A 28-year-old woman comes to the office after finding a lump in her right breast. Her mother died from ovarian cancer at age 34 and her maternal aunt died from breast cancer at age 32. After an appropriate workup, the patient is diagnosed with breast cancer. This patient most likely inherited a mutation in a gene normally responsible for which of the following processes?

Question

A 28-year-old woman comes to the office after finding a lump in her right breast.  Her mother died from ovarian cancer at age 34 and her maternal aunt died from breast cancer at age 32.  After an appropriate workup, the patient is diagnosed with breast cancer.  This patient most likely inherited a mutation in a gene normally responsible for which of the following processes?

Quizplus · Accepted Answer

11ec160b_39ee_1bb1_9249_9da9f2e1ca5b_MD0001_00 Most breast cancer cases occur sporadically in women age >50. Hereditary breast cancer should be suspected in patients diagnosed at a young age, patients with ≥2 primary breast and/or ovarian cancers, and individuals with multiple family members affected by early-onset breast or ovarian cancer. Most cases of hereditary breast and ovarian cancer are associated with mutations in the tumor suppressor genes BRCA1 and BRCA2. Tumor suppressor genes are involved in multiple processes, including: BRCA1 and BRCA2 are involved in repair of double-stranded DNA breaks. Mutations in BRCA1 and BRCA2 result in genetic instability, predisposing cells to an increased risk of malignant transformation. Both BRCA mutations are inherited in an autosomal dominant manner with variable penetrance. Affected women have a 70%-80% lifetime risk for developing breast cancer. Moreover, their lifetime risk of developing ovarian cancer is also increased by up to 40%, although the BRCA2 gene is less likely to lead to ovarian cancer. (Choice A) Angiogenesis is an essential factor in the growth of tumors due to their rapid rate of division and high metabolic demands. Although they stimulate angiogenesis by increasing production of substances such as vascular endothelial growth factor, tumors frequently outgrow their blood supply and become necrotic in the center. (Choice B) Apoptosis refers to programmed cell death in response to irreparably damaged DNA or misfolded proteins. Malignant cells in chronic lymphocytic lymphoma upregulate the protooncogene BCL2, which stabilizes the mitochondrial membrane, thereby preventing cytochrome C leakage, caspase activation, and apoptotic death. (Choice D) Intercellular adhesion is impaired in the majority of malignant tumors, which allows portions of the tumor to break off and metastasize. Adhesion molecules such as E-cadherin are also responsible for transduction of growth signals important for normal tissue growth and regeneration; disruption of intercellular adhesion signaling can promote unchecked cellular proliferation. (Choice E) A large number of malignancies are associated with aberrant signal transduction. For example, overexpression of HER2 (a receptor tyrosine kinase involved in growth signal transduction) causes the development of certain types of aggressive breast cancer. Unlike BRCA1 and BRCA2, HER2 mutations are acquired, not inherited. Educational objective: Hereditary breast cancer is most commonly associated with mutations in BRCA1 and BRCA2. These tumor suppressor genes are involved in DNA repair, and their mutations increase the risk of developing breast and ovarian cancer.

A 28-Year-Old Woman Comes to the Office After Finding a Lump