Pharmaceuticals that cause mammary gland tumors in animals: findings in women

  • Gary D. FriedmanEmail author
  • Sheng-Fang Jiang
  • Natalia Udaltsova
  • James Chan
  • Charles P. QuesenberryJr.
  • Laurel A. Habel


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.


Breast neoplasms Pharmacoepidemiology Cyclophosphamide Furosemide Griseofulvin Indomethacin Isoniazid Metronidazole Nitrofurantoin Reserpine 



Supported by Grant R01 CA 098838 from the National Cancer Institute. The funding agency played no role in conducting or writing up the study, or in the decision to publish it. Dr. Habel is or has been involved in research projects supported by Eli Lilly, Takeda, Merck, Genentech, Genomic Health, Inc., AviaraDx or Roche through contracts with Kaiser Permanente.


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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Gary D. Friedman
    • 1
    • 2
    Email author
  • Sheng-Fang Jiang
    • 1
  • Natalia Udaltsova
    • 1
  • James Chan
    • 3
  • Charles P. QuesenberryJr.
    • 1
  • Laurel A. Habel
    • 1
  1. 1.Division of ResearchKaiser Permanente Medical Care ProgramOaklandUSA
  2. 2.Department of Health Research and Policy, School of MedicineStanford UniversityStanfordUSA
  3. 3.Pharmacy Outcomes Research GroupKaiser Permanente Medical Care ProgramOaklandUSA

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