In a recent meta-analysis, we demonstrated that rich tumor-infiltrating lymphocytes (TILs) were significantly correlated to a favorable breast cancer (BC) outcome largely in estrogen receptor-negative tumors. It is known that TILs predominate in triple-negative (TN) BC, and to the best of our knowledge, there is no published meta-analysis that examined their prognostic value exclusively in that subtype. Therefore, we planned this meta-analysis to explore the clinical utility of rich TILs in TN-BC. According to predefined selection criteria, literature search identified eight eligible studies. The meta-analysis included data on 2,987 patients with early stage BC. The median percentage of lymph node positivity was 47% (95% confidence interval [CI] 23-82%). Over a median follow-up of 113 months (95% CI 80-144 months), it was found that rich TILs were associated with 30% (hazard ratio [HR] = 0.70; 95% CI 0.56-0.87; P = 0.001), 22% (HR = 0.78; 95% CI 0.68-0.90; P = 0.0008), and 34% (HR = 0.66; 95% CI 0.53-0.83; P = 0.0003), reduction in the risk of recurrence, distant recurrence, and death, respectively. In addition, for every 10% increments in rich TILs, there was an approximate 15-20% reduction in any recurrence, distant recurrence, or mortality. Moreover, rich TILs predicted superior overall survival (OS) benefit irrespective of the disease phenotype (TN-BC or core-basal phenotype), TILs location (intratumoral or stromal), or TILs qualification as either TILs-non-specified, cytotoxic (CD8+) or regulatory (forkhead box protein 3, FOXP3+) T cells. Data on 5-negative phenotype population were limited, and rich TILs failed to demonstrate a prognostic significance in this phenotype. To investigate the heterogeneity that was shown in the analyses of disease-free survival and OS, a set of meta-analyses showed that the method used in TILs detection (hematoxylin and eosin stains vs. immunohistochemistry) could explain most of the variability in the pooled estimates. Rich TILs were significantly associated with better survival outcome in early TN-BC and should be considered as a strong prognostic factor in this subtype. The results from the current meta-analysis support integrating immunotherapy with conventional therapy in future BC research.

BackgroundWomen treated for Hodgkin’s lymphoma (HL) have an elevated risk of developing second breast cancer (SBC) compared with the general population. We planned this meta-analysis to quantify the long-term risk of SBC and analyze the contributing risk factors among HL survivors.MethodsAccording to predefined selection criteria, literature search identified 34 studies that were included in the analyses.ResultsAfter eliminating overlapping or duplicate data, 957 incidences of SBC were encountered in 24,505 females with HL over a median follow-up of 14.9 years. The medians: age at the diagnosis of HL, age at diagnosis of SBC, and latency since HL treatment to the development of SBC were 23.7, 35.0, and 17.7 years, respectively. The pooled relative risk (RR) of SBC was 8.23 (95% CI, 5.43-12.47, I2 = 96%), with a median absolute excess rate of 22.9 per 10,000 person-years. The RR was found inversely related to age at diagnosis of HL with the highest rate (68.7; [95%CI, 28.08-168.11], I2 = 79%), occurred in young patients (≤ 15 years old), where the RR in older women (≥ 40 years old) was not significant (0.55; [95% CI, 0.09-3.52]). Analysis of RR by 5-year increments since the treatment of HL showed that the risk was highest after 15–19 years of latency (13.87; [95% CI, 7.91-24.30], I2 = 89%). Analysis of the effect of treatment modalities showed that the RR rates were (4.70; [95% CI, 3.28-6.75], I2 = 74%), (5.65; [95%CI, 2.94-10.88], I2 = 91%), and (1.19; [95% CI, 0.50-2.82], I2 = 65%), for radiotherapy (RT) only, combined RT and chemotherapy (CT), and CT only, respectively. To investigate the demonstrated heterogeneity, meta-regression analysis was performed when feasible. In most such analyses, the natural logarithm of RR was inversely associated with age at HL diagnosis.ConclusionsWe conclude that, the current meta-analysis provided the most recent comprehensive estimate of the risk of SBC in a broad-range of HL survivors. Younger age at diagnosis proved to be a dominant risk factor. The obtained results would serve providing breast cancer screening recommendations for HL survivors.

The association between PIK3CA mutation and resistance to anti-HER2 therapy (AHT) is not precisely defined. This meta-analysis intended to explore the clinical utility of PIK3CA mutation in HER2-positive breast cancer treated with AHT. Literature search identified 19 eligible studies. There were 1720 patients with advanced, 828 with early and 1290 patients treated in the neoadjuvant setting. In metastatic breast cancer, AHT showed no differential objective response benefit between the wild type (WT) and the mutated type (MT) PIK3CA subgroups (odds ratio [OR] = 1.09; 95 % CI 0.60-2.00; P = 0.78). AHT favorable affected progression-free survival (PFS) irrespective of PIK3CA mutation. There was no PFS difference between WT and MT regardless of the offered therapy. In early breast cancer, trastuzumab combined with the same chemotherapy conferred consistent relapse-free survival benefit in WT and MT subgroups (WT: HR = 0.59; 95 % CI 0.44-0.80; P < 0.001 vs. MT: HR = 0.42; 95 % CI 0.24-0.74; P < 0.001). In the neoadjuvant setting, AHT-based therapy produced a 72 % higher pathologic complete response (pCR) rate in WT as compared with that in MT PIK3CA tumors (OR = 1.72; 95 % CI 1.29-2.13; P < 0.001). In that setting, there was no disease-free or overall survival difference based on PIK3CA mutational status. In this meta-analysis, AHT did not achieve differential benefit according to PIK3CA mutation in HER2-positive metastatic or early breast cancer; however, in the neoadjuvant setting, patients harboring WT PIK3CA tumors attained a higher pCR rate.

Breast cancer is the most common cancer in women worldwide. The disease remains a public health concern as recent evidence indicates that the breast cancer burden has increased mainly in developing and low-income countries (DLICs). Despite the demonstrated benefits, the debate about the real benefits and harms of breast cancer screening is ongoing. Many experts believe that the benefits of screening, in terms of reduced breast cancer mortality, outweigh the harms, whereas others think the opposite. In this review, we assess the clinical utility of available screening modalities, present evidence, overdiagnosis, cost-effectiveness, and other pertinent issues. We also examine relevant data from DLICs to underscore the barriers and challenges that impede implementation of screening strategies in those populations. We also provide recommendations concerning rational preventive strategies for breast cancer control for women in DLICs.

The current meta-analysis provided a detailed estimate of the risk of SLC among HL survivors. The obtained results may provide guidelines concerning lung cancer screening for this population.