The unique risk factor profile of triple-negative breast cancer: a comprehensive meta-analysis

Background: Triple-negative breast cancer (TNBC) has a poor prognosis compared with other breast cancer subtypes. This systematic review and meta-analysis examines whether known risk factors for breast cancer are also associated with TNBC in adult women.

Methods: EMBASE, Medline, SCOPUS, and gray literature were queried with no limit on the date or language of publication. The exposures of interest included parity, breastfeeding, duration of breastfeeding, age at menarche, age at first live birth, oral contraceptive (OC) use, duration of OC use, use of menopausal hormone therapy (MHT), family history, body mass index (BMI), alcohol use, smoking, and breast density. The main outcome of interest was TNBC. Study quality was determined using the Newcastle-Ottawa scale for case control studies and cohort studies. We estimated weighted odds ratios from random effects models to study the exposure-outcome associations. Protocol was registered under the number: PROSPERO 2021 CRD42021254594.

Results: Thirty-three studies were included. Family history, longer duration of OC use, and higher breast density were significantly associated with increased risk for TNBC, whereas later age at menarche, later age at first birth, and breastfeeding were protective against TNBC. Parity, MHT, alcohol, smoking, and BMI were not significantly associated with TNBC overall, but higher parity was associated with higher risk among Black women.

Conclusion: Our findings highlight that TNBC has a distinct risk factor profile compared with overall breast cancer. This can be the foundational work in identification of actionable TNBC risk factors to improve prevention and early detection of these poor prognosis breast tumors.