To further control for potential confounding, we compared CCB exposure with use of any other anti-hypertensive medication (AHM). Materials and Methods Study population Information about the WHI methods have been published (3). results from this study, which includes strong control for potential confounding factors, cast doubt on increases in risk with CCBs. Introduction The use of calcium channel blockers (CCBs) has been recently been found to be associated with increased risk of breast cancer (1, 2), although inconsistently. The inconsistency may be due to differences inherent in study design, or inadequately controlled confounding, including factors related to prescription for CCBs. Indeed, a number of important risk factors are shared between hypertension and breast cancer, making interpretation of results from studies that do not restrict to hypertensive women challenging. Given the high prevalence of CCB use and their hypothesized potential to disrupt apoptotic pathways, additional high-quality prospective data are needed. Here Cetirizine Dihydrochloride we examine the association between CCB use and breast cancer risk in the Womens Health Initiative (WHI), a large cohort of postmenopausal women. To further control for potential confounding, we compared CCB exposure with use of any other anti-hypertensive medication (AHM). Materials and Methods Study population Information about the WHI methods have been published (3). From 1993C1998, 161,808 postmenopausal women, ages 50C79 years, were recruited into an observational study (OS) and one or more clinical trials (CT). Women were followed to 2005 and, via an extension study, to 2010. For the present analysis, we excluded at baseline women who: had prevalent breast cancer (n=5,551); did not self-report a history of hypertension (n=95,530), were non-users of CCBs or other AHM (n=26,840) or who used CCBs in combination with other AHM (n=5,325) or were missing these data (n=1); leaving n=28,561 for analysis. Data collection Participants attended baseline screening visits, during which they completed extensive baseline questionnaires. Height and weight were measured by Rabbit polyclonal to nephrin clinical staff. In-person medication inventories were obtained by review of participants pill containers at baseline and year 3 in the OS and additionally in years 1, 6, and 9 in the CT. CCBs were sub-classified into dihydropyridines or non-dihydropyridines and short-acting or long-acting. Duration of medication use was categorized as 5 years, 5C9.9 years, and 10 years. Other AHM data (including diuretics, ACE inhibitors, adrenergic receptor antagonists, angiotensin II receptor antagonists, renin inhibitors, and vasodilators) were obtained in an identical manner. Case ascertainment Incident, first-primary, invasive breast cancers were self-reported annually in the OS and semi-annually in the CT until 2005 and annually thereafter. Cases were confirmed by medical record review by physician-adjudicators. After a median follow-up of 12.7 years, 1,402 invasive breast cancers were identified. Breast cancer subtypes, defined here as joint expressions of ER, PR, and HER2, were abstracted from medical records. Statistical analyses Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between baseline CCB and breast cancer risk relative to other AHM. Categories of CCB duration were compared to the same categories of other AHM in regression models. Regression models were adjusted for breast cancer risk factors thought to potentially confound associations and CT randomization. We performed several sensitivity analyses: 1) in the WHI-CT, CCB and other AHM use were treated as time-varying in regression models; 2) We additionally examined associations of CCB use versus non-use (n=156,255) in the larger WHI cohort (including women hypertension; n=156,255) in order to compare our findings with others that did not account for confounding by shared risk factors. Results Despite their statistical significance, differences by medication for participants baseline characteristics were small (Table 1). Compared to other AHM use, CCB use was not associated with breast cancer risk (HR 1.06, 95% CI: 0.94C1.20) (Table 2). No associations were observed when CCB use was stratified by length of action or drug class. When cancers were stratified on molecular subtype.Associations approximated the null value when CCBs were considered by duration of use, length of action, or drug class. Conclusions We provide additional evidence that CCBs do not influence breast cancer risk in postmenopausal women. Impact The results from this study, which includes strong control for potential confounding factors, cast doubt on increases in risk with CCBs. Introduction The use of calcium channel blockers (CCBs) has been recently been found to be associated with increased risk of breast cancer (1, 2), although inconsistently. to be associated with increased risk of breast cancer (1, 2), although inconsistently. The inconsistency may be due to differences Cetirizine Dihydrochloride inherent in study design, or Cetirizine Dihydrochloride inadequately controlled confounding, including factors related to prescription for CCBs. Indeed, a number of important risk factors are shared between hypertension and breast cancer, making interpretation of results from studies that do not restrict to hypertensive women challenging. Given the high prevalence of CCB use and their hypothesized potential to disrupt apoptotic pathways, additional high-quality prospective data are needed. Here we examine the association between CCB use and breast cancer risk in Cetirizine Dihydrochloride the Womens Health Initiative (WHI), a large cohort of postmenopausal women. To further control for potential confounding, we compared CCB exposure with use of any other anti-hypertensive medication (AHM). Materials and Methods Study population Information about the WHI methods have been published (3). From 1993C1998, 161,808 postmenopausal women, ages 50C79 years, were recruited into an observational study (OS) and one or more clinical trials (CT). Women were followed to 2005 and, via an extension study, to 2010. For the present analysis, we excluded at baseline women who: had prevalent breast cancer (n=5,551); did not self-report a history of hypertension (n=95,530), were non-users of CCBs or other AHM (n=26,840) or who used CCBs in combination with other AHM (n=5,325) or were missing these data (n=1); leaving n=28,561 for analysis. Data collection Participants attended baseline screening visits, during which they completed extensive baseline questionnaires. Height and weight were measured by clinical staff. In-person medication inventories were obtained by review of participants pill containers at baseline and year 3 in the OS and additionally in years 1, 6, and 9 in the CT. CCBs were sub-classified into dihydropyridines or non-dihydropyridines and short-acting or long-acting. Duration of medication use was categorized as 5 years, 5C9.9 years, Cetirizine Dihydrochloride and 10 years. Other AHM data (including diuretics, ACE inhibitors, adrenergic receptor antagonists, angiotensin II receptor antagonists, renin inhibitors, and vasodilators) were obtained in an identical manner. Case ascertainment Incident, first-primary, invasive breast cancers were self-reported annually in the OS and semi-annually in the CT until 2005 and annually thereafter. Cases were confirmed by medical record review by physician-adjudicators. After a median follow-up of 12.7 years, 1,402 invasive breast cancers were identified. Breast cancer subtypes, defined here as joint expressions of ER, PR, and HER2, were abstracted from medical records. Statistical analyses Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between baseline CCB and breast cancer risk relative to other AHM. Categories of CCB duration were compared to the same categories of other AHM in regression models. Regression models were adjusted for breast cancer risk factors thought to potentially confound associations and CT randomization. We performed several sensitivity analyses: 1) in the WHI-CT, CCB and other AHM use were treated as time-varying in regression models; 2) We additionally examined associations of CCB use versus non-use (n=156,255) in the larger WHI cohort (including women hypertension; n=156,255) in order to compare our findings with others that did not account for confounding by shared risk factors. Results Despite their statistical significance, differences by medication for participants baseline characteristics were small (Table 1). Compared to other AHM use, CCB use was not associated with breast cancer risk (HR 1.06, 95% CI: 0.94C1.20) (Table 2). No associations were observed when CCB use was stratified by length of action or drug class. When cancers were stratified on molecular subtype defined by ER, PR, and HER-2, CCB use was associated with elevated risk of triple-negative breast cancers (HR 1.60, 95% CI: 1.04C2.48). In the sensitivity analysis, time-varying CCB use was also not associated with breast cancer risk (HR 0.99, 95% CI: 0.78C1.26). When CCB use was contrasted against non-use (thus, insufficiently controlling for shared hypertension/breast cancer risk factors; n=156,255), associations were elevated (HR 1.30, 95% CI: 0.84C2.02). When we restricted the comparison to women who reported prevalent hypertension (n=60,726; HR 1.08, 95% CI: 0.98C1.18) and who used 1 AHM (n=33,886; HR 1.08, 95% CI: 0.98C1.20) the association was attenuated. Table 1 Distribution of selected baseline characteristics of WHI participants by baseline CCB use, as compared.