Data from Poor outcome in postpartum breast cancer patients is associated with distinct molecular and immunological features

Abstract Purpose: Postpartum breast cancer patients diagnosed after cessation of breastfeeding (post-weaning, PP-BCPW), have a particularly poor prognosis compared to patients diagnosed during lactation (PP-BCDL), or to pregnant (Pr-BC) and nulliparous (NP-BC) patients, irrespective of standard prognostic characteristics. Animal studies point to a role of the involution process in stimulation of tumor growth in the mammary gland. However, in women, the molecular mechanisms that underlie this poor prognosis of PP-BCPW patients remain vastly underexplored, due to of lack of adequate patient numbers and outcome data. Experimental Design: We explored whether distinct prognostic features, common to all breast cancer molecular subtypes, exist in postpartum tumor tissue. Using detailed breastfeeding data, we delineated the post-weaning period in PP-BC as a surrogate for mammary gland involution and performed whole transcriptome sequencing, immunohistochemical and (multiplex) immunofluorescent analyses on tumor tissue of PP-BCPW, PP-BCDL, Pr-BC and NP-BC patients. Results: We found that PP-BCPW patients having a low expression level of an immunoglobulin gene signature, but high infiltration of plasma B-cells, have an increased risk for metastasis and death. Although PP-BCPW tumor tissue was also characterized by an increase in CD8+ cytotoxic T-cells and reduced distance among these cell types, these parameters were not associated with differential clinical outcomes among groups. Conclusion: These data point to the importance of plasma B-cells in the post-weaning mammary tumor microenvironment regarding the poor prognosis of PP-BCPW patients. Future prospective and in-depth research needs to further explore the role of B-cell immunobiology in this specific group of young breast cancer patients.