Immature Granulocyte Count and Delta Neutrophil Index Factors for Axillary Metastasis of Breast Cancer

Background: Breast cancer ranks first among cancer types seen in women in our country and all over the world, and second after lung cancer in cancer-related deaths. Despite the recent increase in its incidence, mortality has decreased due to early diagnosis and advances in neoadjuvant therapy. Classically, lymph node status, tumor size, histological type and grade, age, and ethnicity are prognostic factors for this type of cancer. Bone marrow activation results from malignancies and inflammation. Tumor-related inflammation has gained importance in each stage of tumorigenesis. Host-dependent systemic inflammatory response has been found to be effective in carcinogenesis, tumor development and progression. Inadequately controlled or uncontrolled inflammatory activity may be responsible for malignant transformation. Inflammatory cell stimulation occurs in lymph node metastasis and distant organ metastases like primary tumor.As the cornerstone of the adaptive immune system, lymphocytes inhibit tumor cell proliferation, migration and destroy metastatic lesions. Monocyte-macrophages inhibit angiogenesis, tumor growth and distant spread. On the other hand, tumor-induced neutrophils can accelerate tumor metastasis. Many studies have examined the relationship between the ratios between different cell types, such as the platelet-lymphocyte ratio (PLR), and the neutrophil-lymphocyte ratio (NLR), with malignant tumors(4,10).Apart from these, mean platelet volume (MPV), which can be automatically studied in routine blood counts and shows platelet activation, has been used to show tumor activity in breast, stomach, colon and ovarian cancers.

Recent studies have identified the delta neutrophil index (DNI), which indicates the percentage of immature granulocytes (IG) in peripheral blood due to increased bone marrow activation in inflammatory conditions.It is based on counting granulocyte precursor cells under microscope. With the technological developments,IG count and DNI can be automatically evaluated from complete blood count parameters in automated systems.

In this study,the investigators aimed to determine the diagnostic value of preoperative IG number and DNI level before clinical detection of axillary lymph node metastasis, which plays an important role in the prognosis of breast cancer, and to compare these parameters with other routine inflammation markers such as white blood cell count (WBC), MPV, NLR and PLR.

Material - Methods:Patients who were older than eighteen and operated for breast pathology in Kahramanmaras Sutcu Imam University,Department of General Surgery between February 2015 and February 2020 were evaluated retrospectively.Patient data were obtained from patient epicrisis forms and preoperative laboratory and postoperative pathology results recorded in the computer system.Demographic data of the patients,routine blood tests,preoperative imaging methods, preoperative tumor size,presence of axillary lymph node metastasis and distant organ metastasis,presence of pathological axillary lymph node metastasis in the postoperative period were evaluated.

In the preoperative period, patients without axillary metastases and who did not receive neoadjuvant treatment were examined by dividing them into two groups as pathologically non-metastatic(Group NM) and metastasized(Group M) in axillary lymph node sampling.

White blood cell(WBC)count,neutrophil count,lymphocyte count,platelet count,mean platelet volume(MPV),IG count and DNI(IG percentage)were measured using an automated hematological analyzer from blood samples obtained at the preoperative previous month of surgery.Neutrophil to lymhpocyte ratio(NLR) and platelet to lymphocyte ratio(PLR) were manually calculated from the complete blood cell results.

Background: Breast cancer ranks first among cancer types seen in women in our country and all over the world, and second after lung cancer in cancer-related deaths. Despite the recent increase in its incidence, mortality has decreased due to early diagnosis and advances in neoadjuvant therapy. Classically, lymph node status, tumor size, histological type and grade, age, and ethnicity are prognostic factors for this type of cancer. Bone marrow activation results from malignancies and inflammation. Tumor-related inflammation has gained importance in each stage of tumorigenesis. Host-dependent systemic inflammatory response has been found to be effective in carcinogenesis, tumor development and progression. Inadequately controlled or uncontrolled inflammatory activity may be responsible for malignant transformation. Inflammatory cell stimulation occurs in lymph node metastasis and distant organ metastases like primary tumor.As the cornerstone of the adaptive immune system, lymphocytes inhibit tumor cell proliferation, migration and destroy metastatic lesions. Monocyte-macrophages inhibit angiogenesis, tumor growth and distant spread. On the other hand, tumor-induced neutrophils can accelerate tumor metastasis. Many studies have examined the relationship between the ratios between different cell types, such as the platelet-lymphocyte ratio (PLR), and the neutrophil-lymphocyte ratio (NLR), with malignant tumors.Apart from these, mean platelet volume (MPV), which can be automatically studied in routine blood counts and shows platelet activation, has been used to show tumor activity in breast, stomach, colon and ovarian cancers.

Recent studies have identified the delta neutrophil index (DNI), which indicates the percentage of immature granulocytes (IG) in peripheral blood due to increased bone marrow activation in inflammatory conditions.It is based on counting granulocyte precursor cells under microscope. With the technological developments,IG count and DNI can be automatically evaluated from complete blood count parameters in automated systems.

In this study, investigators aimed to determine the diagnostic value of preoperative IG number and DNI level before clinical detection of axillary lymph node metastasis, which plays an important role in the prognosis of breast cancer, and to compare these parameters with other routine inflammation markers such as white blood cell count (WBC), MPV, NLR and PLR.

Material - Methods:Patients who were older than eighteen and operated for breast pathology in Kahramanmaras Sutcu Imam University,Department of General Surgery between February 2015 and February 2020 were evaluated retrospectively.Patient data were obtained from patient epicrisis forms and preoperative laboratory and postoperative pathology results recorded in the computer system.Demographic data of the patients,routine blood tests,preoperative imaging methods, preoperative tumor size,presence of axillary lymph node metastasis and distant organ metastasis,presence of pathological axillary lymph node metastasis in the postoperative period were evaluated.

In the preoperative period, patients without axillary metastases and who did not receive neoadjuvant treatment were examined by dividing them into two groups as pathologically non-metastatic(Group NM) and metastasized(Group M) in axillary lymph node sampling.

White blood cell(WBC)count,neutrophil count,lymphocyte count,platelet count,mean platelet volume(MPV),IG count and DNI(IG percentage)were measured using an automated hematological analyzer from blood samples obtained at the preoperative previous month of surgery.Neutrophil to lymhpocyte ratio(NLR) and platelet to lymphocyte ratio(PLR) were manually calculated from the complete blood cell results.

Statistical Evaluation:IBM-Statistical Package for Social Sciences (SPSS) version 20 was used for statistical analysis. In the evaluation between independent groups;normal distribution was checked for the kolmogorov-simirnov test.While student t test or Mann Whitney U test was used in the evaluation of numerical data according to the conformity of the data to normal distribution,chi-square test was used in the evaluation of categorical data.Multivariate analysis was performed with parameters found to be significant in the evaluation of univariate analysis and predictive values of preoperative blood parameters were calculated.ROC analysis was performed to evaluate the effectiveness of WBC, NLR, PLR, DNI, IG number and MPV values,and sensitivity,specificity values and cut-off values were obtained. Numerical values are expressed as median(minimum - maximum values), categorical values as percentage (%).

Eligibility Criteria:
Inclusion Criteria:

* Invasive breast cancer (invasive ductal carcinoma, invasive lobular carcinoma, mixed invasive ductal lobular carcinoma, mucinous carcinoma, medullary carcinoma, micropapillary carcinoma)
* Clinically negative axillarry metastasis(without neoadjuvant chemotherapy/radiotherapy)
* Pathologically positive or negative axillary metastasis
* No missing data.

Exclusion Criteria:

* Patients who underwent surgery for benign breast disease (such as fibroadenomas, garnulomatous mastitis, hamartomas)
* Patients with other breast malignancies other than invasive breast carcinoma (ductal carcinoma in situ, fibrosarcomas, neuroendocrine tumors, myofibroblastomas, phyllodes tumors)
* Clinically preoperative positive axillary metastasis
* Preoperative patients with distant organ metastasis
* Patients who received neoadjuvant chemotherapy / radiotherapy in the preoperative period
* Patients with missing data