Understanding and dissecting the role of different subsets of regulatory tumor-infiltrating T lymphocytes (TILs) in the immunopathogenesis of individual cancer is a challenge for anti-tumor immunotherapy. High levels of γδ regulatory T (Treg) cells have been discovered in the breast TILs. However, the clinical relevance of these intra-tumoral γδ T cells is unknown. In this study, γδ T cell populations were analyzed by performing immunohistochemical staining in primary breast cancer tissues from patients with different stages of cancer progression. Retrospective multivariate analyses of the correlations between γδ T cell levels and other prognostic factors and clinical outcomes were completed. We found that γδ T cell infiltration and accumulation in breast tumor sites was a general feature in breast cancer patients. Intra-tumoral γδ T cell numbers were positively correlated with advanced tumor stages, HER2 expression status and high lymph node metastasis, but inversely correlated with relapse-free survival (RFS) and overall survival (OS) of breast cancer patients. Multivariate and univariate analyses of tumor-infiltrating γδ T cells and other prognostic factors further suggested that intra-tumoral γδ T cells were the most significant independent prognostic factor for assessing severity of breast cancer, compared with the other known factors. Intra-tumoral γδ T cells were positively correlated with FoxP3+ cells and CD4+ T cells, but negatively correlated with CD8+ T cells in breast cancer tissues. These findings suggest that intra-tumoral γδ T cells may serve as a valuable and independent prognostic biomarker, as well as a potential therapeutic target for human breast cancer.

Metaplastic breast cancer (MBC) is a rare subtype of invasive breast cancer that tends to have an aggressive clinical presentation as well as a variety of distinct histologic designations. Few systemic treatment options are available for MBC, as it has consistently shown a suboptimal response to standard chemotherapy regimens. These characteristics result in a worse overall prognosis for patients with MBC compared to those with standard invasive breast cancer. Due to its rarity, data focusing on MBC is limited. This review will discuss the clinical presentation, breast imaging findings, histologic and molecular characteristics of MBC as well as potential future research directions.

Background Gene expression profiling (GEP) has been integrated into cancer treatment decision‐making in multiple neoplasms. We prospectively evaluated the prognostic utility of the 31‐GEP test (DecisionDx‐Melanoma, Castle Biosciences, Inc) in cutaneous melanoma (CM) patients undergoing sentinel node biopsy (SNB). Methods One hundred fifty‐nine patients (age 26‐88) diagnosed with melanoma between 01/2013 and 8/2015 underwent SNB and concurrent GEP testing. GEP results were reported as low‐risk Class 1 (subclasses 1A and 1B) or high‐risk Class 2 (subclasses 2A and 2B). Statistical analyses were performed with chi‐square analysis, t tests, log‐rank tests, and Cox proportional hazard models. Recurrence‐free survival (RFS) and distant metastasis‐free survival (DMFS) were estimated using Kaplan‐Meier method. Results Median follow‐up was 44.9 months for event‐free cases. Median Breslow thickness was 1.4 mm (0.2‐15.0 mm). There were 117 Class 1 and 42 Class 2 patients. Gender, age, Breslow thickness, ulceration, SNB positivity, and AJCC stage were significantly associated with GEP classification ( P < 0.05 for all). Recurrence and distant metastasis rates were 5% and 1% for Class 1 patients compared with 55% and 36% for Class 2 patients. Sensitivities of Class 2 and SNB for recurrence were 79% and 34%, respectively. Of 10 SNB‐positive/Class 2 patients, 9 recurred. By multivariate analysis, only SNB result and GEP class were statistically associated with both RFS ( P = 0.008 and 0.0001) and DMFS ( P = 0.019 and 0.001). Conclusions Gene expression profiling Class 2 result and SNB positivity were independently associated with recurrence and distant metastasis in primary CM patients. GEP testing may have additive prognostic utility in initial staging work‐up of these patients.

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