Impact of body mass index on neoadjuvant treatment outcome: a pooled analysis of eight prospective neoadjuvant breast cancer trials

Abstract

Obesity is associated with an increased risk of breast cancer (BC) and poorer outcome. We assessed the impact of body mass index (BMI) on pathological complete response (pCR), disease-free (DFS), and overall survival (OS), according to BC subtypes in patients with primary BC treated with neoadjuvant chemotherapy. 8,872 patients with primary BC from eight neoadjuvant trials were categorized according to BMI: underweight (<18.5 kg/m(2)), normal weight (18.5 to <25 kg/m(2)), overweight (25 to <30 kg/m(2)), obese (30 to <40 kg/m(2)), and very obese (≥40 kg/m(2)). BC subtypes were defined as luminal-like (ER/PgR-positive and HER2-negative), HER2/luminal (ER/PgR-positive and HER2-positive), HER2-like (ER/PgR-negative and HER2-positive), and triple-negative (TNBC; ER/PgR- and HER2-negative). pCR rate was higher in normal weight patients compared with all other BMI groups (P = 0.003). Mean DFS and OS were shorter in obese (87.3 months, P = 0.014 and 94.9 months, P = 0.001, respectively) and very obese (66.6 months, P < 0.001 and 75.3 months, P < 0.001, respectively) compared with normal weight patients (91.5 and 98.8 months, respectively) which was confirmed by subpopulation treatment effect pattern plot analyses and was consistent in luminal-like and TNBC. No interaction was observed between BMI and pCR. Normal weight patients experienced less non-hematological adverse events (P = 0.002) and were more likely to receive full taxane doses (P < 0.001) compared with all other BMI groups. In multivariable analysis, the dose of taxanes was predictive for pCR (P < 0.001). Higher BMI was associated with lower pCR and a detrimental impact on survival. Normal weight patients had the best compliance to chemotherapy and received the highest taxane doses, which seems to be related with treatment outcomes.

Triple‑negative breast cancer and its?association with obesity (Review)

“…However, a Chinese report pointed out that high BMI was an independent prognostic factor for TNBC (97). A pooled analysis of eight prospective neoadjuvant breast cancer trials containing >8,800 patients demonstrated that increasing BMI results in decreasing pathological complete response (pCR) rates and that a high BMI exerts detrimental effects on DFS and OS in TNBC (98). Women with ER/PR-negative tumors exhibit a significant association of obesity with clinical outcome, which is also true for ER/PR-positive breast cancer (99).…”

Effect of Body Mass Index– and Actual Weight–Based Neoadjuvant Chemotherapy Doses on Pathologic Complete Response in Operable Breast Cancer

“…7,12,18 The largest of these 12 included a highly selective European trial population with an over-representation of HER2-positive tumors (72%), capped chemotherapy doses at a BSA of 2.0 m 2 and defined HR positivity as ≥10% expression on IHC, all of which make generalization of results challenging. Importantly, in the German analysis, the overweight/obese patients did require significantly more dose reductions in taxanes and in turn in multivariable analysis, dose reductions (but not BMI) negatively affected pCR.…”

“…Several series have failed to show a consistent association of BMI with pCR. 7–12 The largest of these was a pooled analysis of 8 German neoadjuvant trials, which reported a negative association between higher BMI and pCR in their univariate analysis. 12 However, they did not find BMI to predict for pCR in their multivariable analysis which used data from only 2 of the pooled trials.…”

“…7–12 The largest of these was a pooled analysis of 8 German neoadjuvant trials, which reported a negative association between higher BMI and pCR in their univariate analysis. 12 However, they did not find BMI to predict for pCR in their multivariable analysis which used data from only 2 of the pooled trials. 13–16 Of note, all obese patients in these 2 trials had received doses capped at a body surface area (BSA) of 2.0 m 2 .…”

The Role of Body Mass Index in Triple Negative Breast Cancer

“…Dawood et al [17] investigated the impact of obesity in 2,311 TNBC patients and were not able to determine any relationship between BMI and survival. However, in a pooled analysis of neoadjuvant trials, it was determined that a higher BMI was associated with lower pathological complete response (pCR), and that there was a detrimental effect on the survival with shorter DFS in obese TNBC patients compared to their non-obese counterparts [19].…”