Inflammatory Blood Markers in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

July 18, 2022 updated by: Tawfik Helmy, Ain Shams University

The Prognostic and Predictive Role of Inflammatory Blood Markers in Early and Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Breast cancer is the most threatening disease in women. Neoadjuvant chemotherapy is a commonly used for the treatment. Inflammation plays an important role in tumor proliferation, metastasis, and resistance to chemotherapy. Inflammatory blood markers (IBM) reflect the balance between host inflammatory and immune status. Different IBM have been reported as prognostic factors for survival and predictive factors for pathological complete response and toxicity. Our aim to evaluate these IBM in breast cancer patients receiving neoadjuvant chemotherapy.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Inflammation, recognized as one of the 10 hallmarks of cancer (seventh hallmark of cancer), contributes to tumour proliferation, angiogenesis, metastasis, and resistance to chemotherapy. In general, white blood cell count reflects an individual's systemic and/or local inflammatory status. Neutrophils are known to regulate the tumour microenvironment and produce cytokines, chemokines, and growth factors that may promote angiogenesis as well as tumour cell proliferation and migration. The M2 phenotype tumour-associated macrophages (TAMs) deriving from circulating monocytes exist within the tumour microenvironment and promote metastasis and immunosuppression. It was reported that peripheral monocyte count was associated with the density of the TAMs, and high absolute monocyte count predicted poor survival in cancer patients. Platelets are other cells contributing to cancer-favoured inflammation by various mechanisms. For example, the activated platelets inhibit the interaction between tumour cells and cytolytic immune cells by forming a layer around tumour cells and support tumour growth via the secretion of several factors such as TGF-β. Hence, high platelet counts were reported to be associated with adverse outcomes in breast cancer. In contrast, lymphocytes are responsible for antitumor-specific immune response including T-lymphocyte tumour infiltration and cytotoxic T-lymphocyte-mediated antitumor activity.

Inflammatory blood markers (IBM) have emerged as potential prognostic factors for survival in different types of cancers including breast cancer, as well as predictive factors for histological response after neo-adjuvant chemotherapy. IBM include leucocyte count, lymphocyte count, neutrophil count, and ratios such as platelet to lymphocyte ratio (PLR) or neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR). Starting from these findings, NLR, MLR, and PLR, indices reflecting the balance between inflammation and immunoreaction in cancer, were reported to have predictive value in NAC response in many breast cancer studies.

There are conflicting reports about which index provides the best prediction for the efficacy of NAC in breast cancer. For example, Eren et al. reported that NLR was the only independent predictive factor of pathological complete response (pCR) among blood-derived inflammation markers in multivariate analysis. In another study conducted by Peng et al., multivariate analysis of 808 breast cancer patients showed that the lymphocyte-monocyte ratio was the only independent predictive factor for the efficacy of NAC among these inflammatory markers. In addition, Hu et al. stated that PLR had superior efficacy to NLR in predicting NAC response.

Different studies tried to integrate different peripheral blood immune cells as, Jiang et al., that used systemic immune-inflammation index (SII); is based on neutrophil (N), platelet (P) and lymphocyte (L) counts, and stated that prognostic utility of (SII) was superior to that of NLR and PLR. Also Dong et al used the systemic inflammation response index (SIRI); an integrated indicator based on the counts of peripheral venous blood neutrophils(N), monocytes(M) and lymphocytes(L), and stated the prognostic value of the (SIRI) for pCR was superior to that of NLR.

Pan-Immune-Inflammation-Value (PIV) is a new blood-based biomarker integrating different peripheral blood immune cell subpopulations-neutrophil, platelet, monocyte, and lymphocyte. Due to its potential to represent comprehensively patient's immunity and systemic inflammation, PIV was proposed as a stronger predictor of outcomes in cancer patients receiving cytotoxic chemotherapy, immunotherapy, and targeted therapy. Recently, Ligorio reported that PIV was firmly associated with survival and outperformed NLR, PLR, and MLR in predicting survival in patients with HER-2 positive advanced breast cancer.

Sahin et al., stated that pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in Turkish women with breast cancer who received NAC.

Some studies stated that the SIRI and SII had no significance on toxicities like peripheral neuropathy and neutropenia. However, other studies reported NLR as predictive factor for febrile neutropenia.

These integrated indicators may fully reflect the balance between host inflammatory and immune status compared with NLR, MLR and PLR and other conventional haematological parameters.

These conflicting results have raised the need for a study to evaluate these inflammatory blood markers in patients with breast cancer receiving neo adjuvant chemotherapy.

Study Type

Observational

Enrollment (Anticipated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Invasive breast cancer, Above cT1 stage, all subtypes are included, who completed neoadjuvant systemic therapy.

Description

Inclusion Criteria:

  • Patients aged 18 years old or more.
  • Histologically proven invasive breast cancer.
  • Above cT1 stage, any N Stage with no distant metastasis M0.
  • All subtypes are included, either HR (ER, PR) positive or negative, HER2 positive or negative.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2.
  • Patients who completed their systemic neoadjuvant therapy.
  • Available baseline complete blood picture before starting treatment.

Exclusion Criteria:

  • Second malignancy.
  • Patients with early breast cancer cT1 (≤ 2 cm) N0.
  • Metastatic patients M1.
  • Patients with systemic inflammatory diseases or autoimmune diseases (Type I Diabetes mellitus, Systemic Lupus Erytheromatosis, Rheumatoid Arthritis, Sjogren's syndrome, Behcet disease).
  • Pregnancy-related breast cancer.
  • Patients with chronic diseases (liver cirrhosis, or end-stage renal disease).
  • Patients on systemic steroids as well as those under NSAIDS or other immunomodulators (as Methotraxate, Tacrolimus and Cyclosporine).
  • Patient who received radiotherapy or endocrine or targeted therapy prior to neoadjuvant chemotherapy.
  • Patients who started but didn't complete neoadjuvant systemic therapy.
  • Patients who didn't undergo surgery after neoadjuvant systemic therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between inflammatory blood marker (neutrophil to lymphocyte ration (NLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time Frame: 1 year
  • The neutrophil to lymphocyte ratio (NLR) was provided by the ratio between the absolute count of neutrophils and the absolute count of lymphocytes (NLR = N /L)
  • Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
  • Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
1 year
Correlation between inflammatory blood marker (Platelet to lymphocyte ratio(PLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time Frame: 1 year
  • The Platelet to lymphocyte ratio(PLR) was provided by the ratio between the absolute count of platelets and the absolute count of lymphocytes (PLR= P/L)
  • Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
  • Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
1 year
Correlation between inflammatory blood marker (monocyte to lymphocyte ratio(MLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time Frame: 1 year
  • The Monocyte to lymphocyte ratio (MLR) was provided by the ratio between the absolute count of monocytes and the absolute count of lymphocytes (MLR= M/L)
  • Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
  • Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
1 year
Correlation between inflammatory blood marker (systemic immune-inflammation index(SII)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time Frame: 1 year
  • The systemic immune-inflammation index is based on neutrophil (N), platelet (P) and lymphocyte (L) counts (SII = N × P/L) .
  • Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
  • Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
1 year
Correlation between inflammatory blood marker (systemic inflammation response index (SIRI)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time Frame: 1 year
  • systemic inflammation response index (SIRI) is based on neutrophils(N), monocytes(M) and lymphocytes(L) (SIRI=N×M/L) .
  • Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
  • Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
1 year
Correlation between inflammatory blood marker (Pan-Immune-Inflammation-Value (PIV)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time Frame: 1 year
  • Pan-Immune-Inflammation-Value (PIV) is based on neutrophils(N), monocytes(M),platelet(P) and lymphocytes(L) (PIV=N×M×P/L).
  • Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
  • Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between inflammatory blood marker (neutrophil to lymphocyte ration (NLR)) and disease-free survival (DFS) and overall survival (OS).
Time Frame: 1 year
  • The neutrophil to lymphocyte ratio (NLR) was provided by the ratio between the absolute count of neutrophils and the absolute count of lymphocytes (NLR = N /L)
  • Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
  • Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
1 year
Correlation between inflammatory blood marker (Platelet to lymphocyte ratio(PLR)) and disease-free survival (DFS) and overall survival (OS).
Time Frame: 1 year
  • The Platelet to lymphocyte ratio(PLR) was provided by the ratio between the absolute count of platelets and the absolute count of lymphocytes (PLR= P/L)
  • Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
  • Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
1 year
Correlation between inflammatory blood marker ( Monocyte to lymphocyte ratio (MLR)) and disease-free survival (DFS) and overall survival (OS).
Time Frame: 1 year
  • The Monocyte to lymphocyte ratio (MLR) was provided by the ratio between the absolute count of monocytes and the absolute count of lymphocytes (MLR= M/L)
  • Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
  • Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
1 year
Correlation between inflammatory blood marker (Systemic immune-inflammation index (SII)) and disease-free survival (DFS) and overall survival (OS).
Time Frame: 1 year
  • The systemic immune-inflammation index (SII) is based on neutrophil (N), platelet (P) and lymphocyte (L) counts (SII = N × P/L) .
  • Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
  • Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
1 year
Correlation between inflammatory blood marker (systemic inflammation response index (SIRI)) and disease-free survival (DFS) and overall survival (OS).
Time Frame: 1 year
  • systemic inflammation response index (SIRI) is based on neutrophils(N), monocytes(M) and lymphocytes(L) (SIRI=N×M/L) .
  • Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
  • Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
1 year
Correlation between inflammatory blood marker (Pan-Immune-Inflammation-Value (PIV)) and disease-free survival (DFS) and overall survival (OS).
Time Frame: 1 year
  • Pan-Immune-Inflammation-Value (PIV) is based on neutrophils(N), monocytes(M),platelet(P) and lymphocytes(L) (PIV=N×M×P/L).
  • Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
  • Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ain Shams University

Investigators

  • Study Director: Nivine M Gado, phd, Ain Shams University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 1, 2022

Primary Completion (Anticipated)

July 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

July 14, 2022

First Submitted That Met QC Criteria

July 18, 2022

First Posted (Actual)

July 21, 2022

Study Record Updates

Last Update Posted (Actual)

July 21, 2022

Last Update Submitted That Met QC Criteria

July 18, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MD 134/2022

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Djibouti

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe