{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:36:24Z","timestamp":1790735784991,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Trastuzumab emtansine (T-DM1) is widely used in Human Epidermal Growth Factor Receptor2 (HER2)-positive metastatic breast cancer; however, outcomes vary, and reliable prognostic markers remain limited. We developed the CALA index as a composite biomarker integrating CA15-3, lactate dehydrogenase (LDH), and albumin. This study aimed to evaluate the prognostic value of the CALA index in metastatic breast cancer treated with T-DM1. Methods: This multicenter retrospective study included 168 patients treated with T-DM1 across four tertiary centers. The CALA index was calculated using pretreatment levels of CA15-3, LDH, and albumin. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value, and patients were stratified into groups accordingly. Survival outcomes and independent risk factors were assessed using Kaplan\u2013Meier and Cox regression analyses. Results: The median overall survival (OS) was 26 months (95% CI: 21.3\u201330.7). ROC analysis identified an optimal CALA cutoff value of 118.3. Patients with CALA \u2264 118.3 demonstrated significantly longer OS compared with those with CALA &gt; 118.3 (log-rank p = 0.006), with 1- and 3-year OS rates of 81.2% and 43.2% versus 69.8% and 22.7%, respectively. In univariate analysis, CALA &gt; 118.3 was associated with worse OS (HR: 1.699; 95% CI: 1.151\u20132.506; p = 0.008), and this association remained significant in multivariate analysis (HR: 1.671; 95% CI: 1.088\u20132.565; p = 0.019). Conclusions: The CALA index was associated with overall survival in metastatic breast cancer treated with trastuzumab emtansine and may serve as a practical tool for risk stratification.<\/jats:p>","DOI":"10.3390\/ph19060809","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Composite CA15-3, LDH, and Albumin Index as a Predictor of Survival in HER2-Positive Metastatic Breast Cancer Treated with Trastuzumab Emtansine"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9344-7212","authenticated-orcid":false,"given":"Nagihan","family":"Kolk\u0131ran","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Manisa Celal Bayar University, Manisa 45030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atike P\u0131nar","family":"Erdo\u011fan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Manisa Celal Bayar University, Manisa 45030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"\u015eahbazlar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Manisa Celal Bayar University, Manisa 45030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6820-9738","authenticated-orcid":false,"given":"M\u00fcge","family":"Kurul Yeniay","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, \u0130zmir Katip \u00c7elebi University Atat\u00fcrk Training and Research Hospital, \u0130zmir 35360, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinan","family":"\u00dcnal","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, \u0130zmir Katip \u00c7elebi University Atat\u00fcrk Training and Research Hospital, \u0130zmir 35360, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5513-4351","authenticated-orcid":false,"given":"Mehmet Sinan","family":"Akarca","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Dokuz Eyl\u00fcl University, \u0130zmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Ata\u011f Aky\u00fcrek","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Dokuz Eyl\u00fcl University, \u0130zmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zge","family":"Demirk\u0131ran","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Ayd\u0131n Adnan Menderes University, Ayd\u0131n 09100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4380-9419","authenticated-orcid":false,"given":"Bilgin","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Ayd\u0131n Adnan Menderes University, Ayd\u0131n 09100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9317-942X","authenticated-orcid":false,"given":"Ferhat","family":"Ekinci","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Manisa Celal Bayar University, Manisa 45030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12935-024-03419-w","article-title":"Prognostic significance of hemoglobin, albumin, lymphocyte, and platelet score in breast cancer: A propensity score-matching study","volume":"24","author":"Jiang","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1056\/NEJMoa1209124","article-title":"Trastuzumab emtansine for HER2-positive advanced breast cancer","volume":"367","author":"Verma","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S1470-2045(17)30313-3","article-title":"Trastuzumab emtansine versus treatment of physician\u2019s choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): Final overall survival results from a randomised open-label phase 3 trial","volume":"18","author":"Krop","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100561","DOI":"10.1016\/j.esmoop.2022.100561","article-title":"Final results of the global and Asia cohorts of KAMILLA, a phase IIIB safety trial of trastuzumab emtansine in patients with HER2-positive advanced breast cancer","volume":"7","author":"Wuerstlein","year":"2022","journal-title":"ESMO Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2147\/IJGM.S396871","article-title":"Prognostic significance of preoperative lactate dehydrogenase to albumin ratio in breast cancer: A retrospective study","volume":"16","author":"He","year":"2023","journal-title":"Int. J. Gen. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e36315","DOI":"10.1097\/MD.0000000000036315","article-title":"Peripheral blood inflammatory indexes in breast cancer: A review","volume":"102","author":"Xie","year":"2023","journal-title":"Medicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e19319","DOI":"10.7717\/peerj.19319","article-title":"Prognostic significance of C-reactive protein and albumin-based biomarker in patients with breast cancer receiving chemotherapy","volume":"13","author":"Hutajulu","year":"2025","journal-title":"PeerJ"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sahin, T.K., Akyildiz, A., Dogan, O.T., Kavgaci, G., Guven, D.C., and Aksoy, S. (2024). Prognostic significance of pan-immune-inflammation value in patients with HER2-positive metastatic breast cancer treated with trastuzumab emtansine. Pharmaceuticals, 17.","DOI":"10.3390\/ph17070824"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9800","DOI":"10.1038\/srep09800","article-title":"Prognostic value of pretreatment serum lactate dehydrogenase level in patients with solid tumors: A systematic review and meta-analysis","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.14740\/jocmr2653w","article-title":"Prognostic impact of the tumor marker CA 15-3 in patients with breast cancer and bone metastases treated with palliative radiotherapy","volume":"9","author":"Nieder","year":"2017","journal-title":"J. Clin. Med. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1016\/j.clbc.2019.09.001","article-title":"T-DM1 efficacy in patients with HER2-positive metastatic breast cancer progressing after taxane plus trastuzumab and pertuzumab: An Italian multicenter observational study","volume":"20","author":"Conte","year":"2020","journal-title":"Clin. Breast Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4174\/astr.2016.90.2.57","article-title":"Clinical significance of serum CA15-3 as a prognostic parameter during follow-up periods in patients with breast cancer","volume":"90","author":"Chu","year":"2016","journal-title":"Ann. Surg. Treat. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/j.cca.2010.08.039","article-title":"CA 15-3: Uses and limitations as a biomarker for breast cancer","volume":"411","author":"Duffy","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, L., Ai, L., Jia, L., Zhang, L., Lei, B., and Zhang, Q. (2022). High score of LDH plus dNLR predicts poor survival in patients with HER2-positive advanced breast cancer treated with trastuzumab emtansine. BMC Cancer, 22.","DOI":"10.1186\/s12885-021-09131-6"},{"key":"ref_16","first-page":"353","article-title":"Prognostic role of lactate dehydrogenase in solid tumors: A systematic review and meta-analysis","volume":"94","author":"Petrelli","year":"2015","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1475-2891-9-69","article-title":"Pretreatment serum albumin as a predictor of cancer survival: A systematic review of the epidemiological literature","volume":"9","author":"Gupta","year":"2010","journal-title":"Nutr. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cai, J., Wang, B., Jing, N., and Zhang, Y. (2025). Prognostic value of the HALP score in breast cancer: A systematic review and meta-analysis. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1684940"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"997","DOI":"10.2147\/IJGM.S447201","article-title":"Prognostic value of CRP\u2013albumin\u2013lymphocyte (CALLY) index in breast cancer","volume":"17","author":"Zhuang","year":"2024","journal-title":"Int. J. Gen. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1038\/s41598-018-37633-0","article-title":"Significance of baseline neutrophil-to-lymphocyte ratio for progression-free survival of patients with HER2-positive breast cancer treated with trastuzumab emtansine","volume":"9","author":"Imamura","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ma, Y.Y., Wang, H., Zhao, W.D., Li, Y.F., Wang, J.J., and Chen, X.Y. (2022). Prognostic value of combined lactate dehydrogenase, C-reactive protein, cancer antigen 153 and cancer antigen 125 in metastatic breast cancer. Cancer Control, 29.","DOI":"10.1177\/10732748211053150"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1245\/s10434-024-16454-8","article-title":"Prognostic value of the baseline systemic immune-inflammation index in HER2-positive metastatic breast cancer: Exploratory analysis of two prospective trials","volume":"32","author":"Pang","year":"2025","journal-title":"Ann. Surg. Oncol."},{"key":"ref_23","first-page":"484","article-title":"Importance of prognostic nutritional index in patients with metastatic breast cancer treated with trastuzumab emtansine","volume":"6","author":"Koseci","year":"2022","journal-title":"Eurasian J. Med. Investig."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:36:22Z","timestamp":1779687382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":23,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ph19060809"],"URL":"https:\/\/doi.org\/10.3390\/ph19060809","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}