Triple-whammy

Thursday, I go in for a Herceptin infusion and it’s like old home week in the infusion center that used to be so terrifying. I recognize at least half a dozen nurses and wave hello to them. Crystal, my favorite tech, takes my blood pressure and congratulates me when the scale shows I’m five pounds down. I wonder if perhaps it’s silly to feel so cheery here. I’ve heard so many stories of people who go from “no evidence of disease” back into a recurrence and a re-do of the chemo-radiation nightmare.

A nurse leads me into the treatment bay where the Dignicap cold cap machine resides. I don’t know if they plan it this way, but there always seem to be other breast cancer patients seated in this particular bay.

Across the bay, there’s a woman who’s driven from Chico, nearly three hours away, to get to UC. Next to her sits a woman who comes even farther, from Redding, about four hours away. They make me realize what a privilege it is to be close enough to cycle to cancer treatment.

The woman from Redding has actually just come from a family wedding in San Diego. She holds a coffee thermos cup that says “Grandma” and talks about how nice it was to see her grandchildren in southern California. Her husband, a slender athletic man with salt-and-pepper hair, sits next to her. They look to be in their late 50s, early 60s tops.

As an infusion nurse starts to hook up the port over his wife’s right breast, the man tells me their story in the shorthand that cancer-patients and their families use to quickly sum up what may be years of harrowing treatments: “Original diagnosis in 2004. A recurrence in 2008. Then another recurrence late last year. Now stage 4. A recent surgery shows spots of cancer everywhere, spots on the lungs and liver. Her cancer is ‘triple negative.’ She’s here in order to participate in a clinical trial.”

If breast cancer is scary, then “triple negative” breast cancer is terrifying. Much of the progress that has been made in breast cancer treatment over the last couple decades has been the result of early diagnosis and of being able to test each tumor to see if it responds to the hormones estrogen and progresterone, or if it over-expresses the protein “Her-2.” If your cancer responds to one or more of these things, then there are targeted drugs you can take in addition to traditional chemotherapy, surgery and radiation. As doctors like to say, this “greatly improves outcomes.” In human-speak this means more breast cancer patients are living longer.

I’m lucky: My cancer is estrogen-receptor-positive (80 percent of breast cancers are) and also Her-2 positive (which is why I’m here every three weeks for Herceptin through the fall). My new acquaintance across the bay is not so lucky: Her cancer does not respond to estrogen, nor to progesterone, nor to Herceptin. She’s “triple-negative.” That means that her cancer probably won’t respond very well to standard chemo. In fact, it hasn’t: Her cancer has come back a third time. Unfortunately, it also means that the newer hormone therapy and Herceptin treatments won’t work either.

It turns out that we have the same oncologist. Perhaps this isn’t surprising, because triple-negative breast cancer is one of Dr. Hope Rugo‘s research interests.

My triple-negative friend explains that she will be getting traditional chemo drugs, carboplatin and gemcitabine, but she’ll also be getting Iniparib, or “BSI-201,” a drug being developed by the huge pharmaceutical company Sanofi-aventis.

Iniparib has been touted as one of the most promising of a new class of drugs called PARP-inhibitors. (If you’re really science-minded, “PARP” stands for “poly (ADP–ribose) polymerase,” an enzyme that seems to be key in DNA repair.)

Every time a cell divides, little nicks and glitches may occur in the copying of the DNA. Healthy cells repair these problems, and PARP appears to be necessary to these fixes. PARP-inhibitors work by taking the key PARP enzyme out of the repair toolbox. Cells that can’t repair themselves die, which is the goal of most cancer drugs.

PARP-inhibitors were the talk of the town at the 2009 meeting of the American Society of Clinical Oncologists. Interest intensified throughout 2010, when a Phase II trial showed that combining Iniparib with traditional chemotherapy greatly improved survival: At least two dozen trials of various PARP-inhibitors got going, mostly targeted at breast, ovarian, and prostate cancers.

Then, early in 2011, disappointing news: The Phase III trial of Iniparib, a randomized study that enrolled five times more people than the 120 or so in the Phase II trial, fails to show that Iniparib confers any benefit over traditional chemo.

Corporate spokesmen backtrack, admit the results are disappointing. They then point out that further analysis of the Phase III results shows that women who are going through “second-line” or “third-line” treatment (that means their second or third round of chemo for recurrences) DO seem to benefit from the PARP-inhibitor Iniparib.

That’s how my new acquaintance ends up in the infusion center next to me: She’s a “third-line” patient, meaning this is her third go-round with breast cancer. She’s one of those patients that the Phase III regimen of Iniparib, and chemo drugs carboplatin and gemcitabine seems to help.

She closes her eyes as the infusion nurse hangs up her first bag of drugs.

“The docs say that now we’re playing for time,” her husband whispers to me.

The experts aren’t giving up on PARP-inhibitors. Sanofi-Aventis is continuing to test its drug, obviously. So are many other drug companies. Sanofi-Aventis’s VP of US Medical Operations recently announces that Iniparib might not be a PARP-inhibitor after all, though it appears to have “anti-cancer properties,” whatever that may mean. And other companies are working to understand exactly how messing with the DNA repair of malignant cells might cure some cancers. The science will probably take time to sort itself out.

Unfortunately, that’s exactly what women with triple-negative breast cancer, women like the grandmother from Redding who sits across from me, do not have.