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Obesity Contributes to Higher Mortality among Premenopausal Women with ER+ Breast Cancer


Obesity Contributes to Higher Mortality among Premenopausal Women with ER+ Breast Cancer

No such associations were noted among obese postmenopausal ER-positive or among ER-negative women in a large pooled analysis

Obesity appears to be prognostic of negative outcomes among pre- and perimenopausal women with estrogen receptor (ER)+ breast cancer, Hongchao Pan, PhD, said during the Breast Cancer Oral Abstract Session.

Reporting on data from 80,000 women in 70 clinical trials analyzed by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Dr. Pan, of the University of Oxford, United Kingdom, said there were no correlations with obesity and long-term survival among postmenopausal women with ER+ disease or among women with ER- disease.

“We find definite, independent adverse effect on breast cancer mortality only among premenopausal women who have an ER-positive disease,” Dr. Pan said. “Obesity increases by one-third the risk that the disease will recur within the next 10 years.”

Menopausal Status

In the cohort, there was a 21.5% breast cancer mortality rate after 10 years among obese (defined as a body mass index [BMI] of 30 kg/m2 or higher) premenopausal women with ER+ disease, compared with 16.6% among normal-weight (defined as BMI between 20 and 25 kg/m2) premenopausal women with ER+ disease (2p < 0.00001). Additionally, breast cancer–associated mortality increased among women with higher BMI scores.

The findings surprised researchers, Dr. Pan said, who expected to see an association between obesity and ER+ disease among women of postmenopausal status. Among the 40,000 postmenopausal women with ER+ disease, only women with a BMI of 40 kg/m2 or greater demonstrated a higher likelihood of breast cancer mortality. A slightly increased risk was also seen among the 20,000 women with ER- disease who had a BMI of 40 kg/m2 or greater.

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In a subanalysis of women aged 45 to 54 with ER+ disease, premenopausal women had a mortality rate ratio of 1.34 (1.17-1.55) compared with 1.08 (0.91-1.28) among postmenopausal women, suggesting that “given menopausal status, the effect of obesity appears to be approximately independent of age,” Dr. Pan said.

The type of treatment received did not affect the mortality rate ratio, according to Dr. Pan (Fig. 1).

Helping Patients Manage Weight

Commenting on the study, Sharon H. Giordano, MD, MPH, of The University of Texas MD Anderson Cancer Center, noted that previous studies have linked obesity with worse prognoses among women with breast cancer. It is likely that increased body mass affects tumor biology, including tumor proliferation, increased angiogenesis, and cell survival, she said.

“Factors related to treatment may also contribute to poor outcomes. These patients are often underdosed for chemotherapy, with dose calculated based on calculated BSAs [body surface areas] rather than actual BSAs. These dose reductions have been associated with worse outcomes,” Dr. Giordano said.

“It will be important to decipher if interventions designed to help patients manage their weight after diagnosis will have any impact on long-term outcomes.”

— Dr. Sharon H. Giordano

While largely positive in her analysis of the study, Dr. Giordano did note that the nonrandomized nature of the trial may have contributed to an imbalance in baseline characteristics. Furthermore, there was not adjustment for race and/or ethnicity, factors which could have affected the metabolic activity and outcomes in the study population, Dr. Giordano said.

The pooled analysis of women choosing to participate in clinical trials may also represent a selection bias. According to Dr. Giordano, participants in clinical trials tend to be younger, better educated, and healthier, and so the results may not reflect the general population. The lower rates of obesity in the study population compared with the general population (23% vs. 34%, respectively) may reflect this, she said.

Although the study was not designed to study the effects of weight management on outcomes, it will be important to decipher if interventions designed to help patients manage their weight after diagnosis will have any impact on long-term outcomes, Dr. Giordano said.