The Cancer Chronicles (17 page)

In December, just before Nancy’s first session, her father died of the
stroke that had brought her home to Long Island just three months before. She wanted with every cell of her body—that is how she put
it—to go back there, but the doctors advised against it. We watched a videotape of the funeral instead. Thinking back on those days, a year after her chemo and
radiation had been completed, she wrote a short essay, “
Adriamycin and Posole for
Christmas Eve.”

As it opens it is December 22 and she is beginning the second round of what will be seven two-day sessions of intravenous infusions, one every three weeks. Christmas decorations hang in the chemo lounge, and at the nurse’s station there is a gingerbread house that had been filled earlier in the season with candy and cookies for the patients. It is almost empty now.

To make the many injections as painless as possible, a chemo port has been installed below her right collarbone—a small artificial blister sitting beneath her skin. It is capped with a silicone rubber membrane through which needles can be poked and is connected internally to a plastic catheter threaded into one of her veins. The device will stay in place for the next few months until the therapy is done.

She sees that one of the “first class seats” is vacant—a comfortable leather recliner with a clear view of the Sangre de Cristo Mountains, where we have hiked together so many times. The sky is grey, with hints of a Christmas snow. As she settles in, I pull up a chair and another round of life’s new routine begins. First comes the numbing spray to deaden feeling around the port, and then the premeds, fluids, an anti
nausea drug—all in preparation for the syringe full of
doxorubicin, a.k.a. Adriamycin. It reminds her of red Kool-Aid, and that is the color her urine will turn. While this first cytotoxin is being absorbed by her body, she thinks about Christmas Eve, just two days away, when a few friends will stop by our home for a bowl of posole and tamales, a
Santa Fe tradition. The nurse arrives with the
cisplatin, and Nancy tries to welcome these chemicals flowing in through that hole in her chest as a gift, a lifeline, no matter how sickening they may be. She tries to envision the shock to all those manically dividing cancer cells when their DNA is suddenly jammed shut—all the delicious
apoptotic explosions.

It takes four hours in this room for the day’s drugs to be administered.
Then we drive home for the night and return the following day for the
paclitaxel and four more hours of sitting. Late in the afternoon when the nurse approaches with a shot of
Neulasta, which stimulates
bone marrow to replace the white blood cells killed by the chemo, we know she has made it through session number two. Three weeks to recover and then back again.

The first nights of these interludes were the hardest. She would awaken in the dark, sometimes so quietly that I didn’t hear her rise to go to the bathroom. One morning she told me that she had felt so weak that she lay on the bathroom rug for a while before returning to bed. Why didn’t she call out to me, and how had I slept through that? I read years later that because of the toxic
effects of chemo drugs, family members are advised to sleep separately and not to share a bathroom. We didn’t know that, and I don’t think I would have cared.

Early on Christmas Eve she was feeling a little better, and before our guests arrived we left our house to walk down dark, unpaved streets lined with
farolitos, the traditional little lanterns made with paper bags, sand, and candles. They light the way for the Christ Child, or so the legend goes. We stopped at one of the bonfires, the luminarias, to warm our hands and legs. Her bones ached from the Neulasta. We avoided Canyon Road, which was already becoming crowded, staying on the side streets. When we reached Acequia Madre, the narrow lane that runs along the town’s old irrigation ditch, we came upon something we had never seen. Inside the schoolyard was a man launching flying farolitos—tissue paper balloons fired by candles that ascended and then self-immolated in the sky. I was enough of a traditionalist to feel that this modern touch was an intrusion. I could count on Nancy to see the good in it.

Three weeks pass—I don’t remember doing anything for New Year’s—then back to chemo again. How quickly the unthinkable becomes routine. For all her acceptance of this random blow to life and her gratitude toward the doctors,
Nancy questioned everything, and I was there to help with the research.
Should she be getting
topotecan? She had read that the drug had been used against papillary serous carcinoma and that the response rates of
doxorubicin and
cisplatin were less than desired. Or did the addition of the
paclitaxel tip the scales? “Cisplatin/
adriamycin superior without question,” the
surgeon quickly replied (he and the
oncologist had given us their e-mail addresses).
He attached abstracts from three papers from the
Journal of Clinical Oncology
and
Gynecologic Oncology
to compare. I thought of the surgical report he had written—so clear, precise, and literate. These were doctors who kept up with the research and expressed themselves cogently and persuasively.

One day
Nancy’s oncologist gave us a paper, published just a few months earlier, called “
HER2/neu Overexpression: Has the Achilles’ Heel of
Uterine Serous Papillary Carcinoma Been Exposed?” HER2/neu was a gene that codes for
receptors that respond to human epidermal growth factors—signaling molecules that encourage
mitosis.
It is usually just called HER2. Some
breast cancer cells have too many copies of the gene. Instead of two, one from each parent, there are fifty or a hundred and the cell’s membrane becomes glutted with receptors. Tens of thousands of receptors is normal. A HER2-positive breast cancer cell might have 2 million. Wildly overacting to growth-stimulating signals, the cells multiply with mad determination.
A drug called
Herceptin was designed to seek out the receptors and shut them down—in breast cancer and possibly in other cancers too.

Though more precise than the blunderbuss of chemo, these new “
targeted therapies” weren’t always as targeted as they sound. There was still unwanted damage to healthy cells, and as with other drugs the cancer would evolve antidotes and counterstrategies, mutations that confer
resistance. But given what we had been hearing, the possibility described in the new study seemed like unusually promising news. Many
UPSC cells, the author found, also overexpressed HER2—even more so than in breast cancer—and they withered in the presence of Herceptin. He wasn’t reporting successful results from the clinic—these were in vitro experiments—but another avenue had opened. And almost as quickly, it closed. A diagnostic test was ordered on
Nancy’s cancer cells but it came back negative. The amount of HER2 was normal. Herceptin wasn’t an option, but we wondered what other possibilities might be out there, findings too new to have made it into the journals.

We were helped in the search by some of my colleagues who wrote about science and health for
The New
York Times
—
Sandra Blakeslee, Denise
Grady,
Jane Brody, and
Lawrence Altman, a doctor who decided early on to write about medicine rather than practice it. Altman was the reporter on call when the
Times
needed a story explaining whatever ailment had befallen the president of the United States. (
His name had been mentioned in an episode of
The West Wing
when the fictional President Bartlet held a press conference about his multiple sclerosis.) When we decided to seek an outside opinion from the MD Anderson Cancer Center in Houston, Altman sent an e-mail to
John Mendelsohn, the president, and we had an appointment for the last week in January. We were luckier than most in so many ways.

Anyone with cancer can hardly resist the Anderson allure. “Making Cancer History” was its slogan, and an impressive packet of information quickly arrived. A large brochure with photographs
of smiling doctors and patients described how far Anderson would go beyond what might be expected at the local hospital. Through the office of Patient Guest Relations and the Patient Travel Services one could book discounted airline tickets with no penalties for last-minute changes. There was a concierge. Hotel rooms were available right on the grounds at the
Jesse H. Jones Rotary House International. Maps and parking passes were included in the envelope with instructions for negotiating the vast Anderson campus. “Do not be overwhelmed by our size,” patients were advised. “We are here to guide your journey through our hallways.”

There was a Learning Center with medical reference books and videos, a Leisure Library if you preferred a good novel. A Craft Room, a Music/Game Room—and all of that was beside the point. People came to Anderson because it operates one of the largest and most respected research centers in the world. If there were new things to learn about
UPSC or trials of experimental treatments, Anderson would surely know.

The evening of our arrival we ate a bland but probably healthy supper at the Rotary House restaurant and then returned to our room to wait for the morning. There was a closed-circuit Anderson channel on the television, and when we tuned in it was airing meditation and visualization exercises: Close your eyes and imagine the golden light of health flowing through you. It didn’t sound very scientific, but anything that relieved stress could only be good. We were early the next morning for our appointment with the professor of gynecologic
oncology, one of the grand old men of the field, who also served as special assistant to the president of the cancer center. By now Nancy had shed all of her thick brown hair, but she looked as pretty as ever in her scarf. Another patient, new to cancer, came over to ask what it would be like when her own hair fell out. Would it happen all at once or gradually? She would soon be worrying about other things.

The medical records and microscope slides had been sent in advance from New Mexico, and the doctor had familiarized himself
with the surgical and pathological reports and the chemo protocol. “
UPSC—that’s a tough one,” he said. Nancy went off for a quick medical exam, and when she and the doctor returned we all took seats in his office. He agreed with everything the
oncologists were doing in Santa Fe. It was just what he would have done at Anderson. “You’re getting state-of-the-art care,” he said. We left the building feeling both relieved and a little disappointed. It was reassuring to have his imprimatur. But we had hoped to be bestowed with some new laboratory finding, a promising clinical trial, some kind of Anderson magic.

With the rest of the day to fill, we took a tour of the
Lyndon B. Johnson Space Center south of central Houston and saw the old Mission Control Center, the nexus of operations for Apollo 11 when a human first walked on the moon. Anything seemed possible then. Back in the city we visited the
Rothko Chapel. Years before when we had lived in New York,
Mark Rothko and
Jackson Pollock were two of our favorite artists at the Museum of Modern Art. Pollock’s drip paintings always left me feeling that I was peering inside the frenetic workings of a human brain—ideas looping and sparking in motions that teetered between order and chaos. Pollock stimulated while Rothko, with his big blurred blocks of color, soothed. Inside the octagonally shaped chapel he had taken this serenity to an extreme: eight walls of enormous black canvases. We stared at them trying to find patterns, some subtle meaning.

Things are rarely as simple as they seem, and what appears to be complex may be no more than ripples on the surface of a fathomless ocean. The
mechanics of malignancy I was slowly becoming comfortable with—with a single cell acquiring mutation upon mutation until it spirals down the rabbit hole of cancer—was
neatly described by two scientists,
Douglas Hanahan and
Robert Weinberg, in a sweeping synthesis published in 2000 called “The
Hallmarks of Cancer.” Both authors are respected researchers. Weinberg, a pioneer in the discovery of the first
oncogenes and
tumor suppressors, would be on anyone’s list of the most prominent and original thinkers in his field.

The idea of cancer occurring as an accumulation of
mutations to a normal cell goes back decades. But it was Hanahan and Weinberg who assimilated a growing mass of laboratory results and theoretical insights into six characteristics that a cancer cell must acquire as it
develops, in its pell-mell version of Darwinian
evolution, into the would-be creature called a tumor. It must acquire the ability to stimulate its own growth and to ignore signals admonishing it to slow down. That is where the oncogenes and tumor suppressors come in.
It must learn to circumvent the safeguard of programmed cell death and to defeat the internal counters—the telomeres—that normally limit the number of times a cell is allowed to divide. It must learn to initiate angiogenesis—the sprouting of its own blood vessels—and finally to eat into surrounding tissue and to
metastasize.

More than a decade after it was published, “Hallmarks” was still the most frequently cited paper in the history of the prestigious journal
Cell,
which is as good as saying that it may be the single most influential paper on the biology of cancer. Known as the mono
clonal
theory (a dividing cell and its branching tree of descendants is called a clone), the picture spelled out in “Hallmarks” remains the dominant paradigm, like the big bang theory is in cosmology.
Creation began as a singularity—a primordial dot of mass-energy—and ballooned to form the universe. A cancer begins with one renegade cell—it was Weinberg who popularized that term—expanding to form a tumor. With this rough map in place, the two scientists looked forward to a renaissance in the understanding of cancer: