Purpose CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in operable breast cancer. The fRida trial (NCT02370238) evaluated the addition of R to weekly as first-line therapy for metastatic (m) TNBC. Subjects and Methods Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1–21 in combination with weekly P 80 mg/m2 on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review. Results 123 subjects were randomized (62 to R + P and 61 to placebo + P). PFS was not different between the 2 groups (median 5.5 and 5.6 months for R + P and placebo + P, respectively; HR 1.13, p = 0.5996). ALDH+ and CD24−/CD44+ CSC centrally evaluated by IHC were found in 16 and 34 of the 54 subjects who provided a metastatic tissue biopsy at study entry. Serious adverse events (21.3 and 20% of subjects) and grade ≥ 3 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups. Conclusion fRida is the first randomized, double-blind clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met. Clinical Trial Registration/Date of Registration NCT01861054/February 24, 2015.

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A histopathological review preliminary of 429 patients diagnosed with tumours of the uterine corpus (TUC) cancer between 1984-2010 in the Vigo University Hospital Complex (Spain) were evaluated prospectively for over 5 years. Of these 403 (93.9%) were epithelial tumours: 355 (82.7%) were adenocarcinomas of the endometrioid type, 5 (1.1%) mucinous adenocarcinoma, 10 (2.3%) serous adenocarcinoma, 17 (3.9%) clear cell carcinomas, 11 (2.5%) mixed adenocarcinoma, 4 (0.9%) undifferentiated carcinomas and 1 (0.2%) squamous cell carcinomas. A total 20 (4, 6%) were mesenchymal tumours: 4 (0.9%) endometrial stromal sarcoma, 7 (1.6%) Leiomyosarcoma, 9 (2%) Mixed endometrial stromal and smooth muscle tumour. A total 1 (0.2%) were mixed epithelial and mesenchymal tumours: (0.2%) Adenosarcoma 1. And 5 (1.1%) were Metastases from extragenital primary tumour (3 carcinomas of the breast, 1 stomach and 1 colon). The mean age at diagnosis from total series were 65, 4 years (range 28-101 years). Age was clearly related to histologic type:Endometrial stromal sarcoma 46.0 years, Leiomyosarcomas 57.1 years, Adenocarcinomas of the endometrioid type 65.4 years, Clear cell carcinomas 70.1 years and mixed endometrial stromal and smooth muscle tumours 71.2 years. Five-year disease-free survival rates for the entire group were: Endometrial stromal sarcoma 50%, Leiomyosarcomas 28.6%, Adenocarcinomas of the endometrioid type 83.7%, Clear cell carcinomas 64.7% and mixed endometrial stromal and smooth muscle tumours 44.4%. The 5-year disease-free survival rates of patients with Adenocarcinomas of the endometrioid type tumors were 91.4% for grade 1 tumors, 77.5% for grade 2, and 72.7% for grade 3.In conclusion, we describe 5-year histological and disease-free survival data from a series of 429 patients with TUC, observing similar percentages to those described in the medical literature. The only difference we fi nd with other published series is a slightly lower percentage of serous carcinomas (ESC) that the Western countries but similar to the 3% of all ESC in Japan. Our investigation is focus at the moment on construct genealogical trees for the possible identifi cation of hereditary syndromes and to carry out germline mutation analysis.

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