Data from Poor Outcome in Postpartum Breast Cancer Patients Is Associated with Distinct Molecular and Immunologic Features

Abstract

<div>AbstractPurpose:<p>Patients with postpartum breast cancer diagnosed after cessation of breastfeeding (postweaning, PP-BC<sub>PW</sub>) have a particularly poor prognosis compared with patients diagnosed during lactation (PP-BC<sub>DL</sub>), or to pregnant (Pr-BC) and nulliparous (NP-BC) patients, regardless 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 patients with PP-BC<sub>PW</sub> remain vastly underexplored, due to of lack of adequate patient numbers and outcome data.</p>Experimental Design:<p>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 postweaning 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 patients with PP-BC<sub>PW</sub>, PP-BC<sub>DL</sub>, Pr-BC, and NP-BC.</p>Results:<p>We found that patients with PP-BC<sub>PW</sub> 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-BC<sub>PW</sub> tumor tissue was also characterized by an increase in CD8<sup>+</sup> cytotoxic T cells and reduced distance among these cell types, these parameters were not associated with differential clinical outcomes among groups.</p>Conclusion:<p>These data point to the importance of plasma B cells in the postweaning mammary tumor microenvironment regarding the poor prognosis of PP-BC<sub>PW</sub> patients. Future prospective and in-depth research needs to further explore the role of B-cell immunobiology in this specific group of young patients with breast cancer.</p></div>