Estradiol levels with AI

This comes up frequently on this site. The goal, I believe, is to get estradiol down to an "undetectable level." Blood tests cannot show anything else below a certain level.

The Femara insert says that studies show that 20% of the usual dose accomplishes this. Looking at the half life, it is certainly possible to take it alternate days. My doc okayed that but in the five years I took it, I took it every day.

Apparently studies have shown effectiveness so we don't have blood tests ordered by docs.

The mystery behind AI and how we know it’s working without testing is one of those leap of faith areas that I never feel comfortable in. So I requested the test and it’s
<15 ( lowest lab can predict) .

What May 22 study did you read? Could you post?

I think dosages are definitely being considered in researching efforts.

Article attached (Alternative dosing exemestane)
2022 ASCO ANNUAL MEETING
Reduced-Dose Exemestane Noninferior to Standard Daily Dose in Postmenopausal Women With Early ER-Positive Breast Cancer
May 26, 2022
Key Points:
• The aromatase inhibitor exemestane taken 3 times per week is noninferior to the standard daily dose among postmenopausal women with ER–positive breast cancer, considering the primary endpoint of percent change of circulating estradiol.
• The study's primary limitation was the short treatment duration. Because some side effects develop after a few months, conclusions on tolerability cannot be drawn.
Findings from a noninferiority phase 2b biomarker study indicate that the aromatase inhibitor exemestane taken 3 times per week is noninferior to the standard daily dose among postmenopausal women with estrogen receptor-positive breast cancer. Both dosing regimens reduced circulating estradiol by a median of 98% (P = .9). A third group of patients who took exemestane once per week saw their circulating estradiol decreased by a median of 70%. The results will be presented during the 2022 ASCO Annual Meeting by Andrea De Censi, MD, of the National Hospital Galliera, Genoa, Italy, and the European Institute of Oncology, Milan (Abstract 519).
“The lowest dose was slightly inferior, both on the estradiol suppression as well as on the Ki-67,” Dr. De Censi said. “The lowest dose has some activity, which might still be interesting in future studies examining prevention, but our conclusion is that the winner is the intermediate dose, with the same efficacy and presumed lower toxicity than the daily dose.”
This study grew out of concerns that the toxicities associated with standard-dose exemestane may be prohibitive for women taking it for the prevention of breast cancer or for the treatment of early-stage breast cancer. Dr. De Censi noted that the longtime strategy of developing cytotoxic therapies was based on the premise that higher doses of a drug have greater antitumor activity, a paradigm that ASCO and the U.S. Food and Drug Administration believe needs to change.1
“The bottom line of our research is that tolerability is as important as efficacy in prevention,” he said. “When we pursue breast cancer prevention with hormonal drugs given at the same dose as the treatment setting, we often create menopausal and sexual side effects that are intolerable to the majority of these healthy women who are at high risk for developing breast cancer.”
“The bottom line of our research is that tolerability is as important as efficacy in prevention.”—Dr. Andrea De Censi
The long treatment duration for preventive and early-stage treatment is an especially important consideration, Dr. De Censi explained.
“People are generally not willing to take a drug for years to prevent disease if it significantly decreases their quality of life. Other types of preventive drugs are usually well-tolerated, including aspirin, statins, and antihypertensives. That's what we should be working toward in oncology,” he said.
In this multicenter, double-blind, randomized trial, participants took exemestane for 4 to 6 weeks prior to their initial surgery. Three dosing regimens were used: (1) the standard 25 mg per day; (2) 25 mg 3 times per week; or (3) 25 mg once per week for the presurgical period. Investigators collected blood and tissue biomarkers at baseline and during the final visit.
The study's primary endpoint was a noninferiority percent change of circulating estradiol compared to the standard dose. Secondary endpoints included the change in expression of the prognostic markers Ki-67 and progesterone receptor (PgR) in cancer tissue, blood sex hormones, and toxicity.
The authors observed no differences between the daily and every-other-day groups for estrone, total estrone, and estrone sulfate levels. The once-weekly arm also showed some modulation in all hormones, but the changes were less significant than in the other 2 groups.
Additional findings included reductions in all arms of Ki-67 and PgR, although the reductions were not statistically significant among arms. The median change for Ki-67 was −5.0% vs −7.5% (P = .124) in the every-other-day arm and the daily arm, respectively. For PgR, the reduction was −9 vs −17 (P = .246), respectively. The authors found that both adverse events and menopausal symptoms were similar in all arms.
Ultimately, 173 women were evaluable for response out of 180 participants, which Dr. De Censi characterized as one of the study's strengths.
“The number of patients was reasonably high for a biomarker window-of-opportunity trial, and so the study was powered for the primary endpoint,” he said.
The study's primary limitation was the short treatment duration. “Side effects tend to develop after a few months, so our data cannot draw definitive conclusions on the tolerability of the lower doses,” Dr. De Censi said.
In the future, Dr. De Censi would like to see a longer trial with a larger participant pool, but he is aware of the funding challenges that studies of this type face.
“Pharma companies do not have an incentive to fund this type of research on generic drugs, so we need public funding agencies to support this work,” he said. “I'm proud that the U.S. National Cancer Institute funded our work due to its public health implications.”
Dr. De Censi believes that this study has immediate clinical utility.
“In my clinical practice, when my patients do not tolerate exemestane well, I propose that they take it every other day instead—and many, many times, patients are happy,” he concluded.
— Darcy Lewis
Reference
1. U.S. Food and Drug Administration. Getting the Dose Right: Optimizing Dose Selection Strategies in Oncology – An FDA-ASCO Virtual Workshop. Updated May 2, 2022. Accessed May 5, 2022.

VERY INTERESTING! Thank you. I take Anastrozole but I’m wondering if all AIs are being analyzed.

Me too....it seems to me likely that results would be similar for the other AIs. More research like this is absolutely necessary to spare us unnecessary excess medication.

Indeed

Examestane is a bit different than the others ( steroidal) so I wonder how exchangeable it is. But this is exciting research and more needed!

Half life of Anastrozole is 50 hours!

So that means there is still some circulating Anastrozole until as long as 4 days after the med?
I am sure my surgeon/oncologist would not be happy with me, but I am just starting out with Arimidex and am taking the pill every other day (and even skipped more days this first week).
It seems logical that different doses would be necessary depending on things like body size, amt of circulating estradiol, etc, rather than one size fits all....
I wonder how one can get the very sensitive test of circulating estradiol done, as was apparently done in the study? Maybe I would have to get in to see an endocrinologist??
In another study, it was found that women trying to get pregnant did not have any more recurrences (compared to control group) when stopping adjuvant therapy for as long as 2 yrs, at least at the 3-year follow up period.
All of this is food for thought!

That’s an interesting finding about women trying to get pregnant!

I’m 99 and 98% estrogen positive ( two tumors) so I’m reliable about taking the meds. I did not need chemo and I declined radiation ( was questionable) so this is my one post surgical remedy so to speak. I’m grateful that I’m not having any observable side effects right now … just started month 8.