Abstract C54: Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy

While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes in the normal breast that raise barriers to transformation, but how pregnancy can also increase long-term cancer risk remains unclear. Precancerous lesions accumulate in the breast with age. We show in mice that pregnancy has different effects on the few early lesions that have already accumulated in the otherwise normal breast'it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray' in response to pregnancy/lactation hormones, these precancerous cells can activate STAT5; but during involution, the oncogenic signaling can prevent STAT5 deactivation. The resulting persistent STAT5 signaling prevents the apoptosis normally initiated by oncogene activation and involution. Short-term anti-STAT5 treatment of lactation-completed, early lesions-bearing mice eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy as it may lower long-term breast cancer risk in women who have had a late-age pregnancy and thus are more likely to harbor STAT5-activated progressing early lesions.

Citation Format: Yi Li. Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C54.