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Figure.
Calcium Channel Blocker Use Over Time
Calcium Channel Blocker Use Over Time

Number of women per 100 000 who received prescribed calcium channel blockers (Anatomical and Therapeutic Chemical Classification code C08).

Table.  
Results From Logistic Regression Models
Results From Logistic Regression Models
1.
Anatomical therapeutic chemical classification system. World Health Organization Collaborating Centre for Drug Statistics Methodology website. http://www.whocc.no/. Accessed August 22, 2013.
2.
Li  CI, Daling  JR, Tang  MTC, Haugen  KL, Porter  PL, Malone  KE.  Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med. 2013;173(17):1629-1637.
PubMedArticle
3.
Coogan  PF.  Calcium-channel blockers and breast cancer: a hypothesis revived. JAMA Intern Med. 2013;173(17):1637-1638.
PubMedArticle
4.
National Board of Health and Welfare home page. Socialstyrelsen website. http://www.socialstyrelsen.se/english. Accessed March 12, 2013.
Research Letter
October 2014

Breast Cancer Risk and Use of Calcium Channel Blockers Using Swedish Population Registries

Author Affiliations
  • 1National Board of Health and Welfare in Sweden, Stockholm, Sweden
JAMA Intern Med. 2014;174(10):1700-1701. doi:10.1001/jamainternmed.2014.3867

Calcium channel blockers (CCBs), with Anatomical and Therapeutic Chemical Classification code C08,1 are frequently used for the treatment of cardiovascular disease, mostly hypertension. JAMA InternalMedicine recently published an article2 with a commentary3 showing that 10 years or more of exposure to CCBs is associated with an increased odds of developing breast cancer. Li et al2 also found a significant trend by length of exposure: less than 5.0 years, 5.0 to 9.9 years, and 10.0 or more years.

The Swedish National Board of Health and Welfare is a government agency under the Ministry of Health and Social Affairs.4 An important task is administration and epidemiologic analyses of national registries containing data on social welfare, health care, and causes of death. The collection of registry data is supported by Swedish legislation and it is mandatory for all practitioners to report data. Using these data we have replicated the study by Li et al2 by using population-based registries with high coverage.

Methods

The study was performed within the responsibilities of the National Board of Health and Welfare; therefore, no approval from outside ethical committees was needed. Women who received a diagnosis of breast cancer for the first time in 2011 were identified from the Swedish Cancer Registry. Five age-matched women serving as controls per case were selected from the Swedish Population Registry. The controls had no malignant or benign breast tumor or breast cancer in situ before 2011. Information about the women’s educational level and location of residence was identified from the Population Registry. The National Registry on Prescription Drugs started collecting information about prescribed drugs that were dispensed in July 2005, and the coverage has been thorough from 2006. We were therefore able to obtain information on prior use of CCBs only between January 1, 2006, and December 31, 2011. The population using CCBs was limited to individuals with at least 3 prescriptions during a year to ensure that exposure to the drug was continuous. The odds ratio (OR) of developing breast cancer was modeled using a logistic regression model controlling for age, educational level, location of residence, and history of cancer at sites other than the breast.

Results

The use of CCBs is increasing at a population level. In 2012, 130 per 100 000 women between ages 55 and 74 years used CCBs, compared with 104 per 100 000 in 2007 (Figure). These values indicate a 25% increase during that 5-year period.

From the Swedish Cancer Registry we identified 3583 women with incident breast cancer in 2011; of these, 3461 were either nonusers or continuous users of CCBs. Five age-matched controls were selected for each control, resulting in 17 915 women. Two analyses were performed. The first analysis evaluated the effect of 5 years (2006-2010) of continuous use of CCBs compared with no continuous use during those years. The second analysis evaluated the effect of different lengths of continuous use.

We found a nonsignificant OR of 1.1 after 5 years or more of exposure to CCBs. There was no clear trend in 1 to 5 years of exposure (Table).

Discussion

In this study we replicated the study by Li et al2 using population-based registries with high coverage. This is a cost-effective method and avoids bias arising from recruitment strategies of cases and controls. The results showed that 5 years of exposure to CCBs did not significantly increase the odds of developing breast cancer (OR, 1.1), which is similar to the effect after 5 to 9.9 years in the study by Li et al.2 However, because Li et al showed that long-term use (≥10 years) of CCBs may increase the odds of developing breast cancer, the Swedish National Board of Health and Welfare intends to continuously monitor the incidence of breast cancer in relationship to the use of CCBs.

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Article Information

Accepted for Publication: December 10, 2013.

Corresponding Author: Gudrun Jonasdottir Bergman, PhD, National Board of Health and Welfare in Sweden, Socialstyrelsen, SE-10630 Stockholm, Sweden (gudrun.jonasdottir-bergman@socialstyrelsen.se).

Published Online: August 18, 2014. doi:10.1001/jamainternmed.2014.3867.

Author Contributions: Dr Jonasdottir Bergman had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Jonasdottir Bergman, Danielsson, Borg.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Jonasdottir Bergman, Borg.

Critical revision of the manuscript for important intellectual content: Khan, Danielsson, Borg.

Statistical analysis: Jonasdottir Bergman.

Administrative, technical, or material support: Jonasdottir Bergman, Khan, Danielsson.

Study supervision: Jonasdottir Bergman, Danielsson, Borg.

Conflict of Interest Disclosures: None reported.

Additional Contributions: Magnus Stenbeck, PhD, Maarten Sengers, MSc, and Johan Fastbom, PhD, proofread the manuscript and contributed to the discussion regarding the results, and Helena Schiöler, MSc, helped to extract data from the national registry of prescription drugs. All are colleagues at the National Board of Health and Welfare in Sweden. There was no financial compensation.

References
1.
Anatomical therapeutic chemical classification system. World Health Organization Collaborating Centre for Drug Statistics Methodology website. http://www.whocc.no/. Accessed August 22, 2013.
2.
Li  CI, Daling  JR, Tang  MTC, Haugen  KL, Porter  PL, Malone  KE.  Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med. 2013;173(17):1629-1637.
PubMedArticle
3.
Coogan  PF.  Calcium-channel blockers and breast cancer: a hypothesis revived. JAMA Intern Med. 2013;173(17):1637-1638.
PubMedArticle
4.
National Board of Health and Welfare home page. Socialstyrelsen website. http://www.socialstyrelsen.se/english. Accessed March 12, 2013.
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