Genomic test shows promise as chemotherapy response, survival predictor for women with breast cancer

May 10, 2011 in Cancer

A new genomic test combining multiple signatures – a patient's estrogen receptor status, endocrine therapy response, chemotherapy resistance and sensitivity – shows promise as a predictor of chemotherapy response and survival benefit in women with invasive breast cancer, according to research led by The University of Texas MD Anderson Cancer Center.

The findings, published in the May 11 issue of JAMA, also may determine those for whom standard therapy alone might not offer enough, and/or for whom an appropriate clinical trial in the adjuvant setting could provide additional benefit.

"The research builds on a decade of collaborative work in developing a clinically meaningful chemotherapy predictor, and, if validated in future studies, could guide therapy for about 80 percent of newly diagnosed women with invasive breast cancer who are candidates for chemotherapy," says W. Fraser Symmans, MD, professor in MD Anderson's Department of Pathology.

"The test helps us understand both resistance and response to chemotherapy more specifically, how sensitivity to endocrine therapy would impact a predictor and how to focus on specific subtypes of breast cancer – in this case HER2 negative disease stratified by estrogen receptor (ER) status – because we've learned that they are so intrinsically different," Symmans continues.

The multicenter study enrolled 310 Stage II and III newly diagnosed women with invasive breast cancer (discovery cohort). All were Her2 negative and received the chemotherapy regimen of sequential taxane and anthracycline, followed by endocrine therapy, if hormone receptor positive. Gene expression microarrays from the discovery cohort were used to develop different predictive signatures for drug resistance and response. Using the signatures for endocrine therapy response, chemotherapy resistance and sensitivity, in combination with other genomic predictors to chemotherapy response, breast cancer treatment was predicted in an independent cohort of 198 breast cancer patients with similar diagnosis and treatment (independent cohort).

The study's primary endpoint was distant relapse-free survival (DRFS) and absolute risk reduction (ARR) and the median follow up was three years. Excluding women with known endocrine sensitivity, the algorithm had a positive predictive value (PPV) of 56 percent. In the 28 percent who were predicted treatment-sensitive, their three-year DRFS was 92 percent, ARR was18 percent and they had a five-fold reduction of risk of distant relapse.

When analyzed by ER status, treatment sensitivity was predicted in 30 percent of the ER-positive women and in 26 percent of those who were ER-negative. At three year follow up, DRFS and ARR was 97 percent and 11 percent, respectively, in the ER-positive cohort, compared to 83 percent and 26 percent, respectively, in the ER-negative cohort.

"From a therapeutic standpoint, we know that the treatment a patient receives at initial diagnosis offers the greatest chance for cure. At the same time, we have many potential clinical trials with novel therapeutics and targeted agents in . Currently, we're still not sure who we are curing with chemotherapy and who also could benefit from these novel therapies," says Lajos Pusztai, M.D., D.Phil, professor in the Department of Breast Medical Oncology and an author on the study.

If validated in future studies, these findings could be used as a treatment gatekeeper, explains Pusztai, guiding women and their physicians by affirming the selection of standard chemotherapy or, for those at greater risk for recurrence, to a potentially therapeutic clinical trial in the adjuvant setting, from which they may gain further clinical benefit.

More information: JAMA. 2011;305[18]1873-1881.

Provided by University of Texas M. D. Anderson Cancer Center search and more info website

not rated yet  

Rank not rated yet
Relevant PhysicsForums posts

More news stories

Older prostate cancer patients should think twice before undergoing treatment

Older prostate cancer patients with other underlying health conditions should think twice before committing to surgery or radiation therapy for their cancer, according to a multicenter study led by researchers in the UCLA ...

Cancer created 10 hours ago | popularity not rated yet | comments 0 | with audio podcast

Two radiotherapy treatments show similar morbidity, cancer control after prostatectomy

Intensity-modulated radiation therapy has become the most commonly used type of radiation in prostate cancer, but research from the University of North Carolina suggests that the therapy may not be more effective than older, ...

Cancer created 12 hours ago | popularity not rated yet | comments 0

The compound in the Mediterranean diet that makes cancer cells 'mortal'

New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer ...

Cancer created 12 hours ago | popularity 4.8 / 5 (11) | comments 2 | with audio podcast

CT radiation risk less than risk of examination indicator

(HealthDay)—For young adults needing either a chest or abdominopelvic computed tomography (CT), the short-term risk of death from underlying morbidity is greater than the long-term risk of radiation-induced ...

Cancer created 13 hours ago | popularity not rated yet | comments 0

Team finds mechanism linking key inflammatory marker to cancer

In a new study described in the journal Oncogene, researchers reveal how a key player in cell growth, immunity and the inflammatory response can be transformed into a primary contributor to tumor growth.

Cancer created 19 hours ago | popularity not rated yet | comments 0 | with audio podcast


Genetic predictors of postpartum depression uncovered

Johns Hopkins researchers say they have discovered specific chemical alterations in two genes that, when present during pregnancy, reliably predict whether a woman will develop postpartum depression.

Child maltreatment increases risk of adult obesity

Children who have suffered maltreatment are 36% more likely to be obese in adulthood compared to non-maltreated children, according to a new study by King's College London. The authors estimate that the prevention or effective ...

New immune system discovered

(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.

Early-life traffic-related air pollution exposure linked to hyperactivity

Early-life exposure to traffic-related air pollution was significantly associated with higher hyperactivity scores at age 7, according to new research from the University of Cincinnati (UC) and Cincinnati Children's Hospital ...

Do salamanders hold the solution to regeneration?

Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...

Scientists identify molecular trigger for Alzheimer's disease

Researchers have pinpointed a catalytic trigger for the onset of Alzheimer's disease – when the fundamental structure of a protein molecule changes to cause a chain reaction that leads to the death of neurons ...