- Carriers of the BRCA1 deleterious mutation are more likely than both controls and carriers of the BRCA2 mutation:
- To have high-grade, receptor-negative tumors (and, in particular, triple-negative tumors):
- Containing necrosis, with higher mitotic counts and shorter tumor-doubling times
- To have high-grade, receptor-negative tumors (and, in particular, triple-negative tumors):
- Carriers of the BRCA1 mutation have lesions that are more likely to have:
- Pushing margins and that are less likely to be spiculated:
- Making them harder to detect on mammography and more likely to be detected by MRI than mammography
- Pushing margins and that are less likely to be spiculated:
- Women with a strong family history of both early-onset breast cancer and ovarian cancer in first-degree relatives:
- Is consistent with hereditary breast and ovarian cancer syndrome, and the presence of triple-negative disease is most consistent with the history and diagnosis for a carrier of the BRCA1 deleterious mutation
- Although few studies have evaluated preoperative breast MRI in BRCA carriers after breast cancer has already been diagnosed:
- Breast MRI has been shown to have a survival benefit in the high-risk screening setting, and the lifetime risk of cancer developing in the contralateral breast (which can also be mammographically occult):
- Is nearly 40% in this population
- Breast MRI is a reasonable preoperative option to evaluate the contralateral breast if the woman has dense breasts, risk of being a BRCA carrier, and consequent risk of disease being present or developing in the contralateral breast:
- However, for patients who opt for bilateral mastectomy, breast MRI preoperatively is not mandatory
- Breast MRI has been shown to have a survival benefit in the high-risk screening setting, and the lifetime risk of cancer developing in the contralateral breast (which can also be mammographically occult):
- Although genetic testing has become more widespread and easier to perform in recent years:
- Performing a genetic test without counseling by someone who has genetic training and expertise is not appropriate
- As some BRCA mutations are known to be deleterious, others are variants of undetermined significance:
- This means, as the name suggests, that it is unclear whether the patient is at any greater risk of cancer, and if so, by how much
- This must be part of the discussion because 5% to 10% of mutations are these variants of undetermined significance, and patient perceptions of their own risk in that setting are high, mandating proper education
- Although women with BRCA mutations have bilateral mastectomy as an option to treat a known cancer and prevent a contralateral one:
- The American Society of Clinical Oncology / Society of Surgical Oncology consensus statement on prophylactic mastectomy considers a significant family history an appropriate indication for prophylactic mastectomy, even in the absence of a diagnosed mutation
- Women who have a diagnosed deleterious mutation and those who have not been tested but have a strong family history are also considered appropriate for risk-reducing surgery
- References:
- Guillem JG, Wood WC, Moley JF, et al. ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes. Ann Surg Oncol. 2006;13:1296-1321.
- Kaas R, Kroger R, Peterse JL, Hart AA, Muller SH. The correlation of mammographic and histologic patterns of breast cancers in BRCA1 gene mutation carriers, compared to age-matched sporadic controls. Eur Radiol. 2006;16:2842-2848.
- Lakhani SR, Reis-Filho JS, Fulford L, et al. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res. 2005;11:5175-5180.
- Murray ML, Cerrato F, Bennett RL, Jarvik GP. Follow-up of carriers of BRCA1 and BRCA2 variants of unknown significance: variant reclassification and surgical decisions. Genet Med. 2011;13:998-1005.
- Plevritis SK, Kurian AW, Sigal BM, et al. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA. 2006;295:2374-2384.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 