Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

Abstract

Introduction: Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification.

Methods: We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003-02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype.

Results: Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype.

Conclusions: Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes.

Figure 1

Crude Kaplan-Meier curves for each survival outcome for each body mass index (BMI) category. (A) Overall survival. The lower curve shows patients with BMI ≥35. Overall log-rank P = 0.002; log-rank comparing the curve for BMI ≥35 with the rest was <0.001. (B) Breast cancer survival. The lower curve shows patients with BMI ≥35. Overall log-rank P = 0.052; log-rank comparing the curve for BMI ≥35 with the rest = 0.006. (C) Recurrence-free survival. The lower curve shows patients with BMI ≥35. Overall log-rank P = 0.226; log-rank comparing the curve for BMI ≥35 with the rest = 0.040.

Figure 2

Hazard ratio dose–response curve (dark line) and upper and lower limits of the confidence interval (lighter lines) for body mass index for each survival outcome. (A) Overall Mortality. (B) Breast cancer mortality. (C) Recurrence. Estimates were adjusted for all the variables in the full model.

Figure 3

Hazard ratios and 95% CI associated with severe obesity (body mass index ≥35) compared to the reference group (body mass index <25) for each survival outcome by the categories of each covariate. (A) Overall mortality. (B) Breast cancer mortality. (C) Recurrence estimates were adjusted for all the variables in the full model. The size of the interval and the box are proportional to the amount of information available per stratum. GEICAM, Spanish Breast Cancer Research Group; BCIRG, Breast Cancer International Research Group; pT, pathologic primary tumor size; surg, surgery; HER2: human epidermal growth factor-2; ER, estrogen receptor; PR, progesterone receptor.