Abstract P1-08-05: An association between obesity and more aggressive breast cancer subtype

Abstract

Abstract Background: Obesity has become epidemic in the United States with over one third of the adult population being obese. The incidence of obesity is even higher among African American population with slightly more than half of the population being obese. Elevated body mass index (BMI) has been associated with an increased risk of breast cancer in postmenopausal women. This is believed to be due to higher levels of estrogens, inflammation, and insulin. Given that adipose tissue is the major source of estrogen production via the aromatization of androgens into estrogens in postmenopausal women, there is a concern that obese women may have inadequate estrogen suppression with a fixed dose of aromatase inhibitors (AIs). Multiple recent retrospective analyses of large phase III adjuvant endocrine therapy trials demonstrated that obese patients had worse outcome when treated with AIs. However, it remains unclear whether there is also a difference in the tumor subtype among normal weight, overweight, and obese patients. Method: A retrospective review of breast cancer cases diagnosed from July 2008 and August 2011 was performed. Patient characteristics, BMI, and pathologic findings were collected. An immunohistochemistry (IHC)-based molecular subtypes was assigned based on St. Gallen criteria: Luminal A (ER/PR+, HER2- and Ki67 ≤ 14%), Luminal B (ER/PR+, HER2+ or Ki67 > 14% or grade 3), HER2 enriched (ER/PR-, HER2+), and Triple negative breast cancer (TNBC; ER/PR-, HER2-). Using the WHO classification, normal weight was defined as BMI < 25, overweight BMI 25-30, and obese BMI ≥ 30. Result: 143 patients were included in the analysis. The median age was 55 years. The majorities of our patients were African American (63%) and presented with early stage disease (stage I 29%, stage II 45%, stage III 22%, and stage IV 5%). IHC-based molecular subtypes were luminal A 20%, luminal B 48%, HER2 enriched 7%, and TNBC 25%. 21% were normal weight, 30% overweight and 49% obese. As shown in the table below, comparing between normal weight, overweight, and obese patients, there is a possible association between tumor subtype and BMI status (p = 0.03). The majority of TNBC patients (94.4%) were overweight or obese. Specifically, there is significantly more aggressive luminal B subtype compared to luminal A (52.86% vs. 15.71%) among obese patients (p = 0.017). We further evaluated the effect of obesity and tumor growth in xenograft model of MCF7Ca. Comparing between obese mice fed with high fat vs. lean mice fed with chow diet, there is a significant increase in tumor growth among obese mice (p = 0.04) which corresponds to the high proliferation index measured by Ki67 seen in patients with luminal B subtype. IHC-based molecular subtypes and distribution by weight categoryWeight CategoryLuminal ALuminal BHER2 EnrichedTNBCNormal Weight8 (26.67%)15 (50%)5 (16.67%)2 (6.67%)Overweight9 (20.93%)17 (39.53%)2 (4.65%)15 (34.88%)Obese11 (15.71%)37 (52.86%)3 (4.29%)19 (27.14%) Conclusion: Our study suggests that obesity may provide a microenvironment that support and accelerate tumor growth, particularly in luminal breast cancer subtypes. Furthermore, the poor outcome seen in obese patients may also be in part due to more aggressive tumor subtype. Citation Format: Saranya Chumsri, Paula Rosenblatt, Candace Mainor, Gauri Sabnis, Olga Goloubeva, Angela H Brodie. An association between obesity and more aggressive breast cancer subtype [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-08-05.