Roles of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in prognosis and in differentiation of potential beneficiaries in HER2-positive breast cancer with trastuzumab therapy

Lead Investigator: Zhi Xiao, Xiangya Hospital, Central-South University
Title of Proposal Research: Roles of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in prognosis and in differentiation of potential beneficiaries in HER2-positive breast cancer with trastuzumab therapy
Vivli Data Request: 6759, 5936
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

HER2 is an oncogene and is associated with aggressive tumor growth and poor prognosis. Oncogene is a kind of gene having the potential to cause a normal cell to become cancerous or to strengthen the ability of invasion and metastases of cancerous cell. HER2 is over-expressed in 20-25% of all invasive breast cancer (BC). Trastuzumab (Herceptin®) is an effective therapy for HER2 over-expression BC and can decrease the risk of relapse around 25%. Meanwhile, the situation that HER2-positive BC have no response to trastuzumab treatment exists indeed. The mechanism of trastuzumab resistance is not yet understood, and there is no factor that could predict the sensitivity to trastuzumab of HER2-positive breast cancer.

Statistical Analysis Plan:

To clarify the association of NLR/PLR and disease-free survival, Kaplan-Meier curves and Log- rank tests are presented. Log-rank tests for disease-free survival endpoints provide two-sided p values. P value less than 0.05 is recognized as significant. Cox proportional hazards modeling is used to estimate unadjusted hazard ratios (HRs) and 95% CIs, and to explore the effect of selective crossover on the risk of a progress-free survival event in the observation control group. Exploratory Cox modeling is done to examine interactions between treatment assignment, hormone receptor status, and time on study. Subgroup analyses of progress-free survival and overall survival were done according to different nodal status, tumor size, hormone status and histological grade. Pearson χ2 test was performed to compare categorical parameters of clinicopathological characteristics. All analyses were carried out using SPSS 17.0 for Windows.

Requested Studies:

(Note: study removed as part of Data Request 6759)

A Randomized Three-Arm, Multicenter Comparison of 1 Year and 2 Years of Herceptin Versus No Herceptin in Women With HER2-Positive Primary Breast Cancer Who Have Completed Adjuvant Chemotherapy (HERA)
Sponsor: Hoffmann-La Roche
Study ID: NCT00045032
Sponsor ID: BO16348

(Note: studies added as part of Data Request 6759)

Chemotherapy and Antibody Response Evaluation (CARE): A phase III, multinational, randomized study of recombinant humanized anti-p185HER2 monoclonal antibody (rhuMAb HER2) combined with chemotherapy in patients with HER2 overexpression who have not received cytotoxic chemotherapy for metastatic breast cancer.
Sponsor: Roche
Study ID: H0648G
Sponsor ID: H0648G

A Multicenter, Randomized Comparative Study on the Efficacy and Safety of Herceptin (Trastuzumab) Plus Docetaxel (Taxotere) Versus Docetaxel Alone as First Line Treatment in Patients with HER2-Positive Metastatic Breast Cancer
Sponsor: Roche
Study ID: M77001
Sponsor ID: M77001

A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
Sponsor: Roche
Study ID: NCT00567190
Sponsor ID: TOC4129g

Public Disclosures:

  1. Xiao, Z., Ding, N., Pang, J., Liu, X., He, X., Zhou, W., Xie, H., Feng, J., Wang, G., Tang, J. and Can, J., 2023. 9P Prognostic value of baseline neutrophil/lymphocyte ratio in HER2-positive metastatic breast cancer: Exploratory analysis from the CLEOPATRA trial. ESMO Open, 8(1). Doi: 10.1016/j.esmoop.2023.101233
  2. Ding, N., Pang, J., Liu, X., He, X., Zhou, W., Xie, H., Feng, J., Wang, G., Tang, J., Cao, J. and He, L., 2024. Prognostic value of baseline neutrophil/lymphocyte ratio in HER2-positive metastatic breast cancer: exploratory analysis of data from the CLEOPATRA trial. Breast Cancer Research, 26(1), pp.1-10. Doi: 10.1186/s13058-023-01761-x