BackgroundTrastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression after trastuzumab treatment.MethodsData were collected from women with HER2-positive metastatic breast cancer treated with trastuzumab that experienced a response or stable disease during at least 3 years. Patients having a progression in the first year of therapy with trastuzumab were used as a control. Genes related with trastuzumab resistance were identified and investigated for network and gene functional interrelation. Models predicting poor response to trastuzumab were constructed and evaluated. Finally, a mutational status analysis of selected genes was performed in HER2 positive breast cancer samples.Results103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median duration of response was 55 months. The molecular analysis included 35 patients from the group with complete response and 18 patients in a control poor-response group. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival. Gene ontology analysis demonstrated that PI3K pathway was associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most.ConclusionsTrastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a control group predicted early progression after trastuzumab-based therapy. Multiple alterations in genes related to the PI3K-mTOR pathway seem to be required to confer resistance to this therapy.
Background: Male breast cancer (MBC) accounts for less than 1% of breast cancer, requiring extrapolation of results from studies in women. The aim of the study is to evaluate prognostic and therapeutic factors with special focus in endocrine treatment (ET) on the disease outcome.Methods: Observational, retrospective, single-center study of 53 MBC treated between January 1997 and December 2018 participated in the study. Among the participants, 48 patients had a performance status (PS) 0-1 (91%), 48 were hormone-receptor-positive (91%) and 4 were human epidermal growth factor 2 receptor (HER2) positive (8%). A total of 45 patients (85%) were treated with ET, with 36 patients (68%) receiving treatment in an adjuvant setting. The association analysis was performed using Chi-square test and survival was estimated using Kaplan-Meier with SPSS v25. Results: The cohort had a median age of 68 years old (range: 40-88). We found that 84% had a non-metastatic breast cancer. A breast cancer gene (BRCA) analysis was carried out in 43% of the patients, showing BRCA2 mutated in 26.1% of those analyzed, without obtaining a benefit in overall survival (P=0.698). The analysis showed higher 5-year overall survival (OS) for PS 0 (P=0.010), absence of vascular invasion (P=0.033), Ki67 ?14% (P=0.041) and absence of metastasis at diagnosis (p<0.0001). Patients receiving adjuvant ET above 5 years had a longer median OS (89 vs 69.6 months, P=0.024), disease-free survival (DFS), and distant relapse (84 vs 48 months; P=0.005, and P=0.002, respectively).Conclusions: Several prognostic factors for male breast cancer have been described. Noteworthy, patients receiving adjuvant ET above 5 years had a higher OS and DFS. BRCA did not show prognostic value in OS in this cohort. Further studies with larger sample size are necessary.
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