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Vulvar, perianal, and perineal cancer represent a rare but serious complication of HS.

Exemestane represents an active and well-tolerated treatment option in pretreated patients with advanced breast cancer who have received standard first- and second line hormonal therapies. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed.

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BackgroundThe host’s immune system is crucially involved in cancer development and progression. The ratio of regulatory to effector T-cells, as well as the interplay of T-cells with therapeutic agents, impact on cancer prognosis. The current study aimed to comparatively investigate the effect of metronomic and standard chemotherapy on the number and functionality of peripheral regulatory and effector T-cells in cancer patients.MethodsCD4+CD25+ regulatory and CD4+CD25- effector T-cells were purified from the peripheral blood of 36 cancer patients and co-cultured in the presence of a polyclonal stimulus. The proliferative capacity and frequency of CD4+CD25+/CD4+CD25- T-cells were analysed before and during various chemotherapeutic regimes, by ELISA and flow cytometry, respectively.ResultsChemotherapy shifted immune responses in favour of regulatory T-cells. The relative ratio of regulatory to effector T-cells increased, and the T-cell-mediated suppressive activity of regulatory on effector T-cells was augmented. This effect was more profound in metronomic than in standard chemotherapeutic approaches. Moreover, an association between the chemotherapy strategy followed and the mode of action of specific drugs (anti-mitotic, anti-DNA) was revealed.ConclusionsIn comparison to standard chemotherapeutic strategies, metronomic approaches, though more patient-friendly, result in a significantly more prominent expansion of regulatory T-cells that aggravate the regulatory to effector T-cell imbalance. Our findings impact on the modulation of chemotherapy-treated patients’ anti-tumor immunity and, thus, may be proven useful for selecting the most advantageous drug-delivery strategy, particularly when immunotherapeutics are eventually to be applied.

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Background Circulating tumor cell (CTC) analysis is highly promising for liquid biopsy-based molecular diagnostics. We undertook a comprehensive molecular analysis of in vivo isolated CTCs in breast cancer (BrCa). Methods In vivo isolated CTCs from 42 patients with early and 23 patients with metastatic breast cancer (MBC) were prospectively collected and analyzed for gene expression, DNA mutations, and DNA methylation before and after treatment. 19 healthy donor (HD) samples were analyzed as a control group. In identical blood draws, CTCs were enumerated using CellSearch® and characterized by direct IF staining. Results All 19 HD samples were negative for CK8, CK18, CK19, ERBB2, TWIST1, VEGF, ESR1, PR, and EGFR expression, while CD44, CD24, ALDH1, VIM, and CDH2 expression was normalized to B2M (reference gene). At least one gene was expressed in 23/42 (54.8%) and 8/13 (61.5%) CTCs in early BrCa before and after therapy, and in 20/23 (87.0%) and 5/7 (71.4%) MBC before and after the first cycle of therapy. PIK3CA mutations were detected in 11/42 (26.2%) and 3/13 (23.1%) in vivo isolated CTCs in early BrCa before and after therapy, and in 11/23 (47.8%) and 2/7 (28.6%) MBC, respectively. ESR1 methylation was detected in 5/32 (15.7%) and 1/10 (10.0%) CTCs in early BrCa before and after therapy, and in 3/15(20.0%) MBC before the first line of therapy. The comprehensive molecular analysis of CTC revealed a higher sensitivity in relation to CellSearch or IF staining when based on creatine kinase selection. Conclusions In vivo-CTC isolation in combination with a comprehensive molecular analysis at the gene expression, DNA mutation, and DNA methylation level comprises a highly powerful approach for molecular diagnostic applications using CTCs.