64-year-old Cassie comes to the office because of a new breast mass that she found on her monthly self-examination. A mammogram shows microcalcification clusters so an excisional biopsy is performed. Pathology shows high-grade cells with central necrosis in the lumen and dystrophic calcification in the center of the ducts without invasion of the basement membrane. Later that day, a 58-year-old named Linda comes to the physician's office with eczematous dermatitis of the left nipple and areolar area for the past 24 months. Her history reveals that the lesion has been treated unsuccessfully with topical steroids and has progressively distorted the nipple, resulting in nipple inversion. Physical examination reveals scaly, crusted, and deformed left nipple with multiple plaques overlying the surrounding areola.
At first glance, you’d think Cassie and Linda have nothing in common, but the fact is, they have different forms of breast cancer! Breast cancer is the most common malignancy in women and it’s typically seen in postmenopausal women, over 50 years of age. Most breast cancers are adenocarcinomas and they typically arise from the terminal duct lobular units. Breast cancer can present as a palpable hard mass, most commonly located in the upper outer quadrant of the breast. Now, some breast cancers can be associated with amplification and overexpression of genes for estrogen receptors, progesterone receptors, and HER2/neu receptors. For your exam, you have to remember that these receptors are important therapeutic and prognostic factors of breast cancer. In other words, breast cancers that are associated with overexpression of estrogen and progesterone receptors are more susceptible to anti-estrogen medications, like tamoxifen. On the other hand, HER2/neu receptors, also known as erbB2 receptors, are coded by the ERB-B2 gene. These receptors are transmembrane glycoproteins with tyrosine kinase activity that plays an important role in epithelial growth and differentiation. HER2/neu receptors are present in small amounts in normal breast and ovarian cells; while they are overexpressed in 25-30% of breast cancers as well as in adenocarcinomas of the ovary, lung, stomach, and salivary glands. Moreover, breast cancers that are associated with HER2/neu positivity are linked to more aggressive tumors; however, they are more likely to respond to anti-HER-2 monoclonal antibodies, like trastuzumab. Another high-yield fact is that breast cancers that are estrogen negative, progesterone negative, and HER2/neu negative, or in other words, triple-negative, are linked to a more aggressive form of breast cancer. Finally, breast cancer tends to metastasize first to the axillary lymph nodes, while in the later stages, the most common sites of metastases include lungs, liver, and bones.
Now, switching gears and moving on to risk factors! The most common risk factors in females include advanced age and family history of breast cancer, which is considered the strongest risk factor. The risk of hereditary breast cancer is increased even more in young women who have had more than one close relative with premenopausal breast cancer. Also, a family history of ovarian cancer is linked to an increased risk for ovarian and breast cancer, because both of these cancers are associated with autosomal dominant mutations of BRCA1 and BRCA2 genes. BRCA genes codes for BRCA proteins that acts as a tumor suppressor that controls the cell cycle, helps repair DNA, and regulates transcription of DNA. Moreover, women with the BRCA1 mutation have a 70-80% higher risk for developing breast cancer; and a 40% increased risk for developing ovarian cancer compared to women without the BRCA1 mutation. Another commonly high yield factor on your exam is increased estrogen exposure like nulliparity, late first pregnancy, early menarche, and late menopause. Other risk factors include alcohol consumption, absence of breastfeeding, and obesity in postmenopausal women. Remember that after menopause, estrogen levels typically drop, but adipose tissue converts androstenedione to estrone, which is a weak estrogen. Finally, you shouldn’t forget the influence of race in breast cancer: Caucasians are at the highest risk while people of African descent are at increased risk for the development of triple-negative breast cancer. Alternatively, risk factors for breast cancer in men include BRCA2 mutation and Klinefelter syndrome.
