guidance.Disadvantages High false positive results. (29 %) All suspicious findings on MRI require pathologicconfirmation. 34. OBCALNDaloneMRM+ALNDALND +XRT 35. LRFSRFSBCSS 36. Patients with OBC who present with axillary lymphnode metastasis should receive the standardtreatment. No differences in outcomes were observedbetween patients who received ALND followed bysubsequent breast radiotherapy and patients whounderwent mastectomy plus ALND. 37. MANAGMENTLocal treatment for breast is necessary in conjunction with ALND.Mastectomy A standard approach is to perform a modified radical mastectomy(MRM) at the time of ALND. A breast malignancy will be found upon histologic review of themastectomy specimen in approximately 65 percent of patients.ALND + XRT Observation alone is deterimental. 38. Radiation The role of WBI as a breast-conservingalternative to mastectomy is unclear