{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T20:50:44Z","timestamp":1781383844530,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Center, Republic of Korea","award":["NCC-2110182-3"],"award-info":[{"award-number":["NCC-2110182-3"]}]},{"name":"National Cancer Center, Republic of Korea","award":["NCC- 24H1210-1"],"award-info":[{"award-number":["NCC- 24H1210-1"]}]},{"name":"Dong-A ST","award":["NCC-2110182-3"],"award-info":[{"award-number":["NCC-2110182-3"]}]},{"name":"Dong-A ST","award":["NCC- 24H1210-1"],"award-info":[{"award-number":["NCC- 24H1210-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The role of combining neoadjuvant endocrine therapy with conventional chemotherapy remains unclear; therefore, we conducted an open-label, single-center, nonrandomized phase II trial to assess the effect of this combination. Patients with previously untreated stage II or III HR-positive, HER2-negative breast cancer received concurrent letrozole 2.5 mg with standard neoadjuvant chemotherapy. The primary endpoint was pathologic complete response (pCR) at the time of surgery. We used Simon\u2019s minimax two-stage design; a pCR rate &gt; 6% was necessary at the first stage to continue. Between November 2017 and November 2020, 53 women were enrolled in the first stage of the trial. Their median age was 49 years (range, 33\u201363), and 60% of them were premenopausal. Subsequently, 66% and 34% of patients with clinical stages II and III, respectively, were included; 93% had clinically node-positive disease. Two patients (4%) achieved pCR after neoadjuvant chemo\u2013endocrine treatment, which did not satisfy the criteria for continuing to the second stage. The overall response rate was 83%. During the median follow-up of 53.7 months, the 3-year disease-free survival and overall survival rates were 87% and 98%, respectively. Neutropenia was the most common grade 3\/4 adverse event (40%), but rarely led to febrile neutropenic episodes (4%). Myalgia (32%), nausea (19%), constipation (17%), heartburn (11%), oral mucositis (9%), and sensory neuropathy (9%) were frequently observed, but classified as grade 1 or 2. No deaths occurred during preoperative treatment. The addition of letrozole to standard neoadjuvant chemotherapy was safe and beneficial in terms of overall response rate, but did not provide a higher pCR rate in locally advanced HR-positive, HER2-negative breast cancer. Further research is needed to enhance neoadjuvant treatment strategies for this cancer subtype.<\/jats:p>","DOI":"10.3390\/cancers16183122","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T10:20:10Z","timestamp":1725963610000},"page":"3122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neoadjuvant Chemotherapy with Concurrent Letrozole for Estrogen Receptor-Positive and HER2-Negative Breast Cancer: An Open-Label, Single-Center, Nonrandomized Phase II Study (NeoCHAI)"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3547-3521","authenticated-orcid":false,"given":"Heejung","family":"Chae","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"},{"name":"Cancer Data Center, National Cancer Control Institute, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hoon","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"},{"name":"Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngmi","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cancer Center, Hospital, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-8846","authenticated-orcid":false,"given":"Eun-Gyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jai Hong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Youn","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"},{"name":"Division of Clinical Research, Research Institute, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7576-1512","authenticated-orcid":false,"given":"Seeyoun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Sung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon-Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Proton Therapy, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-3385","authenticated-orcid":false,"given":"Tae Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Proton Therapy, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5575-836X","authenticated-orcid":false,"given":"Keun Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,10]]},"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":"e2013226","DOI":"10.1001\/jamanetworkopen.2020.13226","article-title":"Incidence trends of breast cancer molecular subtypes by age and race\/ethnicity in the US from 2010 to 2016","volume":"3","author":"Acheampong","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S0140-6736(13)62422-8","article-title":"Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis","volume":"384","author":"Cortazar","year":"2014","journal-title":"Lancet"},{"key":"ref_4","unstructured":"(2024, April 12). National Comprehensive Cancer Network Guidelines. Breast Cancer (Version 2, 2024). Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/breast.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.breast.2007.03.004","article-title":"Endocrine therapy for breast cancer: An overview","volume":"16","author":"Cheung","year":"2007","journal-title":"Breast"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1245\/s10434-016-5585-5","article-title":"Trends in neoadjuvant endocrine therapy use and impact on rates of breast conservation in hormone receptor-positive breast cancer: A National Cancer Data Base study","volume":"24","author":"Chiba","year":"2017","journal-title":"Ann. Surg. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1016\/S0140-6736(09)61523-3","article-title":"Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: A phase 3, open-label, randomised controlled trial","volume":"374","author":"Albain","year":"2009","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1093\/jnci\/djr351","article-title":"Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: A multicenter randomized phase III trial","volume":"103","author":"Bedognetti","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/1097-0142(19830215)51:4<581::AID-CNCR2820510404>3.0.CO;2-G","article-title":"Chemotherapy versus combination of chemotherapy and endocrine therapy in advanced breast cancer. A prospective randomized study","volume":"51","author":"Cocconi","year":"1983","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF01803554","article-title":"Efforts to combine endocrine and chemotherapy in the management of breast cancer: Do two and two equal three?","volume":"3","author":"Lippman","year":"1983","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1200\/JCO.1997.15.6.2302","article-title":"Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and\/or progesterone receptor-positive breast cancer: A report of the National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group","volume":"15","author":"Pritchard","year":"1997","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1200\/JCO.2000.18.2.262","article-title":"Comparison of chemotherapy with chemohormonal therapy as first-line therapy for metastatic, hormone-sensitive breast cancer: An Eastern Cooperative Oncology Group study","volume":"18","author":"Sledge","year":"2000","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1200\/JCO.1996.14.10.2731","article-title":"Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. National Cancer Institute of Canada Clinical Trials Group Breast Cancer Site Group","volume":"14","author":"Pritchard","year":"1996","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/S1470-2045(10)70257-6","article-title":"Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial","volume":"11","author":"Cuzick","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1056\/NEJMoa1803164","article-title":"Tailoring adjuvant endocrine therapy for premenopausal breast cancer","volume":"379","author":"Francis","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1200\/JCO.18.00440","article-title":"Adjuvant letrozole and tamoxifen alone or sequentially for postmenopausal women with hormone receptor-positive breast cancer: Long-term follow-up of the BIG 1\u201398 trial","volume":"37","author":"Ruhstaller","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG), Peto, R., Davies, C., Godwin, J., Gray, R., Pan, H.C., Clarke, M., Cutter, D., Darby, S., and McGale, P. (2012). Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet, 379, 432\u2013444.","DOI":"10.1016\/S0140-6736(11)61625-5"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1056\/NEJMoa1612645","article-title":"Adjuvant capecitabine for breast cancer after preoperative chemotherapy","volume":"376","author":"Masuda","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1093\/annonc\/mdz189","article-title":"Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"30","author":"Cardoso","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1200\/JCO.20.03399","article-title":"Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO Guideline [ASCO guideline]","volume":"39","author":"Korde","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s10549-011-1814-6","article-title":"The efficacy and safety of neoadjuvant chemotherapy +\/\u2212 letrozole in postmenopausal women with locally advanced breast cancer: A randomized phase III clinical trial","volume":"132","author":"Mohammadianpanah","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_22","first-page":"291","article-title":"Neoadjuvant chemotherapy with or without concurrent hormone therapy in estrogen receptor-positive breast cancer: NACED-randomized multicenter phase II trial","volume":"69","author":"Sugiu","year":"2015","journal-title":"Acta Med. Okayama"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1158\/1078-0432.CCR-19-3492","article-title":"Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: A comprehensive meta-analysis","volume":"26","author":"Spring","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1093\/annonc\/mds132","article-title":"Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: Results from the GEICAM\/2006-03, a multicenter, randomized, phase-II study","volume":"23","author":"Alba","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/cncr.22789","article-title":"Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer","volume":"110","author":"Semiglazov","year":"2007","journal-title":"Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1002\/cncr.32057","article-title":"Concurrent neoadjuvant chemotherapy and estrogen deprivation in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (CBCSG-036): A randomized, controlled, multicenter trial","volume":"125","author":"Yu","year":"2019","journal-title":"Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1200\/JCO.2010.28.5437","article-title":"Phase III study of doxorubicin\/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial","volume":"29","author":"Eiermann","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1056\/NEJMoa0707056","article-title":"Weekly paclitaxel in the adjuvant treatment of breast cancer","volume":"358","author":"Sparano","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1097\/MBC.0000000000001043","article-title":"Risk of venous thromboembolism and endocrine therapy in older women with breast cancer in the United States","volume":"32","author":"Faiz","year":"2021","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_30","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_31","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_32","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa1911149","article-title":"Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer","volume":"382","author":"Slamon","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_33","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_34","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_35","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_36","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1093\/annonc\/mdy448","article-title":"Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer","volume":"29","author":"Cottu","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1200\/JCO.18.01624","article-title":"Randomized Phase II Study Evaluating Palbociclib in Addition to Letrozole as Neoadjuvant Therapy in Estrogen Receptor-Positive Early Breast Cancer: PALLET Trial","volume":"37","author":"Johnston","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S1470-2045(19)30786-7","article-title":"Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial","volume":"21","author":"Prat","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1158\/1078-0432.CCR-19-1425","article-title":"Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+\/HER2\u2212 Breast Cancer","volume":"26","author":"Hurvitz","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Falo, C., Azcarate, J., Fernandez-Gonzalez, S., Perez, X., Petit, A., Perez, H., Vethencourt, A., Vazquez, S., Laplana, M., and Ales, M. (2024). Breast Cancer Patient\u2019s Outcomes after Neoadjuvant Chemotherapy and Surgery at 5 and 10 Years for Stage II-III Disease. Cancers, 16.","DOI":"10.3390\/cancers16132421"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"207","DOI":"10.4048\/jbc.2023.26.e27","article-title":"Breast Cancer Statistics in Korea, 2019","volume":"26","author":"Choi","year":"2023","journal-title":"J. Breast Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1038\/s41467-018-04129-4","article-title":"Multi-omics profiling of younger Asian breast cancers reveals distinctive molecular signatures","volume":"9","author":"Kan","year":"2018","journal-title":"Nat. Commun."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/18\/3122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:53:17Z","timestamp":1760111597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/18\/3122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,10]]},"references-count":42,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["cancers16183122"],"URL":"https:\/\/doi.org\/10.3390\/cancers16183122","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,10]]}}}