TY - JOUR
T1 - Poor Outcome in Postpartum Breast Cancer Patients Is Associated with Distinct Molecular and Immunologic Features
AU - Lefrère, Hanne
AU - Moore, Kat
AU - Floris, Giuseppe
AU - Sanders, Joyce
AU - Seignette, Iris M.
AU - Bismeijer, Tycho
AU - Peters, Dennis
AU - Broeks, Annegien
AU - Hooijberg, Erik
AU - van Calsteren, Kristel
AU - Neven, Patrick
AU - Warner, Ellen
AU - Peccatori, Fedro Alessandro
AU - Loibl, Sibylle
AU - Maggen, Charlotte
AU - Han, Sileny N.
AU - Jerzak, Katarzyna J.
AU - Annibali, Daniela
AU - Lambrechts, Diether
AU - de Visser, Karin E.
AU - Wessels, Lodewyk
AU - Lenaerts, Liesbeth
AU - Amant, Frédéric
N1 - Funding Information: This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme “[647047 to F. Amant].” This work was supported by the KWF kankerbestrijding, the Dutch Cancer Society “[11132 to F. Amant].” This work was supported by the Fonds Wetenschappelijk Onderzoek, the Flemish Research Foundation or “FWO” “[G0A9219N to F. Amant].” Prof. F. Amant is senior investigator for the FWO. This work was supported by the Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society “[3M150537 to H. Lefrère].” Prof. Giuseppe Floris is recipient of a postdoctoral mandate from KOOR in UZ-Leuven. G. Floris is recipient of a postdoctoral mandate from the Klinische onderzoeks- en opleidingsraad (KOOR) of the University Hospitals Leuven. We thank all participating patients and all (para-) medical staff involved in registering cases in the INCIP database (see www.cancerinpregnancy.org). We would like to acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobanking (CFMPB) for supplying NKI-AVL Biobank material and lab support. We would like to thank Michel Faas for his lab and image analysis support during his student rotation period. We acknowledge institutional funding from the KWF to the Netherlands Cancer Institute. Funding Information: This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme “[647047 to F. Amant].” This work was supported by the KWF kankerbestrijding, the Dutch Cancer Society “[11132 to F. Amant].” This work was supported by the Fonds Wetenschappelijk Onderzoek, the Flemish Research Foundation or “FWO” “[G0A9219N to F. Amant].” Prof. F. Amant is senior investigator for the FWO. This work was supported by the Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society “[3M150537 to H. Lefrère].” Prof. Giuseppe Floris is recipient of a postdoctoral mandate from KOOR in UZ-Leuven. G. Floris is recipient of a postdoctoral mandate from the Klinische onderzoeks-en opleidingsraad (KOOR) of the University Hospitals Leuven. We thank all participating patients and all (para-) medical staff involved in registering cases in the INCIP database (see www.cancer inpregnancy.org). We would like to acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobanking (CFMPB) for supplying NKI-AVL Biobank material and lab support. We would like to thank Michel Faas for his lab and image analysis support during his student rotation period. We acknowledge institutional funding from the KWF to the Netherlands Cancer Institute. Publisher Copyright: © 2023 The Authors; Published by the American Association for Cancer Research.
PY - 2023/9/15
Y1 - 2023/9/15
N2 - PURPOSE: Patients with postpartum breast cancer diagnosed after cessation of breastfeeding (postweaning, PP-BCPW) have a particularly poor prognosis compared with patients diagnosed during lactation (PP-BCDL), 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-BCPW 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 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-BCPW, PP-BCDL, Pr-BC, and NP-BC. RESULTS: We found that patients with PP-BCPW 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. CONCLUSIONS: These data point to the importance of plasma B cells in the postweaning 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 patients with breast cancer.
AB - PURPOSE: Patients with postpartum breast cancer diagnosed after cessation of breastfeeding (postweaning, PP-BCPW) have a particularly poor prognosis compared with patients diagnosed during lactation (PP-BCDL), 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-BCPW 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 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-BCPW, PP-BCDL, Pr-BC, and NP-BC. RESULTS: We found that patients with PP-BCPW 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. CONCLUSIONS: These data point to the importance of plasma B cells in the postweaning 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 patients with breast cancer.
UR - http://www.scopus.com/inward/record.url?scp=85171394116&partnerID=8YFLogxK
U2 - https://doi.org/10.1158/1078-0432.CCR-22-3645
DO - https://doi.org/10.1158/1078-0432.CCR-22-3645
M3 - Article
C2 - 37449970
SN - 1078-0432
VL - 29
SP - 3729
EP - 3743
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -