The Cancer Chronicles (6 page)

There are those times we all come to know when you are sitting in a hospital waiting room surrounded by other people—the older ones flipping through magazines, the younger ones staring into the bottom of their cell phones. I had been through that with my mother after her torn rotator cuff and when the second of her knees was replaced. I had been through it with Nancy for a detached retina after a horseback ride. I knew what to expect. Just when you think you cannot endure another minute, the surgeon walks in, her mask hanging around her neck. She is smiling, pleased to be giving you good news. This time that didn’t happen. “We may be looking at a
carcinoma,” she said.

She had sent a sample of the lump downstairs to pathology for a quick look under a microscope. The misshapen cells resembled
epithelial cells that form the lining of organs. But they had mutated enough to become less differentiated. They were losing their genetic identity. Reverting to this primitive state, cells bear a resemblance to those in an embryo—rapidly dividing, chameleon-like, and capable of doing almost anything.

The diagnosis would have to be confirmed in the laboratory. But there was little doubt about what was happening. I walked with the surgeon to the recovery room where
Nancy lay in an anesthetized blur. I remember her smiling as the surgeon spoke, and I only realized later that she was barely absorbing the information. For the rest of the week I tried to be optimistic, and maybe I unintentionally misled her. My understanding was that the diagnosis was, say, 90 percent certain, that the lab report was a technicality, a way to be absolutely sure. I thought that was Nancy’s understanding too.

A few days later I was upstairs in my office when the doctor called her to break the news. “Extensive
metastatic adenocarcinoma, moderately differentiated.”
Adenocarcinomas are carcinomas of epithelial tissues that contain microscopic glands. They can arise in the colon, lung, prostate, pancreas, almost anywhere. I don’t remember how I knew to walk downstairs. Or did she walk upstairs to me? I had never seen her so upset. She told me that she had hung up the phone and screamed. Somehow cancerous cells had gotten into her
lymphatic system and lodged inside that node in her groin. But where in her body had the cells come from? It would be weeks before we knew. “Metastatic cancer with an unknown primary”—it seemed like the worst possible diagnosis. A tumor was single-mindedly growing, shedding more seeds, metastasizing. But no one knew where.

There were hints from the pathology report describing the character of the cells:

The first line provided a scrap to hang on to. Since the growth of some cancers is driven by estrogen, it might be controlled by blunting
its effect. The abundance of these receptors also helped narrow the diagnosis:

Comment: The estrogen receptor positivity is consistent with an endometrial or ovarian primary rather than a gastrointestinal primary.

So it was probably gynecological. The
endometrium—the lining of the
uterus—is a tissue of epithelial cells, which are vulnerable to carcinomas. I think Nancy had suspected something like that. About a year earlier she had been told by her doctor that she was experiencing unusually early
menopause. The sign was irregular menstrual bleeding, and I still wonder why that was not taken as a warning, an occasion for more tests—whether the cancer might have been discovered then and treated before it had been allowed to spread.

Comment: The tumor has micropapillary architecture suggestive of endometrial, ovarian or

The rest of the sentence was cut off. Monkeys with typewriters recording your fate. And being sure to include the billing code.

The surgeon was so supportive, so sympathetic, so sisterly. On a follow-up visit she gave Nancy a hug. I think we both were stunned when her next move was to hand us a pile of paper—yellow, pink, blue—orders for various procedures. We were to take them to local clinics, stand in line, and apply for an appointment. The chain store imaging center across the street would do a
mammogram, chest
x-ray, and a
CT scan of the abdomen and pelvis. The
colonoscopy factory was booked solid, the surgeon said. Rather than insisting that a patient with metastatic cancer be accommodated—most people’s colonoscopies are routine and could easily be rescheduled—she issued an order for a
barium enema, an ancient, quicker, less definitive test. We asked about a referral to an
oncologist. That would be premature, the surgeon told us, until we knew what kind of cancer this was. She actually said that.

What is a crisis for the patient is routine for the doctor, but this still seems to me like pure idiocy. We went from lab to lab, returning to pick up the results. The mammogram and chest x-ray were negative. The abdominal scan showed the liver, kidneys, pancreas,
bowel, and lower lungs to be normal. So were the adrenal glands. A 1.3 centimeter nodule in the area of the spleen looked “to be a
splenule only”—a benign mass that can sometimes be confused with a tumor. In the pelvic scan a cyst on the left ovary appeared “unlikely to be neoplastic” but the uterus and endometrium were “prominent” and there were benign
fibroids. There was a “question of [a] small constrictive lesion of sigmoid colon.” It was scary reading language whose nuances we were not attuned to understand. Especially disturbing were the results of a blood test:
CA-125, a protein found in higher concentration with some cancers, was elevated. The test was far from conclusive—many other things can cause a high reading—but it hinted at the possibility of
ovarian cancer, the kind that had killed our friend
Vivian.

As we accumulated information we also made phone calls. I talked to a doctor at the
Mayo Clinic in Scottsdale where I had splurged for my fiftieth birthday on an executive physical. She suggested the obvious:
MD Anderson Cancer Center in Houston or
Sloan-Kettering in New York. I contacted those places and—more importantly it turned out—found out who had treated Vivian. Her husband spoke highly of her oncologist, and when I called the doctor’s office in Santa Fe, his secretary squeezed us in for an appointment.

Imagine a tall, thin, aging cross between Jimmy Stewart and John Wayne—I think he was wearing cowboy boots—ambling in and taking charge. He was reassuring in his casualness, someone who had seen it all. He leafed through the test results. “There’s nothing here really.” He said it was unlikely that an ovarian cancer would metastasize to an inguinal lymph node. He was puzzled by the order for a barium enema, which was scheduled for a few days later. “It’s a useless test,” he said. We explained about the long wait for a colonoscopy. He picked up the phone, called one of the physicians who owned the clinic, and we had an appointment two days later. “We are going to cure you,” he said. That at least is my memory.
Oncologists are not supposed to say that. It was encouraging that he didn’t give a damn.

The results of the colonoscopy were negative, and the final step
was a
PET scan. Santa Fe had just gotten its own machine—it was no longer necessary to drive an hour south to Albuquerque—and Nancy was almost first in line. PET stands for positron emission tomography, a triumph of medical technology from the recondite world of particle physics. The patient fasts the night before so the body’s cells are starving. When radio-tagged
glucose is injected it is eagerly consumed. Malignant, rapidly dividing cells are especially voracious, concentrating the radioactive molecules. As these decay they shoot out positrons, particles of antimatter that collide with electrons and produce bursts of
gamma rays. They strike a scintillator, which responds by emitting flashes of light. Nancy’s lower uterus was glowing from the feasting of hyperactive endometrial cells, descendants of a single cell gone mad, a cell that had forgotten it was part of a community, that began running its own show—an isolated act of betrayal that has been played out again and again since the first archaic cells grudgingly agreed to surrender their autonomy for the advantages of living in a collective.

In the days after the diagnosis, I began
reading about how this might have happened. To carry on in harmony, our cells constantly exchange chemical signals, conferring on when to start multiplying and creating new tissue. As each cell receives this information it responds by sending instructions to its nucleus, the central controller, for activating the appropriate combination of genes—pressing the right buttons, hitting an arpeggio of piano keys. A cancer cell is one that has cut itself out of the discussion, solipsistically deciding on its own. Random events—triggered by a cosmic ray, a carcinogenic chemical, or just plain dumb luck—must have altered the DNA inside one of Nancy’s cells, causing it to lose touch. The trouble might have begun with a
mutation to a gene that sends signals telling the cell that it is time to divide. Another mutation might have modified the molecular receptors that respond to the signals, causing them to become hypersensitive. Set on a hair trigger they
fire prematurely. Either way, the cell begins multiplying more rapidly than its neighbors.

In fact these kinds of errors happen all the time. We usually don’t get cancer because other genes react to sudden bursts of activity by reining in growth. But another mutation can cause that safeguard to fail. The nucleus of a cell is constantly receiving messages, weighing the evidence and deciding what to do next. The calculations depend on a tangle of molecular cascades—more things that can go wrong. And they do. All the time. The mistakes are caught and corrected. The DNA is repaired. If that fails, a cell can sense the inner turmoil and send itself suicide signals, killing itself for the common good. But another mutation can undermine that defense.

This is all usually described as though a single cell was sitting motionless and accumulating these defects over the years. I tried to imagine the process as it really is, unfolding dynamically. One hit causes a cell to start dividing repeatedly. Then one of its many progeny acquires another mutation, and its progeny acquire still more. The longer a lineage of cells has lived the more likely it is to have mutated to the brink. That still leaves another barrier against runaway growth: a counter that monitors and limits how many times a cell can divide. With the right mutation a cell can learn to continually reset the count and become immortal. Copying itself again and again, it produces a mass of mutant offspring, a tumor.

And that is still not enough to give you cancer. It takes more mutations for the cell to learn how to invade surrounding tissues, to become
malignant rather than
benign. Even so, the tumor can grow only so large—the size of the tip of a ballpoint pen—before it’s starved for food or drowns in its own waste. For the tumor to continue expanding it must find a way to reach into the circulatory system and suck like a vampire.

With this infusion of nutrients the cells multiply more aggressively than ever, increasing the probability of more mutations—or adaptations, from the point of view of the evolving cancer cell. The phenomenon is what computer scientists call “random generate and
test.” With all the restraints removed, the
genome spins out one variation after another—hopeful monsters trying to gain an upper hand. Some might learn to consume energy more efficiently, others to tolerate harsher environments or to suppress the immune system. Finally the fittest will set sail in the bloodstream or the lymphatic ducts and explore new ground.

As I thought about this I was pulled in opposite directions. With so many checks and balances, a person must be extraordinarily unlucky to get cancer. Then again, with so many things that can go wrong, it is amazing that cancer doesn’t happen all the time.

When
Louis Leakey sat down to recount the discovery of what may be the
earliest sign of
cancer in the genus
Homo,
the first thing he remembered was the mud. It was March 29, 1932, midway through the third East
African archaeological expedition, and it had rained so long and so hard that it took an hour to drive the four miles from the campsite in Kanjera, near the shore of Lake Victoria, to the
Kanam West fossil beds. By the time he and his crew had slogged their way through they were covered with mud, and before long Leakey, who was just beginning an illustrious career as an anthropologist, was on hands and knees scouring the ground for newly exposed bones.

He was coaxing the remains of an extinct pig from the muck when one of his Kenyan workers,
Juma Gitau, walked over with a broken tooth he had just extracted from a cliffside.
Deinotherium,
Leakey noted, a prehistoric elephant-like creature that roamed Africa long ago. Gitau went back to look for more, and as he was scratching away at the cliff face, a heavy mass of calcified clay broke loose. He chopped it with his pick to see what was inside: more
teeth, but not
Deinotherium.
These looked like what a dentist might recognize as human premolars, still set in bone, yet they came from a layer
of sediment
deposited, Leakey believed, in Early
Pleistocene time, about a million years ago.

Back at Leakey’s home base at Cambridge University the Kanam mandible quickly became a sensation—“
not only the oldest known human fragment from Africa,” he proclaimed, “but the most ancient fragment of true
Homo
yet discovered anywhere in the w
orld.” It was radical enough in those days to claim that man had originated in Africa, rather than Asia, where primordial ancestors like
Java man and
Peking man had been discovered. They may have been of approximately the same age as Kanam man, but Leakey found their features to be more apelike in appearance. The Kanam mandible, to his eyes, showed more modern characteristics including remnants of a human-like chin—evidence that
Homo sapiens,
not just its slack-jawed cousins, was far older than previously believed. Differences in the shape of the teeth led Leakey to consider Kanam man a slightly different species:
Homo kanamensis
. It was, he insisted, the direct precursor of us all.