Hormonal factors and breast tumor proliferation: do factors that affect cancer risk also affect tumor growth?

Tumor cell proliferation is one of the most significant predictors of prognosis for women with breast cancer. Personal characteristics that affect hormonal exposure have been implicated in breast tumor etiology, and it is possible that they may also influence tumor cell proliferation. We examined the association between hormone-related breast cancer risk factors and breast tumor proliferation, as reflected in two proliferation measures, Ki-67 and mitotic count.

The study population was 484 women 40 years of age and older, who were members of a managed care organization's breast cancer screening program and were diagnosed with invasive breast cancer between 1988 and 1995. The percent of Ki-67 positive tumor cells averaged over four high powered fields (Ki-67) was log transformed and analyzed in a linear regression model. Mitotic count was dichotomized into high versus low (

Consistent with other studies, there was a significant trend of decreased tumor cell proliferation with increasing age ( p for trend <0.05 for both measures). Higher body weight was associated with higher Ki-67 ( p for trend <0.05), but not with higher mitotic count. We found no significant associations between any reproductive factors (age at menarche, parity, age at first birth, menopausal status and age at menopause) and either measure of tumor cell proliferation. We observed an association between reduced tumor proliferation, as measured by mitotic count and former/current use of hormone replacement therapy (HRT) in comparison to never use (adjusted OR's: former HRT use: 0.40 (95% CI 0.19-0.85); current HRT use: 0.52 (95% CI 0.26-1.04).

Certain factors related to hormonal exposure that influence breast tumor etiology, for example, age, also appear to increase tumor growth. Conversely HRT use, which clearly increases breast cancer risk, may not adversely affect, and possibly may diminish cell proliferation once tumors are established.