Abstract PD5-03: Development of cardiometabolic risk factors following endocrine therapy: The pathways heart study
Authors: Greenlee Heather , Rillamas-Sun Eileen , Iribarren Carlos , Cheng Richard , Neugebauer Romain , Rana Jamal S. , Nguyen-Huynh Mai , Shi Zaixing , Laurent Cecile A. , Lee Valerie S. , Roh Janise M. , Shen Hanjie , Hershman Dawn L. , Kushi Lawrence H. , Kwan Marilyn L. 
Published: March 2022

Purpose: Endocrine therapy is associated with cardiovascular disease among breast cancer (BC) survivors, with observed opposing effects between aromatase inhibitors (AIs) and tamoxifen. AIs deplete endogenous estrogen levels, while tamoxifen has mixed estrogenic and antiestrogenic activity. Yet, observational studies comparing AI vs. tamoxifen use may be confounded by indication and few have tested their associations with cardiometabolic risk factors. Therefore, we examined the association of AI or tamoxifen use on the incidence of newly diagnosed hypertension, diabetes, and dyslipidemia in a cohort of BC survivors within Kaiser Permanente Northern California (KPNC). Methods: The Pathways Heart Study is an ongoing cohort study within KPNC examining incident CVD outcomes and risk factors in 14,942 women with history of BC. Eligibility was: 1) stage I-IV invasive BC diagnosis between Nov 2005 and Mar 2013; 2) &ge;21 years; and 3) active KPNC membership &ge;12 months at diagnosis. KPNC records were used to collect demographic, socioeconomic, and health characteristics. Endocrine therapy was collected from outpatient pharmacy data. Incident hypertension, diabetes, and dyslipidemia were identified from ICD-9/10 codes, laboratory results, and/or medication use. Hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional models were used to determine whether AI and tamoxifen use were associated with incident hypertension, diabetes, and dyslipidemia compared to BC survivors not receiving either of these therapies. For each cardiometabolic risk factor, models adjusted for demographic, socioeconomic, and health characteristics and excluded women with the cardiometabolic risk factor at baseline. Results: Among 14,942 women with a history of BC, mean age at baseline was 61.2±12.8 years and mean follow-up time was 7.0±3.5 years (range 1-13.4). The frequency of use was: AI, n=6,070 (40.6%); tamoxifen, n=1,755 (11.8%); and neither, n=7,117 (47.6%). Regression models showed AI use was associated with increased risk of incident hypertension (HR: 1.1, 95% CI: 1.00-1.21) and increased risk of incident dyslipidemia (HR: 1.18, 95% CI: 1.07-1.3) relative to BC survivors who did not use endocrine therapy. (Table). In contrast, tamoxifen use was associated with decreased risk of dyslipidemia (HR: 0.8, 95% CI: 0.68-0.94) relative to BC survivors who did not use endocrine therapy. Neither AI nor tamoxifen use was associated with risk of incident diabetes. Conclusion: Compared to BC survivors who did not use endocrine therapy, women treated with AIs had a higher risk of incident hypertension and dyslipidemia, while women treated with tamoxifen had a lower risk of dyslipidemia. AIs reduce endogenous estrogen levels, which can alter lipid profiles, although prior studies have been inconsistent, possibly due to differences in steroidal and non-steroidal AIs. More work is needed to understand the implications of these associations on long-term cardiovascular health and how to best manage cardiometabolic risk factors in BC survivors with a history of endocrine therapy use.

Table. Adjusted1 hazard ratios (95% confidence intervals) of incident cardiometabolic risk factors among women with a history of breast cancer, by endocrine therapy useNo Endocrine Therapy(n=7,117)Endocrine TherapyAromatase inhibitor(n=6,070)Tamoxifen(n=1,755)Incident HypertensionRef1.10 (1.00, 1.21)0.98 (0.85, 1.14)Incident DiabetesRef0.99 (0.87, 1.13)0.98 (0.80, 1.20)Incident DyslipidemiaRef1.18 (1.07, 1.30)0.80 (0.68, 0.94)1Adjusted for age, race/ethnicity, baseline body mass index, AJCC stage, menopausal status, smoking status, education level, income, chemotherapy, radiation therapy, and prevalent cardiovascular disease.

Citation Format: Heather Greenlee, Eileen Rillamas-Sun, Carlos Iribarren, Richard Cheng, Romain Neugebauer, Jamal S. Rana, Mai Nguyen-Huynh, Zaixing Shi, Cecile A. Laurent, Valerie S. Lee, Janise M. Roh, Hanjie Shen, Dawn L. Hershman, Lawrence H. Kushi, Marilyn L. Kwan. Development of cardiometabolic risk factors following endocrine therapy: The pathways heart study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-03.