151P Tumor biology and immunology in patients (pts) with breast cancer occurring during pregnancy (BCP) compared to non-pregnant breast cancer pts

BackgroundBreast cancer (BC) is one of the most common malignancies during pregnancy. The incidence is likely to increase as more women tend to delay childbearing into later life and the overall lifetime cancer risk increases with age. Pregnancy presents a complex and unique immunological condition. This study investigated the tumour biology and immunology of BCP cohort compared to non-pregnant BC cohort.MethodsTissue microarrays (TMA) of formalin-fixed paraffin embedded core biopsies or surgical specimens from 125 pregnant BC pts treated with (neo-) adjuvant chemotherapy were constructed. The BCP cohort was matched to an appropriate non-pregnant BC cohort with existing TMAs from the GAIN study by variables age, tumour stage, nodal status (N0 patients were not eligible in the GAIN study), grading and subtype. TMAs were stained via IHC to assess oestrogen and progesterone receptor (ER, PgR), human epidermal growth factor receptor 2 (HER2), Ki-67 (≤20% vs >20%), and immune response relevant markers, such as HLA class I (EMR8-5, MHC I), HLA-G (4H84), PD-L1 (<1% vs ≥1%), TIGIT (BLR047F), Nectin-4 (EPR15613-68) and tumour-infiltrating lymphocytes (TILs, ≤25% vs 26-60% vs >60%). PD-L1 expression was evaluated in tumour and immune cells using the 22C3 antibody. H-scores of HLA class I, HLA-G, TIGIT and Nectin-4 were calculated.ResultsPregnant BC pts were younger than non-pregnant (median 34 [26-47] vs 37 [27-47] years) and had higher Ki-67 expression (>20%: 53.3% vs 38.1%, p=0.025). The H-score of HLA-G was significantly lower (median 4.9 vs 10.6, p=0.012), while the H-scores of HLA class I (median: 27.7 vs 13.8, p=0.029) and Nectin-4 (median: 156 vs 113, p≤0.001) were significantly higher in the BCP compared to the non-pregnant BC cohort. No significant differences were found for TILs, PD-L1 or H-score of TIGIT.ConclusionsThe significantly higher Ki-67 expression in the BCP cohort suggests an increased proliferation in BC cells during pregnancy. Higher Nectin-4 expression in the BCP cohort could be a sign of an altered anti-tumour response. These results suggest differences in tumour proliferation and tumour/host immunogenicity in BCP cohort vs non-pregnant BC cohort.Legal entity responsible for the studyGBG Forschungs GmbH.FundingThis study was financially supported by GBG and Philipps-Universität Marburg.DisclosureC. Solbach: Financial Interests, Personal, Advisory Board: MSD, Roche; Financial Interests, Personal, Other, Lecture: Pfizer, Lilly. A. Schneeweiss: Financial Interests, Personal and Institutional, Research Grant, Travel expenses, Honoraria: Celgene , Roche; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Personal, Other, Honoraria, Travel expenses: Pfizer; Financial Interests, Personal, Other, Honoraria: AstraZeneca , Novartis , MSD , Tesaro, Lilly , Seagen, Gilead , GSK , Bayer , Amgen , Pierre Fabre . C. Denkert: Other, Institutional, Research Grant, Consulting fees: Myriad, Roche; Financial Interests, Personal and Institutional, Royalties, Consulting fees: VmScope digital pathology software; Financial Interests, Personal and Institutional, Advisory Role, Consulting fees: MSD Oncology, Daiichi Sankyo, Merck , Lilly , AstraZeneca , Molecular Health; Financial Interests, Personal and Institutional, Advisory Role, Consulting fees, Support for attending meetings and/or travel: Roche; Other, Personal and Institutional, Other, Paten for Therapy response: WO2015114146A1, WO2010076322A1; Other, Personal and Institutional, Other, Paten for cancer immunotherapy: WO2020109570A1; Non-Financial Interests, Personal, Ownership Interest, cofounder and shareholder until 2016: Sividon Diagnostics. P. Jank: Financial Interests, Institutional, Other, stock ownership: Myriad Genetics, Inc. S. Loibl: Financial Interests, Institutional, Research Grant, honorarium for Ad Boards, paid to institute: AbbVie; Financial Interests, Institutional, Other, honorarium for Ad Boards, paid to institute: Amgen , BMS , Lilly , Merck; Financial Interests, Institutional, Research Grant, honorarium for Ad Boards & Lectures, paid to institute: AstraZeneca; Financial Interests, Institutional, Research Grant, honorarium for Ad Board, paid to institute: Celgene; Financial Interests, Institutional, Other, honorarium for Ad Board, paid to institute: Eirgenix, GSK , Sanofi; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board, paid to institute / Medical Writing: Gilead; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board & Lectures, paid to institute / Medical Writing: Novartis , Pfizer; Financial Interests, Institutional, Other, honorarium for Ad Board & Lecture, paid to institute: Pierre Fabre; Non-Financial Interests, Institutional, Other, honorarium for Ad Boards, paid to institute / Medical Writing: Seagen, Roche; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Boards, paid to institute / Medical Writing: Daiichi Sankyo; Other, Institutional, Other, Patent for Immunsignature in TNBC, paid to institute: EP14153692.0; Other, Institutional, Other, Patent for Signature for CDK 4/6 Inhibitor, paid to institute: EP21152186.9; Other, Institutional, Other, Patent for Predicting response to an Anti-HER2 containing therapy, paid to institute: EP15702464.7; Other, Institutional, Other, Patent for GeparNuevo, paid to institute: EP19808852.8; Other, Institutional, Royalties, Paten for VM Scope GmbH, paid to institute: Digital Ki67 Evaluator. All other authors have declared no conflicts of interest. BackgroundBreast cancer (BC) is one of the most common malignancies during pregnancy. The incidence is likely to increase as more women tend to delay childbearing into later life and the overall lifetime cancer risk increases with age. Pregnancy presents a complex and unique immunological condition. This study investigated the tumour biology and immunology of BCP cohort compared to non-pregnant BC cohort. Breast cancer (BC) is one of the most common malignancies during pregnancy. The incidence is likely to increase as more women tend to delay childbearing into later life and the overall lifetime cancer risk increases with age. Pregnancy presents a complex and unique immunological condition. This study investigated the tumour biology and immunology of BCP cohort compared to non-pregnant BC cohort. MethodsTissue microarrays (TMA) of formalin-fixed paraffin embedded core biopsies or surgical specimens from 125 pregnant BC pts treated with (neo-) adjuvant chemotherapy were constructed. The BCP cohort was matched to an appropriate non-pregnant BC cohort with existing TMAs from the GAIN study by variables age, tumour stage, nodal status (N0 patients were not eligible in the GAIN study), grading and subtype. TMAs were stained via IHC to assess oestrogen and progesterone receptor (ER, PgR), human epidermal growth factor receptor 2 (HER2), Ki-67 (≤20% vs >20%), and immune response relevant markers, such as HLA class I (EMR8-5, MHC I), HLA-G (4H84), PD-L1 (<1% vs ≥1%), TIGIT (BLR047F), Nectin-4 (EPR15613-68) and tumour-infiltrating lymphocytes (TILs, ≤25% vs 26-60% vs >60%). PD-L1 expression was evaluated in tumour and immune cells using the 22C3 antibody. H-scores of HLA class I, HLA-G, TIGIT and Nectin-4 were calculated. Tissue microarrays (TMA) of formalin-fixed paraffin embedded core biopsies or surgical specimens from 125 pregnant BC pts treated with (neo-) adjuvant chemotherapy were constructed. The BCP cohort was matched to an appropriate non-pregnant BC cohort with existing TMAs from the GAIN study by variables age, tumour stage, nodal status (N0 patients were not eligible in the GAIN study), grading and subtype. TMAs were stained via IHC to assess oestrogen and progesterone receptor (ER, PgR), human epidermal growth factor receptor 2 (HER2), Ki-67 (≤20% vs >20%), and immune response relevant markers, such as HLA class I (EMR8-5, MHC I), HLA-G (4H84), PD-L1 (<1% vs ≥1%), TIGIT (BLR047F), Nectin-4 (EPR15613-68) and tumour-infiltrating lymphocytes (TILs, ≤25% vs 26-60% vs >60%). PD-L1 expression was evaluated in tumour and immune cells using the 22C3 antibody. H-scores of HLA class I, HLA-G, TIGIT and Nectin-4 were calculated. ResultsPregnant BC pts were younger than non-pregnant (median 34 [26-47] vs 37 [27-47] years) and had higher Ki-67 expression (>20%: 53.3% vs 38.1%, p=0.025). The H-score of HLA-G was significantly lower (median 4.9 vs 10.6, p=0.012), while the H-scores of HLA class I (median: 27.7 vs 13.8, p=0.029) and Nectin-4 (median: 156 vs 113, p≤0.001) were significantly higher in the BCP compared to the non-pregnant BC cohort. No significant differences were found for TILs, PD-L1 or H-score of TIGIT. Pregnant BC pts were younger than non-pregnant (median 34 [26-47] vs 37 [27-47] years) and had higher Ki-67 expression (>20%: 53.3% vs 38.1%, p=0.025). The H-score of HLA-G was significantly lower (median 4.9 vs 10.6, p=0.012), while the H-scores of HLA class I (median: 27.7 vs 13.8, p=0.029) and Nectin-4 (median: 156 vs 113, p≤0.001) were significantly higher in the BCP compared to the non-pregnant BC cohort. No significant differences were found for TILs, PD-L1 or H-score of TIGIT. ConclusionsThe significantly higher Ki-67 expression in the BCP cohort suggests an increased proliferation in BC cells during pregnancy. Higher Nectin-4 expression in the BCP cohort could be a sign of an altered anti-tumour response. These results suggest differences in tumour proliferation and tumour/host immunogenicity in BCP cohort vs non-pregnant BC cohort. The significantly higher Ki-67 expression in the BCP cohort suggests an increased proliferation in BC cells during pregnancy. Higher Nectin-4 expression in the BCP cohort could be a sign of an altered anti-tumour response. These results suggest differences in tumour proliferation and tumour/host immunogenicity in BCP cohort vs non-pregnant BC cohort.