Body size, received dose-intensity and myelotoxicity of adjuvant chemotherapy in relation to outcome of premenopausal women with N1 breast cancer: Results from a National Cancer Institute of Canada randomized controlled trial

Background: Obesity (body mass index =BMI ≥25kg/m²) has an adverse impact on outcome in women with early stage breast cancer (BC), but it is common to limit chemotherapy dose in very large patients (pts), leading to diminished received dose-intensity (RDI) and myelotoxicity (MT)- both proposed surrogate markers of outcome. We hypothesized that: (1) obese pts would have a worse outcome than leaner pts, independent of RDI, (2) pts with lower RDI would have a worse outcome, (3) pts experiencing significant MT would have better outcome. The study database (JCO 16(8):2651-58, 1998) contains height, weight, clinical variables, RDI and toxicity, allowing exploration of these hypotheses. From 12/89-07/93, 716 pre/perimenopausal pts with N+ BC were randomized to six cycles of adjuvant CMF or CEF. Ideal body weight (IBW) was used for BSA calculation if actual body weight (ABW) exceeded IBW by ≥20kg. Results: Of 710 eligible pts, 130 were dosed on IBW (all obese) and 580 on ABW. Mean BSA and BMI were 1.73m² and 26.38kg/m² respectively. Obesity was prevalent (51.5%), and equally distributed within prognostic subgroups. In multivariate analyses adjusted for known prognostic factors, initial BMI (quadratic variable) was an independent predictor of RFS and OS, p = 0.023 and 0.031 respectively. A concave relationship was seen between BMI and outcome, most favorable for BM130.0-35.4kg/m². RFS and OS rates did not differ if ABW or IBW was used for BSA calculation, overall or in any pt group, all p>0.1. The proportion of pts receiving full RDI (>85% of intended) increased with increasing BMI. RDI was highest in pts dosed by IBW. overall and in the obese subgroup. The proportion of pts experiencing significant MT decreased with increasing BMI. MT was highest in pts dosed on ABW, overall and in the obese subgroup. Conclusions: We confirm the influence of body size on BC outcome. This effect appears to be independent of RDI, MT. and whether IBW or ABW is used for BSA calculation. The relationship between body size, MT, RDI and outcome is complex and remains under study.