{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:21:11Z","timestamp":1770988871171,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Industry Development Institute (KHIDI)","award":["HR20C0025"],"award-info":[{"award-number":["HR20C0025"]}]},{"name":"Korea Health Industry Development Institute (KHIDI)","award":["SMO1220551"],"award-info":[{"award-number":["SMO1220551"]}]},{"name":"Korea Health Industry Development Institute (KHIDI)","award":["SMO1220981"],"award-info":[{"award-number":["SMO1220981"]}]},{"name":"Korea Health Industry Development Institute (KHIDI)","award":["NRF-2020R1F1A1072616"],"award-info":[{"award-number":["NRF-2020R1F1A1072616"]}]},{"name":"Samsung Medical Center","award":["HR20C0025"],"award-info":[{"award-number":["HR20C0025"]}]},{"name":"Samsung Medical Center","award":["SMO1220551"],"award-info":[{"award-number":["SMO1220551"]}]},{"name":"Samsung Medical Center","award":["SMO1220981"],"award-info":[{"award-number":["SMO1220981"]}]},{"name":"Samsung Medical Center","award":["NRF-2020R1F1A1072616"],"award-info":[{"award-number":["NRF-2020R1F1A1072616"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["HR20C0025"],"award-info":[{"award-number":["HR20C0025"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["SMO1220551"],"award-info":[{"award-number":["SMO1220551"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["SMO1220981"],"award-info":[{"award-number":["SMO1220981"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1F1A1072616"],"award-info":[{"award-number":["NRF-2020R1F1A1072616"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: We analyzed real-world practice of second-line treatment in hormone receptor (HR)+ human epidermal growth factor receptor-2 (HER2)\u2212 metastatic breast cancer (MBC) following the first-line CDK4\/6 inhibitor with letrozole. In addition, we evaluated the relationship between second-line treatment strategies and survival outcome. Methods: Using the clinical data warehouse, clinical information including MBC diagnosis, treatment and survival outcomes were collected. Results: In total, 305 patients were treated with the first-line palbociclib plus letrozole, and we evaluated 166 patients who were treated with second-line treatment. Of the 166 patients, 28.5% were treated with capecitabine (C), followed by exemestane with everolimus (EE) (27.3%) or cytotoxic chemotherapy other than capecitabine (T) (18.8%) and fulvestrant-based treatment or endocrine monotherapy (F) (12.7%). Eighteen patients (10.9%) were enrolled in clinical trials (CT). With regard to treatment strategies, and the median progression-free survival of second-line treatment in a metastatic setting (PFS2) was 7.4 months with C, 5.2 months with EE, 4.8 months with T, 3.6 months with F, and 3.6 months with CT (p = 0.066). In patients with visceral organ disease progression, C (31.3%) or T(31.3%) was the most common second-line treatment followed by EE (21.9%). Most of the 47 patients with bone metastasis alone were treated with EE (38.2%), followed by C (23.4%) and F (21.3%) (p = 0.008). The median overall survival of second-line treatment in a metastatic setting (OS2) was 42.3 months with C, 35.7 months with F, 30.7 months with EE, and 23.1 months with T. The median OS2 for those in CT was not reached (p = 0.064). ER driven BC, disease progression site and PFS2 were associated with OS and OS2 in HR+HER2\u2212 MBC (ps &lt; 0.05). Conclusions: We suggested the second line treatment strategy was important to improve prognosis in patients with HR+\/HER2\u2212 MBC, especially given the recent standardization of first-line treatment and the many available second-line options.<\/jats:p>","DOI":"10.3390\/cancers15133431","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:49:27Z","timestamp":1688345367000},"page":"3431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Real World Experience of Second-Line Treatment Strategies after Palbociclib and Letrozole: Overall Survival in Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4223-1929","authenticated-orcid":false,"given":"Ji-Yeon","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"},{"name":"Department of Health Science & Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6834-7217","authenticated-orcid":false,"given":"Junghoon","family":"Shin","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Seok","family":"Ahn","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-9212","authenticated-orcid":false,"given":"Yeon Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"},{"name":"Department of Health Science & Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6459-8118","authenticated-orcid":false,"given":"Young-Hyuck","family":"Im","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"},{"name":"Department of Health Science & Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.3322\/caac.21754","article-title":"Breast Cancer Statistics, 2022","volume":"72","author":"Giaquinto","year":"2022","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.annonc.2021.09.019","article-title":"ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer","volume":"32","author":"Gennari","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1056\/NEJMoa1607303","article-title":"Palbociclib and Letrozole in Advanced Breast Cancer","volume":"375","author":"Finn","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1056\/NEJMoa1609709","article-title":"Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer","volume":"375","author":"Hortobagyi","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/S1470-2045(18)30292-4","article-title":"Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): A randomised phase 3 trial","volume":"19","author":"Tripathy","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1200\/JCO.2017.75.6155","article-title":"MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer","volume":"35","author":"Goetz","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"LBA1003","DOI":"10.1200\/JCO.2022.40.17_suppl.LBA1003","article-title":"Overall survival (OS) with first-line palbociclib plus letrozole (PAL+LET) versus placebo plus letrozole (PBO+LET) in women with estrogen receptor\u2013positive\/human epidermal growth factor receptor 2\u2013negative advanced breast cancer (ER+\/HER2\u2212ABC): Analyses from PALOMA-2","volume":"40","author":"Finn","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1056\/NEJMoa2114663","article-title":"Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer","volume":"386","author":"Hortobagyi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1056\/NEJMoa1903765","article-title":"Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer","volume":"381","author":"Im","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S1384","DOI":"10.1016\/j.annonc.2022.08.009","article-title":"LBA15 MONARCH 3: Interim overall survival (OS) results of abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+, HER2- advanced breast cancer (ABC)","volume":"33","author":"Goetz","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41523-022-00479-x","article-title":"Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+\/HER2\u2212 metastatic breast cancer","volume":"8","author":"Rugo","year":"2022","journal-title":"NPJ Breast Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.1200\/JCO.21.01392","article-title":"Endocrine Treatment and Targeted Therapy for Hormone Receptor\u2013Positive, Human Epidermal Growth Factor Receptor 2\u2013Negative Metastatic Breast Cancer: ASCO Guideline Update","volume":"39","author":"Burstein","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMoa1813904","article-title":"Alpelisib for PIK3CA-Mutated, Hormone Receptor\u2013Positive Advanced Breast Cancer","volume":"380","author":"Ciruelos","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(21)00034-6","article-title":"Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4\/6 inhibitor (BYLieve): One cohort of a phase 2, multicentre, open-label, non-comparative study","volume":"22","author":"Rugo","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2203690","article-title":"Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer","volume":"387","author":"Modi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"759150","DOI":"10.3389\/fonc.2021.759150","article-title":"Which Clinicopathologic Parameters Suggest Primary Resistance to Palbociclib in Combination With Letrozole as the First-Line Treatment for Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer?","volume":"11","author":"Kim","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7127","DOI":"10.7150\/jca.48944","article-title":"Comparative Overall Survival of CDK4\/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer","volume":"11","author":"Lin","year":"2020","journal-title":"J. Cancer"},{"key":"ref_18","first-page":"1","article-title":"Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study","volume":"5","author":"Im","year":"2019","journal-title":"J. Glob. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"vii11","DOI":"10.1093\/annonc\/mds232","article-title":"Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"23","author":"Cardoso","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1200\/JCO.2003.04.194","article-title":"Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: Analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group","volume":"21","author":"Mouridsen","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1016\/S0959-8049(03)00326-5","article-title":"Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: Survival analysis and updated safety results","volume":"39","author":"Nabholtz","year":"2003","journal-title":"Eur. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3748","DOI":"10.1200\/JCO.2000.18.22.3748","article-title":"Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: Results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study","volume":"18","author":"Bonneterre","year":"2000","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100573","DOI":"10.1016\/j.lanepe.2022.100573","article-title":"Real-world time trends in overall survival, treatments and patient characteristics in HR+\/HER2\u2212 metastatic breast cancer: An observational study of the SONABRE Registry","volume":"26","author":"Meegdes","year":"2023","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/s41416-022-01845-z","article-title":"Overall survival of patients with metastatic breast cancer in Sweden: A nationwide study","volume":"127","author":"Valachis","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1200\/JCO.1999.17.2.485","article-title":"Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer","volume":"17","author":"Blum","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1023\/A:1012281104865","article-title":"Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced\/metastatic breast cancer","volume":"12","author":"Oshaughnessy","year":"2001","journal-title":"Ann. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/S1470-2045(19)30565-0","article-title":"Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial","volume":"20","author":"Park","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.annonc.2020.12.013","article-title":"Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: A phase III randomised controlled trial-PEARL","volume":"32","author":"Martin","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ccell.2018.08.008","article-title":"The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers","volume":"34","author":"Razavi","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5172","DOI":"10.1158\/1078-0432.CCR-20-0224","article-title":"ESR1 Mutations and Overall Survival on Fulvestrant versus Exemestane in Advanced Hormone Receptor-Positive Breast Cancer: A Combined Analysis of the Phase III SoFEA and EFECT Trials","volume":"26","author":"Turner","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1158\/1078-0432.CCR-21-3811","article-title":"VERONICA: Randomized Phase II Study of Fulvestrant and Venetoclax in ER-Positive Metastatic Breast Cancer Post-CDK4\/6 Inhibitors\u2014Efficacy, Safety, and Biomarker Results","volume":"28","author":"Lindeman","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"GS3","DOI":"10.1158\/1538-7445.SABCS22-GS3-04","article-title":"GS3-04 Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive\/human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the Phase III CAPItello-291 trial [abstract]","volume":"83","author":"Turner","year":"2023","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8297","DOI":"10.1158\/0008-5472.CAN-06-0503","article-title":"Prevalence and Predictors of BRCA1 and BRCA2 Mutations in a Population-Based Study of Breast Cancer in White and Black American Women Ages 35 to 64 Years","volume":"66","author":"Malone","year":"2006","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","year":"2012","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1158\/2159-8290.CD-18-0264","article-title":"The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial","volume":"8","author":"Cutts","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/s41586-019-1056-z","article-title":"Genomic characterization of metastatic breast cancers","volume":"569","author":"Bertucci","year":"2019","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1200\/JCO.22.00338","article-title":"Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial","volume":"40","author":"Bidard","year":"2022","journal-title":"J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/13\/3431\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:03:38Z","timestamp":1760126618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/13\/3431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,30]]},"references-count":37,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["cancers15133431"],"URL":"https:\/\/doi.org\/10.3390\/cancers15133431","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,30]]}}}