The present analysis in a multiethnic population found positive associations between height and premenopausal breast cancer risk, as well as substantial inverse associations with obesity and other measures of body fatness and abdominal adiposity (current weight, body build, waist circumference, WHtR, BMI in young adulthood, and weight gain). Importantly, inverse associations were limited to ER+/PR+ tumors. For all tumors combined and for ER+/PR+ tumors, the inverse associations were similar for Hispanic, African-American, and non-Hispanic white women.
Compared with the large number of studies that have examined the relation between body size and premenopausal breast cancer risk in non-Hispanic white women (4
), data are relatively sparse and inconsistent for Hispanic (20
) and African-American (11
) women. We found inverse associations of similar magnitude across racial/ethnic groups but our sample size, particularly in African Americans and non-Hispanic whites, was too small to determine whether the race/ethnicity-specific odds ratios we observed were actually statistically different. Our analysis is the first to examine associations between multiple body size measures and breast cancer risk in a single study of Hispanic, African-American, and non-Hispanic white women. The population-based design and similar response rates among eligible cases and controls from all 3 racial/ethnic groups increased the generalizability of our results. Furthermore, we found the inverse associations to be consistent across multiple measures of body size and in agreement with previous reports for non-Hispanic white women (3
The present results should be interpreted in the context of some study limitations. Given the inherent need to rely on self-reporting for most variables, we cannot exclude the possibility of inaccurate recall, which could have resulted in misclassification of confounders and exposure variables. For the assessment of body size, we relied on anthropometric measurements in addition to self-reported measures. Because of concern that cases may have experienced treatment-related weight gain or disease-related weight loss (32
), we calculated current BMI from self-reported weight in the reference year instead of measured weight at interview, except for the small proportion of cases and controls who declined to self-report but allowed actual weight measurement. Inaccurate recall or misreporting of weight in the reference year could have biased the odds ratios for current BMI and weight towards the null. For young-adult measures (weight and BMI) and weight gain, we relied on 2 measures of weight in a woman's 20s. In the early version of the questionnaire, we assessed weight at the ages of 25–30 years; in a later version, we asked about weight in each decade (e.g., at ages 20–29 years). In a sensitivity analysis, we found that each of the young-adult measures was inversely associated with risk, regardless of the weight measure used, both in all women combined and in women with ER+/PR+ tumors.
Consistent with some (33
) but not all (22
) studies in non-Hispanic white women, we found a positive association between height and breast cancer risk in Hispanic women. Results in other populations have been mixed as well. Positive associations with height have previously been reported for African-American (15
) and Nigerian (36
) women. Other studies, like ours, did not find significant trends with height in black (13
) or non-Hispanic white (2
Our finding of a 40% lower risk of premenopausal breast cancer in obese women is consistent with other studies in non-Hispanic whites (3
). Importantly, and in agreement with other studies (42
), the inverse association with BMI was limited to ER+/PR+ tumors in all 3 racial/ethnic groups. Prior studies of BMI in African-American women, black women in Barbados, and Hispanic women have produced mixed results. Palmer et al. (18
) and Nemesure et al. (38
) reported inverse associations with obesity, although in the latter study, no significant association remained after adjustment for BMI at age 18 years. In our analysis of current BMI, additional adjustment for young-adult BMI changed the odds ratio estimates only minimally (data not shown). Other studies found no evidence of inverse associations between BMI and breast cancer risk in African-American (11
), Nigerian (36
), or Hispanic (20
Data on other body size measures are sparse for African-American and Hispanic women. We found substantial inverse associations for current weight and body build, with similar findings in the 3 racial/ethnic groups. Another study found no inverse association between current body build and breast cancer risk in African-American women (19
). Large young-adult body size has been associated with lower risk of breast cancer in non-Hispanic white women (40
), although findings are not consistent (41
). We found significant inverse trends for young-adult BMI, with similar findings in African Americans and Hispanics, but no clear trend in non-Hispanic whites. Some (12
) but not all (17
) other studies in these populations have also reported inverse associations with BMI at age 18 years. BMI at age 18 years may be stronger predictor of premenopausal breast cancer risk than current BMI (18
), but the present results were similar for the 2 BMI measures.
We found a strong inverse trend with weight gain since young adulthood, with similar findings in Hispanic and African-American women, and with associations limited to ER+/PR+ tumors. Results from other studies are inconsistent. Studies in non-Hispanic white women suggest that an inverse association with weight gain may be limited to women who experienced their lowest adult weight after age 21 years (40
), women with a BMI <20 at age 18 years (19
), or women diagnosed with early-stage and lower-grade breast cancer (46
). Several studies found no association with weight gain in non-Hispanic white (19
), African-American (17
), or Hispanic (21
In agreement with other studies (3
), we found no association with WHR overall or in any racial/ethnic group. High WHR has been associated with increased risk of premenopausal breast cancer in both African-American and white women from North Carolina (15
) and in Nigerian women (37
), but most studies, including ours, have found no association (18
). Similarly, a study of breast cancer in Hispanic women found no association with WHR (22
). However, we found inverse associations with waist circumference and with WHtR for ER+/PR+ tumors.
Overall, our findings are generally consistent across race/ethnicity and are in agreement with previous reports for non-Hispanic white women. Our results also confirm those of some, but not all, previous studies in African-American and Hispanic women. Variability in observed associations across studies may be explained, in part, by differences in the proportion of cases with ER−/PR− tumors, which are more common in African Americans and Hispanics than in non-Hispanic whites. Our data clearly show inverse associations with measures of body size only for ER+/PR+ tumors; no associations were found for ER−/PR− tumors. Similarly, Berstad et al. (19
) reported a significant inverse association with BMI in African American women that was limited to ER+/PR+ tumors. No other study in African Americans and Hispanics presented associations with body size measures for premenopausal breast cancer by hormone receptor status. Failure to take hormone receptor status into account may obscure associations with body size and may have contributed to the inconsistent results in African-American and Hispanic women.
The biologic mechanisms underlying associations between large body size and breast cancer risk remain uncertain. The observation that BMI and other body size measures are inversely associated with ER+/PR+ but not ER−/PR− tumors suggests the importance of sex-steroid hormone pathways. Elevated BMI may contribute to lower serum levels of sex hormone–binding globulin (52
) and total estradiol (52
) and higher levels of free testosterone (53
), as well as a higher frequency of anovulatory and irregular menstrual cycles in premenopausal women, which in turn results in reduced production of estrogen and progesterone (54
). In 2 recent studies (18
), however, the inverse association with large body size was not explained by menstrual cycle characteristics, self-reported infertility, or probable polycystic ovary syndrome, suggesting the importance of other mechanisms.
In conclusion, our results suggest that the inverse association between premenopausal breast cancer and larger body size is similar in Hispanic, African-American, and non-Hispanic white women but is limited to ER+/PR+ tumors. Thus, hormone receptor status is important to consider when evaluating the association between body size and premenopausal breast cancer risk. Although our results indicated a lower risk of premenopausal breast cancer in obese women, repeated studies have noted that weight gain and obesity are associated with increased breast cancer risk during the postmenopausal years, when breast cancer occurs much more commonly than during the premenopausal years; thus, avoidance of weight gain before menopause remains advisable.