Diuretic use and the risk of breast cancer

Some antihypertensive medications, particularly calcium channel blockers, have been associated with breast cancer risk, although the evidence is inconsistent. Diuretics comprise the antihypertensive drug class with the longest record of use and are one of the most commonly used drug classes in the United States, yet have received less study than other antihypertensive classes. We have assessed the relation of diuretic use to the risk of invasive breast cancer using 30 years of data from our ongoing hospital-based case–control surveillance study. We used data collected from patients admitted to collaborating hospitals in Boston, New York, Philadelphia and Baltimore from 1976 through 2007. Since 1997, the study has been conducted solely in Philadelphia. The population base for the study comprised people living in zip codes within 50 miles of a participating hospital. Eligible patients were aged 18–79 years, were under the care of a physician participating in the study, were able to complete the interview (for example, not deaf) and did not have certain excluded diagnoses (for example, psychiatric). Nurse interviewers administered standard questionnaires to obtain information on demographic factors, medical and reproductive history, and lifestyle factors. Histories of medication use were elicited by asking about 43 indications for use that included those for which diuretics are used (for example, fluid retention, heart conditions). For each episode of use, the drug name and the duration, timing and frequency of use were recorded. Details of the diagnosis were abstracted from discharge summaries and pathology reports. From 1976 through 1997, 95% of patients approached for an interview participated. Since 1998, 84% of patients have participated. The study was approved by the institutional review boards of all participating institutions. Cases comprised 5989 women aged 22–79 years diagnosed with invasive breast cancer in the year prior to hospital admission, with no prior or concurrent cancers other than non-melanoma cancer of the skin. Controls were frequency matched to the cases on age in 5-year intervals, interview year in five categories and study centre, in a ratio of up to 4:1. Because there was a surplus of younger controls and a deficit of older controls, the control/case ratio of 4:1 was achieved in the younger age categories and cases outnumbered controls in the older age categories. Controls included 5504 women admitted to the hospital with diagnoses that we judged to be unrelated to diuretic use: trauma and infection (40%), arthritis and musculoskeletal disorders (23%), gastrointestinal disorders (19%) and miscellaneous (18%) (for example, thyroid disorders, skin conditions). Controls were aged 22–79 years and had no history of cancer other than non-melanoma cancer of the skin. We classified diuretics into three groups: (1) thiazide-containing drugs (for example, hydrochlorothiazide, chlorthalizone, triamterene plus hydrocholorthiazide), (2) potassium-sparing diuretics that did not contain thiazide (for example, triamterene, spironolactone) and (3) loop diuretics (for example, furosemide, bumetanide). We classified regular diuretic use as use for at least four times per week for at least three continuous months. All other use was classified as sporadic use. Diuretic use that began within the year prior to hospital admission is unlikely to have aetiologic relevance and women whose only use began during the year before admission were excluded. The regular use considered in these analyses consisted of use begun at least one year before admission; the reference category was no diuretic use of any kind. We used logistic regression models to estimate odds ratios and 95% confidence intervals (CIs) for various categories of diuretic use as compared to no use. We present odds ratios from a multivariate model, including covariates that were associated with the regular use of all diuretics combined among controls: race, years of education, menopausal status, parity, body mass index (kg/m), use of female hormones, use of oral contraceptives and alcohol use. Adjustment for age at first birth, age at menarche, age at menopause and family history of breast cancer did not materially change the effect estimates. Test for trend in the odds ratios over duration of use was assessed by including duration as a continuous variable. The odds ratios among regular users of any category of diuretic did not significantly differ from 1.0 (Table 1): adjusted odds ratios were 0.98 (95% CI 0.86–1.12) for use of any diuretic, 1.06 (95% CI 0.92–1.22) for thiazide diuretics, 0.77 (95% CI 0.58– 1.01) for loop diuretics and 1.22 (95% CI 0.61–2.46) for potassium-sparing diuretics. Adjusted odds ratios for duration categories of up to 15 or more years were all consistent with 1.0 and there was no trend in duration for any diuretic class. Results were similar using subgroups of controls. Journal of Human Hypertension (2009) 23, 216–218 & 2009 Macmillan Publishers Limited All rights reserved 0950-9240/09 $32.00