Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer

Abstract

Background: Obesity is associated with both increased breast cancer risk and poorer prognosis after disease onset. However, little is known about the effect of obesity on treatment efficacy. We evaluated the association of obesity with outcomes and with tamoxifen efficacy in women with early-stage, hormone-responsive breast cancer participating in a multicenter cancer cooperative group clinical trial.

Methods: The cohort consisted of 3385 women enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-14, a randomized, placebo-controlled trial evaluating tamoxifen for lymph node-negative, estrogen receptor (ER)-positive breast cancer. Hazards of breast cancer recurrence, contralateral breast tumors, other new primary cancers, and several mortality endpoints were evaluated in relation to body mass index (BMI), using statistical modeling to adjust for other prognostic factors. Median follow-up time was 166 months. All statistical tests were two-sided.

Results: The hazard of breast cancer recurrence was the same among obese (BMI > or =30.0 kg/m2) women as compared with underweight and normal-weight women (BMI <25.0; hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.80 to 1.18). Contralateral breast cancer hazard was higher in obese women than in underweight/normal-weight women (HR = 1.58, 95% CI = 1.10 to 2.25), as was the risk of other primary cancers (HR = 1.62, 95% CI = 1.16 to 2.24). Compared with normal-weight women, obese women had greater all-cause mortality (HR = 1.31, 95% CI = 1.12 to 1.54) and greater risk of deaths due to causes unrelated to breast cancer (HR = 1.49, 95% CI = 1.15 to 1.92). Breast cancer mortality was not statistically significantly increased for obese women (HR = 1.20, 95% CI = 0.97 to 1.49). Tamoxifen reduced breast cancer recurrence and mortality, regardless of BMI.

Conclusions: For women with lymph node-negative, ER-positive breast cancer, obesity was not associated with a material increase in recurrence risk or a change in tamoxifen efficacy. However, because obesity was associated with increased risks of contralateral breast cancer, of other primary cancers, and of overall mortality, it may influence long-term outcomes for breast cancer survivors.

Figures

Fig. 1

Distribution of body mass index (BMI) defined as [weight in kilograms]/[height in meters]2 among the 3385 women in the NSABP B-14 trial included in this analysis.

Fig. 2

Cumulative incidence of breast cancer recurrence by body mass index, unadjusted for patient and disease characteristics. At 10 years after surgery, the numbers of patients remaining in each weight group were underweight/normal-weight women (≤24.9 kg/m2), 1073 patients; overweight women (25.0–29.9 kg/m2), 643 patients; obese women (≥30.0 kg/m2), 395 patients. The cumulative incidences of recurrence (with 95% confidence intervals [CIs]) were 0.214 (95% CI = 0.194 to 0.234) for underweight/normal-weight women, 0.194 (95% CI = 0.170 to 0.219) for overweight women, and 0.188 (95% CI = 0.159 to 0.218) for obese women.

Fig. 3

Cumulative incidence of contralateral breast cancer by body mass index, unadjusted for patient and disease characteristics. At 10 years after surgery, the numbers of patients remaining in each weight group were underweight/normal weight women (≤24.9 kg/m2), 1073 patients; overweight women (25.0–29.9 kg/m2), 643 patients; obese women (≥30.0 kg/m2), 395 patients. The cumulative incidences of contralateral breast cancer (with 95% confidence intervals [CIs]) were 0.033 (95% CI = 0.024 to 0.041) for underweight/normal weight women, 0.044 (95% CI = 0.031 to 0.057) for overweight women, and 0.056 (95% CI = 0.039 to 0.074) for obese women.

Fig. 4

Cumulative incidence of endometrial cancer (A) and other second primary cancers (B) by body mass index, unadjusted for patient and disease characteristics. Note that the y-axis scale differs between the two plots. At 10 years after surgery, the numbers of patients remaining in each weight group were underweight/normal weight women (≤24.9 kg/m2), 1073 patients; overweight women (25.0–29.9 kg/m2), 643 patients; obese women (≥30.0 kg/m2), 395 patients. The cumulative incidences (with 95% confidence intervals [CIs]) of endometrial cancer (A) and other cancers (B) were 0.009 (95% CI = 0.004 to 0.013) and 0.042 (95% CI = 0.032 to 0.052), respectively, for underweight/normal-weight women; 0.012 (95% CI = 0.005 to 0.019) and 0.055 (95% CI = 0.041 to 0.070), respectively, for overweight women; and 0.016 (95% CI = 0.007 to 0.026) and 0.074 (95% CI = 0.054 to 0.094), respectively, for obese women.

Fig. 5

Tamoxifen/placebo hazard ratios according to BMI. Hazard ratios with 95% confidence intervals were computed within BMI categories for breast cancer recurrence (A) and contralateral breast cancer (B). Because underweight and normal-weight women had similar outcomes for these endpoints, these categories were combined. Hazard ratios with 95% confidence intervals were computed within BMI categories (obese, ≥30.0 kg/m2; overweight, 25.0–29.9 kg/m2; normal weight, 18.5–24.9 kg/m2; underweight, ≤18.5 kg/m2) for all deaths (C) and deaths preceded by breast cancer recurrence or occurrence of contralateral breast tumor (D). For all panels, hazard ratios of less than 1.0 indicate a more favorable outcome for women receiving tamoxifen.