PG 6.02 Preventing invasive breast cancer in women at high risk based on benign/in situ pathology

Abstract

1. The higher risk of second primary cancer may affect decisions in BRCA carriers about primary surgical option: breast conservation vs. bilateral mastectomies. 2. The SOFT data show the advantage of ovarian suppression plus hormonal therapy in premenopausal women requiring chemotherapy in treatment of their hormone receptor positive tumors. BRCA carriers would more likely undergo risk-reducing bilateral salpingo-oophorectomies rather than LHRH-agonist therapy. 3. Data from two neoadjuvant trials in triple negative breast cancer (GeparSEXTO and Alliance 4003) show an advantage for the use of platinum in BRCA carriers: The TNT trial shows a similar advantage in metastatic disease. Additional tumor biomarkers may predict response better than BRCA1/2 mutation status. 4. BRCA1/2 mutation carriers are eligible for the BIG/NRG adjuvant parp inhibitor trial, OlympiA, and other neoadjuvant trials. 5. BRCA mutation status may affect interventions to reduce the risk of additional primary cancers of the ovary (RRSO) and melanoma. Family members may use the information to reduce their risks of breast cancer, ovarian cancer, prostate cancer and possibly pancreatic cancer. Mechanisms of acquired resistance against therapies targeting the DNA repair pathways are emerging. In addition, genetic testing now frequently includes evaluation of additional genes that have been associated with increased breast cancer risk, including TP53, PTEN, STK11, and CDH1, as well as an expanding group of moderate penetrance genes. Many women are now offered panels of genes for assessment of their risk either as a comprehensive germline test or following a negative BRCA1/2 examination. These genes do not yet affect treatment options, but may be used to assess risk of additional primary tumors and options for reducing those risks. These data suggest that womenwith early onset breast cancer, triple negative breast cancers and other features suggesting hereditary predisposition underlying the diagnosis should consider genetic evaluation. The results may affect their own breast cancer care, and the cancer risk assessment among their family members. Disclosure of Interest: Grants/research support: Myriad Genetics, Novartis (self); Novartis, Pfizer (spouse). Honoraria or consultation fees: Novartis, Pfizer (spouse); Pfizer (self).