April 10, 2008
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Gene expression profile may determine locoregional recurrence risk

ORLANDO, Fla. – Gene expression profiling could be used as an indicator of locoregional recurrence risk in patients with breast cancer, according to new data.

“Gene expression profile has been shown to predict the risk for locoregional recurrence particularly in node-negative, ER–positive patients treated with tamoxifen, and to a lesser degree in those treated with no adjuvant therapy and in those treated with chemotherapy and tamoxifen,” said Eleftherios Mamounas, MD, associate professor of surgery, Northeastern Ohio University College of Medicine and medical director, Aultman Cancer Center, Canton, Ohio, during his presentation.

The researchers examined the 21-gene recurrence score and studied its capacity to determine the risk for locoregional recurrence in ER–positive, node-negative patients with breast cancer administered tamoxifen in the National Surgical Adjuvant Breast and Bowel Project, B-14 and B-20 trials.

Multivariate analysis showed that recurrence score, type of surgery and patient age were significant predictors of locoregional recurrence in patients administered tamoxifen.

Mamounas also discussed two additional studies that evaluated other genomic profiles as predictors of locoregional recurrence in node-negative and node-positive patients who were treated with mastectomy or with breast conserving surgery and breast radiotherapy.

Mamounas said the results presented could have biological and, eventually, clinical implications for locoregional management, though verification is required through further studies. – by Paul Burress

For more information:

  • Mamounas E. The potential of gene expression profile to identify patients at risk for local and regional recurrence. Presented at: 25th Annual Miami Breast Cancer Conference; Feb. 20-23, 2008; Orlando, Fla.

PERSPECTIVE

When you conduct a clinical trial every group defines the clinical endpoint differently, so disease free survival by the National Surgical Adjuvant Breast and Bowel Project could be different from the Eastern Cooperative Oncology Group. There is an on-going effort to harmonize the definition of endpoints among clinical trial groups.

When you report the results from the studies on genomic profile, saying the genetic profile is predictive of recurrence usually includes both local recurrence and systemic recurrence. However, in the original study that we reported on the 21-gene recurrence score assay, we based our primary analysis purely on distant recurrence censoring the local recurrence because that is what counts most to the patient. On the other hand, in the clinical setting locoregional recurrence also can be important. This presentation has revisited the data from a NSABP trial, B-14, and B-20, and asked the question of whether the gene expression profile could actually predict local recurrence. You have to be careful in doing that kind of analysis because some trial groups do not collect competing risk information. Therefore, once you have for instance, system recurrence, they do not further collect information if the patient later develops local relapse. In the NSABP trials we actually collected data about all the competing risks, so local recurrence could have happened before systemic recurrence or after the systemic recurrence if you look at all the information. That is why Dr. Mamounas was able to conduct this study; when he said local recurrence we are censoring or excluding systemic events. In that setting, it looks like the gene expression data clearly predicted local recurrence rate, therefore the more aggressive tumors are associated with a higher recurrence rate. There is a possibility that eventually you could be able to use this information to guide local therapy or radiotherapy. I do not think that the prediction accuracy is at the level that we can actually eliminate radiation therapy based on this test. There just are no data based on surgery-only treated patients.

– Soonmyung Paik, MD

Director, Division of Pathology, National Surgical Adjuvant Breast and Bowel Project, Pittsburgh