Estrogen replacement therapy and breast cancer: Analysis of age of onset and tumor characteristics

Background: The use of exogenous estrogen has been scrutinized as a risk fa ctor far breast cancer formation. This prospective study addresses the rela tionship between the use of estrogen replacement therapy and the age of ons et of breast cancer. In addition, an analysis of differences in pathologica l features of breast cancer between estrogen users and non-estrogen-users w as evaluated. Methods: A total of 425 women (age, greater than or equal to 50 years) were evaluated during a 4-year period (1994-1997), Data, including the age at d iagnosis, method of detection, family history, use of estrogen therapy, and tumor ploidy, S-phase fraction, histological category, estrogen receptor p ositivity, and grade, were prospectively collected. Data from a control gro up of 657 women without a diagnosis of breast cancer were obtained from the Evanston Northwestern division of the Women's Health Initiative. Significa nt associations between the use of estrogen and pathological parameters wer e determined using the chi(2) test and t-test (P < .05). Results: At the time of breast cancer diagnosis, 140 patients were currentl y receiving estrogen and 202 patients had no history of estrogen use. Eight y-three: patients were excluded from analysis (76 patients had a history of previous but not current use of estrogen therapy, four women used only pro gesterone, and three patients provided incomplete information). There was n o difference between patients with breast cancer using estrogen at the time of diagnosis and those with no history of estrogen use with respect to tum or size, age of menopause, family history, mammographic sensitivity, axilla ry lymph node status, and histological features. Women using estrogen at th e time of diagnosis were younger at the time of breast cancer diagnosis, by an average of 5.1 years (61.3 years vs. 66.4 years, P < .001). Women witho ut a history of breast cancer who were receiving estrogen therapy were an a verage of 2.4 years younger (63.3 years vs. 65.7 years, P < .001) than wome n without: a history of breast cancer who were not receiving estrogen thera py. Patients with breast cancer receiving estrogen also tended to have more grade II tumors (45.9% vs. 36.5%, P = .045) and fewer grade ill tumors (25 .6% vs. 37.0%, P = .015), compared with women not receiving estrogen therap y at the time of their diagnoses. Estrogen receptor positivity was noted to be more frequent for estrogen users presenting with lobular carcinoma (85% vs. 76%, P = .042) and less frequent for estrogen users presenting with du ctal carcinoma (72% vs. 85%, P = .003). Conclusions: A significantly earlier age of diagnosis for women receiving e strogen therapy suggests that exogenous estrogen may accelerate the pathoge nesis of postmenopausal breast cancer. Estrogen therapy may also play a rol e in altering the grade and estrogen receptor positivity for certain histol ogical types of breast cancer.