Technique reveals drug resistance in tumors, could prevent unnecessary chemo.(gene expression profiling)

2003 JAN 9 - (NewsRx.com & NewsRx.net) -- Oncologists at the Duke Comprehensive Cancer Center are testing a new technique called gene expression profiling that subtypes each breast cancer tumor by its genetic defects so that doctors can tailor their treatment to inhibit that particular tumor.

The researchers believe the technique could spare millions of women from needlessly receiving toxic chemotherapy, and they are leading a national clinical trial to study gene profiling.

"Currently, we have no predictive model to determine who will respond to hormonal therapies and who won't, so we prescribe chemotherapy as a backup measure to ensure the cancer's demise," said Matthew Ellis, MD, PhD, director of the breast cancer program at Duke. "This one-treatment-fits-all approach leads to a huge amount of overtreatment, with up to 50% of women unnecessarily receiving chemotherapy."

The new technique uses a commercially available gene chip to create a genetic "fingerprint" of each tumor. Doctors use the chip to categorize each tumor by its genetic defects and predict whether the tumor will respond to standard hormonal therapies or whether it will require additional chemotherapy, said Ellis.

"The gene chip allows us to measure levels of various genes that give rise to drug resistance, so we can paint a picture of what a responding cancer cell looks like and what an unresponsive cell looks like," said Ellis. "With such fingerprints, we can develop new drugs that target the cellular signaling pathways that have malfunctioned."

Ellis presented his study design at the 25th annual San Antonio Breast Cancer Symposium. The multicenter study of 140 women is funded by a $3.7 million grant from the Avon Foundation and the National Cancer Institute.

Participants in the study will provide biopsies of their tumors, then receive the estrogen-depriving drug letrozole before surgery to shrink their cancers. Letrozole reduces the production of estrogen that fuels the growth of up to 80% of all breast cancers. Yet inexplicably, some tumors that are expected to respond to hormonal therapies remain unaffected by treatment. And, some tumors that initially respond to antiestrogen drugs later become resistant. Doctors have long wondered what drives these paradoxical effects, but answers have been slow in coming.