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Meta-Analysis
. 2024 Aug 1;116(8):1210-1219.
doi: 10.1093/jnci/djae056.

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

Nitya Kumar  1 , Sarah Ehsan  2 , Shahana Banerjee  2 , Claudia Fernandez Perez  2 , Isabelle Lhuilier  2 , Jillian Neuner  2 , Tara Friebel-Klingner  3 , Oluwadamilola M Fayanju  2 , Bindhu Nair  1 , Sara Anjum Niinuma  1 , Shivangi Nampoothiri  4 , Anne Marie McCarthy  2
Affiliations
Meta-Analysis

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

Nitya Kumar et al. J Natl Cancer Inst. .

Abstract

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.

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Conflict of interest statement

The authors report no conflicting interests associated with this work.

Figures

Figure 1.
Figure 1.
Odds of triple-negative breast cancer (TNBC) by reproductive risk factors. A) Odds of TNBC in those who had first live birth at 30 years of age or older vs those who had it at 19 years or younger. B) Odds of TNBC in those with 3 or more live births vs 0 live births. C) Odds of TNBC in those who had menarche at 14 years or older vs those who had it at 11 years or younger. D) Odds of TNBC in those who ever breastfed vs those who never did. E) Odds of TNBC in Black participants with 3 or more live births vs 0 live births.
Figure 2.
Figure 2.
Odds of TNBC and use of hormones. A) Odds of TNBC in those with 10 or more years of OC use vs. no use. B) Odds of TNBC in those who ever used MHT vs those who never did. OC = oral contraceptive; MHT = menopausal hormone therapy; TNBC = triple-negative breast cancer.
Figure 3.
Figure 3.
Odds of TNBC by lifestyle factors, family history, BMI, and breast density. A) Odds of TNBC in participants who ever consumed alcohol vs those who never did. B) Odds of TNBC in those with history of breast cancer in 1° relative vs those without. C) Odds of TNBC in ever smokers vs never smokers. D) Odds of TNBC in those with BMI ≥30 kg/m2 vs BMI <25 kg/m2, stratified by menopausal status. E) Odds of TNBC in those with ≥75% mammographic density vs ≤25%. BMI = body mass index.
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