Abstract P6-08-08: Postpartum breast cancer demonstrates increased liver and brain metastasis with a proposed role for postpartum involution

Abstract

Abstract Background: Postpartum breast cancer, which we have defined as a breast cancer diagnosis within 5 years of giving birth (PPBC), has a 3-fold increased risk for metastasis and death when compared to nulliparous women that is independently significant when age at diagnosis, tumor stage, receptor status and year at diagnosis are accounted for. Models of postpartum breast cancer developed by our group have shown that the process of breast involution after lactation ceases or after pregnancy if lactation does not occurs is a key event that drives tumors toward increase metastasis. To further investigate the increased metastatic potential of postpartum involution, we performed a nested cohort study of metastatic young women’s breast cancer. We have also developed an immune-competent mouse model of postpartum breast cancer to fully characterize the metastatic capacity of the postpartum involution milieu. Hypothesis: The reduced survival of postpartum breast cancer is due, in part, to an altered pattern of metastatic spread to the liver driven by postpartum involution. Methods: Two independent cohorts from the University of Colorado (UC) and Dana Farber Cancer Institute (DFCI) were utilized to identify a nested cohort of women with first presentation of systemic metastasis. Location of metastasis was verified and frequency of end organ involvement recorded for the pre-determined targets of liver, bone, brain and lungs. The cohort was compared by parity status of nulliparous or PPBC. For determining the contribution of postpartum involution to metastatic spread and investigate mechanism, an intracardiac immune-competent mouse model of postpartum breast cancer metastasis was developed. Results: Cases of young women diagnosed ≤45 that had documented metastatic disease and for which site of metastasis could be identified were included (n=79). Cases with missing parity data or for whom site specific information was not available were excluded. Overall, the dominant organ for metastatic involvement at first presentation of metastatic disease was the bones. In PPBC, liver was the second most common site of metastasis (35%) and higher than in nulliparous women (24%) where lung metastases were the second most frequent. Individual organs were evaluated by parity status and a notable skewing of frequency of liver and brain metastasis to PPBC was seen. 63% versus 37% of the cases with liver mets and 73% versus 27% of cases with brain involvement were PPBC versus nullipara at first metastatic presentation. No differences were seen in lung or bone metastasis between the parity groups. To test whether the postpartum involution supports increased liver metastasis, mice were injected with mammary tumor cells into the left ventricle. Similar to the human data, significantly increased liver metastasis, but not bone or lung was observed in the postpartum group compared to age-matched nulliparous controls. Conclusion: PPBC demonstrates enrichment for liver and brain metastasis that is in part confirmed through an animal model and supports the role of postpartum involution in increased metastasis and death. Further studies into the mechanism by which increased liver metastasis occur in postpartum breast cancer patients are underway. Citation Format: Virginia F Borges, Erica Goddard, Ann H Partridge, Pepper Schedin. Postpartum breast cancer demonstrates increased liver and brain metastasis with a proposed role for postpartum involution [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-08.