BRCA Mutation Carriers

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.

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.

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.

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.


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.

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