Abstract Objective: Cruciferous vegetables provide glucosinolate-derived compounds (e.g., isothiocyanates) that have inhibited breast cancer growth in experimental models, but epidemiologic evidence for a protective role remains limited and inconsistent. Therefore, we examined associations of cruciferous vegetable intake and total and subgroup-specific glucosinolates with breast cancer risk in the Nurses’ Health Study (NHS) and NHSII. Methods: We followed 76,713 women from the NHS 1984-2019 and 92,810 from the NHSII 1991-2019. Diet was assessed by using validated semiquantitative food-frequency questionnaires at baseline and updated every 4 years during follow-up. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for cumulative average cruciferous vegetable intake—including broccoli, cauliflower, cabbage/coleslaw, Brussels sprouts, and kale, mustard greens, or chard—and for energy-adjusted dietary glucosinolate intake in relation to the risk of invasive breast cancer and its subtypes, using the lowest intake category or quintile as the reference. Results: During 4,500,352 person-years of follow-up, 11,181 incident invasive breast cancer cases were identified across the two cohorts. Higher intake of cruciferous vegetables was associated with a statistically significantly lower breast cancer risk (1 serving/day vs. 1 serving/week; HR=0.91, 95% CI: 0.84-0.98; P-trend0.01), with the association slightly attenuated after adjustment for a modified Alternate Healthy Eating Index (AHEI) (HR=0.93, 95% CI: 0.86-1.02; P-trend=0.08). Although heterogeneity by estrogen receptor (ER) status was nonsignificant, the strongest association was observed for estrogen receptor (ER) negative tumors (1 serving/day vs. 1 serving/week; HR=0.83, 95% CI: 0.67-1.02; P-trend=0.01). Stratified analyses indicated a suggestive interaction by BMI (P-interaction=0.06), with stronger associations for ER-negative tumors among women with BMI25 (HR=0.77, 95% CI: 0.55-1.07; P-trend=0.03) compared to those with BMI≥25 (HR=1.12, 95% CI: 0.83-1.51; P-trend=0.73). Furthermore, participants in the highest quintile of total glucosinolate intake had a lower breast cancer risk, including ER-negative, compared to the lowest quintile (overall HR=0.92, 95% CI: 0.87-0.98; P-trend0.01 and ER-negative HR=0.87, 95% CI; 0.74-1.02; P-trend=0.03). Conclusions: Our findings support that higher intake of cruciferous vegetables may reduce the risk of breast cancer, especially those that are more likely to be aggressive tumors. Dietary glucosinolate intake was associated with a moderately lower risk of breast cancer. These findings contribute to the growing literature suggesting a protective effect of a potentially modifiable factor, cruciferous vegetable intake, on breast cancer risk. Mechanistic research is also needed to understand the relationship of exposures to glucosinolate metabolites with breast cancer risk. Citation Format: A. Romanos-Nanclares, W. C. Willett, M. D. Holmes, W. Y. Chen, B. A. Rosner, H. Eliassen. Cruciferous vegetable intake, dietary glucosinolate and risk of breast cancer in 2 large prospective studies abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF1-07.
Romanos-Nanclares et al. (Tue,) studied this question.