Breast Cancer, Male

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Diagnosis and reasoning

This 60-year-old gentleman has presented with left sided breast pain; examination reveals a tender, irregular, fixed breast lump. This is highly concerning, as the vast majority of breast lumps encountered in men are malignant in nature; while a breast abscess can mimic the physical characteristics seen here, this is a distant second possibilty. That said, the approach here is the same as with female breast lumps, i.e. a triple assessment consisting of clinical examination, imaging, and histology. In this respect, the irregularity of the lump and the deep attachment are further suspicious of a malignant lesion; furthemore, ultrasound shows a hypoechoic mass with posterior acoustic shadowing, which also supports the presence of a cancer. Subsequently, fine needle aspiration reveals cytological findings suspicious of malignancy; in this clinical and imaging context, this is all but diagnostic of male breast cancer. Note also that this is stage IA disease, as the lump is ≤ 2 cm in size. Incisional biopsy is mainly indicated if cytology or a core biopsy are inconclusive; furthermore, the American Society of Clinical Oncology (ASCO) currently recommends that assays for the tumor markers CA 15-3, CA 27.29, and CEA should be not used in the routine surveillance of these patients. The management of male breast cancer parallels that of the female version. Thus, for stage IA disease, left sided mastectomy should be performed in association with sentinel lymph node biopsy (SLNB) or axillary dissection. Note that given the scarcity of tissue in the male breast, this is preferred over breast-conserving surgery. Anti-tuberculous therapy is obviously not indicated here; surgical drainage and antibiotic therapy would have been an option if this were an abscess.


Discussion

Male Breast Cancer (MBC) accounts for less than 1% of all breast cancers in the United States; thus, as might be expected, it is less well understood than breast cancer in women, and many questions regarding the causes, consequences, and optimal care still persist. The mean age of diagnosis is between 65 and 70 years of age, although the disease can affect any age group. While large randomized trials have not been performed, a strong racial predilection has been noted, with Jews being at highest risk. Sephardic Jews present earlier with advanced disease, and Ashkenazi Jews have an increased lifetime risk of male breast cancer. In addition, Black males seem to be affected more than white males and have a higher incidence of axillary node involvement at a higher stage as well. The exact pathophysiology of MBC is not completely known. However, it is accepted that there are some biologic differences between MBC and female breast cancer. The underlying pathophysiology of breast cancer, in general, is thought to begin with carcinoma in situ, with proliferation of cells within the ducts or lobules, without stromal invasion. Left untreated, this leads to locally invasive carcinoma, usually ductal in nature; lobular pathology is exceedingly rare (or non-existent) due to lack of terminal lobules in the male breast. Once past the basement membrane, the malignant cells then spread through the regional lymph nodes and to distant organs. Note also that MBC advances more rapidly than female breast cancer, again because of the lack of breast parenchyma; this is true even when tumors are found at similar sizes. The etiology of MBC is not completely known either; however, many risk factors have been implicated. Conditions that alter the testosterone/estrogen balance in favor of the latter such as Klinefelter's syndrome, obesity, exogenous administration of estrogen, cirrhosis, androgen deficiency, orchitis, epididymitis and finasteride use have been implicated. Klinefelter syndrome has the strongest association of these factors, accounting for about 3% of all cases of MBC and conferring a risk fifty times higher than the general population for the development of MBC. Similar to breast cancer in females, a positive family history of first-degree female relatives affected by the condition is associated with increased risk of MBC. Other risk factors include the presence of the BRCA mutation, androgen receptor gene mutation, Lynch syndrome, CYP 17 polymorphism, and CHEK2 and PTEN mutations. Occupational exposure to heat and electromagnetic radiation have also been thought to be a risk factor for the development of MBC. The most common presentation is a hard subareolar and non-tender mass, usually in the left breast. The diameter of the mass has been reported to range in size from 0.5 cm to 12.5 cm, with a mean diameter of 3 - 3.5cm. Skin ulceration may also be a significant finding. Possibly owing to the small size of the male breast, early presentation with late disease manifested by nipple retraction, discharge or eczema is seen in 40-50% of patients. Less commonly, breast tenderness, itching or symptoms of distant metastasis are noted. On exam, 40-55% of patients are found to have clinically suspicious axillary lymphadenopathy. The diagnosis of MBC should be made on the basis of clinical findings, radiology, and biopsy results. Breast imaging in males is generally more difficult than in females, due to the relative lack of breast tissue. Mammography is the most widely used imaging modality; this typically shows a mass lesion, rather than micro calcifications. A study has shown mammography to have a sensitivity of 92% and specificity of 90% for the diagnosis of MBC. Studies have also shown ultrasound to have a very high sensitivity and specificity, and this is sometimes used as first-line investigation. That said, certain authors do not find ultrasound to be useful in the diagnosis of MBC, and prefer mammography. Fine needle aspiration cytology is of value in establishing a histopathological diagnosis; its sensitivity is reported to be 95.3%, with a specificity of 100% and diagnostic accuracy of 98%. Note that the most common histologic type seen is an invasive ductal carcinoma, followed by intraductal papillary carcinomas. Furthermore, MBC are usually positive for molecular markers such as estrogen receptors (ER) and progesterone receptors (PR), with studies showing >90% and 68% positivity, respectively. Tc-99 Sestamibi uptake scans can be used in cases of malignant masses that may have already metastasized. While beyond the scope of this monograph, note that the TNM staging system is used similarly for male and female breast cancer. The management of MBC is similar to that of female breast cancer; the standard surgical treatment is modified radical mastectomy with axillary dissection. Lumpectomy and radiation (breast conserving therapy) have also been used with similar results. Men with node-negative tumors should be considered for the same adjuvant therapy as women, as there is no evidence to suggest response is different. Regimens include CMF (cyclophosphamide, methotrexate and fluorouracil), CAF (cyclophosphamide, doxorubicin and fluorouracil), trastuzumab and tamoxifen. Node positive tumors can be treated with the same chemotherapy and hormonal therapy regimens that are used in women. Tamoxifen, however, is associated with more treatment-limiting symptoms in males, such as hot flashes, decreased libido and impotence. Locally recurrent disease is generally treated with surgical excision or radiotherapy combined with chemotherapy, while distant metastases are treated initially with hormone therapy along with chemotherapy. Lymph node involvement is the single biggest predictor of survival in patients with MBC. The five-year survival rate is 90% and 84% in cases with node negativity, while in cases with node positivity, the rate drops to 65% at five years and 44% at ten years. When four or more lymph nodes are involved, ten-year survival rate declines further to 14%. When metastasis is not present and lymph nodes are negative, tumor size seems to have a negative impact on survival. The five-year survival rate has been reported to be 74% for tumors less than 2cm and a half (37%) for tumors greater than 5cm. While ER and PR positivity is generally a favorable prognostic indicator in both male and female breast cancer, when adjusted for tumor size, lymph node status, and age, the difference has been found to no longer be statistically significant. Males typically have worse overall survival compared to women; this is partially attributed to delayed detection and an older age of presentation. This is supported by studies showing matched male and female breast cancer patients with equivalent survival.


Take home messages

  1. Male breast cancer is rare, accounting for less than 1% of all breast cancers in the United States
  2. Men tend to present later in the course of the disease, and in the majority of cases, have estrogen or progesterone receptor positive tumors.
  3. The diagnosis is made based on clinical suspicion, radiographic evidence and pathology results from fine needle aspiration cytology.
  4. The treatment is similar to that of female breast cancer, with modified radical mastectomy with axillary node dissection being the mainstay of surgical management.
  5. The overall survival is worse than that of female breast cancer, as patients tend to often present with advanced disease.
  6. Because MBC is relatively less studied than female breast cancer, more research is needed to further evaluate treatment options and improve th prognosis.

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