The estimated risk of developing cancer in the contralateral breast ranges from 16% to 43% for patients with breast cancer who carry a BRCA1 or BRCA2 germline pathogenic variant. This can be problematic for breast cancer survivors already grappling with a multitude of decisions, including risk reduction, fertility preservation, and mastectomy options.

Therefore, researchers sought to assess the risk of contralateral breast cancer (CBC) and develop a prediction model for assessing that risk in BRCA1/2 mutation carriers. Their findings were published in the Journal of Clinical Oncology.

The researchers used a primary cohort of 491 patients with BRCA1/2 variants from a larger series of patients with breast cancer. Of these patients, 66 patients developed CBC after a median follow-up period of 7 years.

Continue Reading

Four variables significantly associated with risk of CBC were identified:

  • Younger age at first breast cancer diagnosis (P =.002)
  • Positive first-degree family history of breast and/or ovarian cancer (P =.011)
  • BRCA1/2 variant located near the 3′ region (P =.013)
  • Endocrine therapy (P =.013)

They established the BRCA-CRisk prediction model, incorporating the 4 variables in the model, and validated the model in an independent cohort of 255 BRCA1/2 carriers. BRCA-CRisk was able to show good prediction performance in distinguishing BRCA1/2 variant carriers with a high risk of CBC from those with a low risk.

“[O]ur prediction model (BRCA-CRisk) provides a useful manual tool for assessing the absolute accumulative risk of CBC in individuals with breast cancer who have a BRCA1 or BRCA2 variant,” the researchers wrote. “Therefore it would assist BRCA1/2 carriers and clinicians in selecting optimal risk-reducing strategies for individuals on the basis of the individual cumulative risk of CBC.”

The study was limited by its sample size, so the BRCA1 and BRCA2 carriers were combined in the analysis. Bias may exist as a result. The sample size of patients with large rearrangement mutations was also small, so the researchers suggest caution if using the model for patients with a large rearrangement mutation.


Sun J, Chu F, Pan J, et al. BRCA-CRisk: a contralateral breast cancer risk prediction model for BRCA carriers. J Clin Oncol. Published online December 8, 2022. doi:10.1200/JCO.22.00833