Navigation Links
Gene alterations associated with response to anthracycline therapy for breast cancer
Date:4/28/2009

Alterations in the topoisomerase II alpha (TOP2A) gene were associated with better patient outcomes following anthracycline-based therapy compared with non-anthracycline-based regimens, according to a study in the April 28 online issue of the Journal of the National Cancer Institute. The increased responsiveness is similar to what is seen in patients whose tumors carry an amplification of the HER2 gene.

Several studies have shown that women whose tumors have amplified HER2 derive benefit from regimens that include anthracyclines, such as epirubicin and doxorubicin, while patients whose tumors lack such alteration do not. Scientists have hypothesized that this difference could be due to alterations in the TOP2A gene, which resides adjacent to HER2 on the chromosome and is often included in the stretch of amplified DNA. TOP2A is a major target of anthracycline.

To determine whether the difference in responsiveness is due to TOP2A, Kathleen I. Pritchard, M.D., of the University of Toronto, and colleagues re-analyzed data from the randomized Mammary 5 trial, conducted by the National Cancer Institute of Canada Clinical Trials Group. This trial compared an anthracycline-containing regimen (cyclophosphamide, epirubicin, and 5-fluorouracil; CEF) with a non-anthracycline-containing regimen (cyclophosphamide, methotrexate, and 5-fluorouracil; CMF) in 710 breast cancer patients. The investigators were able to analyze tumor samples from 438 patients for alteration of the TOP2A gene.

Women whose tumors carried TOP2A gene alterations had 65 percent better relative relapse-free survival and 67 percent better relative overall survival when treated with CEF compared with CMF. The differences were statistically significant. By contrast, women whose tumors were TOP2A-normal had a similar response to the two regimens. The added benefit detected for the women with TOP2A-altered tumors when treated with anthracycline-based therapy is similar to the benefit the researchers detected in women with HER2-positive tumors.

The investigators conclude that TOP2A gene alteration is associated with increased benefit from an anthracycline-containing regimen compared with TOP2A-normal tumors. However, they add that the sample size was too small to determine whether this effect was independent of HER2.

Patients whose tumors are normal for TOP2A and HER2 do not appear to derive additional benefit from the anthracycline-based regimen and therefore could be treated with less toxic regimens, such as CMF, according to the authors. "Our data suggest that measurements of TOP2A alteration and HER2 amplification appear to have similar value in guiding the selection of anthracycline-containing regimens," they conclude.

In an accompanying editorial, Dennis J. Slamon, M.D., Ph.D., of the University of California School of Medicine at Los Angeles, and Michael F. Press, Ph.D., of the University of Southern California Keck School of Medicine in Los Angeles, agree that women whose tumors are TOP2A- and HER2-normal should not receive anthracycline-based therapy: "Currently, the overwhelming bulk of the published and/or reported data indicate that TOP2A alterations are the important predictive factors for determining the likelihood of incremental benefits from treating breast cancer patients with anthracyclines in the adjuvant setting," the editorialists write. "These data also show that TOP2A alterations most often occur in the context of HER2 amplification."


'/>"/>

Contact: Steve Graff
jncimedia@oxfordjournals.org
301-841-1285
Journal of the National Cancer Institute
Source:Eurekalert

Related medicine news :

1. New study shows promise in reducing surgical risks associated with surgical bleeding
2. Fluctuating eye pressure associated with visual field deterioration in glaucoma patients
3. Study, meta-analysis examine factors associated with death from heatstroke
4. Increased distance to physician associated with thicker skin cancer at diagnosis
5. Minorities more likely to have sleep durations associated with increased mortality
6. Income inequality associated with overnourishment and undernourishment in India
7. Maternal depression and controlling behavior associated with increased stress response in infants
8. Nurses describe dedication, frustration associated with their jobs
9. New research shows ACTOS is associated with a 38 percent lower risk of heart attack
10. New research shows ACTOS is associated with a 38 percent lower risk of heart attack
11. Produce for Better Health Foundation Releases Statement on Study Saying Fruit & Vegetable Consumption Not Strongly Associated With Colon Cancer Risk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... "FCPX editors can now reveal their media ... Pro X," said Christina Austin - CEO of Pixel Film Studios. , ProSlice ... X users can now reveal the media of their split screens with growing ...
(Date:6/27/2016)... ... 27, 2016 , ... TopConsumerReviews.com recently awarded their highest five-star rating to Best ... individuals in the United States and Canada wear eyeglasses. Once considered to be a ... and make a fashion statement. Even celebrities use glasses as a way of creating ...
(Date:6/26/2016)... (PRWEB) , ... June 26, 2016 , ... PawPaws ... a new product that was developed to enhance the health of felines. The formula ... , The two main herbs in the PawPaws Cat Kidney Support Supplement ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... Austin residents ... the American College of Mohs Surgery and to Dr. Russell Peckham for medical and ... highly effective treatment for skin cancer. The selective fellowship in Mohs Micrographic Surgery completed ...
(Date:6/25/2016)... ... 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe earned his ... David Geffen School of Medicine at UCLA. He trained in Internal Medicine at Scripps ... in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the opportunity to ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016 According to ... Type (Standard Pen Needles, Safety Pen Needles), Needle Length ... Growth Hormone), Mode of Purchase (Retail, Non-Retail) - Trends ... report studies the market for the forecast period of ... USD 2.81 Billion by 2021 from USD 1.65 Billion ...
(Date:6/23/2016)... 23, 2016 Research and Markets has ... - Forecast to 2022" report to their offering. ... for the patients with kidney failure, it replaces the function ... the patient,s blood and thus the treatment helps to keep ... in balance. Increasing number of ESRD patients ...
(Date:6/23/2016)... -- Research and Markets has announced the addition ... - Forecast to 2022" report to their offering. ... to date financial data derived from varied research sources to ... potential impact on the market during the next five years, ... of sub markets, regional and country level analysis. The report ...
Breaking Medicine Technology: