. 2022 Sep 13;82(9):912-921.

doi: 10.1055/a-1912-7105. eCollection 2022 Sep.

Update Breast Cancer 2022 Part 3 - Early-Stage Breast Cancer

Tanja N Fehm¹, Manfred Welslau², Volkmar Müller³, Diana Lüftner⁴, Florian Schütz⁵, Peter A Fasching⁶, Wolfgang Janni⁷, Christoph Thomssen⁸, Isabell Witzel³, Erik Belleville⁹, Michael Untch¹⁰, Marc Thill¹¹, Hans Tesch¹², Nina Ditsch¹³, Michael P Lux¹⁴, Bahriye Aktas¹⁵, Maggie Banys-Paluchowski¹⁶, Andreas Schneeweiss¹⁷, Cornelia Kolberg-Liedtke¹⁸, Andreas D Hartkopf⁷, Achim Wöckel¹⁹, Hans-Christian Kolberg²⁰, Nadia Harbeck²¹, Elmar Stickeler²²

Affiliations

¹ Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany.
² Onkologie Aschaffenburg, Aschaffenburg, Germany.
³ Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany.
⁴ Immanuel Hospital Märkische Schweiz & Medical University of Brandenburg Theodor-Fontane, Brandenburg, Buckow, Germany.
⁵ Gynäkologie und Geburtshilfe, Diakonissen-Stiftungs-Krankenhaus Speyer, Speyer, Germany.
⁶ Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
⁷ Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany.
⁸ Department of Gynaecology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
⁹ ClinSol GmbH & Co KG, Würzburg, Germany.
¹⁰ Clinic for Gynecology and Obstetrics, Breast Cancer Center, Gynecologic Oncology Center, Helios Klinikum Berlin Buch, Berlin, Germany.
¹¹ Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt am Main, Germany.
¹² Oncology Practice at Bethanien Hospital, Frankfurt am Main, Germany.
¹³ Department of Gynecology and Obstetrics, University Hospital Augsburg, Augsburg, Germany.
¹⁴ Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, St. Vincenz Krankenhaus GmbH, Germany.
¹⁵ Department of Gynecology, University of Leipzig Medical Center, Leipzig, Germany.
¹⁶ Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
¹⁷ National Center for Tumor Diseases (NCT), Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany.
¹⁸ Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.
¹⁹ Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany.
²⁰ Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany.
²¹ Breast Center, Department of Gynecology and Obstetrics and CCC Munich LMU, LMU University Hospital, Munich, Germany.
²² Department of Gynecology and Obstetrics, RWTH University Hospital Aachen, Aachen, Germany.

PMID: 36110894
PMCID: PMC9470293
DOI: 10.1055/a-1912-7105

Update Breast Cancer 2022 Part 3 - Early-Stage Breast Cancer

Tanja N Fehm et al. Geburtshilfe Frauenheilkd. 2022.

. 2022 Sep 13;82(9):912-921.

doi: 10.1055/a-1912-7105. eCollection 2022 Sep.

Authors

Affiliations

¹ Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany.
² Onkologie Aschaffenburg, Aschaffenburg, Germany.
³ Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany.
⁴ Immanuel Hospital Märkische Schweiz & Medical University of Brandenburg Theodor-Fontane, Brandenburg, Buckow, Germany.
⁵ Gynäkologie und Geburtshilfe, Diakonissen-Stiftungs-Krankenhaus Speyer, Speyer, Germany.
⁶ Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
⁷ Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany.
⁸ Department of Gynaecology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
⁹ ClinSol GmbH & Co KG, Würzburg, Germany.
¹⁰ Clinic for Gynecology and Obstetrics, Breast Cancer Center, Gynecologic Oncology Center, Helios Klinikum Berlin Buch, Berlin, Germany.
¹¹ Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt am Main, Germany.
¹² Oncology Practice at Bethanien Hospital, Frankfurt am Main, Germany.
¹³ Department of Gynecology and Obstetrics, University Hospital Augsburg, Augsburg, Germany.
¹⁴ Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, St. Vincenz Krankenhaus GmbH, Germany.
¹⁵ Department of Gynecology, University of Leipzig Medical Center, Leipzig, Germany.
¹⁶ Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
¹⁷ National Center for Tumor Diseases (NCT), Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany.
¹⁸ Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.
¹⁹ Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany.
²⁰ Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany.
²¹ Breast Center, Department of Gynecology and Obstetrics and CCC Munich LMU, LMU University Hospital, Munich, Germany.
²² Department of Gynecology and Obstetrics, RWTH University Hospital Aachen, Aachen, Germany.

PMID: 36110894
PMCID: PMC9470293
DOI: 10.1055/a-1912-7105

Abstract

This review summarizes recent developments in the prevention and treatment of patients with early-stage breast cancer. The individual disease risk for different molecular subtypes was investigated in a large epidemiological study. With regard to treatment, new data are available from long-term follow-up of the Aphinity study, as well as new data on neoadjuvant therapy with atezolizumab in HER2-positive patients. Biomarkers, such as residual cancer burden, were investigated in the context of pembrolizumab therapy. A Genomic Grade Index study in elderly patients is one of a group of studies investigating the use of modern multigene tests to identify patients with an excellent prognosis in whom chemotherapy may be avoided. These and other aspects of the latest developments in the diagnosis and treatment of breast cancer are described in this review.

Keywords: adjuvant treatment; breast cancer; chemotherapy; early stage; endocrine therapy; neoadjuvant treatment.

The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest/Interessenkonflikt B. A. received honoria and travel grants from AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo and Pfizer. C. K.-L. received honoraria from Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, Eisai, and SonoScape as well as honoraria for consultancy work from Phaon Scientific, Novartis, Pfizer, and Celgene as well as research assistance from Roche, Novartis, and Pfizer. Travel grant from Novartis and Roche, employment at Palleos Healthcare, and Managing Director and partner at Phaon Scientific. M. B.-P. received honoraria for lectures and advisory role from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, and study support from Mammotome, Endomag and Merit Medical. E. B. received honoraria from Gilead, Ipsen, Sanofi, Sandoz, SunPharma, AstraZeneca, Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, BBraun and onkowissen.de for clinical research management and/or medical education activities. N. D. has received honoraria from MSD, Roche, AstraZeneca, Teva, Pfizer, Novartis, Seagen,Gilead, MCI Healthcare. P. A. F. reports personal fees from Novartis, grants from Biontech, personal fees from Pfizer, personal fees from Daiichi Sankyo, personal fees from AstraZeneca, personal fees from Eisai, personal fees from Merck Sharp & Dohme, grants from Cepheid, personal fees from Lilly, personal fees from Pierre Fabre, personal fees from SeaGen, personal fees from Roche, personal fees from Hexal, personal fees from Agendia, personal fees from Gilead. T. N. F. has participated on advisory boards for Amgen, Daiichi Sankyo, Novartis, Pfizer, and Roche and has received honoraria for lectures from Amgen, Celgene, Daiichi Sankyo, Roche, Novartis and Pfizer. A. D. H. received speaker and consultancy honoraria from AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo, Hexal and Pfizer. N. H. received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, Gilead, Lilly, MSD, Mylan, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Seagen. W. J. has received research Grants and/or honoraria from Sanofi-Aventis, Daiichi Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene and Johnson & Johnson. H.-C. K. has received honoraria from Pfizer, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lily, SurgVision, Onkowissen, Gilead, Daiichi Sankyo and MSD, travel support from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro and owns stock of Theraclion SA and Phaon Scientific GmbH. D. L. received honoraria from Amgen, AstraZeneca, Eli Lilly, High5md, Gilead, GSK, Loreal, MSD, Novartis, Onkowissen, Pfizer, Seagen, Teva. M. P. L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi Sankyo, PharmaMar and Roche and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, Gilead, AstraZeneca, and Eisai. He is editorial board member of medactuell from medac. V. M. received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead. Consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead. Institutional research support from Novartis, Roche, Seagen, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. E. S. received honoraria from Roche, Celgene, AstraZeneca, Novartis, Pfizer, Tesaro, Aurikamed GmbH, MCI Deutschland GmbH, bsh medical communications GmbH, Onkowissen TV. A. S. received research grants from Celgene, Roche, honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, Clinsol, Connectmedica, Gilead, GSK, I-MED, Lilly, MCI Deutschland, Metaplan, MSD, Nanostring, Novartis, Onkowissen.de, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, Streamedup, Teva, Tesaro, Thieme and travel support from Celgene, Pfizer, Roche. F. S. participated on advisory boards for Novartis, Lilly, Amgen and Roche and received honoraria for lectures from Roche, AstraZeneca, MSD, Novartis and Pfizer. H. T. received honoraria from Novartis, Roche, Celgene, Teva, Pfizer, Astra Zeneca and travel support from Roche, Celgene and Pfizer. C. T. received honoraria for advisory boards and lectures from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. M. T. has participated on advisory boards for AstraZeneca, Clovis, Daiichi Sankyo, Eisai, Gilead Science, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Seagen and Roche and has received honoraria for lectures from Amgen, Clovis, Daiichi Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor and AstraZeneca and has received trial funding by Exact Sciences and Endomag Manuscript support was done by Amgen, ClearCut, pfm medical, Roche, Servier, Vifor. M. U. All honoraria went to the institution/employer: Abbvie, Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD, Myriad Genetics, Pfizer, Roche, Sanofi Aventis, Novartis, Pierre Fabre, Seagen; Gilead. M. W. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer and Roche. I. W. has participated on advisory boards for Novartis, Daichii Sankyo, Lilly, Pfizer and received speaker honoraria from Astra Zeneca, Daichii Sankyo, MSD, Novartis, Pfizer, Roche. A. W. participated on advisory boards for Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai and received honoraria for lectures from Novartis, Pfizer, Aurikamed, Roche, Celgene./ B. A. hat von AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo und Pfizer Honorare und Reisekostenzuschüsse erhalten. C. K.-L. hat folgende Honorare erhalten: Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, Eisai und SonoScape. Beraterhonorare von: Phaon Scientific, Novartis, Pfizer und Celgene. Forschungsuntertützung: Roche, Novartis und Pfizer. Reiseunterstützung: Novartis und Roche. Anstellung bei Palleos Healthcare. Managing Director und Partner bei Phaon Scientific. M. B.-P. hat von Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition und Pierre Fabre Honorare für Vorträge und beratende Tätigkeiten sowie von EndoMag, Mammotome und Merit Medical Studienunterstützung erhalten. E. B. hat von Gilead, Ipsen, Sanofi, Sandoz, SunPharma, AstraZeneca, Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, BBraun und onkowissen.de Honorare für klinisches Forschungsmanagement und/oder medizinische Aus- und Weiterbildung erhalten. N. D. hat von MSD, Roche, AstraZeneca, Teva, Pfizer, Novartis, Seagen, Gilead und MCI Healthcare Honorare erhalten. P. A. F. weist Folgendes aus: Honorare von Novartis, Zuwendungen von Biontech, Honorare von Pfizer, Honorare von Daiichi Sankyo, Honorare von AstraZeneca, Honorare von Eisai, Honorare von Merck Sharp & Dohme, Zuwendungen von Cepheid, Honorare von Lilly, Honorare von Pierre Fabre, Honorare von SeaGen, Honorare von Roche, Honorare von Hexal, Honorare von Agendia und Honorare von Gilead. T. N. F. hat in beratenden Gremien bei Amgen, Daiichi Sankyo, Novartis, Pfizer und Roche mitgewirkt und von Amgen, Celgene, Daiichi Sankyo, Roche, Novartis und Pfizer Honorare für Vorträge erhalten. A. D. H. hat als Referent und Berater von AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo, Hexal und Pfizer Honorare erhalten. N. H. hat für Vorträge und/oder Beratung von Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, Gilead, Lilly, MSD, Mylan, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz und Seagen Honorare erhalten. W. J. hat von Sanofi-Aventis, Daiichi-Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene und Johnson & Johnson Forschungsbeihilfen und/oder Honorare erhalten. H.-C. K. hat von Pfizer, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lily, SurgVision, Onkowissen, Gilead, Daiichi Sankyo und MSD Honorare sowie von Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo und Tesaro Reisekostenzuschüsse erhalten und besitzt Aktien von Theraclion SA und Phaon Scientific GmbH. D. L. hat von Amgen, AstraZeneca, Eli Lilly, High5md, Gilead, GSK, Loreal, MSD, Novartis, Onkowissen, Pfizer, Seagen und Teva Honorare erhalten. M. P. L. hat in beratenden Gremien bei AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi Sankyo, PharmaMar und Roche mitgewirkt und von MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, Gilead, AstraZeneca und Eisai Honorare für Vorträge erhalten. Er ist Mitglied der Redaktion von medactuell von medac. V. M. hat von Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape und Gilead Honorare als Referent erhalten. Beraterhonorare von Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead. Institutionelle Forschungsunterstützung von Novartis, Roche, Seagen, Genentech. Reisekostenzuschüsse von: Roche, Pfizer, Daiichi Sankyo. E. S. hat von Roche, Celgene, AstraZeneca, Novartis, Pfizer, Tesaro, Aurikamed GmbH, MCI Deutschland GmbH, bsh medical communications GmbH und Onkowissen TV Honorare erhalten. A. S. hat von Celgene und Roche Forschungszuschüsse, von Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, Clinsol, Connectmedica, Gilead, GSK, I-MED, Lilly, MCI Deutschland, Metaplan, MSD, Nanostring, Novartis, Onkowissen.de, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, Streamedup, Teva, Tesaro und Thieme Honorare sowie von Celgene, Pfizer und Roche Reisekostenzuschüsse erhalten. F. S. hat in beratenden Gremien bei Novartis, Lilly, Amgen und Roche mitgewirkt und von Roche, AstraZeneca, MSD, Novartis und Pfizer Honorare für Vorträge erhalten. H. T. hat von Novartis, Roche, Celgene, Teva, Pfizer und AstraZeneca Honorare sowie von Roche, Celgene und Pfizer Reisekostenzuschüsse erhalten. C. T. hat für die Mitwirkung in beratenden Gremien und für Vorträge von Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen und Vifor Honorare erhalten. M. T. hat in beratenden Gremien bei AstraZeneca, Clovis, Daiichi Sankyo, Eisai, Gilead Science, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Seagen und Roche mitgewirkt und von Amgen, Clovis, Daiichi Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor und AstraZeneca Honorare für Vorträge sowie von Exact Sciences und Endomag finanzielle Mittel für Versuche erhalten. Manuskriptzuschüsse wurden von Amgen, ClearCut, pfm medical, Roche, Servier und Vifor geleistet. M. U. Alle Honorare gingen an die Institution/den Arbeitgeber: Abbvie, Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD, Myriad Genetics, Pfizer, Roche, Sanofi Aventis, Novartis, Pierre Fabre, Seagen, Gilead. M. W. hat in beratenden Gremien bei AstraZeneca, Lilly, MSD, Novartis, Pfizer und Roche mitgewirkt. I. W. hat in beratenden Gremien bei Novartis, Daichii Sankyo, Lilly und Pfizer mitgewirkt und von AstraZeneca, Daichii Sankyo, MSD, Novartis, Pfizer und Roche Honorare als Referent erhalten. A. W. hat in beratenden Gremien bei Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro und Eisai mitgewirkt und von Novartis, Pfizer, Aurikamed, Roche und Celgene Honorare für Vorträge erhalten.

Figures

**Fig. 1**
Odds ratio for developing triple-negative breast cancer for patients who have had one, two, and three deliveries relative to women who have not delivered a baby .

**Fig. 2**
Online Residual Cancer Burden Calculator .

**Fig. 3**
Event-free 3-year survival rates in the KEYNOTE-522 study by Residual Cancer Burden Group .

**Fig. 4**
Study design of the ASTER-70s study.

**Abb. 1**
Odds Ratio für die Entwicklung eines triple-negativen Mammakarzinoms für Patientinnen mit 1, 2 und 3 Geburten im Verhältnis zu Frauen ohne eine Geburt .

**Abb. 2**
Onlinerechner zur Bestimmung der Residual Cancer Burden .

**Abb. 3**
Ereignisfreie 3-Jahres-Überlebens-Raten in der KEYNOTE-522-Studie nach Residual Cancer Burden-Gruppen .

**Abb. 4**
Studiendesign der ASTER-70s-Studie.

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Update Breast Cancer 2022 Part 3 - Early-Stage Breast Cancer

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Update Breast Cancer 2022 Part 3 - Early-Stage Breast Cancer

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