For Premenopausal Women With ER-Positive Disease, Obesity Is a Major Risk Factor in Breast Cancer Mortality

Hongchao Pan, PhD

Obesity significantly increases the risk of dying of breast cancer in premenopausal women with ER-positive early disease, according to findings from a large, retrospective study involving 80,000 patients. When compared with their normal-weight counterparts, obese women with these characteristics have a 34% higher risk of breast cancer mortality.

Notably, this higher risk was not observed in obese postmenopausal women with ER-positive disease—a finding which surprised researchers who expected obesity to be more of a risk factor after menopause. In addition, obesity did not increase the risk of death from breast cancer among women whose tumors were ER-negative, regardless of menopausal status.

Obesity, defined by the World Health Organization as a body mass index (BMI) ≥30 kg/m², is associated with a somewhat worse prognosis in early breast cancer, according to Hongchao Pan, PhD, of the University of Oxford in the United Kingdom. Pan presented the study findings on behalf of the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) at a presscast held in advance of the 2014 ASCO Annual Meeting later this month.

For this study, which was based on patient data from 70 clinical trials, the researchers used Cox regression analysis to assess how a patient’s BMI may independently affect outcome. In addition to an individual’s BMI at randomization, the EBCTCG gathers information on all trial participants’ estrogen receptor and menopausal status, age, treatment regimen, recurrence, and death, and for most participants, their tumor size and nodal status.

Of the 60,000 patients in the study with ER-positive tumors, obesity was associated with an increase in breast cancer mortality, regardless of menopausal status (2P <.00001). However, when adjusted for tumor characteristics, for the 20,000 of these patients who were premenopausal, the breast cancer mortality rate was one-third higher in obese women than in their normal weight counterparts who had a BMI = 20-25 kg/m² (relative risk [RR] = 1.34; 95% CI, 1.22-1.47; 2P <.00001), with poorer outcomes trending steadily upward as BMI levels rose. Researchers found little independent effect of obesity in the 40,000 postmenopausal women with ER-positive disease (RR = 1.06; 95% CI, 0.99-1.14; 2P = .12).

Pan reported that these findings translate into a 21.5% increase in 10-year breast cancer mortality risk for the subgroup of premenopausal, ER-positive patients who were obese, versus a 16.6% risk in their counterparts of normal weight—a 5% difference (CI, 3.0-6.8).

“Obesity substantially increases blood estrogen levels only in postmenopausal women, so we were surprised to find that obesity adversely impacted outcomes, only in premenopausal women,” said Pan. “This means we don’t understand the main biological mechanisms by which obesity affects prognosis.”

In commenting on the study findings, ASCO President Clifford A. Hudis, MD, FACP, stressed that the study “addresses the backend of the disease, not the initiation of the disease. I am surprised that the effect was less clear in postmenopausal than in premenopausal patients, so I think this is something that we’re going to have to explore further.”

“The bottom line remains that obesity overall is a negative prognostic feature,” Hudis continued, adding that findings such as these may suggest that for certain subsets of obese patients, specific interventions may be beneficial.

“No matter how we look at it, obesity is slated to replace tobacco as the leading overall, modifiable risk factor for cancer,” Hudis said, and in that vein, he added that ASCO rolled out an obesity resource toolkit this week to help oncology practitioners and patients manage the complications of obesity and facilitate communication about the importance of weight management and making healthy lifestyle choices following a cancer diagnosis. The resources can be accessed on ASCO's website at www.asco.org/obesity.

Pan H, Gray RG. Effect of obesity in premenopausal ER+ early breast cancer: EBCTCG data on 80,000 patients in 70 trials. J Clin Oncol. 2014 (suppl; abst 503).

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