Relationship between histamine2-receptor antagonist medications and risk of invasive breast cancer

BACKGROUND: Histamine(2)-receptor antagonist (H(2) blocker) medications are used to treat heartburn, gastroesophageal reflux disease, and ulcers. Some H(2) blockers, specifically cimetidine and ranitidine, also increase serum prolactin concentrations. Given the positive relationship between prolactin levels and postmenopausal breast cancer risk, use of H(2) blockers is a potential breast cancer risk factor. The few previous studies evaluating this association have been null but have been limited by small sample sizes, and none have evaluated risk by either histologic type or estrogen receptor/progesterone receptor status. METHODS: Combining data from two population-based case-control studies conducted in western Washington, we assessed the relationship between use of H(2) blockers and risk of different types of breast cancer among 1,941 cases and 1,476 controls 55 to 79 years old. Odds ratios and 95% confidence intervals (95% CI) were calculated using polytomous logistic regression. RESULTS: Current use of H(2) blockers overall, cimetidine, and famotidine was not associated with an increased risk of either invasive ductal or invasive lobular breast cancer. Current users of ranitidine had a 2.2-fold (95% CI, 1.1-4.3) increased risk of ductal carcinoma that was confined to a 2.4-fold (95% CI, 1.2-4.9) increased risk of estrogen receptor-positive/progesterone receptor-positive ductal carcinoma. CONCLUSIONS: Use of H(2) blockers in general is not associated with an increased risk of breast cancer, although current use of ranitidine may increase risk of hormone receptor-positive ductal carcinoma. Further studies to confirm this finding are warranted.     

A case-control study of analgesic use and ovarian cancer.

A recent case-control study raised the hypothesis that acetaminophen use 1 day or more per week for at least 6 months reduces the risk of epithelial ovarian cancer. We assessed analgesic use in relation to epithelial ovarian cancer risk using data from our case-control surveillance study of medication use and cancer. Patients were interviewed in hospitals in Baltimore, Boston, New York, and Philadelphia during 1976-1998. We compared 780 women with epithelial ovarian cancer to 2053 cancer controls and 2570 noncancer controls. For acetaminophen use 1 day or more per week for at least 6 months, the odds ratio estimate was 0.9 (95% confidence interval, 0.6-1.4) derived with cancer controls and 1.0 (0.6-1.5) with noncancer controls. Estimates for more frequent and longer term use were also compatible with 1.0. The odds ratios among patients with metastatic ovarian cancer were reduced but not statistically significant. The odds ratio for use of nonsteroidal anti-inflammatory drugs 4 or more days per week for at least 5 years, 0.5, was statistically significant. The present results provide only weak support for a reduction in the risk of epithelial ovarian cancer among acetaminophen users. They raise the possibility of an inverse association with long-term nonsteroidal anti-inflammatory drug use.     

Inverse association between prostate cancer and the use of calcium channel blockers.

Calcium channel blockers block calcium signal-mediated apoptosis. It is hypothesized that the use of these drugs may be associated with the development of cancer. This study investigated the association between daily use of calcium channel blockers and prostate cancer in a community-based cohort of men who participated in a longitudinal study of lower urinary tract symptoms. Study subjects were men ages 40 to 79 years by January 1, 1990, and were randomly selected from Olmsted County in Minnesota. At baseline, participants underwent an interview to determine all medications taken on a daily basis, including calcium channel blockers and to elicit a family history of prostate cancer. During follow-up, all men with a histological diagnosis of prostate cancer were identified through patient self-report and by a review of the complete medical record. Over 12,668 person years of follow-up, 15 (6.8%) of 220 calcium channel blocker users and 120 (10.5%) of 1142 nonusers developed prostate cancer (P = 0.09; odds ratio, 0.62; 95% confidence interval, 0.36-1.10). With adjustment for age and family history of prostate cancer, the risk (odds ratio, 95% confidence interval) of prostate cancer was 0.55 (0.31-0.97) in calcium channel blocker users compared with nonusers. In analyses stratified by family history of prostate cancer, the risk of prostate cancer was 0.45 (0.23-0.88) in men without a family history and 2.64 (0.82-8.47) in men with a family history of prostate cancer (P = 0.006). These findings suggest an association between prostate cancer and daily use of calcium channel blockers that varies by family history of prostate cancer.     

Use of mobile phones in Norway and risk of intracranial tumours.

To test the hypothesis that exposure to radio-frequency electromagnetic fields from mobile phones increases the incidence of gliomas, meningiomas and acoustic neuromas in adults. The incident cases were of patients aged 19-69 years who were diagnosed during 2001-2002 in Southern Norway. Population controls were selected and frequency-matched for age, sex, and residential area. Detailed information about mobile phone use was collected from 289 glioma (response rate 77%), 207 meningioma patients (71%), and 45 acoustic neuroma patients (68%) and from 358 (69%) controls. For regular mobile phone use, defined as use on average at least once a week or more for at least 6 months, the odds ratio was 0.6 (95% confidence interval 0.4-0.9) for gliomas, 0.8 (95% confidence interval 0.5-1.1) for meningiomas and 0.5 (95% confidence interval 0.2-1.0) for acoustic neuromas. Similar results were found with mobile phone use for 6 years or more for gliomas and acoustic neuromas. An exception was meningiomas, where the odds ratio was 1.2 (95% confidence interval 0.6-2.2). Furthermore, no increasing trend was observed for gliomas or acoustic neuromas by increasing duration of regular use, the time since first regular use or cumulative use of mobile phones. The results from the present study indicate that use of mobile phones is not associated with an increased risk of gliomas, meningiomas or acoustic neuromas.     

NSAIDs and risk of colorectal cancer according to presence or absence of family history of the disease

Background:We undertook the present analyses to determine whether family history of colorectal cancer in a parent or sibling modifies the inverse association of nonsteroidal anti-inflammatory drug (NSAID) use with colorectal cancer risk. Methods:We used data from two case–control studies of colorectal cancer. The hospital-based Case Control Surveillance Study included 1526 patients with primary colorectal cancer, 4192 cancer controls and 6036 noncancer controls. A population-based study conducted in Massachusetts enrolled 1201 incident cases of colorectal cancer and 1201 community controls. Data on NSAID use and risk factors for colorectal cancer were collected by interview. Results:In both studies there was a reduction in the odds ratios among subjects who used NSAIDs regularly continuing into the previous year, regardless of family history. In the Case–Control Surveillance data, the odds ratio was 0.4 (95% CI 0.2–0.9) among subjects with a family history and 0.5 (95% CI 0.4–0.7) among subjects without a family history. The comparable odds ratios in the Massachusetts data were 0.5 (95% CI 0.3–0.9) and 0.7 (95% CI 0.6–0.9). Conclusions:These data indicate that regular continuing NSAID use is associated with a reduced risk of colorectal cancer among persons with a family history of the disease, as well as those without such a history.     

Beta blocker use and colorectal cancer risk: population-based case-control study

BACKGROUND:

Recently, it has been postulated that long‐term use of beta blockers might decrease the risk of certain types of cancer because of weakening of norepinephrine signaling. Previous studies on colorectal cancer (CRC) yielded inconsistent results, but lacked information on covariates. Thus, the authors investigated the association of beta blocker use and CRC risk in a large population‐based case‐control study (DACHS study).

METHODS:

Between 2003 and 2007, information on beta blocker use and potential confounders was collected by personal interviews for 1762 CRC cases and 1708 control individuals from Germany. The association of CRC risk and beta blocker use and subclasses of beta blockers was estimated by multiple logistic regression. In addition, site‐ and stage‐specific analyses were performed.

RESULTS:

After adjustment for covariates, no association was observed with beta blocker use (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.86‐1.29) or with duration of beta blocker use. Also, the analysis by subclasses of beta blockers (cardioselectivity) and active ingredients (metoprolol, bisoprolol, carvedilol, and atenolol) or by CRC subsite showed no associations. In stage‐specific analyses, long‐term beta blocker use (6+ years) was associated with a significantly higher risk of stage IV CRC (OR, 2.02; 95% CI, 1.25‐3.27).

CONCLUSIONS:

Our adjusted results do not support the hypothesis that beta blocker use is associated with decreased risk of CRC. In contrast, we found a positive association of long‐term beta blocker use and risk of stage IV CRC. The latter result should be further evaluated in future studies. Cancer 2012.© 2012 American Cancer Society.     

Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer.

PURPOSE: Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles. Previous studies of the BRCA2 N372H polymorphism suggested that HH homozygotes have a modestly increased risk of both breast and ovarian cancer. We have examined whether BRCA2 N372H or common amino acid-changing polymorphisms in BRCA1 predispose to ovarian cancer. EXPERIMENTAL DESIGN: A population-based, case control study of ovarian cancer was performed in North Carolina. Cases included 312 women with ovarian cancer (76% invasive and 24% borderline) and 401 age- and race-matched controls. Blood DNA from subjects was genotyped for BRCA2 N372H and BRCA1 Q356R and P871L. RESULTS: There was no association between BRCA2 N372H and risk of borderline or invasive epithelial ovarian cancer. The overall odds ratio (OR) for HH homozygotes was 0.8 [95% confidence interval (CI) = 0.4-1.5] and was similar in all subsets, including invasive serous cases. In addition, neither the BRCA1 Q356R (OR = 0.9, 95% CI 0.5-1.4) nor P871L (OR = 0.9, 95% CI 0.6-1.9) polymorphisms were associated with ovarian cancer risk. There was a significant racial difference in allele frequencies of the P871L polymorphism (P = 0.64 in Caucasians, L = 0.76 in African-Americans, P < 0.0001). CONCLUSIONS: In this population-based, case control study, common amino acid changing BRCA1 and 2 polymorphisms were not found to affect the risk of developing ovarian cancer.     

Transitional cell cancer of the urinary tract and renal cell cancer in relation to acetaminophen use (United States)

Experimental and epidemiologic evidence have suggested that phenacetin use increases the risk of transitional cell cancers of the urinary tract. The drug is no longer marketed but a commonly used metabolite, acetaminophen, has been linked recently to an increased risk of renal cancer. We assessed the relation of acetaminophen use to the risk of transitional cell cancer of the urinary tract and of renal cell cancer with data from a hospital-based study of cancers and medication use conducted from 1976-96 in the eastern United States. We compared 498 cases of transitional cell cancer and 383 cases of renal cell cancer with 8,149 noncancer controls and 6,499 cancer controls and controlled confounding factors with logistic regression. For transitional cell cancer, the relative risk (RR) estimate for regular acetaminophen use that had begun at least a year before admission was 1.1 (95 percent confidence interval [CI] = 0.6-1.9) based on noncancer controls, and 0.9 (CI = 0.5-1.6) based on cancer controls. RR estimates for use that lasted at least five years, and for nonregular use, were also close to 1.0. For renal cell cancer, the corresponding estimates were again close to 1.0. Our results suggest that acetaminophen, as used in present study population, does not influence the risk of transitional cell cancer of the urinary tract or of renal cell cancer.     

Regularity and length of menstrual cycles in women aged 41–46 in relation to breast cancer risk: Results from the DOM-project

Summary The effect of regularity and length of the menstrual cycle on breast cancer risk was studied prospectively in 78 cases and 383 age-matched controls who participated in a breast cancer screening programme, the DOM-project, in Utrecht, the Netherlands. Before entering the screening programme when they were aged 41–46, the women kept a menstrual calendar during at least three consecutive cycles. Cycles were considered to be irregular if any of three cycles was shorter than 21 days or longer than 35 days and/or if variation between cycle lengths was more than five days. Women with irregular cycles had a significantly reduced risk of breast cancer (odds ratio = 0.44; 95% confidence interval 0.22–0.86) after adjustment for age at menarche, age at first birth, parity, Quetelet's index and family history of breast cancer. Among regularly menstruating women, long cycles (28 days or more) were not significantly associated with increased risk of breast cancer (odds ratio 1.17; 95% confidence interval 0.66–2.09).To the extent that irregular menstrual cycles reflect anovulatory cycles, our findings support the hypothesis that the cumulative number of regular ovulatory cycles increases breast cancer risk.     

Cigarette smoking, alcohol consumption and risk of breast cancer in young women

The possible association between cigarette smoking, alcohol consumption and the risk of development of breast cancer before the age of 45 was investigated by means of a population-based case-control study in Sweden and Norway. Information was obtained, by personal interview, from 422 (89.2%) of all eligible patients with breast cancer newly diagnosed between May 1984 and May 1985, and from 527 (80.6%) of all age-matched controls. The possible confounding effects of oral contraceptive (OC) use, education, and reproductive and several other factors were taken into account in multivariate analyses. No association was found between ever smoking (versus never smoking) and breast cancer (odds ratio 1.0; 95% confidence interval (CI) 0.8-1.3). Further, there was no relation between breast cancer and duration of smoking, age at start of regular smoking, length of time since the start of regular smoking, or number of cigarettes smoked per day. There was no significant interaction between smoking, use of OCs, parity, and breast cancer. A moderate or high current consumption of beer, wine, liquor or total alcohol did not increase the risk of breast cancer. An alcohol intake of 5 grams per day or more was associated with a decreased risk of breast cancer (odds ratio 0.6; 95% CI 0.4-0.9), but possible effects of a change in habits after diagnosis, of recall bias and of residual confounding, e.g. by dietary habits, need serious consideration.     

Mammographic density as a surrogate marker for the effects of hormone therapy on risk of breast cancer.

BACKGROUND: Some types of hormone therapy increase both risk of breast cancer and mammographic density, a risk factor for the disease, suggesting that mammographic density may be a surrogate marker for the effects of hormones on risk of breast cancer. This research was undertaken to determine whether the effect of hormone therapy on breast cancer risk is mediated by its effect on mammographic density. METHODS: Individually matched cases and controls from three nested case-control studies in breast screening populations were studied. Cases had developed invasive breast cancer at least 12 months after the initial screen. Information was collected on hormone use and other risk factors at the time of the baseline mammogram, and percent density was measured by a computer-assisted method. RESULTS: There were 1,748 postmenopausal women, of whom 426 (24.4%) were using hormones at the time of their initial screening mammogram. Current use of hormone therapy was associated with an increased risk of breast cancer (odds ratio, 1.26; 95% confidence interval, 1.0-1.6) that was little changed by adjustment for percent density in the baseline mammogram (odds ratio, 1.19; 95% confidence interval, 0.9-1.5). Percent density in the baseline mammogram was among cases greater in current users of hormones that in never-users (difference = 5.0%, P < 0.001), but the difference was smaller and nonsignificant in controls (difference = 1.6%, P = 0.3). CONCLUSION: Although the effects of hormone therapy on mammographic density were greater in cases than controls, we did not find evidence that these effects were causally related to risk of breast cancer.     

SSRI use and breast cancer risk by hormone receptor status

BACKGROUND: There is little evidence linking the use of selective serotonin reuptake inhibitors (SSRIs) with increased breast cancer risk, but one study has found an association with estrogen receptor negative (ER-) and progesterone receptor negative (PR-) tumors. METHODS: We used data collected on 820 invasive breast cancer cases and 2852 hospitalized controls collected from 1990 through 2006. Information on medication use and other variables was collected by nurse interviewers. We used unconditional logistic regression analyses to evaluate the association between regular SSRI use (use at least 4 times/week for at least 3 months) and breast cancer risk overall and by subtype defined by hormone receptor status. RESULTS: The odds ratio for all breast cancer was not elevated among regular users of SSRIs (OR = 0.89, 95% CI 0.62-1.29). None of the odds ratios varied from 1.0 in any category of hormone receptor status. Among women aged 55 and over, the odds ratios were increased for ER- (OR = 1.84, 95% CI 0.66-5.16), PR- (OR = 1.85, 95% CI 0.80-4.27), and ER-PR- (OR = 2.10, 95% CI 0.73-6.02) tumors, but these estimates were compatible with chance. CONCLUSION: We found no association between SSRI use and breast cancer risk, overall or by hormone receptor status. Odds ratios were elevated in older women, particularly for ER- and PR- tumors, but the confidence intervals were compatible with no association.     

Breastfeeding and breast cancer risk by age 50 among women in Germany

Background: Epidemiological evidence which suggests that prolonged breastfeeding protects against breast cancer has accumulated in recent years. Issues with regard to the timing of breastfeeding and effect modification by correlates of breastfeeding and other risk factors of breast cancer remain unresolved. Methods: A population-based case–control family study of breast cancer among women diagnosed by the age of 50, conducted in two geographic areas in Germany, was used to evaluate the effect of breastfeeding on risk of breast cancer. Results: Among parous women in this study (553 cases, 1094 age-matched population controls), having ever breastfed a child for at least 1 month did not confer protection (odds ratio of 0.9 and 95% confidence interval (CI) 0.8–1.2). However, risk of breast cancer significantly decreased with increasing duration of breastfeeding (p for trend = 0.01) and the estimated relative risk was 0.6 (95% CI 0.4–0.9) for 13–24 months of cumulative breastfeeding and 0.5 (95% CI 0.3–1.1) for 25 months or more. Risk was less related to number of children breastfed than to increasing average length of breastfeeding per child (p for trend = 0.03). Conclusions: The reduction in risk associated with duration of breastfeeding was not primarily due to breastfeeding the firstborn and more evident in women who were older ( > 25 years) when they first breastfed and among women who experienced a recent full-term pregnancy. Risks were modified somewhat by a first-degree family history of breast cancer whereby a greater reduction in risk per additional month of breastfeeding was observed among women with a family history than those without (0.9 vs. 1.0). The study results support a protective role of prolonged breastfeeding against the development of breast cancer in predominantly premenopausal women in Germany.     

The steroid 5alpha-reductase type II TA repeat polymorphism is not associated with risk of breast or ovarian cancer in Australian women.

The enzyme 5alpha-reductase type II (SRD5A2) converts testosterone to its more active form 5alpha-dihydroxytestosterone. The 3' untranslated region of the gene contains a (TA)(n) length polymorphism. The (TA)(9) allele has been reported to be associated with higher serum prostate-specific antigen levels in breast tumors and lower risk of relapse in breast cancer patients and more recently has also been reported to be linked to the codon 89 valine variant, which is itself associated with higher serum prostate-specific antigen levels in breast tumors and a more favorable breast cancer prognosis. We investigated whether the SRD5A2 (TA)(n) polymorphism was associated with risk of breast or ovarian cancer in Australian women by studying 946 breast cancer cases and 509 age-matched controls, and 544 ovarian cancer cases and 298 controls of similar age distribution. The (TA)(9) allele frequency was similar in breast cancer cases (0.110), breast cancer controls (0.125), ovarian cancer cases (0.106), and ovarian cancer controls (0.117). There was no difference in genotype distribution between breast cancer cases and controls (P = 0.5), ovarian cancer cases and controls (P = 0.7), or between the two control groups (P = 0.9). Genotypes containing at least one (TA)(9) allele were not significantly associated with risk of breast cancer overall (odds ratio, 0.86; 95% confidence interval, 0.67-1.12; P = 0.3) or in women stratified by age, menopausal status, or family history. Similarly, the (TA)(9) allele was not associated with risk of ovarian cancer (odds ratio, 0.87; 95% confidence interval, 0.61-1.23; P = 0.4) or with ovarian tumor behavior (invasive or low malignant potential), histology, stage, or grade. Given that this study had sufficient power to detect altered risks in the order of 1.4- to 1.7-fold, our results suggest that the SRD5A2 (TA)(9) allele is unlikely to be associated with moderate alterations in breast or ovarian cancer risk.     

Risk of ovarian cancer according to use of antidepressants, phenothiazines, and benzodiazepines (United States)

Objectives:An association of increased risk of ovarian cancer with use of antidepressants or benzodiazepine tranquilizers has been reported from a case–control study. We assessed the association between ovarian cancer risk and the use of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), phenothiazine antipsychotics, and benzodiazepines, in data from the Case–Control Surveillance Study. Methods:From 1976 through 1998, data were collected from hospital patients in Boston, New York, Philadelphia, and Baltimore based on demographic factors, reproductive and medical history, and medication use. In the present analyses, cases of epithelial ovarian cancer (n = 748) were compared with cancer controls (n = 1496) and noncancer controls admitted for trauma and acute infection (n = 1496). We estimated Mantel–Haenszel odds ratios adjusted for age, study center, and year of interview. Results:Odds ratios for regular use (at least 4 days/week for at least 1 month) were compatible with 1.0 for every drug class. For tricyclics and benzodiazepines the upper 95% confidence limits were less than 1.6. For phenothiazines the upper limit was 2.6 with cancer controls and 1.4 with noncancer controls. Only five cases used SSRIs, yielding unstable results. Odds ratios were not increased among women who had used any drug class for at least 5 years, nor among women who had first used them 10 or more years previously. Conclusions:These data do not support an association between regular use of any of the drugs under study with ovarian cancer risk.     

Vitamin supplement use and risk for breast cancer: the Shanghai Breast Cancer Study

Objective The influence of vitamin supplements on breast cancer risk is unclear and the interactive effects of dietary and supplemental sources are unknown. This study investigated (1) the association between self-reported vitamin supplement use (multivitamin, A, B, C, and E) and breast cancer and (2) the combined effect of vitamin supplements in relation to dietary vitamin intakes on breast cancer risk. Methods The Shanghai Breast Cancer Study was a population-based case-control study conducted in Shanghai in 1996-1998 (Phase I) and 2002-2004 (Phase II). Participants were aged 25-64 (Phase I) and 20-70 years (Phase II). The analyses included 3,454 incident breast cancer cases and 3,474 controls. Unconditional logistic regression models were used to determine adjusted odds ratios (ORs) for breast cancer risk associated with vitamin supplement use. Results Overall, breast cancer risk was not related to any vitamin supplement intake. However, a 20% reduction in breast cancer risk was observed with vitamin E supplement use among women with low-dietary vitamin E intake (OR = 0.8; 95% confidence interval (CI), 0.6-1.0). A non-significant 20% risk reduction was observed among vitamin B supplement users with low B dietary intake (OR = 0.8; 95% CI, 0.6-1.1). Frequent use of a vitamin B supplement was adversely associated with breast cancer risk among those with high dietary vitamin B intake (OR = 1.4; 95% CI: 0.9-2.1; P for interaction = 0.07). Conclusions This study suggests that vitamins E and B supplements may confer protection against breast cancer among women who have low dietary intake of those vitamins.     

Are venous thromboembolic events associated with subsequent breast and colorectal carcinoma diagnoses in the elderly? A case-control study of Medicare beneficiaries

BACKGROUND: Multiple epidemiologic studies have reported associations between venous thromboembolic events and subsequent cancer diagnoses, but the published results have not suggested clear cancer screening approaches. METHODS: Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results-Medicare Program, the authors identified patients who were diagnosed with breast and colorectal carcinoma (n = 7166 patients) and compared them with a noncancer control group (n = 126,668 patients) according to their history of hospitalization for deep vein thrombosis (DVT) or pulmonary embolism (PE) in Medicare claims files over the previous 24 months. Using logistic regression analysis, the authors calculated the odds of receiving a diagnosis of breast carcinoma or colorectal carcinoma in the 24 months after admission for DVT or PE. RESULTS: Patients who were hospitalized for DVT or PE had nearly 3.0 times the odds of being diagnosed with colorectal carcinoma (odds ratio [OR], 2.83; 95% confidence interval [95% CI], 1.92-4.17) and > 1.5 times the odds of being diagnosed with breast carcinoma (OR, 1.78; 95% CI, 1.05-3.02) in the subsequent 24 months. CONCLUSIONS: Because hospitalization for DVT or PE is associated with an increased risk of a breast or colorectal carcinoma diagnosis in the subsequent 2 years, physicians should be vigilant in assessing the cancer screening status of patients with new DVT and/or PE to be certain that they are up to date with recommended breast and colorectal screening guidelines.     

Hydralazine and breast cancer

Hydralazine (CAS: 86-54-4; 1-hydrazinonaphthalazine) is a well-established antihypertensive agent. There are no conclusive data on the drug as a human carcinogen, but one of its metabolites, hydrazine (CAS: 302-01-2), has been shown to be carcinogenic in rats and mice. To assess the relationship of hydralazine to human breast cancer, 3,419 women with breast cancer and 3,219 hospital control subjects were studied. Data were obtained by interview in hospitals in the United States and Canada. A total of 1.4% of the cases and 1.2% of the controls had used hydralazine. Compared with never use, the relative risk (RR) estimate for hydralazine that was first used at least 18 months before admission was 0.9 [95% confidence interval (CI), 0.5-1.7] after risk factors for breast cancer and the use of other antihypertensive drugs and diuretics were taken into account by multivariate analysis. The RR estimate for hydralazine use lasting at least 1 year was 0.9 (95% CI, 0.5-1.7). RR estimates for longer durations of use (up to 5 or more yr), and for use within strata of risk factors for breast cancer, were close to 1.0. The results suggest that hydralazine does not increase the risk of breast cancer in humans in the short term. Whether the risk is increased after latent intervals of many years could not be evaluated.