[sarah]

Thanks Lani and Rich for this information. I didn't realize I was in such a minority being ER+. Reading Rich's post elsewhere makes it sound like you had better take them both. bummer, I was hoping to give up the Femara which has the side effects and stay on Herceptin for one more year. A friend suggested Evista/raloxifene which apparently is also good for the bones. Any thoughts or comments?

Here was Rich's post:
Combined ER and HER-targeted therapy in breast cancer treatment
Combined ER and HER-targeted therapy in breast cancer treatment

Citation: THE BREAST, Volume 18, Supplement 1, March 2009, Page S8

K. Osborne1, R. Schiff1

1Breast Center, Baylor College of Medicine, Houston, USA

The estrogen receptor (ER) and HER signaling networks are complex, redundant, evolvable and robust pathways, each with several regulatory controls. Several levels of crosstalk between these two networks act as modulatory circuits that when altered can contribute to resistance to therapies targeting them. Nuclear ER when bound by estrogen increases the expression of ligands binding to HER receptors while at the same time reducing the expression of the receptors themselves. At the same time, the HER signaling pathway reduces expression of ER and progesterone receptor (PR) while it can activate ER functionally through phosphorylation of the receptor and its coactivators. Therefore, blockade of ER signaling by endocrine therapy can increase the cellular content of HER1 and HER2, while blockade of HER signaling can increase the expression of ER and PR. Non-nuclear ER can also activate the HER signaling pathway by several mechanisms at the level of the cell membrane. Although there are several potential mechanisms for resistance to ER and HER-targeted therapy, preclinical data from our group and others, as well as supporting data from recent clinical trials, indicate that upregulation at the HER signaling pathway can cause resistance to ER-targeted therapy and that upregulation of ER signaling can cause resistance to HER-targeted therapy.
These data suggest that optimal treatment in some patients using therapies targeting these two pathways might necessitate simultaneous blockade of both pathways. In preclinical models and, now, data from clinical trials, simultaneous use of endocrine therapy to target ER and therapy targeting the HER receptor network can overcome resistance to endocrine therapy and delay the time to tumor progression. Using a combination of HER inhibitors to completely block the HER pathway together with ER blockade is very potent therapy in preclinical xenograft models of ER+/HER2+ tumors and is able to eradicate tumors even after short term therapy. In ER+ tumors that express initially low levels of HER receptors, the addition of HER receptor blockade to endocrine therapy anticipating upregulation of HER receptors during endocrine therapy delays the emergence of resistance and prolongs time to progression. Combined HER-targeted therapy in this situation does not eradicate these xenograft tumors indicating that other survival pathways still function and that these tumors have not yet become “oncogene addicted” to the HER pathway. There is an urgent need to biopsy patients immediately before embarking on targeted therapy to profile the tumor and to select the optimal patient for this new approach.