medicine - Woodruff Health Sciences Center - Emory University

why Herceptin works
tin resistance. “We don’t really know exactly how it works,
About 25% to 30% of breast cancers are HER2-positive, but mTOR TOR inhibitors basically block cell signaling quite far
which means they test positive for a protein called human downstream from the HER2 receptor,” says O’Regan. “Re-
epidermal growth factor receptor-2 (HER2). This protein searchers here at Emory have demonstrated that mTOR TOR inpromotes
the growth of cancer cells, making HER2-positive hibitors also activate what’s known as the Akt pathway. One
breast cancers more aggressive than other types. They theory is that the activation of the Akt pathway actually
also tend to be less responsive to
resensitizes the cells to Herceptin,
hormone treatment. That’s the bad
but that’s just a theory.”
news. The good news is that this
Whatever the exact mecha-
type of cancer responds extremely
nism, the results from the Phase I
well to Herceptin.
clinical trial were very promising.
Herceptin specifically targets
Twenty-five heavily pre-treated
HER2 cells, killing them while spar-
Herceptin-resistant women received
ing healthy cells, so side effects are
a combination of Herceptin, Taxol
minimal. Its effectiveness has made
and Afinitor. About 45% had their
Herceptin the gold standard of
cancer shrink, and almost 80% had
treatment for HER2-positive breast
disease control, which means their
cancer.
cancer either got smaller or it didn’t
“Most patients with HER2-
get any worse.
positive breast cancer are cured
“Overall, in this kind of
at their initial diagnosis because
setting, you’d expect to see a dis-
they get Herceptin and chemoease
control rate of something like
therapy,” says O’Regan. “five years Oncologist Ruth O’Regan saw promising 40% to 50%,” says O’Regan. “So
ago, these patients had a very high results from clinical trials of Taxol and we were very encouraged by the
recurrence rate over the first five Afinitor in Herceptin-resistant patients. results we got.”
years after diagnosis and were very
O’Regan’s team also studied a
likely to develop metastatic disease.
subset of patients with cancers that
But now with Herceptin, the rate of developing metastatic were not only Herceptin resistant but also were resistant
disease is pretty low—10% or maybe even 5%.”
to taxanes—a group of chemotherapy drugs that includes
The problem is, some cancers are resistant to Hercep- paclitaxel (Taxol) and docetaxel (Taxotere). “So these were
tin. “We know that about 10% of patients who present with very resistant cancers,” says O’Regan. “In that group, the
HER2-positive breast cancer have cancers that are resistant disease control rate was about 85%—even higher than the
to Herceptin at the time of diagnosis,” says O’Regan. “Once Herceptin-resistant group. These results suggest that Afini-
HER2-positive breast cancers become metastatic, almost all tor is reversing resistance to these drugs.”
of them will become resistant to Herceptin at some point.” O’Regan’s team is participating in a multi-site Phase
That’s what happened to Akin. “As soon as I was diag- II clinical trial that they hope will confirm the promising
nosed, Dr. O’Regan started me on Herceptin and Taxol,” results of the Phase I trial. She hopes to have data from
says Akin. “That worked really well for about a year and the Phase II trial early this year. A Phase III trial is ready to
a half, but then the disease started to grow again. So Dr. begin in January.
O’Regan enrolled me in a clinical trial taking Herceptin, “We know this combination isn’t going to cure these
Taxol, and RAD001 (Afinitor). The RAD001 apparently cancers, but the aim of treating metastatic breast cancer is
makes the cancer cells receptive to Herceptin again.” to extend meaningful life,” says O’Regan. “If you can control
the disease for a long time with an agent that is nontoxic,
finding a helper for Herceptin
that is definitely a good outcome. We don’t just want to
Afinitor, an oral mTOR TOR inhibitor, is an investigational drug extend their survival, we want their quality of life to be as
that acts on the pathway that is believed to mediate Hercep- normal as possible.” EM
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