[Debbie L.]

Jane, my understanding of the issue (triple positive cancers being endocrine resistant) is that initially (many years ago, perhaps 10+), there seemed to be some indications that HER2+ cancer tended to be Tamoxifen resistant. But upon further examination, it was realized that it's more a tendency to pan-endocrine resistance. Early studies that seemed to show that AIs might be more effective than Tamoxifen for HER2+ cancers were apparently not reproducible. At least that's what I've read, although I do not have specific evidence to cite right now.

It's probable that anti-HER2 therapy (Herceptin, Lapatinib, probably others) increases the susceptibility to endocrine treatment but the details of how this happens, for how long it happens, etc, is not yet known.

Also, the most recent studies trying to link CYP2D6 metabolism to Tamoxifen efficacy were not able to find a link. Presentations at SABCS 2010 seemed to dramatically decrease interest in this line of inquiry (no link found between CYP2D6 variants and breast cancer recurrence for women taking Tamoxifen). Maybe the jury is still out on that one but I think the consensus among reliable oncologists is that CYP2D6 testing is not of any value.

Never hang your hat on just one (or even two) study reports. It's so tempting to think that we have clear answers. But alas, so often, we do not.

Since you are clearly one to ask the hard (but important) questions, it seems a logical next step for you to get more opinions about your specific situation, from higher up the food chain. Have you consulted with an NCI-designated Comprehensive Cancer Center about endocrine therapy options? http://cancercenters.cancer.gov/canc...ters-list.html It seems like this would be the perfect time for that, if you've not already done it.

Debbie Laxague