Abstract
BackgroundBreast cancer is one of the most common malignancies in women worldwide, and one of the leading causes of cancer-related death. Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic suppressors of the cytotoxic immune reaction. Some authors advocate that PD-L1 expression may help in breast cancer prognosis.MethodsWe will conduct a systematic review of observational or interventional studies evaluating the prognostic ability of PD-L1 expression levels in predicting positive clinical outcomes in Human Breast Cancer. A sensitive search strategy will be employed in MEDLINE, EMBASE, LILACS, The Grey Literature Report, OpenGrey, OAIster, and Cochrane CENTRAL. Two reviewers will independently screen all identified references for eligibility and extract data. The outcomes evaluated will be Overall Survival, Breast Cancer-specific Survival, Disease-free Survival, Recurrence-free Survival, Positive Lymph Node, and Distant Metastasis. The outcomes will be extracted directly from the studies, if available. Methodological quality and bias of included studies will be assessed using a standardized checklist and overall quality of evidence will be assessed through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. If meta-analysis is possible, the measures of association will be calculated using bivariate random-effects models. Statistical heterogeneity will be evaluated with I2 statistics and explored through sensitivity analysis.DiscussionImmunomodulation seems to be a promising strategy in solid tumors. Breast cancer is the most common malignancies in women worldwide, and one of the leading causes of cancer death. PD-1 and PD-L1 are key physiologic suppressors of the cytotoxic immune reaction.Trial registrationSystematic review registration: CRD42019121118 (PROSPERO)
Highlights
Breast cancer is one of the most common malignancies in women worldwide, and one of the leading causes of cancer-related death
Hou et al evaluated PD-L1 and a set of other relevant immune markers in relation to their association with clinical outcome in a series of HER2-positive Breast cancer (BC) cases. They suggest that cytotoxic immune reaction mediated by CD8-positive T cells and PD-L1 expression may predict a better outcome in patients with HER2-positive BC managed with conventional chemotherapy and HER2blocking therapy [16]
The immune microenvironment influences the efficacy of chemotherapy and radiotherapy; these treatments cause an immunogenic death of the malignant cells and/or somatic mutations leading to neoantigens that elicit an adaptive immune response which will clear or keep the escaping tumor cells dormant [43, 44]
Summary
Protocol and registration The protocol for this review was defined a priori and registered online in the PROSPERO international prospective register of systematic reviews (CRD42019121118). Criteria for considering studies for this review In the review, we will include any observational (cohort) or intervention studies (randomized controlled trials) which evaluate the prognostic ability of PD-L1 expression using IHC (using any method and any type of PDL1 clone) in women with breast cancer. We will include studies that evaluate PD-L1 positivity with different cutoffs according to various scoring systems including Histo-score system (H-score), PD-L1 expression in tumor/normal breast samples (T/NB ratio), 4-point scale, Allred score, or Immunoscore (staining intensity and percentage of PD-L1 positive tumor cells). Data collection From eligible studies, we will extract bibliographical and study description data (e.g., title, author, country, study design, language of publication, year of publication, sample size, number of centers), patient characteristics (e.g., total number and number in comparison groups, age), and data related to breast cancer and prognosis. The QUIPS tool rates six bias domains: study participation, study attrition, prognostic factor measurement, outcome measurement, study confounding, and statistical analysis and reporting, as having a high, moderate, or low
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