What happened, in summary

This woman carried a constitutional BRCA1 mutation identified when she was 36 and still healthy, after a family history that included breast and ovarian cancers. At age 40, surveillance found a 25 mm poorly differentiated invasive ductal carcinoma in the upper outer quadrant of the right breast. That tumor was estrogen receptor-positive, progesterone receptor-positive, and HER2-negative. She underwent radical mastectomy with sentinel lymph node biopsy, and pathology classified the tumor as pT2 pN0. Adjuvant treatment included adriamycin, cyclophosphamide, methotrexate, and 5-fluorouracil, followed by tamoxifen and an LH-RH analogue. At age 41, 2 left axillary lymph nodes were biopsied and were reactive rather than metastatic. One year later, she underwent prophylactic salpingo-oophorectomy; the LH-RH analogue was stopped, and tamoxifen was changed to aromatase inhibitors. At age 44, MRI found a new mass in the left breast. Lumpectomy showed acinic cell carcinoma with a microglandular growth pattern. This second tumor was triple-negative, with estrogen receptor, progesterone receptor, and HER2 all negative, and p53 positive. She then underwent radical mastectomy 2 months later, with no residual tumor in the remaining breast tissue and 2 lymph nodes negative. Genetic testing of both tumors showed loss of the wild-type BRCA1 allele, while the 2 cancers carried different somatic TP53 mutations. At 19 months after surgery for the acinic cell carcinoma, she was alive and well with no evidence of disease and was still receiving hormonal therapy. The paired tumors showed how a hereditary BRCA1 mutation can be involved in more than one breast cancer while each cancer still has its own receptor profile, pathology pattern, and separate TP53 mutation.