{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:18:36Z","timestamp":1760059116951,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001203","name":"GSK","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001203","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Niraparib is an oral poly (adenosine diphosphate-ribose) polymerase inhibitor with promising activity for patients with advanced breast cancer harboring germline BRCA1\/2 mutations. Methods: LUZERN (NCT04240106) was a multicenter, open-label, Simon\u2019s two-stage, phase II clinical trial evaluating the efficacy and safety of niraparib with aromatase inhibitors (AIs) for patients with HR-positive\/HER2-negative advanced breast cancer with either a germline BRCA1\/2 mutation (cohort A) or germline BRCA1\/2 wild-type and homologous recombination deficiency (exploratory cohort B). Eligible patients received \u22641 line of chemotherapy and 1\u20132 prior lines of endocrine therapy for advanced disease with secondary resistance to the last AI-based regimen. Patients received niraparib (300 mg or 200 mg) plus an AI. The primary endpoint was the clinical benefit rate (CBR) in cohort A. Results: Between June 2020 and November 2022, 14 patients were enrolled in cohort A (n = 6 for stage I, n = 8 for stage II) and no patients were enrolled in cohort B. One patient was excluded from the efficacy analysis due to no prior AI treatment. Nearly all patients (92.9%) previously received a cyclin-dependent kinase 4\/6 inhibitor, but no patients had received prior platinum-based chemotherapy. Median follow-up was 16.7 months (range: 13.2\u201318.2). The CBR was 46.2% (95% CI: 19.2\u201374.9), meeting the primary endpoint. Median progression-free survival was 5.5 months (95% CI: 1.9\u20138.5), and median overall survival was 18.1 months (95% CI: 9.7\u2013NE). The safety profile was consistent with the known toxicity of both drugs. Conclusions: Niraparib combined with an AI has encouraging antitumor activity and a manageable safety profile in patients with AI-resistant HR-positive\/HER2-negative advanced breast cancer with germline BRCA1\/2 mutations.<\/jats:p>","DOI":"10.3390\/cancers17111744","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T12:15:43Z","timestamp":1747916143000},"page":"1744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Niraparib Plus Aromatase Inhibitors for Hormone Receptor-Positive\/HER2-Negative Advanced Breast Cancer with a Germline BRCA Mutation"],"prefix":"10.3390","volume":"17","author":[{"given":"Laura","family":"Lema","sequence":"first","affiliation":[{"name":"Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Manuel","family":"P\u00e9rez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"International Breast Cancer Center (IBCC), Pangaea Oncology, Quir\u00f3n Group, 08022 Barcelona, Spain"},{"name":"Medica Scientia Innovation Research (MEDSIR), 08005 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvador","family":"Blanch","sequence":"additional","affiliation":[{"name":"Instituto Valenciano de Oncolog\u00eda, 46009 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-6415","authenticated-orcid":false,"given":"Judith","family":"Balma\u00f1a","sequence":"additional","affiliation":[{"name":"Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-0301","authenticated-orcid":false,"given":"Jos\u00e9 \u00c1ngel","family":"Garc\u00eda-S\u00e1enz","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena Filipovich","family":"Vegas","sequence":"additional","affiliation":[{"name":"Complejo Asistencial de \u00c1vila, 05071 \u00c1vila, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bego\u00f1a","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen de la Victoria, 29010 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"de la Haba","sequence":"additional","affiliation":[{"name":"University Hospital Reina Sofia, 14004 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Campolier","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MEDSIR), 08005 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MEDSIR), 08005 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2184-1346","authenticated-orcid":false,"given":"Daniel","family":"Alcal\u00e1-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MEDSIR), 08005 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Sampayo-Cordero","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MEDSIR), 08005 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Cort\u00e9s","sequence":"additional","affiliation":[{"name":"International Breast Cancer Center (IBCC), Pangaea Oncology, Quir\u00f3n Group, 08022 Barcelona, Spain"},{"name":"Medica Scientia Innovation Research (MEDSIR), 08005 Barcelona, Spain"},{"name":"Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain"},{"name":"IOB Madrid, Institute of Oncology, Hospital Beata Mar\u00eda Ana, 28007 Madrid, Spain"},{"name":"Ribera Group, Oncology Department, Hospital Universitario Torrej\u00f3n, 28850 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Llombart-Cussac","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MEDSIR), 08005 Barcelona, Spain"},{"name":"Hospital Universitario Arnau de Vilanova, 46015 Valencia, Spain"},{"name":"Translational Oncology Group, Department of Medicine, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, 46115 Alfara del Patriarca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.breast.2022.08.010","article-title":"Current and future burden of breast cancer: Global statistics for 2020 and 2040","volume":"66","author":"Arnold","year":"2022","journal-title":"Breast"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2147\/TACG.S13226","article-title":"Inherited and acquired alterations in development of breast cancer","volume":"4","author":"Ottini","year":"2011","journal-title":"Appl. Clin. Genet."},{"key":"ref_4","first-page":"1000228","article-title":"BRCA1 and BRCA2 mutations and treatment strategies for breast cancer","volume":"4","author":"Godet","year":"2017","journal-title":"Integr. Cancer Sci. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1093\/annonc\/mdw209","article-title":"Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic","volume":"27","author":"Winter","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Breast Cancer Association Consortium (2021). Breast Cancer Risk Genes\u2014Association Analysis in More than 113,000 Women. N. Engl. J. Med., 384, 428\u2013439.","DOI":"10.1056\/NEJMoa1913948"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1056\/NEJMoa2005936","article-title":"A Population-Based Study of Genes Previously Implicated in Breast Cancer","volume":"384","author":"Hu","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nrc3181","article-title":"BRCA1 and BRCA2: Different roles in a common pathway of genome protection","volume":"12","author":"Roy","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"R33","DOI":"10.1186\/bcr3121","article-title":"Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and\/or BRCA2 mutation carriers","volume":"14","author":"Antoniou","year":"2012","journal-title":"Breast Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1158\/1055-9965.EPI-11-0775","article-title":"Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the Consortium of Investigators of Modifiers of BRCA1\/2 (CIMBA)","volume":"21","author":"Mavaddat","year":"2012","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.annonc.2024.06.013","article-title":"Overall survival in first-line HR+\/HER2- advanced breast cancer in the era of CDK4\/6 inhibitors","volume":"35","author":"Oliveira","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"GS3-01","DOI":"10.1158\/1538-7445.SABCS22-GS3-01","article-title":"Abstract GS3-01, GS3-01 EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+\/HER2- metastatic breast cancer: Updated results by duration of prior CDK4\/6i in metastatic setting","volume":"83","author":"Bardia","year":"2023","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.annonc.2020.11.011","article-title":"Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2\u2013negative advanced breast cancer: Final overall survival results from SOLAR-1","volume":"32","author":"Ciruelos","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1056\/NEJMoa1706450","article-title":"Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation","volume":"377","author":"Robson","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1056\/NEJMoa1802905","article-title":"Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation","volume":"379","author":"Litton","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ygyno.2015.02.017","article-title":"Two decades beyond BRCA1\/2: Homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy","volume":"137","author":"Walsh","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1200\/JCO.2019.37.15_suppl.1092","article-title":"RUBY: A phase II study testing rucaparib in germline (g) BRCA wild-type patients presenting metastatic breast cancer (mBC) with homologous recombination deficiency (HRD)","volume":"37","author":"Patsouris","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.1200\/JCO.20.02151","article-title":"TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes","volume":"38","author":"Tung","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"v53","DOI":"10.1093\/annonc\/mdz239.078","article-title":"Phase II study of olaparib in previously treated advanced solid tumours with homologous recombination repair mutation (HRRm) or homologous recombination repair deficiency (HRD): LYNK-002","volume":"30","author":"Hyman","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"TPS1114","DOI":"10.1200\/JCO.2018.36.15_suppl.TPS1114","article-title":"A phase II clinical trial to analyze olaparib response in patients with BRCA1 and\/or BRCA 2 promoter methylation with advanced breast cancer (GEICAM\/2015-06 COMETA-Breast study)","volume":"36","author":"Andres","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1200\/JCO.2019.37.15_suppl.3006","article-title":"Talazoparib beyond BRCA: A phase II trial of talazoparib monotherapy in BRCA1 and BRCA2 wild-type patients with advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous recombination (HR) pathway genes","volume":"37","author":"Gruber","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1056\/NEJMoa1611310","article-title":"Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer","volume":"375","author":"Mirza","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1001\/jamaoncol.2016.1897","article-title":"Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis","volume":"2","author":"Spring","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1001\/jamaoncol.2019.1029","article-title":"Open-label Clinical Trial of Niraparib Combined with Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer","volume":"5","author":"Vinayak","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5482","DOI":"10.1158\/1078-0432.CCR-21-0310","article-title":"Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: The EORTC 1307-BCG\/BIG5\u201313\/TESARO PR-30\u201350\u201310-C BRAVO Study","volume":"27","author":"Turner","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1093\/annonc\/mdz012","article-title":"OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician\u2019s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer","volume":"30","author":"Robson","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.annonc.2020.08.2098","article-title":"Talazoparib versus chemotherapy in patients with germline BRCA1\/2-mutated HER2-negative advanced breast cancer: Final overall survival results from the EMBRACA trial","volume":"31","author":"Litton","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s40487-021-00162-4","article-title":"A Real-World Evidence Study of CDK4\/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status","volume":"9","author":"Collins","year":"2021","journal-title":"Oncol Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2100140","DOI":"10.1200\/PO.21.00140","article-title":"Cyclin-Dependent Kinase 4\/6 Inhibitor Outcomes in Patients With Advanced Breast Cancer Carrying Germline Pathogenic Variants in DNA Repair\u2013Related Genes","volume":"6","author":"Bruno","year":"2022","journal-title":"JCO Precis. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"103201","DOI":"10.1016\/j.esmoop.2024.103201","article-title":"179O Combination of olaparib, durvalumab and fulvestrant in patients with advanced ER-positive, HER2-negative breast cancer harboring homologous recombination repair (HRR) deficiency or microsatellite instability (MSI): Results of the international phase II DOLAF trial","volume":"9","author":"Guiu","year":"2024","journal-title":"ESMO Open"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/11\/1744\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:38:44Z","timestamp":1760031524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/11\/1744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,22]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cancers17111744"],"URL":"https:\/\/doi.org\/10.3390\/cancers17111744","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2025,5,22]]}}}