The association between body mass index and neoadjuvant chemotherapy response in patients with breast cancer

Obesity, defined as Body Mass Index (BMI) ≥ 30 kg/m², is associated with inferior breast cancer prognosis, but its effect on neoadjuvant chemotherapy response is uncertain. We hypothesized that obesity decreases the odds of pathological complete response (pCR) after neoadjuvant chemotherapy.

We assembled a cohort of women with breast cancer who underwent neoadjuvant chemotherapy and subsequent surgery between January 1, 2016, and December 31, 2020, in Denmark. Patients received six or eight series of EC-TAX (epirubicin, cyclophosphamide, and paclitaxel) based on disease stage. Trastuzumab and pertuzumab were also used for patients with HER2+ disease. BMI was assessed as a categorical variable (normal weight (BMI = 18.5-<25 kg/m²), overweight (BMI = 25-<30 kg/m²), and obesity (BMI ≥ 30 kg/m²)) and as a continuous variable. We used multivariable logistic regression models to compute odds ratios (ORs) for pCR after neoadjuvant chemotherapy according to BMI groups, using normal weight as reference, and stratified by menopausal, estrogen receptor (ER), and HER2 status. We adjusted for age and menopausal status based on a directed acyclic graph.

Among 1819 patients, 417 had pCR. Patients with overweight (N = 585) or obesity (N = 450) had 22% and 27% lower odds, respectively, of pCR (OR_adj=0.78 [95%CI = 0.60-1.00] and OR_adj=0.73 [95%CI = 0.55-0.97]) compared with patients with normal weight (N = 784). In ER/HER2-stratified analyses, we observed lower pCR odds among women with obesity and HER2+ tumors (OR_adj=0.72 [95%CI = 0.47-1.12]) compared with their normal weight counterparts, but no notable association appeared for ER+/HER2- (OR_adj=0.97 [95%CI = 0.49-1.96]) and ER-/HER2- tumors (OR_adj=0.88 [95%CI = 0.49-1.57]). In analyses stratified by menopausal status, obesity was associated with lower pCR odds among postmenopausal women (OR_adj=0.62 [95%CI = 0.41-0.94]), and, to a lesser extent, premenopausal women (OR_adj=0.86 [95%CI = 0.58-1.27]).

Our findings suggest that breast cancer patients with overweight or obesity have lower odds of pCR compared with patients with normal weight. As the results varied by ER and HER2 status, the observed association may depend on subtype. In summary, our results are consistent with earlier studies that propose BMI as a potential prognostic marker of pCR.