Abstract PD2-08: Potential role of prolactin signaling in development and growth of the lobular subtype of breast cancer

Invasive lobular carcinoma (ILC) is the eighth most frequently diagnosed cancer in any organ, and accounts for 8-11% of breast cancer. This histological subtype is characterized by loss of E-cadherin, and favorable prognostic factors, such as low Ki67 and high rates of ER/PR-positive tumors. Only recently is the lobular subtype gaining recognition as a distinct disease, displaying a unique growth pattern, unique molecular changes in addition to loss of E-cadherin, and evidence for late recurrences and reduced response to targeted endocrine therapy. It is widely accepted that a late age at first full term birth (FFTB) increases a women9s risk for breast cancer. Interestingly, several published epidemiological studies have shown that the increased risk after a late age at FFTB is preferential for the lobular subtype of breast cancer compared to the ductal subtype. We therefore hypothesized that pregnancy hormones like prolactin play an integral role in the development and progression of ILC. Interrogation of the Cancer Genome Atlas (TCGA) data revealed a high expression of milk protein genes as well as prolactin signaling molecules, specifically Stat5a and Stat5b in lobular carcinomas compared to ductal carcinomas. We developed a lactation score including 7 milk protein genes and found that in the TCGA data set ILC tumors have a significantly higher lactation score than IDC tumors. Additionally, we found that ILC cell lines express increased prolactin receptor mRNA and protein levels compared to IDC cell lines. Prolactin treatment in ILC and IDC cells reveals divergent signaling pathways - prolactin stimulates ERK activation in IDC but not ILC cells. We are currently further delineating the prolactin signaling pathways, and resulting phenotypes, comparing ILC and IDC cells. We expect these experiments to move the field forward by establishing a relationship between prolactin and lobular carcinoma. Citation Format: Oesterreich S, Katz TA, Logan G, Levine K, Nagle A, Huo Z, Tseng GC, Rui H, Lee AV, Butler LM. Potential role of prolactin signaling in development and growth of the lobular subtype of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD2-08.