Featured Research

from universities, journals, and other organizations

Gene Alterations Associated With Response To Anthracycline Therapy For Breast Cancer

Date:
April 28, 2009
Source:
Journal of the National Cancer Institute
Summary:
Alterations in the topoisomerase II alpha gene were associated with better patient outcomes following anthracycline-based therapy compared with non-anthracycline-based regimens, according to a new study. The increased responsiveness is similar to what is seen in patients whose tumors carry an amplification of the HER2 gene.

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 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.

Related Articles


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 ampli¬fication 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."


Story Source:

The above story is based on materials provided by Journal of the National Cancer Institute. Note: Materials may be edited for content and length.


Journal References:

  1. O'Malley et al. Topoisomerase II Alpha and Responsiveness of Breast Cancer to Adjuvant Chemotherapy. J Natl Cancer Inst, 2009, 101: 644-650
  2. Slamon D. and Press M. Alterations in the TOP2A and HER2 Genes: Association with Adjuvant Anthracycline Sensitivity in Human Breast Cancers,. J Natl Cancer Inst, 2009, 101: 615-618

Cite This Page:

Journal of the National Cancer Institute. "Gene Alterations Associated With Response To Anthracycline Therapy For Breast Cancer." ScienceDaily. ScienceDaily, 28 April 2009. <www.sciencedaily.com/releases/2009/04/090428162012.htm>.
Journal of the National Cancer Institute. (2009, April 28). Gene Alterations Associated With Response To Anthracycline Therapy For Breast Cancer. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2009/04/090428162012.htm
Journal of the National Cancer Institute. "Gene Alterations Associated With Response To Anthracycline Therapy For Breast Cancer." ScienceDaily. www.sciencedaily.com/releases/2009/04/090428162012.htm (accessed October 24, 2014).

Share This



More Health & Medicine News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) — The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) — An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins