In November 1998, Nancy Pelton was diagnosed with HER2-positive breast cancer, an aggressive form that strikes one in four women with the disease. A mutation in the HER2 gene in certain women causes excess production of a protein that fuels the proliferation of tumor cells. At the time, the 46-year-old tax accountant and mother of two from Bakersfield, California, had read about a new breast cancer drug from Genentech called Herceptin, but her doctor told her she would hopefully never need it because the drug was approved only for patients with a recurrence of the disease.

 

Instead, surgeons removed a small tumor from Pelton’s breast. She underwent four rounds of chemotherapy followed by seven weeks of radiation therapy and was then treated with the drug Taxol once every three weeks. By August 1999, Pelton was done with her treatments and walked away with a clean bill of health.

 

But this was not to last. By the summer of 2001, she began to feel pain in her armpits. Doctors discovered that the disease had returned. They removed 13 cancerous lymph nodes and gave her fresh rounds of chemotherapy and radiation. In February 2002, doctors added a new, more targeted weapon to the fight, Herceptin, the drug Pelton had heard about four years earlier. Unlike traditional chemotherapy drugs that indiscriminately kill fast-dividing cells in the body, Herceptin works by inhibiting the overproduction of a protein that fuels the tumor growth in HER2-positive breast cancer patients. More than five years later, she remains on the drug, going once a week for an hour-long intravenous infusion of Herceptin. Her breast cancer has remained in check.

 

“I don’t think the public knows enough about the types of cancer. It’s still too generic,” says Pelton. “If someone I know has breast cancer, or a friend comes to me about someone they know with breast cancer, I’ll say, ‘Okay, are they estrogen-positive or are they HER2-positive?’ They’ll say, ‘I don’t know. What’s that?’”

 

Indeed, as Pelton knows all too well, diseases can target different patients, and in different ways. Lucky for her and others, one-size-fits-all drugs and treatments are giving way to more tailored therapies. And Herceptin, in many ways, has come to exemplify this approach dubbed personalized medicine. That’s because it was one of the first drugs to require the use of diagnostics, in this case to determine if a patient was HER2-positive. Its use represents a new direction in therapeutics, which are increasingly targeted to interact with specific genes or molecular pathways involved in a disease. Now approaching its 10th anniversary, the drug last year won regulatory approval as a treatment for patients with early-stage HER2-positive breast cancer. The move has the potential for changing the course of treatment for the estimated 50,000 women diagnosed each year in the United States with HER2-positive breast cancer.

 

Born out of a chance meeting at the Denver airport between two researchers in 1986, Herceptin was an unlikely success for South San Francisco, California-based Genentech. A humanized monoclonal antibody, it was developed against a backdrop of spectacular industry failures around antibody technologies, which can target a specific biological process involved in a disease. It also faced great skepticism from within Genentech’s ranks because no such drugs had yet been approved and many people questioned whether the technology would ever lead to an approved product.

 

Late in the development of the drug, a big problem arose. With the company in the midst of a late-stage clinical trial, it became clear that the only hope of winning regulatory approval for Herceptin would require finding a partner to develop and commercialize a companion diagnostic similar to the home-brew assay the company was using in its trials. The diagnostic test would enable doctors to determine whether a breast cancer patient was over-expressing the HER2 gene. Turned down by a Roche subsidiary that had no interest in developing a diagnostic for what it saw as too small a market, a team from Genentech found themselves sitting over a meal of codfish in the dead of a Copenhagen winter negotiating with a Danish company a deal that was announced in 1998.