Risk Prediction Model for Contralateral Breast Cancer in BRCA Carriers With Breast Cancer

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In a Chinese study reported in the Journal of Clinical Oncology, Sun et al developed a risk prediction model (BRCA-CRisk) to assess the risk of contralateral breast cancer in patients with breast cancer and BRCA1/2 pathogenic/likely pathogenic variants. 

Study Details

The model was developed in a primary cohort of 491 patients with BRCA1/2 pathogenic/likely pathogenic variants derived from a large series of unselected patients with breast cancer treated at Peking University Cancer Hospital between October 2003 and May 2015. The model was further tested in an independent cohort of 205 patients with BRCA1/2 pathogenic/likely pathogenic variants treated at three hospitals in China. Contralateral breast cancer was defined as contralateral breast cancer diagnosed at least 3 months after the first primary breast cancer diagnosis.

Key Findings

Over a median follow-up of 7.0 years (range = 0.4–17.8 years), 66 of 491 patients in the primary cohort developed contralateral breast cancer. Median time from first breast cancer diagnosis to contralateral breast cancer diagnosis was 5.2 years (range = 0.4–13.6 years). Contralateral breast cancer occurred in 30 of 198 BRCA1 carriers and 36 of 293 BRCA2 carriers. Contralateral breast cancer rates at 5 and 10 years were 10.0% (95% confidence interval [CI] = 5.5%–14.3%) and 19.2% (95% CI = 12.0%–25.9%) among BRCA1 carriers and 5.3% (95% CI = 2.5%–7.9%) and 18.1% (95% CI = 11.4%–24.3%) among BRCA2 carriers, respectively. Cumulative risk of contralateral breast cancer for both BRCA1 and BRCA2 carriers increased after 10 years.

On multivariate analysis in the primary cohort, four factors were found to be significantly associated with contralateral breast cancer risk and were incorporated into the risk prediction model:

  • Younger age at first breast cancer as a continuous variable (P = .002)
  • Positive first-degree family history of breast or ovarian cancer (hazard ratio [HR] = 1.89, 95% CI = 1.16–3.08, P = .011)
  • Variant located near the 3’ region of BRCA (HR = 2.01, 95% CI = 1.23–3.30, P = .006)
  • Receipt of endocrine therapy (HR = 0.54, 95% CI = 0.33–0.88, P = .013).

The risk model yielded receiver operating characteristic area under the curve (AUC) values for 5- and 10-year cumulative risk for contralateral breast cancer of 0.775 and 0.702, respectively.

Median follow-up in the independent cohort was 5.0 years (range = 0.4–22.1 years). Contralateral breast cancer was diagnosed in 24 of 205 patients, including 15 BRCA1 and 9 BRCA2 carriers. The risk model yielded AUC values for 5- and 10-year cumulative risks for contralateral breast cancer of 0.750 and 0.691, respectively.

The investigators concluded, “[The] BRCA-CRisk model provides a useful tool for assessing the absolute cumulative risk of contralateral breast cancer for BRCA1/2 carriers and may help carriers and clinicians optimally select risk-reducing strategies on the basis of individual contralateral breast cancer risk.”

Yuntao Xie, MD, PhD, of the Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Natural Science Foundation of China. For full disclosures of the study authors, visit

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