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Male breast cancer

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Represents 0.6% of all breast cancers and <1% of all cancers in men.

More than 2800 cases per year occur in the U.S., with 530 anticipated deaths.

Lifetime risk is approximately 1 in 800-1000.

Incidence of male breast cancer is increasing.

Risk factors include family history and germ-line mutations in BRCA2.

In a cohort study, including 2836 men, the cumulative 20 year risk of breast cancer specific mortality was 12.4% for stage 1, 26.2% for stage II and 46% for stage III: the risk of breast cancer specific mortality at 20 years is high in men with hormone receptor positive breast cancer with kinetics different from those in women.

The lifetime risk of male breast cancer is estimated at 1-5% for  BRCA1 and 5-10% for BRCA2 variant carriers versus 0.1% in the general population.

BRCA1 and BRCA2 variants account for up to 2% and 30% of male breast cancers..

Risk factors include BRCA mutations, mutations in PTEN, mutations in CHEK2, obesity, Klinefelter syndrome, gynecomastia, previous chest wall radiation, and positive family history.

Increased risk in men who have female relatives with breast cancer of 2.5 fold.

Family history, environmental factors, hormonal changes, as well as gene mutations (BRCA) likely contribute to breast cancer incidence in men.

20% of men with breast cancer have of first degree relative with the disease.

A positive family history associated with a 2-5 times increase in relative risk.

Many tend to be older at the time of diagnosis compared to women with a median age at diagnosis of 67 years.

Men are typically 5-10 years older than women a diagnosis.

Increases steadily with age.

Comprises 6% and 20% of all cancers of the breast in Egypt and Zambia as a result of hepatic schistosomiasis with hepatic dysfunction and increase in endogenous estrogen and alterations in androgen-estrogen ratios.

Linked to BRCA 1 and 2, Klinefelter’s syndrome and Cowden’s syndrome.

BRCA mutations account for as many as 4-40% of cases, with BRCA 2 being a much more common association than the BRCA 1 abnormality.

Approximately 15% of all male breast cancers associated with BRCA2, with a range from 3.2-40%.

Association with BRCA1 mutations ranges from 4.5-10.5%.

Among men with BRCA mutation the lifetime risk of breast cancer approximates 8% with the BRCA2 mutation and 2% for the BRCA1 mutation.

Develops more in old age among men then among women.

Circulating estradiol levels are significantly associated with a high risk for breast cancer in men, with a similar association in female patients.

Mean age of diagnosis 67 years for male breast cancer versus 62 years in women.

Male breast cancer patients have a more advanced stage and a greater tumor size with lymph node involvement compared with women.

Many patients are diagnosed in late stages of disease, resulting in poor prognosis compared with female patients.

Pathologic type is most often invasive ductal carcinoma.

Spread of the disease to lymph nodes is more common in men and typically requires more aggressive treatment than in women with breast cancer.

The hormone receptor positive status ER +80-90%, and progesterone receptor positive 73-81%.

HER-2/neu status positive in 5-15% of cases.

Breast cancers associated with Klinefelter’s syndrome and BRCA mutations occurring nearly a decade earlier in life than typical male breast cancer, age 58 compared with age 67, respectively.

Increased incidence in Jewish men.

Associated with prolactin like medications and occurs in higher incidence in men with hepatic dysfunction.

Associated with occupations that expose workers to hot environment such as steel mills or blast furnaces and also seen in higher risk with soap, perfume industries and, in individuals exposed to exhaust fumes and petroleum products.

Gynecomastia not associated with this entity.

The risk of breast cancer in men is significantly increased in BRCA2 mutation carriers.

The most common presenting symptoms are a palpable lump, tenderness, and enlargement.

Breast examination is very sensitive, but lacks specificity in the detection of breast cancer.

Findings on physical examination suspicious for malignancy warrants further evaluation with imaging.

Normal or benign physical exam findings generally do not require imaging evaluation.

98% of male breast cancers are below the nipple.

Approximately 50% of breast cancer in men occur under the nipple-areolar complex.
In men with breast cancer the risk of the development of a second breast cancer is approximately 0.6-1.75%.

The risk of development of a second cancer not involving the breast in men with breast cancer is approximately 15% in the most common types of lesions are prostate,:, lung, and nonmelanoma skin cancer.

Principal imaging techniques are ultrasound and mammography.

Bilateral mammogram should always be performed and standard mediolateral oblique and craniocaudal views should be obtained.

Magnification and spot compression views may be obtained as needed.

Men have more advanced stage of disease at diagnosis of breast cancer than women.

Stage at the time of diagnosis: Stage I, 37%, Stage II, 21%, Stage III, 33%, Stage IV, 9%.

More likely to have ER and PR positive disease than women with greater than 90% ER+ and 81% PR+ tumors.

Diagnostic delay ranges from 6-10 months.

Survival rates for men and women are very similar stage for stage.

However, a study of 16,025 males and 1,800,708 female patients with breast cancer there was a 19% higher adjusted overall mortality rate in males compared with female counterparts (Wang F).

Lesions are typically low grade.

More frequently hormone receptor positive than female breast cancer (Masci G et al).

Tumor size and axillary lymph node involvement are predictors of overall survival.

Hormone receptor status and tumor grade do not appear to be independent factors influencing survival.

64-87% have invasive ductal cancer.

Only 5-10% of cases are ductal carcinoma-in-situ compared to 50-55% of female diagnosis.

Papillary carcinoma second most common type of breast cancer histology, approximately 2.5%.

Lobular and inflammatory carcinomas are rare in men.

Usually presents with a discrete palpable breast mass, nipple changes, nipple discharge or skin retraction.

Most patients can be evaluated and diagnosed clinically and mammography is unnecessary and should be reserved for cases with clinical suspicion.

Mammography does not provide much information because of the small breast size.

Male breast cancer mortality and survival rates have improved and the general population with the efficacy of adjuvant hormonal therapy, mainly tamoxifen.

The treatment of men with tamoxifen is associated with the side effects including: hot flashes, sexual dysfunction, weight gain, mood changes, venous thromboembolic events, leg cramps, and  neurocognitive dysfunction.

Traditional surgical approach has been a modified radical mastectomy, as opposed to a breast conserving surgery, because of relatively small amount of breast tissue, and the central location of most male breast cancers.

Breast conserving surgery is safe with good long-term outcomes in limited studies.

Tumor size and lymph node status are independent predictors for overall survival.

Sentinel lymph node biopsy is an accurate diagnostic procedure and is considered to be a standard part of surgical evaluation.

5 year survival rates estimated with node-positive and node-negative breast cancer 68.5% and 87.5%, respectively (Kidwell KM et al).

Radiation guidelines are the same as for women.

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