Increased BMI associated with risk for second cancer among breast cancer survivors
Higher BMI appeared associated with a statistically significant increased risk for second cancers among women diagnosed with invasive breast cancer, according to a study published in Journal of the National Cancer Institute.
“Most people might be shocked to realize that being overweight or obese significantly contributes to risk [for] cancer — this must change,” Heather Spencer Feigelson, PhD, MPH, cancer epidemiologist and senior investigator at Kaiser Permanente Institute for Health Research, told Healio. “Physicians must talk to their patients about this and help them find strategies to increase their physical activity and reduce their weight.”

Breast cancer survivors have an 18% greater risk for developing second cancers compared with the general population, according to prior research, but whether higher BMI further increases that risk remained unclear.

“Previous studies had shown an association of increased BMI and second breast cancers, but few had data on treatment, and none had examined obesity-associated cancers specifically,” Feigelson said. “BMI is an important topic because it is one of the few modifiable risk factors for breast cancer, and over 40% of the adult U.S. population is obese.”
Feigelson and colleagues used Kaiser Permanente’s electronic medical record database linked to tumor registries to study correlations of BMI and second cancers among 6,481 women (mean age, 61.2 years; standard deviation, 11.8; 82.2% white) diagnosed with non-metastatic (stages I-III) first invasive primary breast cancer between 2000 and 2014 within Kaiser Permanente Colorado or between 1990 and 2008 within Kaiser Permanente Washington. Most of the women had either overweight (33.4%) or obesity (33.8%), stage I disease (62%), and ER-positive (80%) or PR-positive (69.3%) disease at diagnosis.
All second cancers, obesity-related second cancers, any second breast cancer and ER-positive second breast cancers served as outcomes of interest. Researchers estimated associations of these outcomes with BMI using BMI as a continuous variable (per 5 kg/m2) and as a categorical variable (normal, 18.5 kg/m2 to < 25 kg/m2; overweight, 25 kg/m2 to < 30 kg/m2; obese, 30 kg/m2).
They estimated RRs and 95% CIs for second cancers associated with BMI using multivariable Poisson regression models, adjusting for site, year of diagnosis, treatment, and demographic and tumor characteristics.
Mean follow-up was 88 months (range, 12-322), during which 822 women (12.7%) developed a second cancer; 508 (61.8%) of these were obesity-related and 333 (40.5%) were breast cancer.
Results of multivariable models showed for every 5 kg/m2 increase in BMI, risk increased by:
- 7% (RR = 1.07; 95% CI, 1.01-1.14) for any second cancer diagnosis;
- 11% (RR = 1.11, 95% CI, 1.02-1.21) for a second breast cancer;
- 13% (RR = 1.13; 95% CI, 1.05-1.21) for obesity-related cancers; and
- 15% (RR = 1.15, 95% CI, 1.04-1.27) for a second ER-positive breast cancer.
Researchers observed similar patterns when analyzing BMI as a categorical variable.
“Our results provide another piece of evidence showing how overweight and obesity contribute to cancer risk,” Feigelson said. “Specific weight loss strategies, including nutritional and physical activity guidelines and potentially bariatric surgery, should be considered for breast cancer survivors. BMI is a modifiable risk factor, and weight loss to reach a healthy body weight among breast cancer survivors may result in significant health and quality-of-life benefits.”
Study limitations included a lack of information on physical activity after initial diagnosis, as well as an inability to evaluate BMI variation over time. The researchers recommended investigating how changes in weight affect risk for second cancers among survivors.
“We need additional studies on the benefits of intentional weight loss among cancer survivors,” Feigelson added. “It would be great to know how much weight loss is necessary to see a benefit. For example, does a breast cancer survivor need to reach a ‘normal’ BMI, or is there benefit associated with any amount of weight loss? It would also be ideal to incorporate measures of sitting time and physical activity into the analysis, which we did not have in our study.”
Another step forward in examining the associations between lifestyle factors and second cancers would be to pool data from prospective cancer cohorts, cancer survivor cohorts or clinical trials that gathered information on lifestyle factors before and after cancer diagnosis and followed survivors for cancer outcomes, according to a related editorial by Yikyung Park, ScD, associate professor of surgery, and Graham A. Colditz, MD, DrPH, associate director of prevention and control at Alvin J. Siteman Cancer Center and Niess-Gain professor of surgery and professor of medicine, both at Washington University School of Medicine in St. Louis.
“Although the heterogeneities across cohorts and trials can challenge the data harmonization, data pooling for a second cancer study is feasible, and once created, it will accelerate the identification of risk factors for second cancer,” Park and Colditz wrote, adding that collaborative studies are “urgently needed” due to the burden of second cancers among survivors and the knowledge gaps in identifying modifiable risk factors.
References:
Feigelson HS, et al. J Natl Cancer Inst. 2021;doi:10.1093/jnci/djab053.
Park Y and Colditz GA. J Natl Cancer Inst. 2021;doi:10.1093/jnci/djab054.
Heather Spencer Feigelson, PhD, MPH, can be reached at Kaiser Permanente Institute for Health Research, 2550 S. Parker Road, Suite 200, Aurora, CO 80014; email: heather.s.feigelson@kp.org.