Background:Trastuzumab resistance hampers its well-known efficacy to control HER2-positive breast cancer. The involvement of PI3K/Akt pathway in this mechanism is still not definitively confirmed.Methods:We selected 155 patients treated with trastuzumab after development of metastasis or as adjuvant/neoadjuvant therapy. We performed immunohistochemistry for HER2, ER/PR, epidermal growth factor 1-receptor (EGFR), α-insulin-like growth factor 1-receptor (IGF1R), phosphatase and tensin homologue (PTEN), p110α, pAkt, pBad, pmTOR, pMAPK, MUC1, Ki67, p53 and p27; mutational analysis of PIK3CA and PTEN, and PTEN promoter hypermethylation.Results:We found 46% ER/PR-positive tumours, overexpression of EGFR (15%), α-IGF1R (25%), p110α (19%), pAkt (28%), pBad (22%), pmTOR (23%), pMAPK (24%), MUC1 (80%), PTEN loss (20%), and PTEN promoter hypermethylation (20%). PIK3CA and PTEN mutations were detected in 17% and 26% tumours, respectively. Patients receiving adjuvant trastuzumab with α-IGF1R or pBad overexpressing tumours presented shorter progression-free survival (PFS) (all P⩽0.043). Also, p110α and mTOR overexpression, liver and brain relapses implied poor overall survival (OS) (all P⩽0.041). In patients with metastatic disease, decreased PFS correlated with p110α expression (P=0.024), whereas for OS were the presence of vascular invasion and EGFR expression (P⩽0.019; Cox analysis).Conclusion:Our results support that trastuzumab resistance mechanisms are related with deregulation of PTEN/PI3K/Akt/mTOR pathway, and/or EGFR and IGF1R overexpression in a subset of HER2-positive breast carcinomas.

As compared with adjuvant FAC, adjuvant TAC improved the rate of disease-free survival among women with high-risk, node-negative breast cancer. (Funded by GEICAM and Sanofi-Aventis; ClinicalTrials.gov number, NCT00121992.).

The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects. The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG, particularly in the final part of chemotherapy treatment.

Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.

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Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

A-->T significantly reduced febrile neutropenia compared with AT in MBC patients and maintains comparable antitumoral efficacy. A-->T represents a valid option for the treatment of MBC.