A 45-year-old woman presents to her physician after discovering a palpable left breast mass. She has a significant family history notable for early-onset breast cancer in her mother (age 38) and maternal grandmother (age 42), as well as ovarian cancer in an aunt. Physical examination reveals a firm, fixed 2-cm mass in the upper outer quadrant of the left breast. Mammography and biopsy confirm invasive ductal carcinoma with ER+, PR+, HER2− immunophenotype. Genetic testing reveals a BRCA1 mutation. Which of the following best explains why BRCA1 mutation carriers have markedly elevated lifetime risk for breast and ovarian malignancies?

1. A)Germline mutations in mismatch repair genes that cause microsatellite instability and accumulation of secondary mutations
2. B)Haploinsufficiency of a tumor suppressor gene required for homologous recombination DNA repairGABARITO
3. C)Constitutive activation of RAS/MAPK signaling pathways leading to uncontrolled cellular proliferation
4. D)Somatic amplification of HER2 and other oncogenes on chromosome 17q
5. E)Epigenetic silencing of estrogen receptor genes resulting in hormone-independent growth