Long-term efficacy and safety of anastrozole for adjuvant treatment of early breast cancer in postmenopausal women

For more than 20 years, tamoxifen has been the gold standard for the adjuvant treatment of postmenopausal women with hormone-responsive early breast cancer. However, recent randomized trials have shown efficacy and tolerability benefits with the third-generation aromatase inhibitor anastrozole, resulting in an increased use of this agent in the adjuvant setting. Data on anastrozole’s long-term efficacy and tolerability are therefore of interest in clinical practice and will be reviewed here, especially in the light of the 100-month analysis of the ATAC (Anastrozole, Tamoxifen Alone or in Combination) trial

3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response

The Her2 receptor is overexpressed in up to 25 % of breast cancers and is associated with a poor prognosis. Around half of Her2+ breast cancers also express the estrogen receptor and treatment for such tumours can involve both endocrine and Her2-targeted therapies. However, despite preclinical data supporting the effectiveness of these agents, responses can vary widely in the clinical setting. In light of the increasing evidence pointing to the interplay between the tumour and its extracellular microenvironment as a significant determinant of therapeutic sensitivity and response here we investigated the impact of 3D matrix culture of breast cancer cells on their therapeutic sensitivity

Additional file 3: Figure S2. of 3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response

Effects of AKT and MAPK inhibition on apoptosis in BT474 and MDAMB361 cells. Cell lines grown in 2D or 3D culture were exposed to AKT inhibitor (MK-2206) or MEK inhibitor (U0126) prior to cell lysis and Western blotting using an antibody that recognizes full length (116kDa) and cleaved (85kDa) forms of PARP, the latter form apparent upon apoptosis. Neither AKT or MAPK inhibition resulted in a significant loss of full length PARP or a corresponding gain in cleaved PARP for either cell line. In contrast, cleaved PARP was seen to increase in response to the apoptosis inducer, camptothecin, included as a positive control. (DOC 59 kb

Additional file 2: Figure S1B. of 3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response

Process of recovery of cells from 3D culture for experimental analysis. Cells were recovered from the 3D cultures for counting, immunocytochemical analysis or Western blotting as shown using a modification of a previously reported method (Arnold 2001). (DOC 52 kb