We have recently reported in NSCLC that BRCA1 deficiency is associated with an enhanced response to DNA damage based chemotherapy and also PARP inhibitors. In concordance, reduced BRCA1 mRNA expression has been correlated with a better outcome following platinum chemotherapy, Clofarabine and clinical trials report on significant anti tumour activity following PARP inhibitor treatment in BRCA1 deficient patients. We would therefore predict that MPM tumours lacking expression of BRCA1 might also represent a molecularly defined subgroup of tumours with sensitivity to PARP inhibition. To conclude, we have identified a subset of patients harbouring BRCA1 immunonegative MPM. Based on our findings, this molecularly defined subgroup may be expected to exhibit resistance to vinorelbine, PDK 1 Signaling a question that could be addressed in a prospective clinical study.
Acknowledgment This work was supported by an educational research grant from Pierre Fabre. SB is supported igf-1r by an NCI/R&DNI HPSS office joint research project in cancer. JEQ is funded by a Breast Cancer Campaign Research Fellowship. DAF is supported by a Cancer Research UK Clinician Scientist Fellowship. Breast cancer tops both the incidence and mortality of malignant diseases in women worldwide, accounting for 23% of the total new cancer cases and 14% of the total cancer deaths in 2008. The incidence of breast cancer increases with age. Because of a progressively aging population, it can be expected that the number of elderly breast cancer patients will increase in the future.
However, the therapeutic approach for elderly breast cancer patients is currently not based on the reliable evidence, because elderly FAK inhibition patients are often excluded from or underrepresented in clinical trials. Barriers to the enrollment of elderly patients are mainly based on the bias that elderly patients will not tolerate or benefit from chemotherapy, in which elderly patients are often accompanied with impaired bone marrow function, abnormal drug metabolism, and high rates of comorbidities, which can increase the incidence of treatment related complications. So, there is an urgent need to develop and institute appropriate standards of care for elderly women with breast cancer. Anthracycline and taxane have been widely accepted as the two most active chemotherapeutic agents for breast cancer.
Their institutionalized increasing use in the adjuvant and neoadjuvant setting has led to a growing number of patients who are pretreated with them or no longer tolerate them, making the subsequent treatment a concern. Gemcitabine and vinorelbine, either alone or in combination, have shown activity in metastatic breast cancer pretreated by anthracycline and taxane. Single agent gemcitabine can achieve disease control rate of 35%, median progression free survival of 4.5 months and median overall survival of 9.8 months on relapsing or failing of both anthracycline and taxane. Gemcitabine is suitable for elderly patients due to its low toxic profile, manifested by the mild myelosuppression and minimal nonhematologic toxicity. Single agent vinorelbine is active for MBC pretreated by anthracycline and taxane, with disease control rate of 49%, median PFS of 3.8 months, and median OS of 12.6 months. Vinorelbine is well tolerated.