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Research Unravels New Ways to Treat HER2-Positive Breast Cancer

New therapies and combinations make progress in HER2-positive breast cancer.

BY ELIZABETH WHITTINGTON @eyoste
PUBLISHED SATURDAY, AUGUST 11, 2012
When Debra Tincher received a diagnosis of stage 2 breast cancer in 1997, testing for HER2-positive breast cancer wasn’t standard. She went through treatment and was cancer-free for more than 10 years, teaching kindergarten in Hamilton, Ohio.

In 2009, Tincher learned she had a recurrence—this time her hormone-positive, HER2-positive breast cancer was metastatic. She went the traditional treatment route, but when the cancer progressed, she knew it was time to pursue other options.

The clinical trial her physician offered wasn’t a hard sell, even with it being a phase 1 study. Because Tincher had severe side effects with the first drug on the study, her doctor offered to move her on to the next one in the clinical trial, an investigational HER2-targeted agent called T-DM1.

As her doctor drew a diagram on the whiteboard in the examination room, Tincher listened to an explanation of how the drug worked. Her doctor explained that T-DM1 was a new type of drug that fused a potent chemotherapy drug to Herceptin (trastuzumab), an antibody approved more than a decade before that targets the HER2 receptor on a cancer cell.

“The only question was if I wanted to remain in the trial and try T-DM1,” she says. “Hearing all the positive feedback, there was no doubt in my mind.”

Tincher had been following the story of T-DM1 through early-phase clinical trials—the Food and Drug Administration’s rejection of the drug’s application for accelerated approval in 2010 and the positive phase 3 study that was the top headline from the annual meeting of the American Society of Clinical Oncology (ASCO) this summer.

“Some people are very hesitant to go on a clinical trial. They see it as a last resort option, and that’s not necessarily true,” Tincher says. “I’m very happy to have found this one with my doctor.”

As a Metastatic Breast Cancer Network board member, Tincher is working on the organization’s national conference set for Oct. 13 in Chicago where she hopes to learn about more advancements in breast cancer, including news on HER2-positive cancers.

About a fifth of all breast cancers are considered HER2-positive, which means they contain an abundance of human epidermal growth factor receptor 2, or HER2, on the cell surface. These cancers tend to be more aggressive and were considered more fatal than other types of breast cancer until HER2-targeted agents, such as Herceptin, entered the scene.

Nearly 15 years after Herceptin was approved for metastatic HER2-positive breast cancer, there are now several treatments that zero in on the HER2 pathway and the HER family. There are four proteins that make up the HER receptor family: HER1 (more commonly known as EGFR or epidermal growth factor receptor), HER2, HER3 and HER4. While researchers developed Herceptin to block the HER2 receptor on the outside of the cell, they have since been able to develop other therapies that can block HER activity in other ways.

[Chart: The HER2 Family]

Patients will have their tumor tested for HER2 overexpression at initial diagnosis and following a recurrence, because HER2 status—as well as hormone receptor status—can change. Depending on how strongly the cancer expresses HER2 proteins will determine whether the patient would benefit from HER2-targeted therapy.

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