115 postmenopausal women who were age 40 years and older (mean 63.9 years), 614
562 mammography examinations (96% screening, 4% diagnostic) were performed, and 4446 women developed breast cancer within 12 months of an examination. Women aged 60–69 years and black and Native American or Native Alaskan women had the highest proportions of overweight and obese (). Almost entirely fat breast density was most prevalent among overweight and obese women. Mammography use decreased with increasing BMI, with 14.2% of women with a normal BMI having had mammography 3 or more years ago or a first screening or diagnostic examination compared with 19.3% of obese II/III women (P
< .001). Few examinations were recorded as a first diagnostic examination, and the proportion was similar across BMI categories. A total of 18.5% of underweight women had mammography examinations 3 or more years ago or had a first screening or diagnostic examination ().
The rates per 1000 mammography examinations of breast cancer overall and of large, advanced-stage, and high nuclear grade invasive cancer adjusted for age, race/ethnicity, and mammography registry increased statistically significantly with higher BMI (data not shown), and the findings were similar when we additionally adjusted for mammography use (). Adjusted rates for breast cancer overall increased across BMI groups (6.6 normal, 7.4 overweight, 7.9 obese I, 8.5 obese II/III; Ptrend < .001) in the entire study population and similarly increased across BMI groups when limiting analyses to white (6.9 normal, 7.8 overweight, 8.2 obese I, 8.8 obese II/III; Ptrend < .001) or Hispanic (4.9 normal, 5.6 overweight, 7.4 obese I–III; Ptrend = .002) women.
Table 2 Rates and odds ratios (ORs) with 95% confidence intervals (CIs) of breast cancer and of large, advanced-stage, high-grade, and estrogen receptor (ER)–positive and –negative invasive breast cancer within 12 mo of a mammography examination (more ...)
The rates of large invasive breast cancer (2.3 normal, 2.6 overweight, 2.9 obese I, 3.2 obese II/III; Ptrend < .001) and of advanced-stage breast cancer (0.8 normal, 0.9 overweight, 1.3 obese I, 1.5 obese II/III; Ptrend < .001) increased between 1.3- to 1.8-fold with each higher BMI category. Adjusted advanced breast cancer rates increased across BMI groups when analyses were limited to white women (0.8 normal, 0.9 overweight, 1.4 obese I, 1.5 obese II/III; Ptrend < .001) similar to that observed in the overall study population (). Too few black, Hispanic, and Native American or Native Alaskan women had advanced disease (n = 12, n = 67, and n = 8, respectively) to perform stratified analyses by BMI category.
The rate of high nuclear grade invasive breast cancer (1.5 normal, 1.7 overweight, 1.7 obese I, 1.9 obese II/III; Ptrend = .10) increased with each higher BMI category. The rate of ER-positive tumors increased with higher BMI (Ptrend < .001), but the rate of ER-negative tumors did not (Ptrend = .8). Underweight women had lower or similar rates of breast cancer overall and of large, advanced-stage, and high nuclear grade invasive cancer compared with women with a normal BMI (). Adjusting for breast density in all models either did not change or strengthened trends in results (data not shown).
Rates of advanced cancer across BMI groups from underweight to obese II/III were stratified by mammography use (within 1 year, within 2 years, or within 3 years or longer or first screening examination) to investigate whether differences in mammography use explain the differences by BMI (). If the only influence of BMI on cancer risk was through the potential association of BMI with mammography use, then the rates of cancer would be the same across BMI categories for any given mammography use category but would still be successively higher among women who underwent less frequent mammography. We observed statistically significantly higher rates and odds of advanced-stage breast cancer across increasing BMI categories for women with 2 years (Ptrend < .001) and 3 years or more (Ptrend = .001) between mammography examinations and a non–statistically significant increasing trend for women with 1 year between mammography examinations (Ptrend = .1). Women with 3 years or more between mammography examinations had higher rates of advanced breast cancer across BMI categories than women who underwent more frequent mammography (). The rate of increase or slope of linear trend in breast cancer rates across increasing BMI categories did not statistically significantly differ by mammography use for breast cancer overall (test for interaction, P = .19) or for large (test for interaction, P = .32), advanced-stage (test for interaction, P = .10), high nuclear grade (test for interaction, P = .62), ER-positive (test for interaction, P = .74), or ER-negative (test for interaction, P = .59) breast cancer. Although the increasing linear trend across BMI categories for advanced-stage disease was not as strong among the 1-year mammography group as it was among the other mammography groups, the results in illustrate that differences in mammography use only partially explain the differences in rates of advanced disease seen across BMI categories.
Figure 1 Rate of advanced cancer (stage IIb, III, or IV) within 12 mo of a mammography examination per 1000 mammography examinations by body mass index (BMI) kg/m2 and mammography use adjusted for age, race, and registry distribution of the study population. Time (more ...)
The proportions of breast cancers that were stage IIb or III/IV were highest among overweight and obese women (). The rate of breast cancer increased by between 0.3 and 0.5 cancers per 1000 mammography examinations from normal to obese II/III categories for early (stage 0 and I) and advanced (stage IIb or III/IV) stages (). Women who had their first diagnostic examinations had high rates of breast cancer per 1000 examinations, regardless of BMI (204 normal, 209 overweight, 209 obese I, and 142 obese II/III).
Table 3 Rates and odds ratios (ORs) with 95% confidence intervals (CIs) of breast cancer by stage groups within 12 mo of a mammography examination per 1000 examinations by body mass index (BMI), adjusted for age, ethnicity/race, and mammography registry and use (more ...)
We measured the rate of breast cancer by method of detection (screen- or non–screen-detected) and the sensitivity of mammography to determine whether a greater proportion of breast cancers not detected in overweight and obese women could have led to a higher rate of advanced disease. The rate of non–screen-detected cancer was low and did not vary by BMI, whereas the rate of screen-detected cancer was higher among overweight and obese women than among lower weight women. The sensitivity of screening mammography was similar or higher among overweight and obese compared with underweight and normal-weight women (). Thus, it seems unlikely that differences in breast cancer detection across BMI categories led to a higher rate of advanced disease in obese and overweight women than among lower weight women.
Table 4 Sensitivity and 95% confidence intervals (CIs) of screening mammography and rate of screen-detected and non–screen-detected cancer within 12 mo of a mammography examination per 1000 screening examinations by body mass index (BMI) and mammography (more ...)
For women with a BMI of 25 kg/m2 or greater who underwent mammography, the population attributable fraction for breast cancer, large invasive cancer, and advanced-stage breast cancer was 8.9%, 12.0%, and 16.3%, respectively, adjusting for age, race, and mammography registry and use.