Does anyone know of a test that...

[Pray]

can tell if Arimidex is working? When I was on Tamoxifen I had a test done to see if it was working? Thank you for any info. It is appreciated!

Your Friend,

Nancy

[JennyB]

Sorry Nancy I'm on Femera and haven't had a test for that either I just get blood tests every 3 months to make sure I'm still in 'chemopause'!
Hope someone can help
Jenny x

[Hopeful]

You can get ER levels tested via a blood test. Mine were below the detectable limit of the test when I was on AI's. If that is your definition of "working," you can be tested for it.

Hopeful

[Lani]

Hopeful, I think you mean Estrogen (usually estradiol, E2) levels, rather than ER (estrogen receptor) levels--those only being able to be tested on the tumor itself, circulating tumor cells (blood), if any, or disseminated tumor cells (bone marrow). I suppose one could also test for estrone(another form of estrogen), but don't think that is commonly done

[Hopeful]

Sorry for the inaccurate indentification of what was being tested for; we use "ER" in common parlance in this forum as synonymous with "estrogen."

Hopeful

[Pray]

Thank you Ladies I appreciate your input! I don't see my onc. until the middle of Nov. Just wondering. I hope everyone has a great day!

Your Friend,

Nancy

[Hopeful]

Nancy,

I posted a link to a related paper in the articles of interest forum, but here is an article about a test not yet used in clinical practice that may give a better answer to your question:

Elsevier Global Medical News. 2011 Sept 21, S London

SAN FRANCISCO (EGMN) - A new gene-based biomarker assay may help to estimate prognosis and make decisions about extended endocrine therapy in women with estrogen receptor-positive early breast cancer, new data suggest.

Researchers tested the biomarker, the Breast Cancer Index (BCI), among 249 women with estrogen receptor-positive early breast cancer from the MA.17 trial, in which women received 5 years of adjuvant tamoxifen therapy and, if still disease free, were then randomized to an additional 5 years of either letrozole (Femara) or placebo.

Study results, reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology, showed that with each 5-unit increase in the 10-unit BCI score, women's odds of late recurrence nearly tripled.

The index as a whole was not helpful in predicting the benefit of added letrozole therapy in reducing recurrence risk. But one of its components, called H/I, was helpful: Women having a high H/I were about half as likely to have a recurrence if they received letrozole instead of placebo.

In the future, these findings might be used to develop a management algorithm for women with estrogen receptor-positive breast cancer, according to lead investigator Dr. Dennis C. Sgroi, director of breast pathology at the Massachusetts General Hospital in Boston.

"If patients are disease free after 5 years of adjuvant endocrine therapy, we might be able to then test them with the BCI. If this assay identifies these patients to be at low risk, there will be no further therapy for these patients. However, if they are at high risk by BCI, we can then explore the H/I component," he explained.

"If they have high H/I, that indicates that these patients are likely to benefit from extended adjuvant therapy," he continued. "For patients who have low H/I, one might consider using extended adjuvant therapy, or these patients might be considered as a future focus for research in clinical trials."

The investigators identified 83 women from the MA.17 trial who had had a recurrence and had primary tumor tissue available. They then matched the women by age, N stage, T stage, and prior receipt of chemotherapy in a 1:2 ratio with 166 women who had not had a recurrence and had primary tumor tissue available. Tissue was analyzed by reverse transcriptase-polymerase chain reaction to determine the BCI.

The BCI has two components, Dr. Sgroi explained. The HOXB13/IL17BR (H/I) component is based on expression of two genes regulated by estradiol. The molecular grade index (MGI) component is based on five genes related to pathological grade.

"We have shown in the past that these two biomarkers are complementary, as the combination of the two biomarkers outperforms each individually," he noted. "In addition, we have shown that the combination biomarker outperforms standard clinicopathological parameters currently used to predict disease recurrence."

In a multivariate analysis, with each 5-unit increase in the BCI score, women's odds of recurrence increased 2.91-fold (P = .014). The findings were similar when categories were used: Women with high or intermediate scores had 2.21-fold higher odds of recurrence than did their counterparts with low scores (P = .019).

The BCI as a whole did not predict the benefit of extended therapy with letrozole, but the H/I component did, Dr. Sgroi reported. In a multivariate analysis, women who had a high H/I had a 58% reduction in the odds of recurrence if they received letrozole instead of placebo (P = .037).

"Most notably, there was a statistically significant interaction between the H/I biomarker and treatment (P = .02), indicating that the magnitude of letrozole benefit depends on the expression level of H/I," he said. "These results suggest that patients with tumors expressing high H/I will benefit from extended endocrine therapy." (emphasis added)

Dr. Sgroi reported receiving research funding from bioTheranostics Inc. The study was supported in part by Novartis, the manufacturer of letrozole.

Hopeful

[Pray]

Thank you Hopeful! I appreciate the time and effort you put into putting this info. up!

You are appreciated.

Gods to all of you wonderful People!

Your Friend,

Nancy

[Debbie L.]

Hi Pray.

The answer to your question depends upon what exactly you mean by "working". If you mean is it keeping estrogen levels low in your blood -- yes, that can be tested although I've heard it said that the low end of the estrogen curve is hard to test for (the low end being anything below "normal" menopausal levels).

If you mean is it "working" as in guaranteed to keep cancer at bay -- alas, there's no way to know that for any one individual, and that includes those whose estrogen levels are successfully suppressed. We know what percentage of a big group it seems to "work" for -- but have no way to know who will be in which group ahead of time. So we have individualized and/or targeted treatment with Arimidex, but wouldn't it be even nicer if we could dial it down closer.

I asked you this in some other thread, I think. I've never heard of a test that tells whether Tamoxifen is working. There was interest in an enzyme called CYP2D6 for awhile, because in theory it is involved in the metabolism of some drugs, including Tamoxifen, and it was speculated that those with variations in the CYP2D6 gene would not benefit from Tamoxifen. But that has apparently been proven to be a wrong theory, to the satisfaction of practicing oncologists -- and is no longer considered an appropriate test. It never WAS an officially-recommended test but some oncs jumped on the bandwagon a little early on that one and did do the test and use it to prescribe (or not) Tamoxifen, for awhile. Is that the test you had? Here's Susan Love's page from January of this year on this subject:
http://www.dslrf.org/breastcancer/content.asp?CATID=19&L2=3&L3=7&L4=0&PID=&sid=132&cid=1146

She actually leaves a little more wiggle-room for further studies to look at this again. Most oncologists I've heard discuss this are not even interested anymore, considering it a done (dead) deal.

Debbie Laxague

[Debbie L.]

Me again. I didn't see your post, hopeful, when I did mine. Maybe I hadn't refreshed my browser or something.

Anyway, I can't quite tease out the importance of this concept (how many women might it help -- either in getting them on an effective drug or sparing them the side effects of an innefective one?).

I think at least one set of figures that are missing is the percent of women at 5 years with the high BCI scores, and then the percentage of that group that are also high H/I. With all these variables, it doesn't seem like they had enough women to proclaim significance but apparently they did. Does anyone know if this has been published? I'd love to see it all spelled out in a nice table. Graphics seem to speak louder than words, for me.

Debbie Laxague

[Hopeful]

Debbie,

The article was done on a presentation at ASCO. Here is a link to the abstract:

http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=111&abstractID=86153

The population for the study came from the NCIC CTG MA.17 cohort.

Hopeful

[Pray]

Hi Debbie,

I am so sorry if I neglected to get back to you on the Tomoxifen test my onc. did. I will do so soon.

It just so happens I requested copies of all my records and I should be getting them in the next week or so. I will call my onc. tomorrow and find out the name and my results and let you know as soon as they tell me. Some times it takes them 24 hrs. to retrieve them.

Your friend,

Nancy

[Pray]

Hi Debbie,

Sorry it took so long for me to get back to you. You were right the tomoxifen test was just the CYP2D6 MUT/Tamoxifen RESIST.

Your Friend,

Nancy

[Jackie07]

I had the CYP2D6 test done after I'd already had almost 5 years worth of Tamoxifen. BCBS required the testing in 2010. Soon afterwards (a month?) I switched to another insurance plan (affliated with the hospital system we use) and my oncologist (same one for 7 [now 8] years) asked me if I was still taking Tamoxifen.

Because I had had prophylactic hysterectomy/oophorectomy (plus full doses of chemo in 2003 and 2007), I was sure I'd be given aromatase inhibitor... But my oncologist continued me on Tamoxifen. Then I found a new research article stating that using Tamoxifen after 5 years still makes some difference (cutting from 6% down to 3% - something like that [a significant 50% reduction].)

[Debbie L.]

Hi Nancy, I'd almost forgotten the question (smile), I'm glad I happened to notice this thread.

Here's one write-up of last year's SABCS presentation on CYP2D6 and Tamoxifen. I got the impression that with this, most felt the issue was settled (a theory that made sense was not proven to apply in real life).

http://www.medscape.com/viewarticle/734021

I'll try to copy/paste also:

CYP2D6 Does Not Predict Tamoxifen Effectiveness, New Studies Show
Zosia Chustecka


December 10, 2010 (San Antonio, Texas) — New analyses of data from 2 large trials have found no association between the CYP2D6 genotype and the effectiveness of tamoxifen in preventing breast cancer recurrence, in contrast to several previous positive studies.


The new findings come from retrospective analyses of 2 huge trials — the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial comparing tamoxifen and anastrozole, and the Breast International Group (BIG) 1-98 trial comparing tamoxifen and letrozole.
They were presented here at the 33rd Annual San Antonio Breast Cancer Symposium (SABCS).
The fact that both studies were negative led experts to recommend that CYP2D6 testing not be used routinely to decide whether or not to prescribe tamoxifen.
Even the strongest proponent of this approach, Matthew Goetz, MD, from the Mayo Clinic in Rochester, Minnesota, who led the original studies showing an association, concedes.


Although criticizing some aspects of the new analyses in a discussion after the presentation, he concluded that physicians should not routinely test for CYP2D6 status before deciding whether to prescribe tamoxifen or an aromatase inhibitor, an approach that he had been advocating (http://www.medscape.com/viewarticle/716753) until now.


"We should stop offering these tests outside of clinical trials," Edith Perez, MD, from the Mayo Clinic in Jacksonville, Florida, told Medscape Medical News.
The rationale behind CYP2D6 testing is that women who have an inherited deficiency of this gene are poor metabolizers of tamoxifen, and have lower levels of the active metabolite endoxifen. In previous positive studies, including those by Dr. Goetz and colleagues, these poor metabolizers have shown less benefit from tamoxifen and higher rates of breast cancer recurrence.
This has always been a controversial area. To date, there have been 14 separate studies that have shown this association; however, 15 other studies have not found this effect, Dr. Goetz told the meeting.

"This is another beautiful theory in danger of being slain by ugly fact," said Peter Ravdin MD, codirector of the SABCS and director of the Comprehensive Breast Health Clinic at the Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio.


Both of the analyses presented at the meeting were negative; this "will bury the idea that CYP2D6 is a biomarker here," he told Medscape Medical News.
Negative Finding From ATAC Analysis
Both of the analyses were retrospective and involved going back to women who had taken part in large trials and testing them for the CYP2D6 genotype.


The analysis of data from the ATAC trial was presented by James Rae, MD, from the University of Michigan in Ann Arbor, and colleagues. They genotyped 588 of the 3116 women (18%) who took part in the trial, and categorized the women as poor, intermediate, or extensive metabolizers of tamoxifen.


There was no difference in breast cancer recurrence in any of these categories in either the tamoxifen or the anastrozole group (which served as a control group in this instance). If the theory about CYP2D6 was correct, the poor metabolizers would have been expected to do worse.


Dr. Rae and colleagues also found that there was no effect on clinical outcome from the concomitant use of CYP2D6 inhibitors, such as selective serotonin reuptake inhibitors (SSRIs). About 9% of women were taking drugs that are known to be potent inhibitors, he said.
This finding is in contrast with previous research that has shown that women taking drugs that are potent inhibitors of CYP2D6, especially SSRIs, have an increased risk for breast cancer recurrence. The theory here is that these drugs inhibit the metabolism of tamoxifen, so they have lower levels of the active metabolite endoxifen, which is responsible for the beneficial effect. As a result of that research, it has been recommended (http://www.medscape.com/viewarticle/721306) that clinicians avoid prescribing certain drugs in women taking tamoxifen.
Dr. Rae concluded his presentation by saying that the "evidence is not sufficient" to recommend either CYP2D6 genotyping or to recommend avoiding the concomitant use of SSRIs in women taking tamoxifen.
Negative Finding From BIG 1-98

Dr. Brian Leyland-Jones The other analysis was based on data from the BIG 1-98 trial, presented by Brian Leyland-Jones, MD, PhD, from Emory University in Atlanta, Georgia. In this case, 48% of participants underwent genotyping (1243 of 2459 women). The researchers found that 9% were poor metabolizers, 27% were intermediate metabolizers, and 59% were extensive metabolizers; it was unclear in the remaining 5%.


This analysis found no difference in the different metabolizers on the effect that tamoxifen had on the breast-cancer-free interval. There was also no difference in any of the different metabolizers in the letrozole group (which served as a control group in this analysis).


In addition, these researchers found no association between the incidence of hot flashes and metabolizer status. This was based on another theory, which suggested that women who are extensive metabolizers of tamoxifen — who would thus have high levels of the active metabolite endoxifen and derive the most benefit from tamoxifen — would also experience a higher level of adverse effects from the drug, including hot flashes. However, Dr. Leyland-Jones reported that in their analysis, the extensive metabolizers had the lowest incidence of hot flashes.


"This is important," Dr. Leyland-Jones told Medscape Medical News, because some physicians are using an absence of hot flashes as a sign that tamoxifen is not working and stopping the drug. "Our data show that hot flashes should not be used as a surrogate pharmacodynamic marker for tamoxifen efficacy," he said.


Dr. Leyland-Jones concluded that CYP2D6 genotype testing is "not justified" in determining whether or not to prescribe tamoxifen. In addition, he emphasized that the presence or absence of hot flashes should not be used to determine the efficacy of tamoxifen.


Controversy Unresolved
In his discussion of both presentations, Dr. Goetz pointed out that the analyses were both retrospective, and they did not take into account adherence to tamoxifen or the concomitant use of over-the-counter drugs. In addition, the analysis for hot flashes did not adjust for concomitant use of drugs that are prescribed to treat hot flashes, such as venlafaxine and gabapentin, he said.


Nevertheless, Dr. Goetz agreed with the recommendation from both presenters that CYP2D6 testing should not be used routinely.
However, he disagreed with the conclusion on drugs that inhibit CYP2D6, and recommended that physicians exercise caution in the concomitant use of such drugs in women taking tamoxifen.


The controversy surrounding this issue is unlikely to be resolved by retrospective analyses, given that CYP2D6 only partially explains the variability of responses to endoxifen, the active metabolite, Dr. Goetz said. He reported that his team is developing endoxifen as a drug in its own right, and that a clinical trial is planned to start in 2011.





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