Can pretreatment lactate dehydrogenase to albumin ratio predict pathological complete response after neoadjuvant chemotherapy in breast cancer patients?

  • Gözde Savaş Gazi university
  • Nazan Günel gazi university
  • Ahmet Özet gazi university
Keywords: LAR, LDH, albumin, neoadjuvant chemotherapy, breast cancer, complete response

Abstract


Background: The aim of this study is to evaluate the predictive significance of platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), lymphocyte monocyte ratio (LMR), systemic immune-inflammation (SII), prognostic nutritional index (PNI), The hemoglobin, albumin, lymphocyte, and platelet (HALP) score and lactate dehydrogenase to albumin ratio (LAR) for pCR in breast cancer with neoadjuvant chemotherapy (NACT).

Methods: A total of 121 patients who received NACT between February 2012 and November 2021 were included. LAR, NLR, PLR, MLR, SII, PNI and HALP were calculated according to formulas. The cut-off value for markers were obtained by Receiver operating characteristic curve (ROC) analyses. Independent predictive factors for pCR were determined using multivariate regression analysis. 

Results:  The pCR rate was achieved in 31.4% of patients. Median values of NLR, PLR, MLR, SII, PNI and HALP were similar in pCR (+) and pCR (-) (p > 0.05). Median LAR value was significantly higher in pCR (+) than pCR (-) (50.80 vs 42.62, respectively (p=0.002)). The optimal cutoff value of LAR was 46.27. Multivariate analysis showed that LAR ³46.27 and HER-2 positivity were the independent predictive factors for pCR [OR = 2.851 (95% CI = 1.142-7.119, P = .025), OR = 3.431 (95% CI = 1.163-10.123, P = 0.026), respectively].

Conclusion: LAR is a simple, inexpensive, and convenient method for predicting pCR in breast cancer with NACT. 

References

1-    Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 ;72(1):7-33.


2-    Cardoso F, Kyriakides S, Ohno S, et al. ESMO Guidelines Committee. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30(8):1194-1220.


3-    Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017 ; 376 (22): 2147-2159. 


4-    Huang CS, Yang Y, Kwong A, Chen SC, Tseng LM, Liu MC, et al. Trastuzumab emtansine (T-DM1) versus trastuzumab in Chinese patients with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy for HER2-positive breast cancer in the phase 3 KATHERINE study. Breast Cancer Res Treat. 2021;187(3):759-768. 


5-    Derouane F, van Marcke C, Berlière M, Gerday A, Fellah L, Leconte I, et al. Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine. Cancers (Basel). 2022;14(16):3876.


6-    Zhou Q, Dong J, Sun Q, Lu N, Pan Y, Han X. Role of neutrophil-to-lymphocyte ratio as a prognostic biomarker in patients with breast cancer receiving neoadjuvant chemotherapy: a meta-analysis. BMJ Open. 2021;11(9): e047957. 


7-    Cullinane C, Creavin B, O'Leary DP, O'Sullivan MJ, Kelly L, Redmond HP, et al. Can the Neutrophil to Lymphocyte Ratio Predict Complete Pathologic Response to Neoadjuvant Breast Cancer Treatment? A Systematic Review and Meta-analysis. Clin Breast Cancer. 2020;(6): e675-e681


8-    Li B, Zhou P, Liu Y, Wei H, Yang X, Chen T, et al. Platelet-to-lymphocyte ratio in advanced Cancer: Review and meta-analysis. Clin Chim Acta. 2018; 483:48-56.


9-    Dong J, Sun Q, Pan Y, Lu N, Han X, Zhou Q. Pretreatment systemic inflammation response index is predictive of pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. BMC Cancer. 2021; 21(1):700. 


10- Lis CG, Grutsch JF, Vashi PG, Lammersfeld CA. Is serum albumin an independent predictor of survival in patients with breast cancer? JPEN J Parenter Enteral Nutr. 2003;27(1):10-5.


11- Liu X, Meng QH, Ye Y, Hildebrandt MA, Gu J, Wu X. Prognostic significance of pretreatment serum levels of albumin, LDH and total bilirubin in patients with non-metastatic breast cancer. Carcinogenesis. 2015;36(2):243-8.


12-  Yuce E, Karakullukcu S, Bulbul H, Alandag C, Saygin I, Kavgaci H. The effect of the change in hemoglobin-albumin-lymphocyte-platelet scores occurring with neoadjuvant chemotherapy on clinical and pathological responses in breast cancer. Bratisl Lek Listy. 2023;124(1):59-63. 


13- Lou C, Jin F, Zhao Q, Qi H. Correlation of serum NLR, PLR and HALP with efficacy of neoadjuvant chemotherapy and prognosis of triple-negative breast cancer. Am J Transl Res. 2022;14(5):3240-3246. 


14- Büyükşimşek M, Oğul A, Mirili C, Paydaş S. Inflammatory Markers Predicting Pathological Complete Response in Cases with Breast Cancer Treated by Neoadjuvant Chemotherapy. Eur J Breast Health. 2020;16(4):229-234. 


15- Forkasiewicz A, Dorociak M, Stach K, Szelachowski P, Tabola R, Augoff K. The usefulness of lactate dehydrogenase measurements in current oncological practice. Cell Mol Biol Lett. 2020; 25:35. 


16- Pelizzari G, Basile D, Zago S, Lisanti C, Bartoletti M, Bortot L, et al. Lactate Dehydrogenase (LDH) Response to First-Line Treatment Predicts Survival in Metastatic Breast Cancer: First Clues for A Cost-Effective and Dynamic Biomarker. Cancers (Basel). 2019;11(9):1243.


17- von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–804.


18- Giuliano AE, Edge SB, Hortobagyi GN. Eighth Edition of the AJCC Cancer Staging Manual: Breast Cancer. Ann Surg Oncol. 2018;25(7):1783-1785.


19-  Huertas-Caro CA, Ramirez MA, Gonzalez-Torres HJ, Sanabria-Salas MC, Serrano-Gómez SJ. Immune Lymphocyte Infiltrate and its Prognostic Value in Triple-Negative Breast Cancer. Front Oncol. 2022; 12:910976.


20- Dan J, Tan J, Huang J, Zhang X, Guo Y, Huang Y, et al. The dynamic change of neutrophil to lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients. Breast Cancer. 2020; 27(5): 982-988. 


21- Ji Y, Wang H. Prognostic prediction of systemic immune-inflammation index for patients with gynecological and breast cancers: a meta-analysis. World J Surg Oncol. 2020;18(1):197. 


22- Dong J, Sun Q, Pan Y, Lu N, Han X, Zhou Q. Pretreatment systemic inflammation response index is predictive of pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. BMC Cancer. 2021 Jun; 21(1): 700. 


23- Chen L, Kong X, Wang Z, Wang X, Fang Y, Wang J. Pretreatment systemic inflammation response index in patients with breast Cancer treated with neoadjuvant chemotherapy as a useful prognostic Indicator. Cancer Manag Res. 2020; 12:1543–67.


24- Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8(6):519–30.


25-  Ding J, Karp JE, Emadi A. Elevated lactate dehydrogenase (LDH) can be a marker of immune suppression in cancer: interplay between hematologic and solid neoplastic clones and their microenvironmentsCancer Biomark. 2017;19(4):353–363.


26-  Liu D, Wang D, Wu C, Zhang L, Mei Q, Hu G, et al. Prognostic significance of serum lactate dehydrogenase in patients with breast cancer: a meta-analysis. Cancer Manag Res. 2019; 11:3611-3619.


27-  Feng JF, Wang L, Yang X, Jiang YH. Prognostic value of lactate dehydrogenase to albumin ratio (LAR) in patients with resectable esophageal squamous cell carcinoma. Cancer Manag Res. 2019 Jul; 11:7243-7251. 


28- Xie Z, Zhou H, Wang L, Wu Y. The Significance of the preoperative lactate dehydrogenase/albumin Ratio in the Prognosis of Colon Cancer: a retrospective study. PeerJ. 2022;10: e13091.



29- Gao S, Wu M, Chen Y, Lou W, Zhou G, Li J, et al. Lactic dehydrogenase to albumin ratio in prediction of unresectable pancreatic cancer with intervention chemotherapy. Future Oncol. 2018; 14(14):1377-1386.

Published
2025/01/27
Section
Original paper