British journal of cancer
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British journal of cancer · Mar 2016
Multicenter StudyPhase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer.
Rucaparib is an orally available potent selective small-molecule inhibitor of poly(ADP-ribose) polymerase (PARP) 1 and 2. Rucaparib induces synthetic lethality in cancer cells defective in the homologous recombination repair pathway including BRCA-1/2. We investigated the efficacy and safety of single-agent rucaparib in germline (g) BRCA mutation carriers with advanced breast and ovarian cancers. ⋯ Rucaparib is well tolerated and results in high levels of PARP inhibition in surrogate tissues even at the lowest dose levels. Rucaparib is active in gBRCA-mutant ovarian cancer and this activity correlates with platinum-free interval. The key lessons learned from this study is that continuous rucaparib dosing is required for optimal response, the recommended phase 2 dose (RP2D) for continuous oral scheduling has not been established and requires further exploration and, thirdly, the use of a PD biomarker to evaluate dose-response has its limitations.
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British journal of cancer · Mar 2016
Effect of organised mammography screening on stage-specific incidence in Norway: population study.
We aimed to estimate the effect of organised mammography screening on breast cancer stage distribution by comparing changes in women eligible for screening, based on birth cohort, to the concurrent changes in younger, ineligible women. ⋯ Introduction of organised mammography screening was followed by a significant increase in localised and no change in advanced-stage cancers in women eligible for screening relative to younger, ineligible women.