To the two above posts by Robin in which in vitro evidence of ERB inhibitors such as lapanitib (Tykerb) or transtazumab (Herceptin) upregulating the ER pathway one can add this small study in humans which seems to confirm the lab findings:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&li st_uids=16417653&query_hl=1&itool=pubmed_DocSum
Breast Cancer Res. 2006;8(1):R4. Epub 2005 Dec 7
Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy.
Munzone E,
Curigliano G,
Rocca A,
Bonizzi G,
Renne G,
Goldhirsch A,
Nole F.
Department of Medicine, Division of Medical Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. elisabetta.munzone@ieo.it
INTRODUCTION: The amounts of estrogen receptor (ER) and progesterone receptor (PgR) in a primary tumor are predictive of the response to endocrine therapies of breast cancer. Several patients with ER-positive primary tumors relapse after adjuvant endocrine therapy with no ER expression in the recurrent tissue; much fewer with a recurrent disease after an ER-negative primary tumor may become endocrine responsive. These sequences of events indicate that a phenotype based on ER expression may not be a permanent feature of breast cancer.
METHODS:
Ten patients with advanced breast cancer whose tumors overexpressed HER-2, but not ER or PgR, were treated with weekly trastuzumab at standard doses with or without chemotherapy.
RESULTS:
Three out of 10 patients showed overexpression of ERs first appearing after 9, 12 and 37 weeks, respectively, from the initiation of trastuzumab. Two of these patients were subsequently treated with endocrine therapy alone: one of them received letrozole for 3 years without evidence of progression. CONCLUSION:
Therapeutic targets enabling the appearance of an endocrine responsive disease may increase treatment options for patients with breast cancer. Furthermore, these clinical data suggest that an ER-negative phenotype is a multi-step process with a reversible repression modality, and that some ER-negative tumors may either revert to an ER-positive phenotype, allowing an endocrine treatment to be effective.
One wonders if the fast success of treatment seen in some women taking an aromatase inhibitor (such as letrozole,Anastrozole,fulvestrant...) in addition to Herceptin is in part explained by attacking both ER & HER pathways.
If someone has a contact with a knowledgeable researcher or clinician it would be interesting to have his opinion on these questions:
1. Over the long term are all takers of ERB inhibitors likely to need endocrine treatments for ER+? Or which subset of patients?
2. Should anti estrogens treatments be started concurrently with Tykerb or Herceptin (even if there is no initial evidence of ER+ disease)?
Would the benefits (hopefully faster & better outcomes) outweight the increased side effects?
3. If on the othe hand the antiestrogen treatments are to begin after reversion from HER+ to ER+ what are the tests providing the earliest diagnostic of the reversal? (if possible non invasive to avoid frequent biopsies or bone marrow aspirations which are also limited in scope by their localized nature)
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