Abstract PD2-2: Body mass index (BMI) and treatment outcome of breast cancer patients receiving neoadjuvant therapy (NACT)
Authors: Fontanella C , von Minckwitz G , Mergler B , Neven P , Blohmer JU , Costa SD , Denkert C , Eidtmann H , Gerber B , Vanoppen M , Hanusch C , Hilfrich J , Huober J , Schneeweiss A , Paepke S , Jackisch C , Keyur M , Nekljudova V , Untch M , Loibl S 
Published: August 2014

Abstract
Background: Obesity is associated with an increased risk of breast cancer (BC) and a poorer outcome. We assessed the impact of BMI on response to NACT according to BC subtypes.
Methods: We retrospectively evaluated 8874 BC patients treated in 7 neoadjuvant trials with an anthracycline-taxane based chemotherapy from June 1999 to June 2011. The dosage of the chemotherapy was not adapted for BMI. We defined pCR1 as ypT0 ypN0, pCR2 as ypT0/is ypN0, overall survival (OS) as time from diagnosis to death of any cause, and disease-free survival (DFS) as time from diagnosis to recurrence of tumor or death from any cause. BC subtypes were defined as Luminal A/B (hormone receptor HR-pos/HER2-neg), HER2/Luminal (HR-pos/HER2-pos), HER2/like (HR-neg/HER2-pos), and TNBC (HR-neg/HER2-neg). BMI1 (&lt;25kg/m2), BMI2 (25-29.9kg/m2), and BMI3 (≥30kg/m2) were defined according to WHO classification. We performed univariate analyses (cross-tabulation and X2-test) and multivariate logistic regression analyses (including HR and HER2 status, tumor and nodal stage) to investigate the effect of BMI on pCR1-2. Kaplan-Meier analyses were used to estimate survival over time.
Results: Distribution of subtypes did not differ significantly by BMI (p = 0.994), with approx. 23.5% of TNBC, 48.5% of Luminal A/B, 16% of HER2/luminal and 12% of HER2/like in all BMI groups. Univariate analysis found a significant association between BMI groups and pCR2 rate (22.5% for BMI1, 21.2% for BMI2, and 18.3% for BMI3; p = 0.002), but only a trend in association with pCR1 (p = 0.101). Association with pCR2 was also significant in Luminal A/B patients (n = 3250, p = 0.046). In TNBC (n = 1570) only a marginal trend in association was found (p = 0.104). No association was found in HER2/Luminal (n = 1077, p = 0.483) and HER2/like (n = 806, p = 0.358). In multivariate analyses, BMI groups predicted pCR2 (p = 0.035; BMI2 OR = 0.94, CI 0.82-1.08, p = 0.416; BMI3 OR = 0.80, CI 0.67-0.95, p = 0.009), but not pCR1 (p = 0.494). Survival analyses showed a significant decrease in OS and DFS for obese patients (OS 98.6 months for BMI1, 97.6 for BM2 and 94.1 for BMI3, overall p&lt;0.001; DFS 91.3, 90.0 and 86.2 months respectively, overall p = 0.005). In Luminal A/B patients OS was 103.9, 99.0 and 97.1 months respectively (overall p = 0.001) and DFS was 96.4, 92.1 and 90.5 months, respectively (overall p = 0.025). In TNBC patients OS was 85.0, 90.3 and 73.2 months respectively (overall p = 0.008) and DFS was 77.5, 77.7 and 66.7 months (p = 0.014), respectively (overall p = 0.050). No statistical differences were observed in HER2/Luminal (OS p = 0.354, DFS p = 0.094) and HER2/like (OS p = 0.449, DFS p = 0.179). For 6984 patients with residual invasive cancer after neoadjuvant treatment, OS was 94.6 months for BMI1, 95.8 for BMI2 (p = 0.858), and 90.9 for BMI3 (overall p&lt;0.001). DFS was 87.2, 87.6 and 83.1 months, respectively (overall p = 0.005). No statistical differences were observed in patients who achieved a pCR irrespective of the definition.
Conclusion: Our data demonstrate a lower pCR2 rate in obese/overweight BC patients receiving NACT and a detrimental impact of obesity on OS and DFS, especially in patients with residual disease. Results are consistent among TNBC and Luminal A/B patients.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD2-2.