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Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen

  1. Author:
    Diwan, B. A.
    Anderson, L. M.
    Ward, J. M.
    1. Year of Conference: 1997
  2. Conference Name: Annual Meeting of the American Association for Cancer Research
    1. 38
    2. Pages: A3105
  4. Type of Work: Meeting Abstract
  1. Abstract:

    Tamoxifen (TAM) is widely used in adjuvant breast cancer therapy after surgery. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. Since TAM has been recently used as a prophylactic therapy in a number of clinical trials world-wide, a major concern has been the possible increased risk of reproductive tract abnormalities in babies of women who become pregnant while using this drug. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg BW) given ig to pregnant CD-1 mice (1x/day, 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of oviduct was commonly seen in TAM-exposed offspring, reaching 100% incidence by 52 wks. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (5 mg/kg, 43%; 7.5 mg/kg, 55%) and polypoid adenomas (5 mg/kg, 26%; 7.5 mg/kg, 41%) between 52 and 78 wks. A low incidence of such lesions [endometrial hyperplasia, 12.5% (p=0.02 compared to 5 mg/kg TAM); polypoid adenomas, 8% (p=0.01 compared to 7.5 mg/kg TAM)] was found in control offspring. Deciduomas (15%) occurred at young ages (24 wks or younger) while leiomyomas (14%), leiomyosarcoma, and ovarian tumors (14%) were found in older mice. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.

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