What question did this study set out to answer?

To assess whether adherence to a healthy lifestyle affects breast cancer risk in postmenopausal women with varying genetic susceptibilities.

April 5, 2026

Abstract 5035: The impact of genetic and lifestyle factors on the risk of invasive postmenopausal breast cancer in the multiethnic cohort study

Key Result

A high healthy lifestyle index score was associated with a 34% lower risk of breast cancer (HR 0.66) in postmenopausal women, regardless of their genetic risk.

Key Points

To assess whether adherence to a healthy lifestyle affects breast cancer risk in postmenopausal women with varying genetic susceptibilities.
Constructed a Healthy Lifestyle Index Score (HLIS) based on dietary and lifestyle factors.
Used multivariable Cox proportional hazards models to estimate breast cancer risk.
Stratified data by polygenic risk score (PRS) to examine interaction effects.
Adjusted models for various demographic and health-related factors.
Higher HLIS was linked to a lower risk of breast cancer, with significant reductions in risk observed.
Breast cancer risk was 12% lower in the intermediate HLIS tertile and 34% lower in the high tertile compared to the low tertile.
The polygenic risk score was associated with an increased risk of breast cancer.
The association between HLIS and breast cancer risk was consistent across different PRS strata.

Structured PICO

Does high adherence to a healthy lifestyle reduce the risk of invasive postmenopausal breast cancer in diverse postmenopausal women regardless of polygenic risk score?

Population

22,725 postmenopausal women (non-Hispanic White [22.2%], African American [12.9%], Native Hawaiian [8.1%], Japanese American [37.5%], and Latino [19.2%])

Intervention

High adherence to a Healthy Lifestyle Index Score (HLIS)

Comparator

Low adherence to a Healthy Lifestyle Index Score (HLIS)

Outcome

Development of invasive postmenopausal breast cancerhard clinical

Adherence to a healthy lifestyle is associated with a significantly reduced risk of breast cancer in postmenopausal women across diverse racial/ethnic groups, independent of underlying genetic risk.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Background: Adherence to a healthy lifestyle has been consistently associated with reduced breast cancer risk, but whether this benefit varies by genetic susceptibility remains unclear, particularly among racially and ethnically diverse populations. This study evaluated whether the association between a Healthy Lifestyle Index Score (HLIS) and breast cancer risk differs by a 313-variant polygenic risk score (PRS) among postmenopausal women in the Multiethnic Cohort (MEC). Methods: HLIS (range: 0-7) was constructed based on the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and included nine dietary and lifestyle components: fruit and vegetable intake, total fiber intake, red meat intake, alcohol consumption, physical activity, body mass index (BMI), waist circumference (WC), smoking status, and sugar-sweetened drink intake. HLIS was categorized into tertiles (low, intermediate, high) according to its distribution among non-cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models with age as the time metric. The parsimonious model was adjusted for family history of breast cancer, educational attainment, type of menopause, parity, daily energy intake, PRS, and the top 10 principal components (PCs), while the extended model was additionally adjusted for history of diabetes, age at menopause, age of menarche, and hormone use. Analyses were further stratified by PRS (above vs. below the median), and interaction was tested using a likelihood ratio test. Results: Among the 22,725 postmenopausal women (non-Hispanic White 22.2%, African American 12.9%, Native Hawaiian 8.1%, Japanese American 37.5%, and Latino 19.2%), 1,174 developed breast cancer during an average follow-up of 12.2 years. Higher HLIS was associated with a significantly lower risk of breast cancer. Compared to women in the low HLIS tertile, breast cancer risk was 12% lower (HR = 0.88; 95% CI: 0.77-1.00; P = 0.05) in the intermediate tertile and 34% lower (HR = 0.66; 95% CI: 0.56-0.77; P 0.001) in the high tertile, with similar results in the extended model. This inverse association appeared to be driven by BMI (obese vs. normal: HR=1.36, 95% CI: 1.13-1.64, P=0.001) and WC (≥88 cm vs. 80 cm: HR=1.43, 95% CI = 1.19-1.72, P 0.001). PRS was significantly associated with breast cancer risk (per-SD HR = 1.37; 95% CI: 1.29-1.45; P 0.001). The inverse association between HLIS and breast cancer risk was similar across PRS strata, with no significant interaction (P-int = 0.48). Conclusion: In this multiethnic cohort of postmenopausal women, adherence to a healthy lifestyle was associated with a reduced risk of breast cancer, regardless of low or high PRS, supporting the importance of lifestyle modification as a key preventive strategy for breast cancer across diverse populations. Citation Format: Chenya Zhao, Gertraud Maskarinec, David Conti, Christopher A. Haiman, Loïc Le Marchand, Lynne R. Wilkens, Fei Chen, Eunjung Lee. The impact of genetic and lifestyle factors on the risk of invasive postmenopausal breast cancer in the multiethnic cohort study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5035.

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