Abstract

Abstract Background: Stably persistent offspring-origin cells in a woman’s circulation and tissues decades after pregnancy, also known as fetal microchimerism, is deficient in women with biologically unselected breast cancer and suggests a protective role. Although the finding is in harmony with the well-known association of parity with protection against future breast cancer, it has recently emerged that certain tumor types such as triple negative breast cancer are positively associated with parity. Here we tested the hypothesis that fetal microchimerism is positively associated with triple negative breast cancer in young women. Methods: Buffy coat specimens were obtained from a subset (n=450) of pathologically confirmed low-risk luminal and high-risk triple negative breast cancer patients and control participants from a population-based cohort study of all women aged 20-44 diagnosed with invasive breast cancer in the three county Seattle-Puget Sound metropolitan area from 2004-2010. Using quantitative PCR, DNA extracts from these specimens were tested for the presence and concentration of Y chromosome sequence DYS14, a marker of male fetal microchimerism. Results: At this interim analysis of 405 specimens, 29.3% (56/191) of the healthy controls tested positive. Using controls as a reference group, 37.8% (34/90; OR .68; 95% CI .39-1.2) of women who developed luminal breast cancer tested positive for the presence of DYS14, while 26.6% (33/124; OR 1.14; 95% CI .67-1.96) of women who developed triple negative breast cancer tested positive. Discussion: A preliminary analysis does not suggest an association between fetal microchimerism and breast cancer pathologic subtype in young women. Additional analyses are pending and will be presented at the meeting. Young women may regulate fetal microchimerism differently and surprisingly our data may suggest that as fetal microchimerism emerges later in life in the circulation, so does the protection against breast cancer – a finding consistent with population based studies of parity as a risk factor for breast cancer. Citation Format: David A Mahoney, Veronica L Winget, VK Gadi, Christopher I Li, Peggy L Porter, Jean A McDougall. Breast cancer pathologic subtype and fetal microchimerism [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 P3-07-34.

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