A 42-year-old man of white ethnicity comes to the office for an annual visit. He has a history of hyperlipidemia, type 2 diabetes mellitus, and hypertension, all of which are well controlled with medication. His 34-year-old sister was recently diagnosed with breast cancer. The patient says, "Luckily they caught it early, and her doctors think she can be cured. I feel strange asking this, but am I also at risk for breast cancer?" The patient has smoked a half pack of cigarettes daily for 20 years but does not use alcohol or illicit drugs. He works as an accountant and is married; he and his wife have 2 healthy teenage daughters. Family history includes ovarian cancer in his mother and Klinefelter syndrome in his brother. Vital signs are within normal limits. BMI is 32 kg/m², which has increased since his last visit. The chest appears normal and symmetric. There is a rubbery, nontender disk of tissue beneath both areolas. No lymphadenopathy is present. Cardiopulmonary auscultation is normal. The abdomen is soft and nontender with no masses or organomegaly. Which of the following, if present, would confer the highest risk of breast cancer in this patient?

Question

Quizplus · Accepted Answer

Explanation: Breast cancer is an uncommon condition in men. In the United States, approximately 2,500 cases are diagnosed annually. However, certain underlying genetic and hormonal abnormalities are associated with an elevated risk of male breast cancer, including: BRCAmutations - these autosomal dominant mutations increase the risk of male breast cancer up to 100-fold; BRCA2 mutations are considered the single greatest risk factor. Klinefelter syndrome - the presence of an extra X chromosome increases the estrogen-to-androgen ratio and results in a 20-fold increase in the risk of male breast cancer. Klinefelter syndrome is due to a sporadic error in cell division and is not an inherited disorder. Therefore, a family history of Klinefelter syndrome does not increase risk of breast cancer (Choice B). Hepatic dysfunction, marijuana use, obesity - these conditions also increase the estrogen-to-androgen ratio, but confer a much lower risk of male breast cancer compared to BRCA mutations or Klinefelter syndrome (Choice D). This patient's sister developed breast cancer before age 40, and his mother had ovarian cancer, indicating a potential family history of BRCA mutation. He would likely benefit from genetic counseling followed by BRCA testing. (Choice C) This patient who has bilateral, rubbery, nontender disks of tissue beneath the areolas likely has gynecomastia. Gynecomastia is typically due to an increased estrogen-to-androgen ratio and is linked to a mildly increased risk of male breast cancer. However, this risk is much lower than that conferred by BRCA mutation. (Choice E) Although patients of white ethnicity (particularly Ashkenazi Jews) are most likely to have BRCA mutations, white ethnicity alone is not associated with elevated rates of male breast cancer. Educational objective: Male breast cancer is an uncommon condition. Risk is greatest in those with BRCA mutations and Klinefelter syndrome. Conditions that alter the estrogen-to-androgen ratio (eg, hepatic dysfunction, marijuana use, obesity) confer a mildly elevated risk. References: Etiologic factors for male breast cancer in the U.S. Veterans Affairs medical care system database. (http://www.ncbi.nlm.nih.gov/pubmed/19330525)

A 42-Year-Old Man of White Ethnicity Comes to the Office