Studies of the association between breast size, as a proxy for mammary gland mass, and breast cancer risk have given equivocal results. Most have been case-control studies with limited statistical power. We conducted a prospective analysis of the relation between breast size as measured by self-reported bra cup size and breast cancer risk among premenopausal women enrolled in the Nurses' Health Study II. Bra cup size at age 20 was assessed among 89,268 premenopausal women aged 29-47 in 1993. Subsequent incident cases of invasive breast cancer were assessed until 2001. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model adjusting for potential confounders and risk factors for breast cancer. During 622,732 person-years of follow-up, 803 premenopausal women were newly diagnosed with invasive breast cancer. For women with a BMI below 25 kg/m 2 , those with a bra cup size of ''D or larger'' had a significantly higher incidence of breast cancer than women who reported ''A or smaller'' (covariate adjusted HR 5 1.80; 95% CI 1.13-2.88; p trend 5 0.01). There was no significant association among women with a BMI of 25 kg/m 2 or higher. Stratifying by BMI at age 18 at a cutoff point of 21 kg/m 2 gave similar results. Larger bra cup size at a young age is associated with a higher incidence of premenopausal breast cancer, though this association is limited to leaner women. ' 2005 Wiley-Liss, Inc.Both cell number and rate of cell division have been proposed to predict overall cancer risk. [1][2][3] Following this theory, breast cancer risk might be positively correlated with the total number of mammary gland cells and more generally, mammary gland mass. [4][5][6] Because a large number of susceptible cells should correspond to increased risk, breast size, as a proxy for mammary gland mass, could serve as a plausible risk factor for breast cancer. Several indirect lines of evidence support the theory that breast size may influence breast cancer risk: (i) Breast cancer occurs more frequently in the left breast, 7 and the left breast is typically slightly larger than the right breast, 8 and (ii) breast cancer is overwhelmingly more common in women than in men.In 1969, Wynder noted that studies of breast cancer in Japanese women indicated that subjects with breast cancer had larger breasts than controls. 9 Several studies have indicated that women who undergo breast augmentation surgery have a decreased risk of breast cancer, 10,11 presumably because these women compose a group of smaller-breasted, lower-risk individuals. Women who undergo surgical reduction mammoplasty, which reduces breast size, also experience lower than expected rates of breast cancer. 12 Ecological evidence supports the association between breast size and breast cancer risk. On average, breast size is smaller in women in Asian countries compared to those in western countries, and correspondingly, breast cancer is much less common in Asia. 13 With respect to male breast cancer, patients suffering from ...