Influence of body mass index on outcomes in hormone-sensitive disease remains uncertain

Obese women with hormone receptor-positive, operable breast cancer are more likely to experience inferior disease-free survival and overall survival after adjuvant chemotherapy than nonobese women. Given the growing obesity epidemic in the U.S., currently at 72 million adults, breast cancer specialists will have to contend with more of this type of patient.

In general, clinical trial populations tend to include healthier people, so this selection process would tend to include healthy obese individuals,” said Joseph A. Sparano, MD, from the Eastern Cooperative Oncology Group (ECOG).

Dr. Sparano and colleagues evaluated the effect of obesity on outcomes in several ECOG adjuvant therapy trials including E1199, E5188, and E3189. They looked at the link between body mass index (BMI), DFS, and OS using multivariate models adjusted for age, tumor size, nodal status, race, surgery type, prior radiotherapy, menopausal status, treatment arm, and treatment adherence.

Using a BMI of 30 kg/m² or higher, they found that in the E1199 trial, obesity was associated with older age, postmenopausal status, and black race. Obese subjects with estrogen-receptor positive, progesterone-receptor positive, or both subtypes of cancer plus HER2-negative disease had inferior DFS (hazard ratio [HR] 1.24; P = .026) and OS (HR 1.42; P = .003). This effect was not seen for HER2-positive and/or triple-negative disease (SABCS 2010 abstract S2-1).

“Not only did the obese subjects seem to have a higher risk of recurrence, but they seem to have a shorter period of time between the time of recurrence and death,” Dr. Sparano said.

Finally, there was no evidence for differences in chemotherapy delivery, endocrine therapy or adherence, or toxicity in the obese patients. A review of E5188 (ER-positive, node-positive breast cancer) and E3189 (ER-negative, node-positive breast cancer) confirmed the relationship of obesity and outcomes in HR-positive disease.

Dr. Sparano stated the clinical implications for this study:

•Host-related factors, such as hyperinsulinemia, may be contributing to recurrence
•Additional research is required to pinpoint these host-related factors
•Targeted interventions may reduce recurrence risk and eliminate these disparities in outcomes. One option might be to treat obese ER/PR-positive patients with a dose of anti-ER therapy to address higher circulating levels of estrogen.

TEAM results

Researchers from the TEAM trial investigated whether the activity of exemestane (Aromasin) and tamoxifen given as adjuvant therapy was affected by BMI. The TEAM* patients were treated with exemestane (25 mg daily) vs tamoxifen (20 mg daily) or with exemestane vs tamoxifen followed by exemestane. Both regimens were given for five years.

Weight and height was known in 4,741 patients, and the mean BMI was 26.9 kg/m², with 39% of the patients deemed overweight and 23% considered obese.

At 2.75 years in the exemestane vs tamoxifen arm, disease relapse in patients using exemestane was 6.8% in overweight women and 7.5% in obese women (P = .57). In overweight patients on tamoxifen, disease relapse rate was 8.8% while obese women had a relapse rate of 12.5% (P = .06). In comparison, women at normal weight had relapse rates of 8.1% for exemestane and 9.1% for tamoxifen.

At a median follow-up of 5.1 years, disease relapse in those patients taking exemestane occurred in 14.8% of normal weight patients, 15.1% of overweight patients, and 15.1% of obese women. For those on tamoxifen, 17% of normal weight women experienced relapse vs 16.9% of overweight women and 18.3% of obese women (SABCS 2010 abstract S2-3). For DFS, the HR was 0.88 in overweight patients and 0.75 in obese patients. For OS in overweight women, the HR was 0.89 and in obese women, 0.71 (SABCS 2010 abstract S2-3).

“In the TEAM population, we did not find a worse outcome in overweight obese patients compared with normal weight patient at follow-up of five years,” said Caroline Seynaeve, MD, from the Daniel den Hoed Cancer Center at Erasmus Medical Center in Rotterdam, the Netherlands. “Also, we did not find significant differences by treatment regimen based on BMI.”

An SABCS audience member asked Dr. Seynaeve about the difference between her group’s results and those presented by the Austrian ABCSG-12 trial group earlier this year. In the latter, obese women taking anastrozole (Arimidex) had worse outcomes compared with those on tamoxifen, leading the investigators to suggest that the type of aromatase inhibitor (reversible vs irreversible) may have been the culprit ().

Dr. Seynaeve responded that the Austrian study had premenopausal women in it while TEAM was carried out in postmenopausal women. In addition, longer follow-up in the TEAM population is planned. “Because the data is not concordant at this moment is not to say that it won’t become concordant,” she said.


*TEAM = Tamoxifen Exemestane Adjuvant Multinational study