title: Pharmaceuticals that cause mammary gland tumors in animals: findings in women.
abstract: Risk of breast cancer in women was assessed for eight pharmaceuticals that produce mammary tumors in experimental animals, using nested case-control analyses in two cohorts with prescription records in a comprehensive medical care program. The two cohorts were: (1) earlier cohort: 78,118 female members who received prescriptions in 1969-1973, of whom 2,467 developed breast cancer, and (2) later cohort: 3,289,408 female members who received prescriptions in 1994-2006 of whom 24,528 developed breast cancer. Longest follow-up was until June 30, 2006. Ten randomly selected concurrent control women were age-matched to almost every case. Relative risks were estimated by conditional logistic regression. Case ascertainment was lagged by 2 years, or unlagged and subdivided by number of prescriptions received. Some analyses were controlled for hormone use and sensitivity analyses were conducted to estimate the effects of uncontrolled confounding. In the later cohort furosemide, and metronidazole showed statistically significant but very small increases in relative risk (ranging from 1.07 to 1.13). Of these, only furosemide showed increased risk in the earlier cohort: 2-year lag relative risk 1.66 (95% confidence interval 1.23-2.24) or as low as 0.97, assuming uncontrolled positive confounding. Griseofulvin showed significant increases in the later cohort: relative risk for three or more prescriptions 1.48 (1.08-2.03) or as low as 1.23 assuming uncontrolled positive confounding and non-significant increases were noted in the earlier cohort. Our findings are limited by their inconsistency across the two cohorts and our inability to directly control for most established breast cancer risk factors. Although inconclusive, our findings suggest a need for more research on furosemide and griseofulvin.
authors.affiliation: Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA 94612, USA. gdf@dor.kaiser.org
authors.forename: Gary D
authors.initials: GD
authors.lastname: Friedman
authors.forename: Sheng-Fang
authors.initials: SF
authors.lastname: Jiang
authors.forename: Natalia
authors.initials: N
authors.lastname: Udaltsova
authors.forename: James
authors.initials: J
authors.lastname: Chan
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects; D000981:Antiprotozoal Agents / Q000009:adverse effects; D001943:Breast Neoplasms / Q000139:chemically induced*; D016022:Case-Control Studies; D004232:Diuretics / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005665:Furosemide / Q000009:adverse effects; D006118:Griseofulvin / Q000009:adverse effects; D006801:Humans; D008795:Metronidazole / Q000009:adverse effects; D008875:Middle Aged; D017891:Pharmacoepidemiology / Q000379:methods*; D012307:Risk Factors; D018426:SEER Program; D012680:Sensitivity and Specificity
chemical_list: D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D004232:Diuretics; D008795:Metronidazole; D006118:Griseofulvin; D005665:Furosemide