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Old 06-25-2008, 10:38 AM   #1
Nguyen
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Responding to same endocrine treatment again.

Does anyone here responding to the SAME endocrine treatment (such as Femara, Anastrozole, etc) after treatment stopped DUE to acquired resistance.

For some patients and chemotherapy, the tumour can reverse the acquired resistance to that chemotherapy after not being treated with that chemotherapy for a period time (a few years if I remember correctly).

I was wondering about this with respect to endocrine treatment, then found the abstract below.

- Nguyen
Stopping Treatment Can Reverse Acquired Resistance to Letrozole

Gauri J. Sabnis1, Luciana F. Macedo1, Olga Goloubeva2, Adam Schayowitz1 and Angela M.H. Brodie1,2
1 Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine and 2 University of Maryland Greenebaum Cancer Center, Baltimore, Maryland
Requests for reprints: Angela M.H. Brodie, Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Health Science Facility I, Room 580G, 685 West Baltimore Street, Baltimore, MD 21201. Phone: 410-706-3137; Fax: 410-706-0032; E-mail: abrodie@umaryland.edu .

Key Words: aromatase inhibitors • estrogen • letrozole • ER • Her-2
Using the intratumoral aromatase xenograft model, we have observed that despite long-lasting growth inhibition, tumors eventually begin to grow during continued letrozole treatment. In cells isolated from these long-term letrozole-treated tumors (LTLT-Ca), estrogen receptor- (ER) levels were decreased, whereas signaling proteins in the mitogen-activated protein kinase cascade were up-regulated along with human epidermal growth factor receptor 2 (Her-2). In the current study, we evaluated the effect of discontinuing letrozole treatment on the growth of letrozole-resistant cells and tumors. The cells formed tumors equally well in the absence or presence of letrozole and had similar growth rates. After treatment was discontinued for 6 weeks, letrozole was administered again. Marked tumor regression was observed with this second course of letrozole treatment. Similarly, in MCF-7Ca xenografts, a 6-week break in letrozole treatment prolonged the responsiveness of the tumors to letrozole. To understand the mechanisms of this effect, LTLT-Ca cells were cultured in the absence of letrozole for 16 weeks. The resulting cell line (RLT-Ca) exhibited properties similar to MCF-7Ca cells. The cell growth was inhibited by letrozole and stimulated by estradiol. The expression of phosphorylated mitogen-activated protein kinase (MAPK) was reduced and ER and aromatase levels increased compared with LTLT-Ca cells and were similar to levels in MCF-7Ca cells. These results indicate that discontinuing treatment can reverse letrozole resistance. This could be a beneficial strategy to prolong responsiveness to aromatase inhibitors for patients with breast cancer. [Cancer Res 2008;68(12):4518–24]
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Old 11-25-2008, 09:03 PM   #2
Nguyen
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From "track 15" of this interview:

http://www.breastcancerupdate.com/medonc/2008/4/ellis.asp

Track 15
DR LOVE: Can you describe your study of estrogen at high and low doses for metastatic breast cancer?
DR ELLIS: We’ve recently completed a multicenter study with 66 patients, evaluating 30 versus six milligrams of generic estradiol for patients who experienced disease progression while receiving an aromatase inhibitor. In this study, if the patient benefits from estrogen therapy, she is switched back to the aromatase inhibitor she was receiving before the progression.
The study is designed to determine whether oscillating between an aromatase inhibitor and estrogen therapy will produce a prolonged clinical benefit, and some tumors do appear to respond in that way. We will be presenting the data at the annual San Antonio Breast Cancer Symposium in December of this year.
Essentially, we’re seeing 10 to 15 percent actual responses — some quite dramatic — and approximately a 30 percent clinical benefit rate. Interestingly, the responses can be predicted by a PET flare.
We obtained a baseline PET image, and then 24 hours after treatment we examined the difference in glucose uptake. We found that the patients with a dramatic glucose uptake were the ones who went on to respond, so a biomarker for response does exist.
The 6-mg dose was as effective as and safer than the higher dose. We were careful to exclude patients with uncontrolled hypercalcemia and a history of thrombotic events or myocardial infarction.
In the trial, we saw no venous thrombotic events and found that the therapy was well tolerated. However, the flare reactions that you read about in textbooks are real.
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Old 11-26-2008, 07:39 AM   #3
Hopeful
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There is currently a study being conducted in Europe to test a new method of administration of AI's. Women who have already had 5 years of tx are being tested on a 3 month on, 3 month off dosing schedule vs. I believe continuous dosing.

IMO, these studies show that we can do a better job with the exisiting drugs on the market if we work at determining the optimum way to use them. Too little work is done with dosing schedules and amounts once they hit the market.

Hopeful
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Old 11-26-2008, 05:46 PM   #4
Rich66
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I've wondedred for some time if a rotating cycle of various chemos and/or AIs would work. That would be one hell of a study...
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