Identification of modifiable risk factors in the pursuit of preventing cancer has become an increasingly popular area of research. Common risk factors of interest include environmental exposures, diet, and certain medications.  One category of medication that has been of interest is antihypertensives. 

In the past, there have been some conflicting studies on the connection between antihypertensives and the increased risk of cancer.  Recently, a case control study published by Li et al, attempted to further clarify the association between several different antihypertensive medications and breast cancer.1 

This particular study focused on two common forms of breast cancer, invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), in women between the ages of 55 and 74 years in the Seattle, WA area. The different types of blood pressure medications included were diuretics (Related Clinical Chart: Diuretics for Hypertension), beta blockers (BBs), angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs). 


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CCBs were further categorized into short- and long-acting, as well as dihydropyridine (DHP) and non-DHP.  Both type and duration of use of each antihypertensive were used when comparing the two different types of breast cancer with the control group. 

Patients who were taking any form of CCB for more than 10 years were the only group to have an increased risk for IDC (odds ratio [OR], 2.4; 95% CI: 1.2-4.9; P=0.04) and ILC (OR, 2.6; 95% CI: 1.3-5.3; P=0.01).  There was no major difference within the breast cancer groups regarding estrogen receptor (ER) status in these patients receiving CCB for more than 10 years.

ACEI use for more than 10 years showed a trend towards decreased risk of IDC (OR, 0.7; 95% CI: 0.5-1.2) and ILC (OR, 0.6; 95% CI: 0.4-1.0), although it was not statistically significant.  None of the other antihypertensive agents were found to have a significant increased risk of IDC or ILC regardless of their duration of use.

Why are CCBs different? There are several proposed mechanisms that may explain how CCBs play a role in cancer.  Cellular apoptosis can be initiated through voltage-gated calcium channels, which may be blocked by CCBs.2  Inhibition of apoptosis could potentially lead to prolonged survival of carcinogenic cells that had previously been “programmed” to undergo destruction. 

In addition to this mechanism, the influx of calcium within the cell also contributes to cellular differentiation, which may be inhibited by CCBs.  Therefore, CCBs would not necessarily be considered carcinogens themselves, but rather have pro-oncogenic properties within the cell cycle and signal transduction. 

As with many clinical studies analyzing the oncogenic potential of medications, additional data is needed before definitive statements and recommendations can be made.  While this data is still accumulating, it is worthwhile to be cognizant of the type of medication and length of time it is being used, regardless of the specific medical problem for which they are being treated.  Studies such as these are often mentioned in the media, undoubtedly sparking questions from the patient.


References

1. Li CI, Daling JR, Tang MT C, et al. Use of Antihypertensive Medications and Breast Cancer Risk Among Women Aged 55 to 74 Years. JAMA Intern Med. 2013 Aug 5. doi: 10.1001/jamainternmed.2013.9071

2. Pahor M, Guralnik JM, Salive ME, et al. Do calcium channel blockers increase the risk of cancer? Am J Hypertens. 1996;9(7):695.