Hormonal environment in the induction of breast cancer in castrated rats using dimethylbenzanthracene: influence of the presence or absence of ovarian activity and of treatment with estradiol, tibolone, and raloxifene

Menopause. 2005 Sep-Oct;12(5):601-8. doi: 10.1097/01.gme.0000172269.32573.34. Epub 2005 Sep 1.

Abstract

Objective: The influence of hormone therapy on the induction or the promotion of breast cancer has yet to be determined. Recent studies establish a cause-effect relation between hormones and cancer, although epidemiological data and studies of tumor behavior give rise to doubts. The aim of the study was to observe and evaluate the influence of different hormonal environments on the induction of breast cancer in a well-established experimental model.

Design: In this experimental animal study, breast cancer was induced by using a single intragastric dose of 20 mg of dimethylbenzanthracene in prepubertal Sprague-Dawley rats randomized into five groups: group 1 (control); group 2 (castrated prepubertal animals); and groups 3, 4, and 5 (castration of prepubertal animals followed by hormonal treatment starting at puberty [11 weeks] with tibolone, raloxifene, and estradiol, respectively). Follicle-stimulating hormone and estradiol levels were measured at 6, 11, 16, and 31 weeks.

Results: Absence of ovarian activity was observed in groups 2, 3, 4, and 5, as well as the expected variations in hormone levels in all groups. Breast cancers were obtained in 100% of the animals in the control group, with an average of four (two to seven) tumors per animal in this group. Only one cancer appeared in groups 2, 3, and 4, and none appeared in group 5.

Conclusions: In this experimental model and using the hormone treatments chosen, neither the treatments nor the absence of ovarian activity induced breast cancer.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / pharmacology
  • Animals
  • Breast Neoplasms / chemically induced*
  • Carcinogens / pharmacology
  • Estradiol / blood
  • Estradiol / pharmacology*
  • Estrogen Receptor Modulators / pharmacology*
  • Female
  • Follicle Stimulating Hormone / blood
  • Models, Animal
  • Norpregnenes / pharmacology*
  • Ovariectomy
  • Ovary / drug effects*
  • Raloxifene Hydrochloride / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Carcinogens
  • Estrogen Receptor Modulators
  • Norpregnenes
  • Raloxifene Hydrochloride
  • Estradiol
  • 9,10-Dimethyl-1,2-benzanthracene
  • Follicle Stimulating Hormone
  • tibolone