Introduction:

pCR following NAC is associated with improved long term outcomes. Though obesity is associated with chemo-resistance, its impact on pCR is less clear, likely because most studies were unable to account for NAC dose adjustments. An association between taxane dose reduction and BMI has previously been shown in European populations. However, most patients (pts) with increased BMI had doses capped at BSA of 2. We studied the impact of BMI on NAC dosing when treatment is based on actual weight and whether dosing adjustments preferentially impact pCR rate.

Methods: Pts prospectively enrolled in the University of Iowa Breast Molecular Epidemiologic Resource from 2010-14 with invasive bc who received at least one cycle of NAC were eligible. Pts were stratified by BMI category: normal (BMI ≤25) or overweight-obese (BMI >25). Planned total dose was calculated based on both dosing and number of cycles. Dose reduction was defined as any decrease in total intended dose. pCR was defined as no residual invasive disease in breast and lymph nodes. To investigate the relationship between BMI, dose reductions, and pCR, chi-square tests and logistic regression models were used.

Results: 87 pts were eligible. 22 (26%), 25 (29%) and 51 (59%) of pts had HER2 positive, triple negative and hormone receptor positive bc (HER- or +), respectively. 62 (71%) pts had Stage I-II bc. All pts received a combination of taxanes with other agents (Cytoxan, 5FU, Carboplatin, Gemcitabine) with or without an anthracycline (Adriamycin or Epirubicin) or anti HER 2 therapy (Pertuzumab, Traztuzumab or Lapatinib) and were initially dosed based upon actual body weight. Taxanes were planned at treatment initiation in all pts. Anthracyclines were given to 71 (82%) pts. pCR was achieved in 28 (32%) pts. Association between BMI and NAC dosing are shown in -

Table 1: Association between NAC dosing and BMI category

  Normal Overweight-Obese 
36 51   
  No Yes No Yes   
Taxane dose reduction 30(83%) 6(17%) 29(57%) 22(43%) <0.01 
Non taxane dose reduction 28(78%) 8(22%) 40(78%) 11(22%) 0.94 
  Normal Overweight-Obese 
36 51   
  No Yes No Yes   
Taxane dose reduction 30(83%) 6(17%) 29(57%) 22(43%) <0.01 
Non taxane dose reduction 28(78%) 8(22%) 40(78%) 11(22%) 0.94 

. Relative to normal weight pts, overweight-obese pts were more likely not to achieve a pCR (OR 2.09, CI 0.84-5.21, p=0.11) and have residual disease in the breast alone (OR 2.92, CI 1.18-7.24, p=0.02). Overweight-obese pts with taxane reductions, relative to overweight-obese pts without taxane reductions, were at elevated odds of not achieving a pCR (OR 2.03, CI 0.53-7.73) -.

Table 2: Impact of taxance dose reduction on pCR by BMI category

    Normal Overweight-Obese 
    No pCR pCR No pCR pCR 
Taxane reduction No 19(63%) 11(37%) 20(69%) 9(31%) 
  Yes 2(33%) 4(67%) 18(82%) 4(28%) 
    Normal Overweight-Obese 
    No pCR pCR No pCR pCR 
Taxane reduction No 19(63%) 11(37%) 20(69%) 9(31%) 
  Yes 2(33%) 4(67%) 18(82%) 4(28%) 

Interaction between BMI and taxane dose reduction on pCR trended towards significance (p=0.10), a trend not seen for non-taxane drugs. The most common adverse event resulting in taxane dose reduction was neuropathy (10/28 pts).

Conclusion: Overweight-obese women experienced significantly higher rates of taxane dose reductions during NAC for bc with initial full-weight dosing. BMI status may modify the effects of taxane dose reduction on the likelihood of not achieving a pCR, Further investigation of this outcome in a larger cohort is warranted.

Citation Format: Raman R, Mott SL, Schroeder MC, Thomas A. Impact of body mass index (BMI) and neo-adjuvant chemotherapy (NAC) dosing on pathologic complete response (pCR) in operable breast cancer (bc). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-14.