Relationship Between Long Durations and Different Regimens of Hormone Therapy and Risk of Breast Cancer

Abstract

The influence of the duration of combined hormone replacement therapy (CHRT) with estrogen and progestin and of different patterns of treatment was examined in 975 women 65 to 79 years of age who had invasive breast cancer. A large majority of tumors were ductal carcinomas, and most cancers were positive for both estrogen and progesterone receptors. Control subjects were age-matched women from the same general population. For women given unopposed estrogen therapy, even for 25 years or longer, the breast cancer risk was not notably greater than for those reporting no use of any form of HRT, although a small effect could not be ruled out. Women using CHRT at any time had a 1.7-fold increase in all breast cancers and a 2.7-fold increase in risk of invasive lobular carcinoma. Risk was increased 1.5-fold for invasive ductal carcinoma, and there was a 2.0-fold increase in risk of estrogen receptor (ER)/progesterone receptor (PR)-positive cancers. The most marked increase in risk was in women using CHRT for 5 years or longer. Comparable results were found in women who had used CHRT sequentially or continuously. Current CHRT was associated with 1.9-fold, 1.7-fold, and 3.1-fold increases in the risk of all histologic types of breast cancer, ductal carcinomas, and lobular breast cancers, respectively. There was no apparent increase in the risk of ER+/PR- or ER-/PR- tumors. Patterns of progestin use were not closely associated with cancer risk in either women using CHRT at any time or current users. These findings reinforce the increase in breast cancer risk observed when progestin is added to HRT, whether CHRT is used sequentially or continuously.