Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk

Triple-negative breast cancer accounts for less than 20% of breast cancers overall, but is the predominant subtype among carriers of mutations in BRCA1. However, few studies have assessed the association between breast cancer family history and risk of triple-negative breast cancer. We examined the relationship between having a family history of breast cancer in first-degree relatives and risk of triple-negative breast cancer, and risk of two other breast cancer subtypes defined by tumor marker expression. We evaluated data collected by the Breast Cancer Surveillance Consortium from 2,599,946 mammograms on 1,054,466 women, among whom 15% reported a first-degree family history of breast cancer. Using Cox regression in this cohort, we evaluated subtype-specific associations between family history and risk of triple-negative (N = 705), estrogen receptor-positive (ER+, N = 10,026), and hormone receptor-negative/HER2-expressing (ER−/PR−/HER2+, N = 308) breast cancer among women aged 40–84 years. First-degree family history was similarly and significantly associated with an increased risk of all the subtypes [hazard ratio (HR) = 1.73, 95% confidence interval (CI): 1.43–2.09, HR = 1.62, 95% CI: 1.54–1.70, and HR = 1.56, 95% CI: 1.15–2.13, for triple-negative, ER+, and ER−/PR−/HER2+, respectively]. Risk of all the subtypes was most pronounced among women with at least two affected first-degree relatives (versus women with no affected first-degree relatives, HR_{triple-negative} = 2.66, 95% CI: 1.66–4.27, HR_ER+ = 2.05, 95% CI: 1.79–2.36, HR_ER−_/PR−_/HER2+ = 2.25, 95% CI: 0.99–5.08). Having a first-degree family history of breast cancer was associated with an increased risk of triple-negative breast cancer with a magnitude of association similar to that for the predominant ER+ subtype and ER−/PR−/HER2+ breast cancer.