{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T17:02:03Z","timestamp":1780938123650,"version":"3.54.1"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer is influenced by multiple tumor- and host-related factors, and readily available pretreatment biomarkers of response are still limited. This study aimed to evaluate the association between pretreatment systemic inflammatory and nutritional parameters and pCR assessed by the Miller\u2013Payne grading system, with a specific focus on the independent predictive value of pretreatment serum albumin compared with established inflammatory ratios. Methods: A total of 226 patients with breast carcinoma who received NACT between May 2017 and September 2023 were retrospectively evaluated. Pretreatment laboratory parameters\u2014including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), serum albumin, and the CRP\/albumin ratio (CAR)\u2014were recorded. Pathological response was assessed using the Miller\u2013Payne grading system by two breast pathologists blinded to laboratory data. Univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed, complemented by bootstrap validation of the optimal cut-off, a sensitivity analysis using the contemporary ypT0\/is ypN0 definition of pCR, and a subgroup analysis by molecular subtype. Results: pCR was observed in 41 patients (18.1%). Pretreatment serum albumin levels were significantly lower in responders than in non-responders (p = 0.027), whereas NLR, PLR, CRP, and CAR were not significantly associated with response. In multivariable analysis, pretreatment serum albumin, Ki-67, and HER2 status emerged as independent predictors of pCR. ROC analysis demonstrated moderate discriminatory ability for albumin (AUC = 0.64); the optimal cut-off was 4.22 g\/dL (bootstrap 95% CI 3.50\u20134.53 g\/dL), with values below this threshold associated with a higher likelihood of pCR. The association between low pretreatment albumin and pCR was particularly pronounced in the triple-negative subgroup (3.30 vs. 4.02 g\/dL, p = 0.027). The albumin signal remained significant under the stricter ypT0\/is ypN0 definition of pCR in univariable analysis (OR 0.47, p = 0.045). Conclusions: Pretreatment serum albumin, independent of systemic inflammatory ratios, is associated with pCR to NACT in breast cancer and may serve as a candidate biomarker for pretreatment risk stratification, particularly when interpreted alongside established tumor-related predictors such as Ki-67 and HER2 status. The association appears especially relevant in the triple-negative subgroup, suggesting that patients with TNBC and low pretreatment serum albumin may warrant heightened multidisciplinary attention during NACT. Validation in larger, prospective, multicenter cohorts is needed before routine clinical implementation.<\/jats:p>","DOI":"10.3390\/jcm15124429","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:25:16Z","timestamp":1780935916000},"page":"4429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Pretreatment Serum Albumin and Systemic Inflammatory Markers with Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5097-0505","authenticated-orcid":false,"given":"Sel\u00e7uk","family":"Cin","sequence":"first","affiliation":[{"name":"Department of Pathology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-300X","authenticated-orcid":false,"given":"Merve","family":"Tokocin","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Ba\u011fc\u0131lar Training and Research Hospital, University of Health Sciences, Istanbul 34200, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3075-6063","authenticated-orcid":false,"given":"\u00d6zgecan","family":"G\u00fcndo\u011far","sequence":"additional","affiliation":[{"name":"Department of Pathology, Gaziosmanpa\u015fa Training and Research Hospital, University of Health Sciences, Istanbul 34255, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0656-497X","authenticated-orcid":false,"given":"Merve","family":"Cin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Istanbul Training and Research Hospital, University of Health Sciences, Istanbul 34080, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Muhammedo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ba\u011fc\u0131lar Training and Research Hospital, University of Health Sciences, Istanbul 34200, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0619-5868","authenticated-orcid":false,"given":"Murat","family":"Y\u00fcce","sequence":"additional","affiliation":[{"name":"Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahu Senem","family":"Demir\u00f6z","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16979","DOI":"10.1038\/s41598-019-53606-3","article-title":"Neutrophil-lymphocyte ratio in metastatic breast cancer is not an independent predictor of survival, but depends on other variables","volume":"9","author":"Yufera","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_2","unstructured":"(2026, May 21). SEER Cancer Stat Facts: Breast Cancer, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/breast.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"746","DOI":"10.3332\/ecancer.2017.746","article-title":"The past and future of breast cancer treatment-from the papyrus to individualised treatment approaches","volume":"11","author":"Ades","year":"2017","journal-title":"Ecancermedicalscience"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13203","DOI":"10.1038\/s41598-020-70077-z","article-title":"Neutrophil to lymphocyte ratio and breast cancer risk: Analysis by subtype and potential interactions","volume":"10","author":"Matabuena","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ciarka, A., Pi\u0105tek, M., P\u0119ksa, R., Kunc, M., and Senkus, E. (2024). Tumor-Infiltrating Lymphocytes (TILs) in Breast Cancer: Prognostic and Predictive Significance across Molecular Subtypes. Biomedicines, 12.","DOI":"10.3390\/biomedicines12040763"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1001\/jama.2024.3056","article-title":"International Immuno-Oncology Biomarker Working Group. Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer","volume":"331","author":"Jonas","year":"2024","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13078","DOI":"10.1038\/s41598-020-69965-1","article-title":"Prognostic value of neutrophil-to-lymphocyte ratio in human epidermal growth factor receptor 2-negative breast cancer patients who received neoadjuvant chemotherapy","volume":"10","author":"Bae","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e19319","DOI":"10.7717\/peerj.19319","article-title":"Prognostic significance of C-reactive protein (CRP) 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","first-page":"e40775","DOI":"10.1097\/MD.0000000000040775","article-title":"High C-reactive protein is associated with the efficacy of neoadjuvant chemotherapy for hormone receptor-positive breast cancer","volume":"103","author":"Hu","year":"2024","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0960-9776(03)00106-1","article-title":"A new histological grading system to assess response of breast cancers to primary chemotherapy: Prognostic significance and survival","volume":"12","author":"Ogston","year":"2003","journal-title":"Breast"},{"key":"ref_11","first-page":"483","article-title":"Human neutrophil-mediated cytotoxicity to tumor cells","volume":"66","author":"Gerrard","year":"1981","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/1097-0142(19820701)50:1<62::AID-CNCR2820500113>3.0.CO;2-0","article-title":"Neutrophil-mediated tumor cell destruction in cancer ascites","volume":"50","author":"Katano","year":"1982","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14216","DOI":"10.1038\/s41598-024-63318-y","article-title":"Predictive efficacy of the preoperative neutrophil-lymphocyte ratio in lymph node metastasis of cN0 hormone receptor-positive breast cancer","volume":"14","author":"Wang","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"425","DOI":"10.4048\/jbc.2019.22.e41","article-title":"The Role of Neutrophil-lymphocyte Ratio and Platelet-lymphocyte Ratio in Predicting Neoadjuvant Chemotherapy Response in Breast Cancer","volume":"22","author":"Kim","year":"2019","journal-title":"J. Breast Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ebaid, N.F., Abdelkawy, K.S., Said, A.S.A., Al-Ahmad, M.M., Shehata, M.A., Salem, H.F., and Hussein, R.R.S. (2025). Is the Neutrophil-to-Lymphocyte Ratio a Predictive Factor of Pathological Complete Response in Egyptian Breast Cancer Patients Treated with Neoadjuvant Chemotherapy?. Medicina, 61.","DOI":"10.3390\/medicina61020327"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, Y., Chen, K., Xiao, X., Nie, Y., Qu, S., Gong, C., Su, F., and Song, E. (2016). Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients: A retrospective study. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2352-8"},{"key":"ref_17","first-page":"182","article-title":"Neutrophils-to-lymphocytes, lymphocytes to-monocytes and platelets-to-lymphocytes ratios\u2014Predictive biomarkers for response to neoadjuvant chemotherapy in breast cancer","volume":"25","author":"Caziuc","year":"2020","journal-title":"J. BUON"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1007\/s12032-012-0432-4","article-title":"Pretreatment neutrophil\/lymphocyte ratio is superior to platelet\/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients","volume":"30","author":"Azab","year":"2013","journal-title":"Med. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"znae132","DOI":"10.1093\/bjs\/znae132","article-title":"Predictive value of pretreatment circulating inflammatory response markers in the neoadjuvant treatment of breast cancer: Meta-analysis","volume":"111","author":"Dowling","year":"2024","journal-title":"Br. J. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Arici, M.O., Kivrak Salim, D., Kocer, M., Alparslan, A.S., Karakas, B.R., and Ozturk, B. (2024). Predictive and Prognostic Value of Inflammatory and Nutritional Indexes in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy. Medicina, 60.","DOI":"10.3390\/medicina60111849"},{"key":"ref_21","first-page":"393","article-title":"Predictive Value of Pretreatment Neutrophil to Albumin Ratio in Response to Neoadjuvant Chemotherapy of Breast Cancer","volume":"16","author":"Deng","year":"2024","journal-title":"Breast Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tang, Q., Li, X., and Sun, C.R. (2024). Predictive value of serum albumin levels on cancer survival: A prospective cohort study. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1323192"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jvs.2016.10.110","article-title":"Preoperative hypoalbuminemia is associated with poor clinical outcomes after open and endovascular abdominal aortic aneurysm repair","volume":"66","author":"Inagaki","year":"2017","journal-title":"J. Vasc. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s13019-020-01133-y","article-title":"The influence of postoperative albumin levels on the outcome of cardiac surgery","volume":"15","author":"Putzu","year":"2020","journal-title":"J. Cardiothorac. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28","DOI":"10.12998\/wjcc.v7.i1.28","article-title":"Correlation of serum albumin and prognostic nutritional index with outcomes following pancreaticoduodenectomy","volume":"7","author":"Rungsakulkij","year":"2019","journal-title":"World J. Clin. Cases"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/j.0894-0959.2004.17603.x","article-title":"Serum albumin: Relationship to inflammation and nutrition","volume":"17","author":"Don","year":"2004","journal-title":"Semin. Dial."},{"key":"ref_27","first-page":"16424","article-title":"Predicting pathological complete response after neoadjuvant chemotherapy in breast cancer by clinicopathological indicators and ultrasound parameters using a nomogram","volume":"14","author":"Zhang","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Qu, F., Luo, Y., Peng, Y., Yu, H., Sun, L., Liu, S., and Zeng, X. (2024). Construction and validation of a prognostic nutritional index-based nomogram for predicting pathological complete response in breast cancer: A two-center study of 1,170 patients. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1335546"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.21873\/invivo.12003","article-title":"Implications of Low Serum Albumin as a Prognostic Factor of Long-term Outcomes in Patients with Breast Cancer","volume":"34","author":"Fujii","year":"2020","journal-title":"Vivo"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00384-010-1113-4","article-title":"Low preoperative serum albumin in colon cancer: A risk factor for poor outcome","volume":"26","author":"Lai","year":"2011","journal-title":"Int. J. Color. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1245\/s10434-006-9093-x","article-title":"Serum albumin as a significant prognostic factor for patients with gastric carcinoma","volume":"14","author":"Carrillo","year":"2007","journal-title":"Ann. Surg. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1080\/01635581.2012.718034","article-title":"Serum albumin is superior to prealbumin for predicting short-term recurrence in patients with operable colorectal cancer","volume":"64","author":"Fujii","year":"2012","journal-title":"Nutr. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcdb.2017.05.023","article-title":"ROS signalling in the biology of cancer","volume":"80","author":"Moloney","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.freeradbiomed.2022.05.019","article-title":"Albumin at the intersection between antioxidant and pro-oxidant in patients on peritoneal dialysis","volume":"187","author":"Robajac","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101184","DOI":"10.1016\/j.jhepr.2024.101184","article-title":"Albumin reprograms the B cell transcriptional landscape and improves neutrophil antimicrobial function in patients with decompensated cirrhosis","volume":"6","author":"Aguilar","year":"2024","journal-title":"JHEP Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1080\/07853890.2019.1693056","article-title":"Impaired albumin function: A novel potential indicator for liver function damage?","volume":"51","author":"Sun","year":"2019","journal-title":"Ann. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/nrc1456","article-title":"High interstitial fluid pressure\u2014An obstacle in cancer therapy","volume":"4","author":"Heldin","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1104819","article-title":"Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy","volume":"307","author":"Jain","year":"2005","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100186","DOI":"10.1016\/j.medidd.2024.100186","article-title":"Albumin is a reliable drug-delivering molecule: Highlighting points in cancer therapy","volume":"22","author":"Asrorov","year":"2024","journal-title":"Med. Drug Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e70013","DOI":"10.1002\/mef2.70013","article-title":"Neoadjuvant Strategies for Triple Negative Breast Cancer: Current Evidence and Future Perspectives","volume":"4","author":"Huang","year":"2025","journal-title":"MedComm\u2014Future Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ozkan, E.M., Karadag, I., Inanc, M., and Ozkan, M. (2026). Dynamic Immune-Nutritional Indices as Powerful Predictors of Pathological Complete Response in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy. J. Clin. Med., 15.","DOI":"10.3390\/jcm15020418"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:41:38Z","timestamp":1780936898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["jcm15124429"],"URL":"https:\/\/doi.org\/10.3390\/jcm15124429","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]}}}