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      Pathological Complete Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer: The Relationship Between Inflammatory Biomarkers and Molecular Subtypes

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      1 , , 2 , 2 , 3 , 4 , 5
      ,
      Cureus
      Cureus
      breast cancer, chemotherapy, plr, nlr, pcr, luminal, triple negative, her-2

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          Abstract

          Purpose

          Among patients with breast cancer, pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is an important prognostic predictor of survival. This study aimed to investigate the relationship between platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) along with overall pCR.

          Method

          A total of 150 patients with breast cancer who were first administered NAC and then operated on were retrospectively evaluated. Neutrophil-lymphocyte ratio and PLR obtained from the complete blood count analysis performed immediately before NAC treatment were analyzed. The cut-off value was calculated as 150 for PLR and 2.24 for NLR. We studied the predictive value of NLR and PLR levels for the pathologic response of breast cancer to NAC.

          Results

          Pathological complete response was observed in 34.7% (n = 52) of the patients, pCR in the breast in 42.7% (n = 64), and that in the axilla in 44% (n = 66). There was a statistically significant difference between the pCR rates according to the PLR levels (p = 0.013). In addition, a statistically significant difference was found in the pCR rates in the breast and axilla according to PLR levels (p = 0.018, p = 0.009). Patients with low PLR in the human epidermal growth factor receptor 2 (HER-2) group had significantly higher axillary pCR rates than in those with high PLR (p = 0.019).

          Conclusions

          A low PLR level showed high chemotherapy sensitivity independent of molecular subtypes in the treatment of breast cancer with NAC. The PLR level can serve as a predictive marker of the therapeutic effect of NAC on the breast and axilla. Low PLR levels in HER-2 enriched groups can predict pCR in the axilla.

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          Most cited references28

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          Molecular portraits of human breast tumours.

          Human breast tumours are diverse in their natural history and in their responsiveness to treatments. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identified for which variation in messenger RNA levels could be related to specific features of physiological variation. The tumours could be classified into subtypes distinguished by pervasive differences in their gene expression patterns.
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            Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.

            Pathological complete response has been proposed as a surrogate endpoint for prediction of long-term clinical benefit, such as disease-free survival, event-free survival (EFS), and overall survival (OS). We had four key objectives: to establish the association between pathological complete response and EFS and OS, to establish the definition of pathological complete response that correlates best with long-term outcome, to identify the breast cancer subtypes in which pathological complete response is best correlated with long-term outcome, and to assess whether an increase in frequency of pathological complete response between treatment groups predicts improved EFS and OS. We searched PubMed, Embase, and Medline for clinical trials of neoadjuvant treatment of breast cancer. To be eligible, studies had to meet three inclusion criteria: include at least 200 patients with primary breast cancer treated with preoperative chemotherapy followed by surgery; have available data for pathological complete response, EFS, and OS; and have a median follow-up of at least 3 years. We compared the three most commonly used definitions of pathological complete response--ypT0 ypN0, ypT0/is ypN0, and ypT0/is--for their association with EFS and OS in a responder analysis. We assessed the association between pathological complete response and EFS and OS in various subgroups. Finally, we did a trial-level analysis to assess whether pathological complete response could be used as a surrogate endpoint for EFS or OS. We obtained data from 12 identified international trials and 11 955 patients were included in our responder analysis. Eradication of tumour from both breast and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) was better associated with improved EFS (ypT0 ypN0: hazard ratio [HR] 0·44, 95% CI 0·39-0·51; ypT0/is ypN0: 0·48, 0·43-0·54) and OS (0·36, 0·30-0·44; 0·36, 0·31-0·42) than was tumour eradication from the breast alone (ypT0/is; EFS: HR 0·60, 95% CI 0·55-0·66; OS 0·51, 0·45-0·58). We used the ypT0/is ypN0 definition for all subsequent analyses. The association between pathological complete response and long-term outcomes was strongest in patients with triple-negative breast cancer (EFS: HR 0·24, 95% CI 0·18-0·33; OS: 0·16, 0·11-0·25) and in those with HER2-positive, hormone-receptor-negative tumours who received trastuzumab (EFS: 0·15, 0·09-0·27; OS: 0·08, 0·03, 0·22). In the trial-level analysis, we recorded little association between increases in frequency of pathological complete response and EFS (R(2)=0·03, 95% CI 0·00-0·25) and OS (R(2)=0·24, 0·00-0·70). Patients who attain pathological complete response defined as ypT0 ypN0 or ypT0/is ypN0 have improved survival. The prognostic value is greatest in aggressive tumour subtypes. Our pooled analysis could not validate pathological complete response as a surrogate endpoint for improved EFS and OS. US Food and Drug Administration. Copyright © 2014 Elsevier Ltd. All rights reserved.
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              Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy.

              To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response. Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses. RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort. RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                30 April 2021
                April 2021
                : 13
                : 4
                : e14774
                Affiliations
                [1 ] General Surgery, Kovancılar State Hospital, Elazığ, TUR
                [2 ] General Surgery, University of Health Sciences, Haydarpaşa Numune Training and Research Hospital, İstanbul, TUR
                [3 ] Pathology, University of Health Sciences, Haydarpaşa Numune Training and Research Hospital, İstanbul, TUR
                [4 ] Oncology, University of Health Sciences, Haydarpaşa Numune Training and Research Hospital, İstanbul, TUR
                [5 ] Emergency Medicine, University of Health Sciences, Haydarpaşa Numune Training and Research Hospital, İstanbul, TUR
                Author notes
                Kübra Kaytaz Tekyol kubrakaytaz@ 123456gmail.com
                Article
                10.7759/cureus.14774
                8164848
                34094739
                d3b8fe95-c825-471c-95ce-c08ba7838809
                Copyright © 2021, Kaytaz Tekyol et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 April 2021
                Categories
                Pathology
                General Surgery
                Oncology

                breast cancer,chemotherapy,plr,nlr,pcr,luminal,triple negative,her-2
                breast cancer, chemotherapy, plr, nlr, pcr, luminal, triple negative, her-2

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