Interaction between Hormonal Receptor Status, Age and Survival in Patients with BRCA1/2 Germline Mutations: A Systematic Review and Meta-Regression

<div><p>Background</p><p>Germline mutations in the <i>BRCA1</i> and <i>BRCA2</i> genes are the most frequent known hereditary causes of familial breast cancer. Little is known about the interaction of age at diagnosis, estrogen receptor (ER) and progesterone receptor (PgR) expression and outcomes in patients with <i>BRCA1</i> or <i>BRCA2</i> mutations.</p><p>Methods</p><p>A PubMed search identified publications exploring the association between <i>BRCA</i> mutations and clinical outcome. Hazard ratios (HR) for overall survival were extracted from multivariable analyses. Hazard ratios were weighted and pooled using generic inverse-variance and random-effect modeling. Meta-regression weighted by total study sample size was conducted to explore the influence of age, ER and PgR expression on the association between <i>BRCA</i> mutations and overall survival.</p><p>Results</p><p>A total of 16 studies comprising 10,180 patients were included in the analyses. BRCA mutations were not associated with worse overall survival (HR 1.06, 95% CI 0.84–1.34, p = 0.61). A similar finding was observed when evaluating the influence of <i>BRCA1</i> and <i>BRCA2</i> mutations on overall survival independently (<i>BRCA1</i>: HR 1.20, 95% CI 0.89–1.61, p = 0.24; <i>BRCA2</i>: HR 1.01, 95% CI 0.80–1.27, p = 0.95). Meta-regression identified an inverse association between ER expression and overall survival (β = -0.75, p = 0.02) in <i>BRCA1</i> mutation carriers but no association with age or PgR expression (β = -0.45, p = 0.23 and β = 0.02, p = 0.97, respectively). No association was found for <i>BRCA2</i> mutation status and age, ER, or PgR expression.</p><p>Conclusion</p><p>ER-expression appears to be an effect modifier in patients with <i>BRCA1</i> mutations, but not among those with <i>BRCA2</i> mutations.</p></div

Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis

BACKGROUND: Inflammation influences cancer development and progression. An elevated platelet to lymphocyte ratio (PLR), a marker of inflammation, has been linked to poor prognosis in several malignancies. Here, we quantify the prognostic impact of this biomarker. METHODS: A systematic review of databases was conducted to identify publications exploring the association of blood PLR and overall survival (OS) in solid tumors. Data were pooled in a meta-analysis. Pooled HRs for OS by disease group and by PLR cutoff groups were computed and weighted using generic inverse-variance and random-effect modeling. RESULTS: Twenty studies comprising 12,754 patients were assessed. Cutoffs for PLR defining risk groups ranged from 150 to 300 and were dichotomous (12 studies; group 1) or split into three groups (300, 8 studies; group 2). Higher PLR was associated with significantly worse OS in group 1 [HR = 1.87; 95% confidence interval (CI, 1.49-2.34); P < 0.001] and with a nonsignificant association in group 2 (HR per higher category = 1.21; 95%CI, 0.97-1.50; P = 0.10). The size of effect of PLR on OS was greater for metastatic disease (HR[group 1] = 2.0; 95% CI, 1.6-2.7; HR[group 2] = 1.6; 95% CI, 1.1-2.4) than for early-stage disease (HR[group 1] = 1.5; 95% CI, 1.0-2.2; HR[group 2] = 1.0; 95% CI, 0.8-1.3). A significant association was observed for colorectal, hepatocellular, gastroesophageal, ovarian, and pancreatic carcinoma in group 1 and for colorectal cancers in group 2. CONCLUSION: A high PLR is associated with worse OS in various solid tumors. Further research of its regulation and relevance in daily practice is warranted. IMPACT: PLR is a readily available and inexpensive biomarker with independent prognostic value in solid tumors

Meta-regression.

<p>Association of <i>BRCA1</i> germline mutational status and proportion of patients with estrogen receptor expressing tumors.</p

Meta-regression (weighted by total sample size of studies); studies with HRs with and without adjustment for age (upper part) and hormonal receptors excluded (lower part) only.

<p>Meta-regression (weighted by total sample size of studies); studies with HRs with and without adjustment for age (upper part) and hormonal receptors excluded (lower part) only.</p

Meta-regression (weighted by total sample size of studies).

<p>Meta-regression (weighted by total sample size of studies).</p

Selection of included studies.

<p>Selection of included studies.</p