Characterization of HER2‐low breast cancer in young women with germline <i>BRCA1/2</i> pathogenetic variants: Results of a large international retrospective cohort study-Reference-Cited by-同舟云学术

Characterization of HER2‐low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Published:2024-05-16 Issue:16 Volume:130 Page:2746-2762
ISSN:0008-543X
Container-title:Cancer
language:en
Short-container-title:Cancer

Author:

Schettini Francesco¹²³^ORCID,Blondeaux Eva⁴,Molinelli Chiara⁵⁶,Bas Raphaëlle⁷,Kim Hee Jeong⁸,Di Meglio Antonio⁹^ORCID,Bernstein Molho Rinat¹⁰,Linn Sabine C.¹¹¹²,Pogoda Katarzyna¹³^ORCID,Carrasco Estela¹⁴,Punie Kevin¹⁵,Agostinetto Elisa¹⁶^ORCID,Lopetegui‐Lia Nerea¹⁷^ORCID,Phillips Kelly‐Anne¹⁸¹⁹²⁰,Toss Angela²¹²²^ORCID,Rousset‐Jablonski Christine²³²⁴²⁵,Acheritogaray Marion²⁶^ORCID,Ferrari Alberta²⁷²⁸,Paluch‐Shimon Shani²⁹,Fruscio Robert³⁰,Cui Wanda¹⁸¹⁹,Wong Stephanie M.³¹^ORCID,Vernieri Claudio³²³³,Dieci Maria Vittoria³⁴³⁵,Matikas Alexios³⁶,Rozenblit Mariya³⁷,Villarreal‐Garza Cynthia³⁸^ORCID,De Marchis Laura³⁹⁴⁰^ORCID,Puglisi Fabio⁴¹⁴²,Vasconcelos de Matos Leonor⁴³^ORCID,Mariño Monica⁴⁴,Teixeira Luis⁴⁵,Graffeo Rossella⁴⁶,Rognone Alessia⁴⁷,Chirco Alessandra⁴⁸,Antone Nicoleta⁴⁹,Abdou Yara⁵⁰^ORCID,Marhold Maximilian⁵¹,Božović‐Spasojević Ivana⁵²,Cortés Salgado Alfonso⁵³^ORCID,Carmisciano Luca⁵⁴,Bruzzone Marco⁴,Curigliano Giuseppe⁵⁵⁵⁶^ORCID,Prat Aleix¹³⁵⁷⁵⁸⁵⁹^ORCID,Lambertini Matteo⁵⁶^ORCID

Affiliation:

1. Translational Genomics and Targeted Therapies in Solid Tumors group August Pi i Sunyer Biomedical Research Institute (IDIBAPS) Barcelona Spain

2. Department of Medical Oncology Hospital Clinic of Barcelona Barcelona Spain

3. Department of Medicine and Health Sciences University of Barcelona Barcelona Spain

4. U.O. Epidemiologia Clinica IRCCS Ospedale Policlinico San Martino Genova Italy

5. Department of Internal Medicine and Medical Specialties (DiMI) School of Medicine University of Genova Genova Italy

6. Department of Medical Oncology U.O. Clinica di Oncologia Medica IRCCS Ospedale Policlinico San Martino Genova Italy

7. Department of Medical Oncology Universite Paris Cité Institut Curie Paris France

8. Division of Breast Surgery Department of Surgery Asan Medical Center University of Ulsan College of Medicine Seoul South Korea

9. Cancer Survivorship Group INSERM U981 Gustave Roussy Villejuif France

10. Susanne Levy Gertner Oncogenetics Unit The Danek Gertner Institute of Human Genetics Chaim Sheba Medical Center affiliated to Tel Aviv University Tel Hashomer Israel

11. Department of Medical Oncology Netherlands Cancer Institute (NKI) Amsterdam The Netherlands

12. Department of Pathology University Medical Center Utrecht Utrecht The Netherlands

13. Department of Breast Cancer and Reconstructive Surgery Maria Sklodowska‐Curie National Research Institute of Oncology Warsaw Poland

14. Hereditary Cancer Genetics Unit Medical oncology Department Vall d´Hebron University Hospital Vall d´Hebron Institute of Oncology (VHIO) Barcelona Spain

15. Department of General Medical Oncology and Multidisciplinary Breast Center Leuven Cancer Institute University Hospitals Leuven Leuven Belgium

16. Institut Jules Bordet and l'Université Libre de Bruxelles (U.L.B.) Hôpital Universitaire de Bruxelles (HUB) Brussels Belgium

17. Department of Medical Oncology Cleveland Clinic Taussig Cancer Institute Cleveland Ohio USA

18. Department of Medical Oncology Peter MacCallum Cancer Centre Melbourne Victoria Australia

19. Sir Peter MacCallum Department of Oncology The University of Melbourne Melbourne Victoria Australia

20. Centre for Epidemiology and Biostatistics School of Population and Global Health The University of Melbourne Melbourne Victoria Australia

21. Department of Oncology and Haematology Azienda Ospedaliero‐Universitaria di Modena Modena Italy

22. Division of Oncology Department of Medical and Surgical Sciences University of Modena and Reggio Emilia Modena Italy

23. Department of Surgery Leon Berard Cancer Center Lyon France

24. Unité INSERM U1290 Université Claude Bernard Lyon 1 Lyon France

25. Hopital Femme Mère Enfant Hospice civils de Lyon Bron France

26. Department of Gynecology Cote Basque Hospital Center Bayonne France

27. Hereditary Breast and Ovarian Cancer (HBOC) Unit and General Surgery 3 ‐ Senology Breast Cancer Center Fondazione IRCCS Policlinico San Matteo Pavia Italy

28. University of Pavia Pavia Italy

29. Sharett institute of oncology Hadassah University Hospital & Faculty of Medicine Hebrew University Jerusalem Israel

30. UO Gynecology Department of Medicine and Surgery University of Milan‐Bicocca IRCCS San Gerardo dei Tintori Monza Italy

31. Stroll Cancer Prevention Centre, Jewish General Hospital, and McGill University Medical School Montreal Quebec Canada

32. Medical Oncology Department Breast Unit Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy

33. Oncology and Hematology‐Oncology Department University of Milan Milano Italy

34. Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche Università di Padova Padova Italy

35. Oncologia 2 Istituto Oncologico Veneto IRCCS Padova Italy

36. Department of Oncology/Pathology Karolinska Institute and Breast Center Karolinska University Hospital Stockholm Sweden

37. Medical Oncology Yale University New Haven Connecticut USA

38. Breast Cancer Center Hospital Zambrano Hellion ‐ TecSalud Tecnologico de Monterrey Monterrey Mexico

39. Division of Medical Oncology Department of Radiological, Oncological and Pathological Sciences Sapienza University of Rome Rome Italy

40. Medical Oncology Department of Hematology Oncology Dermatology, Umberto 1 University Hospital Rome Italy

41. Department of Medical Oncology Centro di Riferimento Oncologico di Aviano (CRO) IRCCS Aviano Italy

42. Department of Medicine University of Udine Udine Italy

43. Breast Cancer Unit Champalimaud Clinical Center Champalimaud Foundation Lisbon Portugal

44. Hospital Universitari Son Espases Palma Palma Spain

45. Department of Senology Université Paris Cité Assistance Publique‐Hôpitaux de Paris Saint Louis University Hospital Paris France

46. Oncology Institute of Southern Switzerland EOC‐IOSI Bellinzona Switzerland

47. Department of Oncology IRCCS Ospedale San Raffaele Milano Italy

48. Medical Oncology Unit ASST Papa Giovanni XXIII Bergamo Italy

49. Institute of Oncology "Ion Chiricuta" Cluj‐Napoca Romania

50. University of North Carolina ‐ Lineberger Comprehensive Cancer Center Chapel Hill North Carolina USA

51. Division of Oncology Department of Medicine I Medical University of Vienna Vienna Austria

52. Institute for Oncology and Radiology of Serbia University of Belgrade Faculty of Medicine Belgrade Serbia

53. Medical Oncology Department Hospital Universitario Ramón y Cajal Madrid Spain

54. Department of Clinical and Experimental Medicine University of Pisa Pisa Italy

55. Early Drug Development for Innovative Therapies Division IRCCS European Institute of Oncology (IEO) Milan Italy

56. Department of Oncology and Hemato‐Oncology University of Milan Milan Italy

57. Institute of Cancer and Blood Disorders Hospital Clinic of Barcelona Barcelona Spain

58. Reveal Genomics Barcelona Spain

59. Institute of Oncology (IOB)‐Hospital Quirón Salud Barcelona Spain

Abstract

AbstractBackgroundBreast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)‐low‐expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset.MethodsWomen aged ≤40 years with newly diagnosed early‐stage HER2‐negative BC (HER2‐0 and HER2‐low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi‐square test and Student t‐test were used to describe variable distribution between HER2‐0 and HER2‐low. Associations with HER2‐low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease‐free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05.ResultsOf 3547 included patients, 32.3% had HER2‐low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple‐negative (TN) tumors. HER2‐low vs. HER2‐0 BC were more often of grade 1/2 (p < .001), hormone receptor–positive (p < .001), and node‐positive (p = .003). BRCA2 PVs were more often associated with HER2‐low than BRCA1 PVs (p < .001). HER2‐low versus HER2‐0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64–0.95) and overall survival (HR, 0.65; 95% CI, 0.46–0.93) in the TN subgroup. Luminal A–like tumors in HER2‐low (p = .014) and TN and luminal A‐like in HER2‐0 (p = .019) showed the worst DFS.ConclusionsIn young patients with HER2‐negative BC and germline BRCA1/2 PVs, HER2‐low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal‐like disease. HER2‐low status was associated with a modestly improved prognosis.

Funder

Associazione Italiana per la Ricerca sul Cancro

Publisher

Wiley

Reference50 articles.

1. Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival

2. Characterization of the HER2 status in BRCA-mutated breast cancer: a single institutional series and systematic review with pooled analysis

3. Breast Cancer Risk Genes — Association Analysis in More than 113,000 Women

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