Study patients and variable collection
This is a retrospective analysis of collected data. The study sample consisted of 406 consecutive Turkish women with breast cancer scheduled to undergo NAC before attempting cytoreductive surgery at the Department of Oncology or the Department of General Surgery, Uludag University Medical Center (Bursa, Turkey). The following variables were extracted from clinical records in all participants: age; menopausal status; surgical approach; pre- and post-treatment pathological stage; histology type; pre- and post-treatment tumor stage; pre- and post-treatment axillary lymph node status; pre- and post-treatment expression of estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67; post-treatment tumor grade; use of chemo-, radio- and hormonal therapy; and use of trastuzumab.
The staging of the patients was carried out according to the American Joint Committee on Cancer (AJCC) Staging Manual, eighth edition.
A pretreatment complete blood count was obtained in the week preceding NAC, and the NLR was calculated from absolute counts of neutrophils and lymphocytes.
Ethical statement
The study protocol complied with the tenets of the Helsinki declaration. The Clinical Research Ethics Committee of the Bursa Uludag University Faculty of Medicine approved the study and all exemptions from informed consent due to the retrospective nature (Approval number: 2020-8/43).
Outcomes
The primary outcome measure was pCR to NAC. The Miller-Payne system15 was used to grade response to NAC, as follows: grade 1, no change or some alteration to individual malignant cells, but no reduction in overall cellularity (pNR); grade 2, minor loss of tumor cells, but overall cellularity still high; up to 30% loss (pPR); grade 3, between an estimated 30% and 90% reduction in tumor cells (pPR); grade 4, marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain; 90% loss of tumor cells (almost pCR); and grade 5, no malignant cells identifiable in sections from the site of the tumor; only vascular fibroelastotic stroma remains, often containing macrophages; however, ductal carcinoma in situ may be present (pCR). Secondary outcome measures included disease-free survival (DFS) and overall survival (OS). DFS and OS were calculated as the time (in months) from the date of breast cancer diagnosis to the date of disease recurrence and death, respectively.
Statistical analysis
The optimal cutoff point for NLR was determined using receiver operating characteristic (ROC) curve analysis taking disease recurrence as the endpoint of interest. Patients were divided into two groups (high versus low) according to the optimal cutoff value (NLR = 1.95; low NLR ≤ 1.95, high NLR >1.95). The general characteristics of the study patients are presented using descriptive statistics (median, ranges, counts, and percentages). Intergroup differences were assessed with the Mann-Whitney U test (continuous variables) or the chi-square test (categorical variables). Survival curves were plotted using the Kaplan-Meier method and compared with the log-rank test. All calculations were performed with SPSS, version 22.0 (IBM, Armonk, NY, USA). Two-tailed p values <0.05 were considered statistically significant.