Abstract 38P
Background
Women aged ≤45 years face a 10-30% increased risk of developing breast cancer (BC) within the first decade postpartum compared to nulliparous women, with the risk rising with the age of pregnancy. Furthermore, the prognosis for BC diagnosed up to 5-10 years postpartum (PPBC) is worse even after adjusting for clinicopathological factors. Previous studies point to short lactation and subsequent abrupt breast involution as major tumorigenic factors. However, the lack of systematically collected breastfeeding and parity data from YWBC obscures the validation of this theory.
Methods
FFPE primary tumors from 35 cases of HR+ YWBC were categorized as nulliparous, pregnant, or postpartum (PPBC ≤5 years) based on the time of diagnosis. Reproductive history and breastfeeding duration data were collected. GeoMx Digital Spatial Protein platform was employed to analyze an average of 3 regions of interest per tumor, focusing on 41 markers for immune cell and cell death profiling. Tumor and stromal compartments were marked by PanCK and CD45, respectively.
Results
In YWBC, Luminal B tumors exhibited higher immune cell presence in both tumor and stroma compared to Luminal A. HR+ lymph node-positive disease displayed elevated stromal infiltrating lymphocytes. In the PPBC subgroup, the CD68 macrophage marker showed significant up regulation in both compartments, compared to other samples (pval 0,001 FDR<0,05). Longitudinal analysis showed no substantial changes in the immune milieu across the three trimesters of pregnancy. However, markers of M2 macrophages, endothelial progenitor cells, GZMB, among others, significantly increased in the stromal and tumor compartments in correlation with breastfeeding duration (p-value <0.01).
Conclusions
Our results, with the resolution provided by GeoMX, suggest that immune cell markers remain stable during pregnancy, possibly due to the mammary gland focusing on epithelial proliferation at that stage. After birth, breastfeeding duration significantly impacts the immune milieu, correlating with an increase in both immunosuppressive and tumor-killing markers, even before formal involution.
Legal entity responsible for the study
Health Research Insititute of the Balearic Islands.
Funding
Health Insititute Carlos III; IdISBa.
Disclosure
L. Sanz Gomez: Financial Interests, Institutional, Invited Speaker: Pfizer, AstraZeneca, Daiichi Sankyo. O. Cordoba: Financial Interests, Personal and Institutional, Advisory Board: ASCIRES; Financial Interests, Institutional, Research Grant: Roche diagnostics, Neomedic, Remex, Ethicon, Takeda. P.G. Nuciforo: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD Oncology, Bayer; Financial Interests, Personal, Other, Consultant: Targos Molecular Pathology GmbH. C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd., Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Pierre Fabre, PintPharma, Puma, Roche Farma, Sanofi Avenits, Seagen, Zymeworks, Pharmalex Spain SLU; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim, Bristol Meyers Squibb, Genentech, Innoup, Millenium; Financial Interests, Personal, Other, SC: Byondis B.V., GSK, Macrogenics, Menarini, Merus, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, GSK, Immunomedics, Innoup Farma, Macrogenics, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). All other authors have declared no conflicts of interest.