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Purpose: This study compares immunohistochemical (IHC) versus molecular subtyping (BluePrint and MammaPrint) in the population of patients enrolled in MINDACT and outcome based on molecular subtyping (MS) versus surrogate pathological subtyping (PS) as defined by the 2013 St. Gallen guidelines.Methods: MS classified patients in the following subtypes: Luminal A, Luminal B, HER-2-, and Basal-type. IHC/FISH for pathological subtyping (ER, PgR, HER-2, and Ki67) was centrally assessed in the European Institute of Oncology (n = 5806). Hazard ratios for distant-metastasis-free survival (DMFS) by subtype were adjusted for chemotherapy and endocrine therapy administration and thus independent of adjuvant treatment allocation.Results: PS Luminal cancers classified as HER-2+ or Basal-type by MS did not have a significantly lower DMFS than the Luminal-type cancers by MS (95.9%): HR = 1.40, 95% CI 0.75–2.60 (p = 0.294). More patients were identified with Luminal A disease by MS (63%) as compared with PS (47%) with comparable 5-year DMFS (≥96.0%). Among the 500 patients with PS TN cancers, MS identified 24 (5%) patients as Luminal-type with 5-year DMFS estimated at 100% versus 71.4% for MS HER-2+ or 90.1% for MS Basal-type.Conclusions: MS was able to re-stratify 54% of patients with a Luminal-B PS subtype to a low-risk Luminal A-type group with comparable outcome. Among TN EBC, 5% were classified as Luminal by MS with Luminal-like outcome. Molecular classification can help to identify a larger group of patients with low risk of recurrence compared with the more contemporarily used classification methodology including high-quality assessed Ki67. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of docetaxel plus capecitabine (DC) combination as salvage treatment in anthracycline- and taxane-pretreated patients with metastatic breast cancer (MBC). Patients and treatment: Patients with MBC who had disease progression after initial chemotherapy with anthracyclines ( n = 29; 100 %) and taxanes ( n = 11; 37.9 %) were treated with oral capecitabine 950 mg/m twice daily on days 1-14 and docetaxel 75 mg/m on day 1 every 3 weeks. Nineteen (65.5 %) patients received this regimen as second line and 10 (34.5 %) as ≥3rd line of therapy. All patients were evaluable for response and toxicity. Results: Complete response occurred in two (6.9 %) patients and partial response in eleven (37.9 %) for an overall response rate of 44.8 % (95 % CI 26.7-62.9 %). Eleven women (37.9 %) had stable disease and five (17.2 %) progressive disease. Of the eleven patients previously treated with anthracyclines and taxanes, five (45.5 %) responded to DC combination. The median duration of response was 5.7 months (range 3.4-64.2), the median time to disease progression 9.3 months (range 1.2-58), and the median overall survival 25.5 months. No toxic death occurred. Neutropenia grade 4 occurred in 58.6 % of patients and three of them (10.3 %) developed neutropenic fever. Non-hematological toxicities were manageable with grade 3 hand-foot syndrome occurring in 6.9 % of the patients, fatigue in 3.4 %, and neurotoxicity in 3.4 %. Conclusion: The DC combination is a valuable regimen as salvage treatment in anthracycline- or anthracycline and taxane-pretreated patients with MBC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the docetaxel-gemcitabine (DG) combination administered every 2 weeks as salvage therapy in anthracycline- and taxane-pretreated patients with metastatic breast cancer (MBC). Patients and treatment: Thirty women with MBC who had disease progression after chemotherapy with anthracyclines, or anthracyclines and taxanes were treated with docetaxel 50 mg/m² and gemcitabine 1,500 mg/m² on days 1 and 14 in cycles of 28 days. All patients had received prior anthracyclines, and fourteen (46.6%) had also received prior taxanes. All patients were evaluable for toxicity and 24 for response to treatment. Results: Complete response occurred in four (13.3%) patients and partial response in 10 (33.3%) for an overall response rate of 46.7% (95% CI 28.8-64.5). Seven patients (23.3%) had stable disease and nine (30%) progressive disease. Of the 14 patients previously treated with both anthracyclines and taxanes, seven (50%) responded. The median duration of response was 4.8 months (range 1.9-15.3), the median time to disease progression 6.6 months (range 0.5-16.9) and the median overall survival 16.8 months (range 1.3-53.2). There was no treatment-related toxic death. Neutropenia was the only grade 4 toxicity occurring in three (10%) patients. None of them developed neutropenic fever. Grade 3 thrombocytopenia occurred in two (6.7%) patients. Non-hematological toxicities were manageable. Conclusion: The DG combination administered biweekly is very well tolerated and effective in anthracycline- and taxane-pretreated patients with MBC. A previous treatment with taxanes does not preclude a good clinical response to this regimen. [ABSTRACT FROM AUTHOR]

Background: We explored the predictive significance of BRCA1, TXR1 and TSP1 expression in non-small-cell lung cancer (NSCLC) patients treated with docetaxel in association with cisplatin or gemcitabine.Methods: To analyse BRCA1, TXR1 and TSP1 mRNA expression from microdissected primary tumours of 131 patients with stage IIIB (wet) and IV NSCLC, RT-qPCR was used.Results: The mRNA levels of TXR1/TSP1 were inversely correlated (Spearman's test: -0.37; P=0.001). Low TXR1 mRNA levels were associated with higher response rate (RR; P=0.018), longer median progression-free survival (PFS; P=0.029) and median overall survival (mOS P=0.003), whereas high TSP1 expression was correlated with higher RR (P=0.035), longer PFS (P<0.001) and mOS (P<0.001). Higher BRCA1 mRNA expression was associated with higher RR (P=0.028) and increased PFS (P=0.021), but not mOS (P=0.4). Multivariate analysis demonstrated that low TXR1/high TSP1 expression was an independent factor for increased PFS (HR 0.49; 95% CI 0.32-0.76; P<0.001) and mOS (HR 0.37; 95% CI 0.2-0.58; P<0.001), whereas high BRCA1 expression was correlated with increased PFS (HR 0.53; 95% CI 0.37-0.78; P=0.001).Conclusions: These data indicate that TXR1/TSP1 and BRCA1 expression could be used for the prediction of taxanes' resistance in the treatment of NSCLC. [ABSTRACT FROM AUTHOR]