Abstract PD4-07: Are aromatase inhibitors associated with higher myocardial infarction risk in breast cancer patients? A Medicare population study
Authors: Kamaraju S , Smith E , Shi Y , Laud P , Neuner J 
Published: March 2017

Purpose: Aromatase Inhibitors (AIs) are the current standard of care for post-menopausal adjuvant endocrine breast cancer therapy either following or in place of tamoxifen. While their short-term side effect profile was favorable in most studies, findings were mixed regarding cardiotoxicity, and cardiac outcome definitions were not consistent across studies. Given the five or more year duration of adjuvant endocrine therapy, risk of cardiotoxicity in older patients with pre-existing comorbidities remains a particular concern. We examined Myocardial Infarction (MI) as the cardiac outcome in subjects who received AIs vs. tamoxifen in a cohort of Medicare-based breast cancer survivors.

Patients and Methods: We identified women age ≥ 67 years diagnosed with breast cancer from 6/30/2006 to 6/01/2008 in the Surveillance, Epidemiology, and End Results-Medicare (SEER) database , with the following eligibility criteria: stage I-III breast cancer, continuous enrollment in Medicare Parts A and B for 24 months prior to the diagnosis and Part D enrollment for one month after the breast cancer diagnosis to the end of follow up (12/31/2012), adjuvant endocrine therapy (tamoxifen or AI fill) within 12 months after diagnosis. The main study outcome was the time to first diagnosis of MI after initiation of AIs or tamoxifen. MI was defined precisely by ICD9 and ICD10 codes relating both to incidence and death from MI. We developed and assigned stabilized inverse proportion weights to balance the groups, and performed a Fine and Gray hazards model for the outcomes of MI and death for the treatment groups of AIs vs tamoxifen.

Results: Of the cohort of 5,648 women, 4,690 were treated with AIs and 958 with tamoxifen; a total of 251 patients developed and/or died of MI during the study period while 476 died of other causes. The Fine and Gray Model results in a hazard ratio (HR) were not significantly different from one for weighted AI vs Tamoxifen groups [HR=1.01, C.I. 0.72-1.42]. Covariates which significantly affected the risk of MI were previous diabetes, prior other heart disease, prior congestive heart failure, prior MI, and prior peripheral vascular disease. Other covariates included in the weighted model, were age, American Joint Committee on Cancer (AJCC) cancer stage, chemo, Estrogen and progesterone receptor status, low income subsidy, marital status, prior hypertension, prior stroke, per capita income, race, radiation, SEER region, and urbanization.

Conclusions: The occurrence of MI is very low in this cohort (4.4%), reassuring the clinicians that the older adults with comorbidities may not be at a higher risk of MI with adjuvant endocrine therapy. However, the confidence interval for the hazard ratio of AIs vs Tamoxifen is very wide, indicating that a larger sample may be needed for the power of the study to be conclusive.

Citation Format: Kamaraju S, Smith E, Shi Y, Laud P, Neuner J. Are aromatase inhibitors associated with higher myocardial infarction risk in breast cancer patients? A Medicare population study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD4-07.