Abstract

Abstract Background: Triple negative breast cancer (TNBC) has poor prognosis compared to other breast cancer subtypes. Objectives: This systematic review and meta-analysis examines whether established breast cancer risk factors are associated with TNBC in adult females.Data Sources: Studies were searched on EMBASE, Medline, SCOPUS and grey literature with no limit on the date of publication. The search string included MeSH terms of the exposures of interest and TNBC. References of included studies were also searched. Study Selection: The exposures of interest included parity, breastfeeding, duration of breastfeeding, age at menarche, age at first live birth, oral contraceptive (OCP) use, duration of OCP use, use of hormone replacement therapy (HRT), family history, body mass index (BMI), alcohol use, smoking and breast density. Studies that compared exposures of interest between women diagnosed with TNBC versus cancer-free women.Main outcomes and Measures: The main outcome of interest was TNBC. The effect measures, weighted odds ratios, were estimated from random effects models. Sensitivity analyses stratified by menopausal status and using the leave one out meta-analysis (LOOM) method were performed.Data Extraction and Synthesis: Data extraction and synthesis was performed as per PRISMA guidelines. Four reviewers independently screened the search results in a blinded manner and conflicts were resolved by discussion. Study quality was determined using the Newcastle-Ottawa scale for case control studies and cohort studies. Data extraction was performed independently by four reviewers and one reviewer checked 30% of work of each other reviewer. Odds ratios were extracted and data were meta-analyzed using a random effects model. Results: Thirty-three studies were included. Family history, longer duration of oral contraceptive use, and higher breast density were significantly associated with increased risk for TNBC, and later age at menarche and breastfeeding were protective against TNBC. Later age at first birth was protective against TNBC. Parity, HRT, alcohol, smoking, and BMI were not significantly associated with risk for TNBC. Conclusion: These findings further clarify differences in etiology between ER/PR+HER2- and TNBC, highlighting the need to identify additional actionable risk factors for TNBC to improve prevention and early detection of these poor prognosis breast tumors. Citation Format: Nitya Kumar, Sarah Ehsan, Shahana Banerjee, Claudia Fernandez Perez, Isabelle Lhuilier, Jilian Neuner, Tara-Friebel Klinger, Bindhu Nair, Sara Anjum Niinuma, Shivangi Nampoothiri, Anne Marie McCarthy. The associations of breast density, hormone use, family history, reproductive and lifestyle factors with triple negative breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B083.

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