Abstract 617: Aggressive phenotypes of luminal breast cancer demonstrate associations with body mass index analogous to triple-negative breast cancer
Authors: Abubakar Mustapha , Guo Changyuan , Koka Hela , Zhou Bin , Tang Eric , Deng Joseph , Hu Nan , Lu Ning , Yang Xiaohong R. 
Published: August 2019

Abstract
Background
Results from epidemiological studies are in support of heterogeneous relationships between body mass index (BMI) and breast cancer (BC) subtypes. Compared with luminal BC (LBC), pre-menopausal obesity is more frequently associated with triple-negative (TN) BC, while the converse has been reported for post-menopausal obesity. Given the dynamic range of hormone receptor expression in LBC, categorical combinations of immunohistochemical (IHC) markers for subtype definition may mask etiological heterogeneity within this subtype. Herein, we leveraged quantitative measures of tumor clinicopathological and IHC characteristics to define phenotypes of luminal BC and to assess relationships with BMI.
Methods
Participants were 6,412 women with invasive breast cancer who were diagnosed and treated in a tertiary hospital in Beijing, China between 2008-2016. We computed the Nottingham prognostic index (NPI)-score (based on tumor size, grade and lymph nodes) and IHC4-score (based on ER, PR, HER2 and KI67) and stratified LBC patients into four subgroups using quartiles of these scores: Lum-Q1 (least aggressive), Lum-Q2, Lum-Q3, and Lum-Q4 (most aggressive). Multinomial logistic regression models, adjusted for age, parity, menarcheal age, and family history, were used to test the associations between BMI [Kg/m2: underweight (&lt;18.5); normal (18.5-25); overweight (25-30); obesity (&gt;30)] and luminal subgroups, overall and by age categories (as proxy for menopausal status). We also included TNBC as a comparison group.
Results
The most aggressive LBC patients (Lum-Q4), defined by the NPI-score, were significantly more likely to be overweight [OR (95% CI) vs normal = 1.44 (1.12-1.86)] and obese [OR (95% CI) vs normal = 1.55 (0.98-2.46)] than the least aggressive LBC (Lum-Q1) patients, regardless of menopausal status. On the other hand, Lum-Q4 patients, defined by the IHC4-score, were significantly more likely to be underweight [OR (95% CI) vs normal = 2.21 (1.07-4.56)] in all women but less likely to be overweight [OR (95% CI) vs normal = 0.65 (0.50-0.85)] and obese [OR (95% CI) vs normal = 0.53 (0.35-0.82)] among post-menopausal women compared to Lum-Q1 patients (P-interaction (BMI & age) = 0.004). These associations were very similar to those when comparing TNBC to Lum-Q1 patients (defined by either NPI or IHC4 scores).
Conclusion
Aggressive phenotypes of LBC demonstrate associations with BMI that are analogous to TNBC. Discordant BMI associations with NPI and IHC4, and by menopausal status for the IHC4-score only, may be indicative of a positive association between excess adiposity and tumor clinicopathological parameters in the NPI-score, regardless of menopausal status. Conversely, its association with the IHC4-score may be driven by complex hormonal mechanisms that vary by menopausal status. Future analysis will focus on disentangling these relationships.
Citation Format: Mustapha Abubakar, Changyuan Guo, Hela Koka, Bin Zhou, Eric Tang, Joseph Deng, Nan Hu, Ning Lu, Xiaohong R. Yang. Aggressive phenotypes of luminal breast cancer demonstrate associations with body mass index analogous to triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 617.