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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 12  |  Issue : 2  |  Page : 67-72

Role of peripheral blood parameters (neutrophil-to-lymphocyte, lymphocyte-to-monocyte and neutrophil-to-monocyte ratios) in breast cancer


1 Department of Biochemistry, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, Uttar Pradesh, India
2 Department of Biochemistry, Index Medical College, Indore, Madhya Pradesh, India
3 Department of Biochemistry, Autonomous State Medical College, Ghazipur, Uttar Pradesh, India
4 Department of Surgery, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, Uttar Pradesh, India
5 Department of Health Research, New Delhi, India

Date of Submission04-Feb-2022
Date of Decision24-Mar-2022
Date of Acceptance04-Apr-2022
Date of Web Publication26-Apr-2022

Correspondence Address:
Dr. Anand Narayan Singh
Department of Biochemistry, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur - 208 002, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmrp.cmrp_10_22

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  Abstract 

Background: Nowadays, the role of inflammation in malignancies is well understood, and it has been characterised at several phases of tumourigenesis (initiation, promotion, invasion and metastasis). Different studies suggested that the neutrophils/lymphocyte ratio (NLR) is linked with breast cancer (BC) survival and prognosis.
Aim: In the present study, our aim was to study the blood parameters (neutrophils, lymphocytes, NLR, lymphocyte-to-monocyte ratio [LMR] and neutrophil-to-monocyte ratio [NMR]) in BC. We examined the correlation between white blood cells, NLR, LMR, NMR and BC.
Materials and Methods: It was a case–control study, which included 97 individuals, in which 44 were confirmed BC patients by histopathological examination and 53 were healthy controls. Their personal and social status information were collected in questionnaire form.
Results: The mean neutrophil count was higher in the case group as compared to the control group (65.45 ± 5.92/68.67 ± 9.13, P = 0.001). Lymphocyte count was significantly lower in the case group as compared to the control group (26.25 ± 8.78 vs. 29.79 ± 5.14, P = 0.00). NLR was higher in the case group as compared to the control group, 3.03 ± 1.36 versus 2.35 ± 1.02, P = 0.00. The monocyte level was significantly higher in BC patients as compared to the control group, i.e. 2.80 ± 0.79 versus 2.66 ± 1.07, P = 0.01, in the case group. The LMR was 13.55 ± 7.21 in the control group and 10.35 ± 5.57, P = 0177, in the case group. NMR was significantly higher in the control group as compared to the case group (30.42 ± 17.02 vs. 26.53 ± 8.50, P = 0.002).
Conclusions: Low NMR value can be related to a greater survival rate. We concluded that complete blood count, NLR and NMR can be an alternative marker in BC risk.

Keywords: Breast cancer, complete blood count, lymphocyte, neutrophils, neutrophil–lymphocyte ratio


How to cite this article:
Tripathi P, Nigoskar S, Singh R, Kala S, Yadav GD, Athar M, Prakash J, Singh S, Verma MK, Singh AN. Role of peripheral blood parameters (neutrophil-to-lymphocyte, lymphocyte-to-monocyte and neutrophil-to-monocyte ratios) in breast cancer. Curr Med Res Pract 2022;12:67-72

How to cite this URL:
Tripathi P, Nigoskar S, Singh R, Kala S, Yadav GD, Athar M, Prakash J, Singh S, Verma MK, Singh AN. Role of peripheral blood parameters (neutrophil-to-lymphocyte, lymphocyte-to-monocyte and neutrophil-to-monocyte ratios) in breast cancer. Curr Med Res Pract [serial online] 2022 [cited 2022 May 19];12:67-72. Available from: http://www.cmrpjournal.org/text.asp?2022/12/2/67/343927




  Introduction Top


Breast cancer (BC) is the most frequent cancer among women, and the risk of developing it grows as they get older. Worldwide, non-communicable diseases (NCDs) accounted for 71% of entire deaths. In India, NCDs accounted for 63% of total death, and among them, cancer was one of the major causes (9%).[1] The estimated number of cancer patients in India was 1,392,179 by 2020, and the most common cancer site was breast, lung, mouth, cervix uteri and tongue.[2] The majority of the patients were diagnosed with locally advanced stage for BC (57%).[2]

BC is the most common neoplasia in women and also one of the root causes of death from cancer. It is a malignant tumour, which starts in the breast cells. BC can be occurring in both men and women, but the men BC is uncommon.[3] BC is mostly asymptotic at an early stage, so the huge majority of individuals were diagnosed at the last stage and most of them have lost their chance to cure. The major determinants of BC are personal and family history of BC, obesity, age, radiation, genetics, pregnancy and breastfeeding, hormonal therapy, impenetrable breast tissue, sluggish behaviour, smoking and alcohol consumption.[4] BC is linked with systemic inflammation. This systemic inflammation response can vary with tumour growth, invasion, angiogenesis and metastasis.

Neutrophil counts are the amplest leucocyte in blood and are advised as the first line of defence.[5] Neutrophils secrete proteinases into the surrounding tissue, which causes destruction to the host cell.[6] Neutrophils are also able to release a variety of cytokines and chemokines, which can affect the inflammatory response, along with the immunological response.[7] Apart from antimicrobial properties, neutrophils can also be seen in infiltrating different types of malignancies. Neutrophil/lymphocyte ratio (NLR) is less expensive and is a simple parameter of systemic inflammation. Complete blood count and its neutrophil (polymorph) count, lymphocyte count and NLR are indicators of systemic inflammation.[8] NLR ratio is associated with the prognosis in several types of cancer such as hepatocellular carcinoma, gastrointestinal tract cancers, on-small cell carcinoma and cervical carcinoma.[9]

Inflammatory cells play a crucial role in the development of cancer and may be account for cancer mutability.[10] Activated inflammatory cells produce reactive oxygen species and reactive nitrogen species, which leads to damage of DNA. Damage of DNA and genomic instability contribute to cancer development[11] or disrupt DNA repair system.[12]

Elevated levels of NLR are the signal of systemic inflammation, which is recognised as a diagnostic factor in different types of cancers.[13] A meta-analysis study revealed that an increase in NLR was correlated with decreased overall survival.[14] Pre-operative NLR can be allowed to a clinician along with the diagnosis and prognosis in benign proliferative breast disease.

Neutrophils are the most persistent (40%–75%) type of white blood cells (WBCs) in mammals and also a vital part of the innate immunity system.[15] Neutrophils have an important role in tumour progression and anticancer effect. Neutrophils obtain an anticancer effect after their activation. Different studies have explained that increased NLR ratio was also associated with more advanced or aggressive BC. Because of this reason, NLR ratio has been suggested as a prognostic role in cancer.[16]

The immune system has an important role in cancer by affecting cancer development and progression.[17] Lymphocyte cells are a necessary factor during cancer immunosurveillance. The lower level of absolute eosinophil counts has been associated with inferior outcomes in different types of cancer such as BC, lung cancer, colorectal cancer, ovarian cancer, renal cancer and others.[18] The aim of our study was to evaluate the association between complete blood count and NLR/lymphocyte/monocyte ratio (LMR)/NMR ratio in BC patients.


  Materials and Methods Top


This case–control study was conducted at the Department of Surgery and Department of Biochemistry, GSVM Medical College Kanpur, from January 2019 to June 2020. BC patients at GSVM Medical College, Kanpur, were enrolled in this case–control study.

Women in the age group of 25–65 years diagnosed with BC attending the Surgery OPD at GSVM Medical College, Kanpur, were included in the case group. All the BC patients included in the study were confirmed by histopathological examination, fine-needle aspiration cytology (FNAC) and magnetic resonance imaging (MRI) with their clinical staging. The patients were included based on their medical history, their family history and personal information. Before conducting this study, patients were informed a consent about the purpose of the study. The patients who were not interested in the study or refused to give their consent were also excluded from the study.

Subjects diagnosed with BC, confirmed by histopathological examination, age of 25–65 years were enrolled as a case group. Healthy controls were included in the study. Participants suffering from any acute infections or chronic disease such as tuberculosis (TB)/AIDS, advanced liver or renal disease, associated with any other 2nd malignancy in the past or present and patients on steroid therapy were excluded from the study.

A total of 44 BC patients confirmed by histopathological and cytological (FNAC) investigation were included in the study. For collecting their social and personal data such as age, religion, occupation, education, smoking, drinking and dietary habits, patients were administered a questionnaire. Their clinical history and diagnosis of BC were also recorded. We also collected their personal information/causative factor of BC such as age at first child birth, breast feeding, menarche age, menopausal age and family history regarding cancer. Their blood pressure, pulse rate and body weight were also measured. Histopathological reports, mammography, breast MRI, ultrasound reports of breast and whole abdomen, blood counts parameters, NLR, LMR and NMR values of the patients were evaluated. The BC staging was performed using tumour–node–metastasis (TNM) staging system of the American Joint Committee on Cancer.

This study was ethically approved by the Institution Ethical Committee of the GSVM Medical College, Kanpur, UP India (EIC Number: 90/E.C. Meeting/April/2019 date: 14/05/2019).

Statistical analysis

Statistical analysis was performed using the SPSS software. The independent-samples t-test was used to assess the differences between the case and controls. The differences among the three groups were assessed by the one-way ANOVA for the continuous variables and the data were presented as mean ± standard deviation. A post hoc test was used for pairwise multiple comparisons between means. Tukey's post hoc test used studentised range statistics to make all of the pairwise comparisons between groups. P < 0.050 was considered statistically significant.


  Results Top


The distribution of parameters of BC patients is shown in [Table 1]. It reveals the association of risk factors for BC. The average age of patients diagnosed with BC was 45.36 ± 12.13 (n = 44) years. The average age of the control group was 45.08 ± 4.56 (n = 53). The mean age of menarche was 13.94 ± 1.00 (n = 53) in the control group and 13.95 ± 1.10 (44) in BC patients. Menopausal age was 47.00 ± 2.00 (n = 5) in the control group and 50 ± 3.937 (n = 5) in the case group.
Table 1: Demographic distributions of breast cancer patients

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In the study, 40.9% (n = 18) of the patients were illiterate in the case group, whereas only 1.9% (n = 1) were in the control group. They never attended the school. In the case group, 11.4% (n = 5) had a grade school and 1.9% (n = 1) were in the control group. In the case group, 15.9% (n = 7) passed Jr., high school and 3.8% (n = 2) in the control group; 13.6% (n = 6) were in high school in the case and 5.7% (n = 3) in the control groups. In the case group, 6.8% (n = 3) of patients were in college and 17.0% (n = 9) in the control group; 4.5% (n = 2) of patients were graduate in the case group and 34.0% (n = 18) in the control group. 6.8% (n = 3) of patients were 12th grade passed in the case group and 35.8% (n = 19) were in the control group. In the case group, 70.5% (n = 31) of patients were homemakers and 69.81% (n = 37) in the control group. In the case group, 22.7% (n = 10) were farmer and 24.52% (n = 13) were in the control group. In the case group, 2.3% (n = 1) were in official job and 3.77% (n = 2) in the control group. In the case group, 4.5% (n = 2) were student, whereas in the control group, 5.66% (n = 3) were student.

We also collected individual status of smoking, alcohol consumption, habit of tobacco chewing, HIV, HBsAg and TB status. There was no history of smoking, HIV, HBsAg and TB. Out of 97 individuals, 0.9% (n = 1) were with a history of alcohol consumption, whereas 3.6% (n = 4) were with a history of tobacco chewing.

[Table 2] shows patients' characteristics of the tumour group. Out of 44 cases, 21 (47.7%) had a right side and 23 (52.2%) had a left side BC. The FNAC reports were as follows: ductal carcinoma (93.2%), adenocarcinoma (2.3%), cystosarcoma phylloids (2.3%) and pleomorphic carcinoma (2.3%). According to histological type, ductal invasive carcinoma was in 38%, invasive lobular carcinoma 3% and sarcoma and cystosarcoma phylloids 2% and 1%, respectively. Histological grading was Grade I − 9.0%, Grade II − 56.8% and Grade III − 34%. TNM staging: 2.2% were T0 stage, 9% were in T2 stage, 79.5% were in T3 stage and 9% were in T4 stage.
Table 2: Patients characteristics of tumour group

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[Table 3] shows risk of BC according to WBCs and NLR. Complete blood count of case and control groups was analysed after that neutrophil/lymphocytes ratio (NLR) was calculated. Lymphocyte count was significantly lower in the case group as compared to the control group (26.25 ± 8.78/29.79 ± 5.14). The mean neutrophil count was 65.45 ± 5.92 in the control group and 68.67 ± 9.13 in the case group. Neutrophil count was significantly high in the case group.
Table 3: Complete blood count of case and control groups

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NLR was significantly higher in the case group as compared to the control group (3.03 ± 1.36/2.35 ± 1.02). The LMR was found 13.55 ± 7.21 in the control group and 10.35 ± 5.57 in the case group. Neutrophils/monocyte ratio was significantly higher in the control group, 30.42 ± 17.02, as compared to the case group, 26.53 ± 8.50. The mean monocyte level was significantly lower in the control group, i.e., 2.66 ± 1.07 (n = 53), and 2.80 ± 0.79 (n = 44) in the case group. The mean eosinophil count was higher in the case group in comparison to the control group (2.59 ± 1.30/2.34 ± 1.37). No association was found in basophil count between the case and control groups. The mean haemoglobin level was slightly higher in the control group 12.21 ± 0.89 and lower 12.12 ± 1.18 in the case group. The mean total leucocyte count was significantly higher in the control group than the case group (8540.00 ± 2401.96/8775.47 ± 1465.88).


  Discussion Top


Goal of the study was to examine and compare NLR, LMR and NMR ratios and other parameters of complete blood count between BC and healthy controls. Various studies revealed that the age of BC in women was between 45 and 50 years.[19] We found the similar result in the present study, i.e., the mean age was 45.36 ± 12.13 in BC. Elderly age may be a risk factor for BC.

The level of education has an impact on BC. In the current study, 40.9% of individuals were illiterate. BC is caused by a lack of awareness and education about the disease. In a study, it was showed that those who had a higher level of education were better aware of the risk factors for BC.[20] Raising public knowledge about BC and providing training in breast self-examination could help avoid the disease.

Absolute neutrophils and lymphocyte count can be altered by different pathological and physiological events, but NLR cannot be affected by these factors.[21] The present study showed that the neutrophil count in the case group was significantly higher than that in the control group. Previously, the same result was observed.[22]

An elevated number of neutrophils in the tumor stroma has been linked to a poor prognosis. Neutrophils enhance tumour angiogenesis and promote tumour progression and metastasis by secreting cytokines and chemokines. A higher neutrophil count was also found in a study, 'Breast Cancer Cell-Neutrophil Interactions Enhance Neutrophil Survival and Pro-Tumorigenic Activities 2020'.[23] Our study also revealed a positive association between neutrophil count and BC. Neutrophil count is the most common type of WBCs in humans and also play a vital role in the innate immunity system.[15] Inflammation has a key role in the development and improvement of various malignancies. Many tumours appear from the site of chronic irritation, infection, irritation and inflammation. Inflammatory cells also play an important role in growth and progression of many tumours.[24] Previous study was concluded that NLR can be used as prognostic factors in BC patients under going nCT (neoadjuvant chemotherapy).[25]

Eosinophil count has no significant role in BC patients in the present study. Increased eosinophil count is termed eosinophilia, which can be due to allergies, parasites, skin disorder, autoimmune disorder, endocrine disorder or tumours. TLC count was significantly lower in the case group as compared to the control group (P < 0.00) and has no significant role in BC. Haemoglobin level was lower (P > 0.06) in the case group as compared to the control group.

In our study, lymphocyte level was significantly higher in the control group in comparison with the case group. It is well known that the immune system plays a crucial role in the history of cancer by influencing cancer development and progression.[26] The lymphocyte is an important effector cell among WBCs in cancer immunosurveillance.[27] Low ALC (absolute lymphocyte count) has been correlated with inferior outcomes in different cancers such as BC, colorectal cancer, lung cancer ovarian cancer and others.[18] The same finding revealed in this study that lymphocyte count was significantly lower in BC as compared to the control group.

In the present study, we also examined the association of CBC (complete blood count) with BC. The average levels of leucocyte, neutrophils and neutrophil/lymphocyte count in BC patients were found to be significantly greater than the healthy controls. This study revealed that the NLR ratio was significantly higher (P = 0.00) in BC compared to the control group. This study suggested that BC risk increased with increasing NLR ratio. Higher NLR is associated with poor survival in diagnosed patients with different types of cancer.[14] High NLR is associated with an adverse OS (overall survival) and DFS (disease-free survival) in BC patients.[28] Multiple studies concluded that higher neutrophil–lymphocyte ratio was associated with adverse survival.[29] In the present study, monocyte level was significantly higher (P = 0.01) in BC patients as compared to the control group. It is well known that monocyte is a type of WBCs, which fights from infection and helps other WBCs in removing dead or damage tissues, destroy cancer cells ,and provide immunity against foreign substance. In malignancy, the monocyte counts also exceed than their normal range. Lower count of monocyte can also be seen after chemotherapy usually because of lower level of other WBC count.[30]

This study revealed that the NMR ratio was significantly low (0.002) in BC as compared to the control group. Low NMR value can be related with a greater survival rate. Given that the major difference between the high and low NMR groups was in neutrophils, this result would support the theory that neutrophils play a key role in tumour progression, producing a favourable environment for tumour growth.[31]


  Conclusions Top


Distinct types of host cells influence tumour formation. Many cancers have been found to have neutrophils invading them. The above study revealed that the neutrophil count and NLR ratio in BC patients were significantly higher than that in the healthy control group. Neutrophils can promote tumour cell migration and metastasis by inducing tumour growth and angiogenesis. NLR may be a common prognostic marker. More researches are needed to see if the NLR ratio can be utilised as an independent predictor of BC.

The limitation of this study is that there are relatively small numbers of eligible patients. Studies on a large scale are needed to confirm the results.

Acknowledgements

We are thankful to all members of the Department of Biochemistry, GSVM Medical College Kanpur, India, and the Department of Health Research, New Delhi, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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