Research On Tamoxifen Leads To Recommendation For CYP2D6 Gene Test
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phoenixrising
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New info coming out of San Antonio Breast Cancer Symposium.
Research On Tamoxifen Leads To Recommendation For CYP2D6 Gene Test
Main Category: Breast Cancer
Also Included In: Genetics; Menopause
Article Date: 15 Dec 2008 - 4:00 PST
Findings from a new study have prompted Mayo Clinic researchers to recommend CYP2D6 gene testing for postmenopausal women about to begin tamoxifen therapy. This data confirms that women with an inherited deficiency in the CYP2D6 gene, which is important for the metabolism of tamoxifen, have a nearly fourfold higher risk of early breast cancer recurrence compared to women who have not inherited the deficiency. The research findings, announced jointly by investigators from Mayo Clinic and the Austrian Breast and Colorectal Cancer Study Group (ABCSG) confirmed results from a previous study conducted by Mayo Clinic.
VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. Goetz describing the research, are available here on the Mayo Clinic News Blog.
The latest findings were presented at the Cancer Therapy & Research Center-American Association for Cancer Research (CTRC-AACR) 31st annual San Antonio Breast Cancer Symposium.
Tamoxifen, approved by the Food and Drug Administration (FDA) to both prevent development of estrogen-receptor-positive (ER+) breast cancer and as a therapy to stop ER+ breast cancer from coming back, is a "pro-drug"; it must be metabolized in the liver to become active. Mayo researchers had previously discovered that the drug is less effective in postmenopausal breast cancer patients who had a deficiency in the CYP2D6 gene, which is key for activating tamoxifen and many other drugs. However, until now, testing for the gene has not been done routinely at most medical centers.
"These new results validate our earlier findings," says the study's lead investigator, Matthew Goetz, M.D., an assistant professor of oncology and pharmacology at Mayo Clinic, "and strongly suggest that going forward, postmenopausal patients being considered for tamoxifen therapy should be tested for CYP2D6 before beginning therapy."
The research teams examined DNA from a subset of postmenopausal women treated in the ABCSG-8 study, which previously randomized nearly 3,900 women whose ER+ breast cancer had been surgically treated. One group was randomized to five years of tamoxifen therapy, and the other randomized to tamoxifen for two years followed by three years of anastrozole, an aromatase inhibitor. The initial results of ABCSG-8, reported in 2005, concluded that women who switched to anastrozole had a 40 percent reduced risk of breast cancer recurrence compared to staying on tamoxifen.
The aim of the new study was to determine whether CYP2D6 genetic variation would identify a subgroup of patients at higher risk of recurrence within the context of the ABCSG-8 trial. "Among the patients randomized to tamoxifen, poor metabolizers had a 3.8-fold increase in risk of developing breast cancer recurrence than extensive metabolizers across the five-year span," said Michael Gnant, M.D., professor of Surgery at the Medical University of Vienna, Austria, and president of ABCSG. "That is the key message coming out of this great collaboration between the Mayo Clinic team and the Austrian Breast and Colorectal Cancer Study Group."
However, the researchers also demonstrated that among patients who switched to anastrozole, there was no increased risk of breast cancer recurrence for CYP2D6 poor metabolizers in years three to five. The benefit of switching to anastrozole, says Dr. Goetz, may be most pronounced in the group of patients with deficient CYP2D6 metabolism. "Poor metabolizers who were fortunate to not develop breast cancer recurrence in the first two years of tamoxifen appear to be rescued by anastrozole," he says.
The findings reported by Mayo and ABCSG highlight the emerging science of pharmacogenomics. Researchers in this field are studying whether genetic differences in how patients metabolize or process drugs can be used to individualize therapy.
Additionally, in collaboration with bioTheranostics (a molecular diagnostics testing firm), the researchers examined whether a tumor-based test, HOXB13: IL17BR gene expression ratio, and a 5-gene molecular grade index were prognostic markers of distant breast cancer recurrence. Dr. Goetz and his colleagues confirmed that high expression of both HOXB13:IL17BR and molecular grade index, found in 25 percent of the tumors, led to a nearly threefold higher risk of recurrence elsewhere in the body compared to patients whose tumors were considered to be low risk according to these gene markers.
These findings suggest that the combined index will identify patients with early stage breast cancer who haveith a higher risk of distant metastases when treated only with hormonal therapy, the researchers say.
Research On Tamoxifen Leads To Recommendation For CYP2D6 Gene Test
Main Category: Breast Cancer
Also Included In: Genetics; Menopause
Article Date: 15 Dec 2008 - 4:00 PST
Findings from a new study have prompted Mayo Clinic researchers to recommend CYP2D6 gene testing for postmenopausal women about to begin tamoxifen therapy. This data confirms that women with an inherited deficiency in the CYP2D6 gene, which is important for the metabolism of tamoxifen, have a nearly fourfold higher risk of early breast cancer recurrence compared to women who have not inherited the deficiency. The research findings, announced jointly by investigators from Mayo Clinic and the Austrian Breast and Colorectal Cancer Study Group (ABCSG) confirmed results from a previous study conducted by Mayo Clinic.
VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. Goetz describing the research, are available here on the Mayo Clinic News Blog.
The latest findings were presented at the Cancer Therapy & Research Center-American Association for Cancer Research (CTRC-AACR) 31st annual San Antonio Breast Cancer Symposium.
Tamoxifen, approved by the Food and Drug Administration (FDA) to both prevent development of estrogen-receptor-positive (ER+) breast cancer and as a therapy to stop ER+ breast cancer from coming back, is a "pro-drug"; it must be metabolized in the liver to become active. Mayo researchers had previously discovered that the drug is less effective in postmenopausal breast cancer patients who had a deficiency in the CYP2D6 gene, which is key for activating tamoxifen and many other drugs. However, until now, testing for the gene has not been done routinely at most medical centers.
"These new results validate our earlier findings," says the study's lead investigator, Matthew Goetz, M.D., an assistant professor of oncology and pharmacology at Mayo Clinic, "and strongly suggest that going forward, postmenopausal patients being considered for tamoxifen therapy should be tested for CYP2D6 before beginning therapy."
The research teams examined DNA from a subset of postmenopausal women treated in the ABCSG-8 study, which previously randomized nearly 3,900 women whose ER+ breast cancer had been surgically treated. One group was randomized to five years of tamoxifen therapy, and the other randomized to tamoxifen for two years followed by three years of anastrozole, an aromatase inhibitor. The initial results of ABCSG-8, reported in 2005, concluded that women who switched to anastrozole had a 40 percent reduced risk of breast cancer recurrence compared to staying on tamoxifen.
The aim of the new study was to determine whether CYP2D6 genetic variation would identify a subgroup of patients at higher risk of recurrence within the context of the ABCSG-8 trial. "Among the patients randomized to tamoxifen, poor metabolizers had a 3.8-fold increase in risk of developing breast cancer recurrence than extensive metabolizers across the five-year span," said Michael Gnant, M.D., professor of Surgery at the Medical University of Vienna, Austria, and president of ABCSG. "That is the key message coming out of this great collaboration between the Mayo Clinic team and the Austrian Breast and Colorectal Cancer Study Group."
However, the researchers also demonstrated that among patients who switched to anastrozole, there was no increased risk of breast cancer recurrence for CYP2D6 poor metabolizers in years three to five. The benefit of switching to anastrozole, says Dr. Goetz, may be most pronounced in the group of patients with deficient CYP2D6 metabolism. "Poor metabolizers who were fortunate to not develop breast cancer recurrence in the first two years of tamoxifen appear to be rescued by anastrozole," he says.
The findings reported by Mayo and ABCSG highlight the emerging science of pharmacogenomics. Researchers in this field are studying whether genetic differences in how patients metabolize or process drugs can be used to individualize therapy.
Additionally, in collaboration with bioTheranostics (a molecular diagnostics testing firm), the researchers examined whether a tumor-based test, HOXB13: IL17BR gene expression ratio, and a 5-gene molecular grade index were prognostic markers of distant breast cancer recurrence. Dr. Goetz and his colleagues confirmed that high expression of both HOXB13:IL17BR and molecular grade index, found in 25 percent of the tumors, led to a nearly threefold higher risk of recurrence elsewhere in the body compared to patients whose tumors were considered to be low risk according to these gene markers.
These findings suggest that the combined index will identify patients with early stage breast cancer who haveith a higher risk of distant metastases when treated only with hormonal therapy, the researchers say.
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Comments
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Thanks Jan for the extensive
Thanks Jan for the extensive info. I will ask my oncologist next time I see him about testing for this gene. Merry Christmas, Lili0 -
I'm not clinicallyKathiM said:I'll ask mine, too...
Although my menopause was surgical. Still, I AM an old-lady 53...hummm....
Thanks for the news!!!!
Hugs, Kathi
I'm not clinically menopausal, but I will ask also. I do not see how menopause would affect the gene mutation...maybe they just didn't do the test on everybody which is why they are posting narrow results. Thanks for the info. Joyce0 -
I think they just used postJoycelouise said:I'm not clinically
I'm not clinically menopausal, but I will ask also. I do not see how menopause would affect the gene mutation...maybe they just didn't do the test on everybody which is why they are posting narrow results. Thanks for the info. Joyce
I think they just used post menopausal women in the study cause that's the most common. The testing is for anyone using Tamoxifen to see if they are getting any benefit from it. Apparently you can still get side effects and not fully metabolize it. I don't think all oncs agree with the testing..........yet.0 -
I just began on tamoxifenphoenixrising said:I think they just used post
I think they just used post menopausal women in the study cause that's the most common. The testing is for anyone using Tamoxifen to see if they are getting any benefit from it. Apparently you can still get side effects and not fully metabolize it. I don't think all oncs agree with the testing..........yet.
I will bring this up at my next appointment. They're getting used to me learning about things online. I'm 48 and just stopped my periods during chemo so they consider me pre menopausal but everything else came back but not my period so I'm not sure.0 -
I stopped during chemo too.Cindyjoy said:I just began on tamoxifen
I will bring this up at my next appointment. They're getting used to me learning about things online. I'm 48 and just stopped my periods during chemo so they consider me pre menopausal but everything else came back but not my period so I'm not sure.
I stopped during chemo too. They can do a blood test to see if you are in menopause or not. That's what they did for me to determine if they could switch me from Tamoxifen to Aromasin.0
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