Risk of Breast Cancer With Long-term Use of Calcium Channel Blockers or Angiotensin-Converting Enzyme Inhibitors Among Older Women

Marsha A. Raebel; Chan Zeng; T. Craig Cheetham; David H. Smith; Heather Spencer Feigelson; Nikki M. Carroll; Kristin Goddard; Heather M. Tavel; Denise M. Boudreau; Susan Shetterly; Stanley Xu

Disclosures

Am J Epidemiol. 2017;185(4):264-273. 

In This Article

Abstract and Introduction

Abstract

Controversy exists about breast cancer risk associated with long-term use of calcium channel blockers (CCBs) or angiotensin-converting enzyme inhibitors (ACEis), respectively. Our objective in this study was to separately evaluate associations between duration of CCB or ACEi use and breast cancer in hypertensive women aged ≥55 years at 3 sites in the Kaiser Permanente health-care system (1997–2012). Exposures included CCB or ACEi use of 1–12 years' duration, determined from pharmacy dispensings. Outcomes included invasive lobular or ductal carcinoma. Statistical methods included discrete-time survival analyses. The cohort included 19,674 (17.9%) CCB users and 90,078 (82.1%) ACEi users. Two percent (n = 397) of CCB users and 1.9% (n = 1,733) of ACEi users developed breast cancer. Compared with 1–<2 years of use, in adjusted analysis, there was no association between CCB use for 2–<12 years and breast cancer: All 95% confidence intervals included 1. Increasing duration of ACEi use was associated with reduced breast cancer risk: Compared with 1–<2 years of use, the adjusted hazard ratio was 0.76 (95% confidence interval: 0.63, 0.92) for 5–<6 years of use and 0.63 (95% confidence interval: 0.43, 0.93) for 9–<10 years of use. We conclude that among older women with hypertension, long-term CCB use does not increase breast cancer risk and long-term treatment with ACEis may confer protection against breast cancer.

Introduction

Controversy exists about whether antihypertensive agents are associated with breast cancer in women, particularly whether long-term use of calcium channel blockers (CCBs) is associated with increased risk and whether long-term use of angiotensin-converting enzyme inhibitors (ACEis) is associated with decreased risk.[1–10] Most previous studies of antihypertensive agents and breast cancer have had key limitations, including the facts that duration of CCB or ACEi use was not assessed, few women with many years of use were studied, use was determined from self-reports, and/or concomitant use of antihypertensive medications was not considered.[1–9,11]

There are important implications if alterations in breast cancer risk with long-term CCB or ACEi use are confirmed.[12] In the United States, breast cancer is the most commonly occurring cancer in women and the second-leading cause of cancer death.[13] Additionally, ACEis and CCBs both rank among the top classes of medications prescribed in the United States.[14]

The primary objective of this study was to assess risk of incident invasive breast cancer in a large cohort of women with varying durations of CCB or ACEi use. Specifically, we separately evaluated associations across discrete durations of CCB or ACEi use of 1–12 years and then, as a secondary objective, we compared risks between groups. To evaluate these associations, we employed comprehensive electronic health record, administrative, medication dispensing, and tumor data from older women with hypertension enrolled in a large integrated health-care delivery system.

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