Tumor-infiltrating lymphocytes (TILs) have potential value for stratifying the treatment of breast cancer (BC), though their precise use remains unclear. We aimed to investigate the utility of TILs using an alternative approach in different settings. We reviewed patients with triple-negative (TN) or human epithelial growth factor receptor 2 (HER2)-positive invasive ductal carcinomas from a single institutional cohort and classified archived hematoxylin–eosin-stained samples in terms of TIL score as low (<10 %), intermediate, and high (>50 %). The prognostic and predictive values of TILs were analyzed retrospectively in both adjuvant and neo-adjuvant settings. In the adjuvant setting, the presence of TILs at primary surgery was a significant favorable prognostic factor among 154 TNBCs [relapse-free survival (RFS): p = 0.015], but not among 183 HER2+ BCs (RFS: p = 0.097). The TNBC low-TIL group tended to relapse earlier. In the neo-adjuvant setting, detection of TILs on biopsy before primary systemic therapy was associated with the ratio of patients achieving pathological complete response among 48 TNBCs (p = 0.024), but not among 58 HER2+ BCs (p = 0.30). The presence of TILs in surgical specimens after systemic therapy had prognostic value in HER2+ BC (RFS: p = 0.007). The impact of TILs differs between patients with TN and HER2+ BC treated with standard therapies. Our three-grade scale for TILs may contribute to our understanding of the importance of the tumor microenvironment in routine practice. TILs after primary systemic therapy may be useful for the further stratification of treatment of HER2+ BC.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3848-2) contains supplementary material, which is available to authorized users.
Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with BRCA1/2-wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.5%), with recurrence for 4 SNVs/indels and 1 CNV. Comparisons with non-cancer east-Asian populations and European familial breast cancer cohorts revealed significant enrichment of PALB2, BARD1, and BLM mutations. Younger onset was associated with but not predictive of these mutations. Significant somatic loss-of-function alterations were confirmed on the wildtype alleles of genes with germline mutations, including PALB2 additional somatic truncations. This study highlights Japanese-associated germline mutations among patients with BRCA1/2 wildtype HBOC syndrome and a strong family history, and provides evidence for the medical care of this high-risk population.
9629 Background: Fosaprepitant is effective in the prevention of chemotherapy-induced nausea and vomiting. In January 2012, we started using fosaprepitant in anthracycline- and cisplatin-based regimens and observed a tendency for an increase in dermal and vascular adverse events (AEs) at local infusion sites, particularly in the anthracycline group. In this study, we tested the hypothesis that fosaprepitant use is associated with dermal and vascular AEs differentially between anthracycline- and cisplatin-based regimens. Methods: We conducted a retrospective cohort study consisting of all patients who were administered anthracycline- or cisplatin- based regimens in 2011 and 2012 at St. Luke’s International Hospital, Tokyo. Aprepitant was used in 2011 and fosaprepitant was used in 2012. All other factors including pre- and post-hydration, premedication, and injection schedule were the same. Dermal and vascular AEs was defined as any grade pain or skin changes at local infusion sites or infusion veins. Factors we considered include fosaprepitant use, chemotherapy regimen, age, number of prior regimens, and body mass index. Interaction analysis using multivariate logistic regression was used to evaluate the association between treatment regimen, fosaprepitant, and risk of AEs. Results: A total of 268 patients (aged 54.3±12.3) were included, of which 120 (44.8%) used fosaprepitant. Among fosaprepitant users, 50 patients (41.7%) developed dermal and vascular AEs, whereas only 16 patients (10.8%) experienced AEs among non-users (P< .001). When stratified by regimen, fosaprepitant was associated with a statistically significant increased risk of AEs (OR 12.10; 95% CI 5.45-26.93) in the anthracycline group. In contrast, no association was observed in the cisplatin group (OR 1.04; 95% CI 0.29-3.75). Statistically significant evidence of interaction was found (P< .001) between regimen and fosaprepitant in the risk of AEs. Conclusions: Our results support the finding that using fosaprepitant in anthracycline-based regimens increases dermal and vascular AEs. In response, we discourage the use of fosaprepitant in anthracycline-based regimens through peripheral lines.
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