Abstract 645: Pregnancy inhibits mammary carcinogenesis by altering the mammary epithelial and stromal interactions

Abstract

Abstract A full-term pregnancy before the age of 20 is the only known natural phenomenon that can drastically reduce the risk of breast cancer in women of all ethnic backgrounds worldwide. This universal protective effect of early pregnancy is clearly of major consideration in devising prevention strategies against breast cancer. It is well known that parous subjects have an altered systemic hormonal milieu with a significant decrease in circulating GH and PRL. Determining how these hormonal alterations impact the mammary gland of early parous rats is expected to improve our understanding of the dynamics of mammary carcinogenesis. The inguinal mammary fat pad was cleared of the host mammary gland in 3-4-week-old rats. One group of rats were exposed to N-Methyl-N-Nitrosourea (MNU) at 7 weeks of age, and another group of rats were not exposed to MNU. A subset of rats from each of these experimental groups were mated at 9 weeks and allowed to go through a full-term pregnancy. All animals were terminated 6 weeks post-weaning. Mammary epithelial cells (MECs) were isolated using the collagenase cell dissociation procedure. The isolated MECs (5 × 105) were transplanted into the gland-free fat pads of respective hosts. In brief, we studied the following groups to understand the influence of early parity on epithelial-stromal interactions involved in mammary carcinogenesis: 1) carcinogen treated MECs from Age-matched nulliparous (AMNP) rats were transplanted into untreated parous rats; 2) carcinogen treated MECs from parous rats were transplanted into untreated AMNP rats; 3) untreated MECs from AMNP rats were transplanted into carcinogen treated parous rats and 4) untreated MECs from parous rats were transplanted into carcinogen treated AMNP rats. All experimental animals were palpated weekly for the presence of mammary cancers. The cancerous nature of the palpable tumors was confirmed by histopathological analysis. Digital images of immunocytochemistry result was analyzed using Image Pro Plus software. Carcinogenesis experiments were terminated nine months after carcinogen administration. Incidence, multiplicity, and latency of mammary cancers was determined for each group and analyzed for significance by the appropriate statistical test. Our data demonstrated that transplantation of MECs from AMNP rats into parous hosts did not develop into palpable tumors while MECs from parous rats when transplanted to AMNP hosts developed mammary tumors. Analysis of the mammary gland wholemounts and molecular markers clearly indicated that parity alters key signaling mechanisms and inhibits progression of mammary lesions. These findings suggests that the mammary epithelial-stromal interactions in the parous rats is altered making it resistant to mammary carcinogenesis. Citation Format: Ramadevi Subramani Reddy, Adriana Galvez, Diego A. Pedroza, Animesh Chatterjee, Courtney Perry, Elizabeth Penner, Rajkumar Lakshmanaswamy. Pregnancy inhibits mammary carcinogenesis by altering the mammary epithelial and stromal interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 645.