The National Cancer Institute estimates that nearly 40,000 women will die of breast cancer in 2013. After analyzing past medical records, University researchers hope to reduce that number with the increased use of Herceptin, a treatment currently used in 20 percent of breast cancer cases.
Herceptin, which was only thought to be effective in patients who tested positive for the HER2 protein, was shown to have positive affects in HER2-negative patients as well. These previously unknown benefits could directly impact 65 percent of breast cancer patients who do not currently receive it as a part of their treatment..
Max Wicha, the director of the University’s Comprehensive Cancer Center, and the study’s primary author, explained that the treatment, called adjuvant therapy, involves the use of drugs after the tumor is removed.
“One of the biggest advances in breast cancer treatments has been the development of these targeted drugs that can target specific genetic defects and cancers,” Wicha said. “We give the therapy, even though — after the cancer is removed — there’s no direct evidence that the woman has the cancer.”
Use of Herceptin in this manner has been shown to prevent cancer from reoccurring in half of HER2-postive patients.
“We know that some of the women, despite the fact that we removed the cancer, get a recurrence of the cancer, sometimes years later,” Wicha said. “That’s what is fatal — that the cancer spreads or metastasizes elsewhere … The purpose of the adjuvant therapy is to kill any microscopic tumor cells that may have escaped from the (original) tumors, so that they don’t come back.”
To determine the effectiveness of Herceptin on HER2-negative patients, University researchers analyzed medical data from HER2-negative patients who had been incorrectly diagnosed as positive for the protein. Those studies were supposed to be limited to HER2-positive patients. However, researchers realized that several of the patients didn’t actually have the HER2 gene, and had gotten Herceptin by mistake.
After analyzing the data from these women, the researchers found that the HER2-negative patients showed similarly favorable results to the HER2-postive patients, contradicting what was formerly understood about the drug.
The HER2 protein, formally known as Human Epidermal growth factor Receptor-2, is encoded by the human gene controlling growth. In HER2-positive patients, the protein is over-expressed in breast cancer stem cells, leading to tumor growth.
“In many of these women, although the assay says they are HER2-negative, the protein for the HER2 gene is still expressed in a small population of cells in the tumor,” Wicha said. “These are the cells that we call the cancer stem cells.”
Breast cancer stem cells only account for 1 to 5 percent of cancerous cells in an afflicted individual. Current radiation treatments, although effective in destroying many cancerous cells, are not strong enough to destroy stem cells, allowing tumors to regenerate unless the patient has constant treatment.
Currently, the researchers are conducting a one-year clinical trial to test the use of Herceptin in HER2-negative patients.
“If we’re right, it could save many thousands of women’s lives,” Wicha said.
Until the results of the trial are established, the researchers are not recommending use of the drug on patients who don’t have the protein, despite the encouraging indicators.
“It has less side effects than chemotherapy, but about 2 percent of women develop heart problems from it,” Wicha said. “That’s why you don’t give it lightly or to everyone … It’s going to be important to identify those women who really have … HER2 in the cancer stem cells (to receive the treatment).”
Last Friday, the U.S. Food and Drug Administration approved Kadcyla for treatment on HER2-positive patients with late stage, metastatic breast cancer. Kadcyla is comprised of Herceptin, which targets the HER2-positive cells, and DM1, a compound that inhibits cell replication.
“It may be even more effective at knocking out these stem cells because it basically targets the chemotherapy right to the stem cells,” Wicha said.
Kadcyla, the fourth FDA-approved product for the treatment of HER2-postive patients with late stage breast cancer, is currently produced by Genentech, a subsidiary of Roche, the Swiss-based pharmaceutical company. Despite promising results in the testing phase, the drug carries a wide array of side effects, including possible liver toxicity, heart toxicity and death, according to the FDA.
Despite the recent University findings, a spokesperson for the FDA wrote in an e-mail that the recent approval is unrelated to the research, because Kadcyla is not currently approved for use on HER2-negative patients.
However, Wicha said the University hopes to participate in a national clinical trial testing Kadcyla on HER2-negaitve patients later this year.