The roles of specific fatty acids in breast cancer etiology are unclear, particularly among premenopausal women. We examined 34 individual fatty acids, measured in blood erythrocytes collected between 1996 and 1999, and breast cancer risk in a nested case‐control study of primarily premenopausal women in the Nurses' Health Study II. Breast cancer cases diagnosed after blood collection and before June 2010 (n = 794) were matched to controls and conditional logistic regression was used to estimate OR's (95% CI's) for associations of fatty acids with breast cancer; unconditional logistic regression was used for stratified analyses. Fatty acids were not significantly associated with breast cancer risk overall; however, heterogeneity by body mass index (BMI) was observed. Among overweight/obese women (BMI ≥ 25), several odd‐chain saturated (SFA, e.g. 17:0, ORQ4vsQ1(95% CI) =1.85 (1.18–2.88), ptrend=0.006 pint<0.001), trans (TFA, e.g. 18:1, ORQ4vsQ1(95% CI) =2.33 (1.45–3.77), ptrend<0.001, pint=0.007) and dairy‐derived fatty acids (SFA 15:0 + 17:0 + TFA 16:1n‐7t; ORQ4vsQ1(95% CI) =1.83(1.16–2.89), ptrend=0.005, pint<0.001) were positively associated, and n‐3 polyunsaturated fatty acids (n‐3 PUFA, e.g. alpha‐linolenic acid; ORQ4vsQ1(95% CI) =0.57 (0.36–0.89), ptrend=0.017, pint=0.03) were inversely associated with breast cancer. Total SFA were inversely associated with breast cancer among women with BMI < 25 (ORQ4vsQ1(95% CI) =0.68 (0.46–0.98), ptrend=0.05, pint=0.01). Thus, while specific fatty acids were not associated with breast cancer overall, our findings suggest positive associations of several SFA, TFA and dairy‐derived fatty acids and inverse associations of n‐3 PUFA with breast cancer among overweight/obese women. Given these fatty acids are influenced by diet, and therefore are potentially modifiable, further investigation of these associations among overweight/obese women is warranted.
