Body Mass Index and Risk of Second Cancer Among Women With Breast Cancer

Heather Spencer Feigelson, PhD, MPH; Clara Bodelon, PhD, MS; J. David Powers, MS; Rochelle E. Curtis, MA; Diana S. M. Buist, PhD, MPH; Lene H. S. Veiga, PhD; Erin J. Aiello Bowles, MPH; Amy Berrington de Gonzalez, DPhil; Gretchen L. Gierach, PhD, MPHS


J Natl Cancer Inst. 2021;113(9):1156-1160. 

In This Article

Abstract and Introduction


Background: Breast cancer survivors are at increased risk for developing second primary cancers compared with the general population. Little is known about whether body mass index (BMI) increases this risk. We examined the association between BMI and second cancers among women with incident invasive breast cancer.

Methods: This retrospective cohort included 6481 patients from Kaiser Permanente Colorado and Washington of whom 822 (12.7%) developed a second cancer (mean follow-up was 88.0 months). BMI at the first cancer was extracted from the medical record. Outcomes included: 1) all second cancers, 2) obesity-related second cancers, 3) any second breast cancer, and 4) estrogen receptor–positive second breast cancers. Multivariable Poisson regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for second cancers associated with BMI adjusted for site, diagnosis year, treatment, demographic, and tumor characteristics.

Results: The mean age at initial breast cancer diagnosis was 61.2 (SD = 11.8) years. Most cases were overweight (33.4%) or obese (33.8%) and diagnosed at stage I (62.0%). In multivariable models, for every 5 kg/m2 increase in BMI, the risk of any second cancer diagnosis increased by 7% (RR = 1.07, 95% CI = 1.01 to 1.14); 13% (RR = 1.13, 95% CI = 1.05 to 1.21) for obesity-related cancers, 11% (RR = 1.11, 95% CI = 1.02 to 1.21) for a second breast cancer, and 15% (RR = 1.15, 95% CI = 1.04 to 1.27) for a second estrogen receptor–positive breast cancer.

Conclusions: We observed a statistically significant increased risk of second cancers associated with increasing BMI. These findings have important public health implications given the prevalence of overweight and obesity in breast cancer survivors and underscore the need for effective prevention strategies.


Breast cancer is the most common cancer in women. Most US women are diagnosed with early-stage breast cancer with corresponding 5-year relative survival rates ranging from 86% to 99%.[1,2] As a result, there are approximately 3.9 million breast cancer survivors in the United States today.[1,2] Women diagnosed with breast cancer have an 18% increased risk for developing a second cancer compared with the general population.[3,4] This increased risk is likely due to shared risk factors between the first and second cancers, genetic susceptibility, and long-term effects of breast cancer treatment.[3]

Obesity is strongly associated with an increased risk of several types of cancer;[5–7] an estimated 55% of all cancers in women and 24% of all cancers in men are associated with overweight (body mass index [BMI] = 25.0–29.9 kg/m2) or obesity (BMI ≥ 30 kg/m2).[7] The International Agency for Research on Cancer (IARC) working group has listed 14 types of cancer as having sufficient evidence for an association with overweight or obesity.[6] The role that obesity plays in second cancer risk has received less attention.[8–10] Most prior studies of breast cancer survivors have focused only on the development of a contralateral breast cancer,[11–13] but it is important to understand the role that overweight and obesity plays in the development of other second cancers as well, especially those that have previously been associated with obesity.[6]

This study examined the association between BMI at initial breast cancer diagnosis and the incidence of second primary cancers among a large cohort of women diagnosed with invasive breast cancer within 2 Kaiser Permanente (KP) health plans. Studying the association in this setting provides several advantages, including long-term follow-up for second cancer diagnosis, detailed treatment and clinical data, and measures of BMI close to the date of the initial breast cancer diagnosis.