Pandora's DNA: Tracing the Breast Cancer Genes Through History, Science, and One Family Tree

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Pandora's DNA: Tracing the Breast Cancer Genes Through History, Science, and One Family Tree Page 14

by Lizzie Stark


  Adding to the confusion is that the more we look for cancer, the more we seem to find it. A study that examined the breasts of women who died in unrelated accidents found that mammography had only discovered 18 percent of the tumors identified by pathologists who looked at many thin sections of each breast. Mammograms don’t catch everything, and in fact, that’s good. As Löwy puts it,

  An enhancement of radiologists’ capacity to see tiny clusters of microcalcifications does not automatically produce a more desirable outcome for the patient. Excessively sensitive imagegenerating machines may identify more precancer and thus produce more clinically ambivalent results. And vice versa: less sensitive radiology equipment can produce a lower proportion of false positive results and detect less “pseudo-disease” (that is, changes in tissue that will not produce clinical symptoms of cancer in a woman’s lifetime).

  Sensitive detection tests may pick up precancer that would not necessarily become lethal and kill you, as in the clinically ambiguous diagnosis of LCIS, lobular carcinoma in situ. LCIS is a condition predictive of invasive cancer, according to Dr. Mary Daly, who chairs the NCCN Guidelines panel for genetic/familial high risk assessment for breast and ovarian cancers. Women with LCIS have a higher likelihood of developing invasive cancer later, but not necessarily in the same spot or even the same breast as the original LCIS. The condition is not cancer but rather a marker of increased risk for cancer. Still, once you know you’ve got this predictive condition, will you be able to rest without doing anything? In this way, detection tests can lead to medical interventions, such as surgery or chemoprevention, which may feel psychologically necessary while not necessarily prolonging life.

  In fact, there’s good evidence that we’re overtreating breast cancer, Brawley tells me. “We can tell from breast cancer in the United States that 20 percent of the breast cancer we diagnose was not going to kill anybody if it was not diagnosed…. Twenty percent looks malignant but is programmed to behave benignly.” Some flavors of breast cancer will metastasize and kill you, while others will just hang out in your breast and do nothing. Unfortunately, we don’t know how to tell them apart—they both look like cancer under a microscope. And so women with cancer are subjected to arduous treatments. Still, there’s an upside. As Brawley puts it, “Yes, we cured some people of breast cancer who didn’t need to be cured. But my prospective randomized studies tell me that we cured some people who needed to be cured [too].” The problem is even worse with prostate cancer, where it’s 60 percent of localized tumors that don’t need to be cured, Brawley says.

  When I began looking into mammography, I thought I would find easy and clear evidence that it definitely helped reduce cancer death. Instead, I feel more confused than ever. Malcolm Gladwell posed one of the core questions about mammography in the New Yorker in 2004. “You’d expect that if we’ve been catching fifty thousand early-stage cancers every year, we should be seeing a corresponding decrease in the number of late-stage invasive cancers. It’s not clear whether we have,” a fair point, although according to the National Cancer Insitute’s most recent statistics, the breast cancer death rate declined on average by about 1.9 percent per year between 2001 and 2010. If screening works, how come up to 30 percent of all breast cancers are still destined to become metastatic killers? A 2011 Danish meta-study of mammography trials found that “reported reductions in breast cancer mortality cannot be explained by differences in screening effectiveness” and that “screening appeared ineffective.” And a 2012 paper in the New England Journal of Medicine that examined mortality data for women over forty found that mammography only reduced the diagnosis of late-stage cancer by about eight cases per one hundred thousand women. As the authors concluded, “Despite substantial increases in the number of cases of early-stage breast cancer detected, screening mammography has only marginally reduced the rate at which women present with advanced cancer.” Is potentially saving eight lives worth giving one hundred thousand women mammograms, which carry with them the risk of further exploratory surgery, such as biopsies? It depends, I selfishly suppose, on whether I am one of those eight.

  When I ask Dr. Brawley about the Danish study and about Gladwell, he tells me that they both “have their point that metastatic disease has stayed at a stable rate for the last forty years. The people who are pro screening have a point that there’s a 30 percent risk reduction in breast cancer mortality risk.” It’s unclear why breast cancer death has decreased, but Brawley suspects it’s probably a combination of advances in cancer treatment, advances in screening, and improvements in physical health. “The one thing we’ve proved reduces breast cancer risk is physical exercise,” he reminds me.

  So where does that leave the young BRCA woman? In a pretty confusing place. Mammograms may or may not be effective. Breast MRIs, which use magnetic waves to look inside women’s breasts, penetrate the breasts of young women more easily but also have a higher rate of false positives than mammograms. As Brawley explains it, “If I do an MRI on ten women age forty-five that I pull off the street, I’m going to find an abnormality in half of them, and with those numbers, probably none of the abnormalities are going to be cancer.” And that’s not all. “The other catch-22 is that we don’t know that finding these lesions through MRI also saves lives. Many of us, myself included, believe that early detection is better than late detection, but we have to separate what we believe from what is scientifically proven,” Brawley says. On one level, BRCA carriers like me are at a high risk of cancer, so statistically it makes more sense to screen us than women in the general population. Or as Brawley puts it, “We want to do MRI on high-risk women because the MRI so commonly finds something that looks like cancer, that if we only image the people who are at high risk, the likelihood that the mass is high risk is much better.”

  Still, so far, adding MRIs to mammograms mostly suggests that you’re three to five times more likely to get called back about false positive results and that there’s a pretty good chance your cancer will be detected—but it says nothing about whether such screening actually does the job of preventing cancer death.

  On top of all this, screening for breast cancer involves shooting radiation into your breasts to take a picture via mammography. And guess what can also cause cancer? Radiation. Of course, radiation is all around us—we are exposed to about 3 mSv (millisieverts) of radiation each year from stuff like radon gas at home, cosmic rays, and so on. A mammogram exposes women to about 0.4 mSv of radiation—about the same amount as what you absorb in seven weeks of living. That’s not very much. Still, radiation exposure is cumulative. It’s one thing to get a yearly mammogram once you turn fifty. If I live to eighty, that’s thirty years of mammograms and about 12 mSv of radiation—the same amount I’d absorb in four years of living. Although now NCCN recommends delaying mammography in BRCA carriers until age thirty, at the time I began screening, physicians recommended that I start screening ten years before my mother developed breast cancer—that is, at age twenty. Assuming I live to eighty, that would be sixty years of annual or biannual mammograms, and at least 24 mSv of radiation—the same amount as eight years of living. As the American Cancer Society website puts it, “Most studies on radiation and cancer risk have looked at people exposed to very high doses of radiation, such as uranium miners and atomic bomb survivors. The risk from low level radiation exposure is not easy to calculate from these studies.” How paranoid is it to wonder whether my intensive screening might begin to contradict its primary purpose?

  Not all that paranoid, as it turns out. “Quite honestly, there’s a lot of discussion in the professional community,” Dr. Brawley tells me, particularly because BRCA is active in repairing DNA, and radiation from mammography damages DNA, raising “the theoretical possibility that women with BRCA are more likely to get breast cancer [from mammography] than women without BRCA,” and a few studies support that claim. Dr. Daly is more reassuring. She reminds me that as technology has improved, the doses of radiation used in mammography have dec
reased and that much of the historical data on radiation revolves around people who had major chest radiation due to treatments for Hodgkin’s or who had stuff like acne treated with radiation in their teens. “So it’s not clear any of that historical data applies to current practice,” she says.

  The bottom line, Dr. Brawley tells me, is that it’s complicated. “Cancer screening is always harmful and sometimes beneficial,” he says, “And we need to figure out when the screening test has benefits that are greater than the harms.” The benefit-to-harm ratio is a complicated calculus. Lung cancer provides a good illustration of the point, because we know a lot about it, in part because people who contract lung cancer tend to die within a few years, which means it’s easier and cheaper to study—in contrast, because women often live decades after developing breast cancer, studies require more participants and longer, costlier follow-up. In the 1960s, the ACS did a study on lung cancer screening using X-rays, Brawley tells me. In 1975, the results were in: the screened arm of the trial had a higher death rate than the unscreened arm because screening found suspicious zones, which led to surgical biopsies that ended in death. “It was death by biopsy,” Brawley says. Even now, he says, we know that lung spiral CT, a scan that uses radiation to look at soft tissue, “actually does save lives. However, for every 5.4 lives saved, there is one life that is lost to medical complications.” Or consider breast self-exams, the favorite rah-rah cause of each October. Two studies performed in Chinese and Russian women—more than 388,000 of them—showed that setting aside thirty to forty-five minutes each month to really feel your breasts thoroughly had zero impact on breast cancer mortality. The only thing it did was make women more likely to find suspicious zones that might lead to more biopsies. Women being aware of their breasts—touching and watching them in the normal course of business—is what is being promoted now. Finally, Brawley tells me about an old study on ovarian cancer done in a few thousand nuns that estimated that screening one hundred thousand nuns would uncover three cases of localized ovarian cancer. “You would end up saving three women from ovarian cancer and killing five women from surgery to figure out why they had an abnormal screen,” he says. The harm-to-benefit ratio is no good. More surveillance is not necessarily better.

  So where does that leave someone at high risk, someone like me? Most of the studies done have looked at screening in the general population and not in women at high risk of developing breast cancer. Truly, I’d like to see some studies performed on my risk group to determine the basic efficacy of ovarian and breast surveillance in preventing cancer death. I shouldn’t hold my breath, though. Large studies are expensive to produce, weighed against the comparatively small number of BRCA carriers who would benefit, and they require lots of patients. Are there even enough BRCA women who would be willing to be randomly assigned to the screening or nonscreening arm of such a trial? Would such a study even be ethical? I guess living with the flawed human screening we have now, and living with the uncertainty generated, is all part of what it means to be a mutant.

  7 | A Tale of Too Many Mastectomies

  If we had to pick one, I’m unsure whether my family would select an Amazon or Saint Agatha for our mascot. The Amazons, a mythological tribe of warrior women, cut off their right breasts so they could better draw their bows, exchanging femininity for fearsomeness on the field of battle. They’re even named for their breastlessness—a common derivation suggests it comes from the Greek a (without) mazos (breast). At the other end of the spectrum, there’s Saint Agatha, a Sicilian virgin who dedicated herself to God in the mid-third century. The Roman prefect Quintianus cut off her breasts because she wouldn’t have sex with him or sacrifice to the Roman gods. You can tell that mostly male artists painted her, because she’s often shown holding a plate with her disembodied breasts on it, gazing over them with dead eyes and a smooth, untroubled expression, as if these body parts meant no more to her than a plate of bread. In fact, she is the patron saint of bread and bell makers because her severed anatomy resembled buns and bells. She’s the patron saint of breast cancer patients too.

  The Amazons and Saint Agatha represent two extremes in how we narrativize cancer patients. On one hand, they are fierce, defiant warriors taking control of their health and doing the difficult thing to improve survival, no matter the side effects. On the other hand, they are martyrs, submitting to vicious disfigurement at the hands of the medical establishment, giving up something valuable to protect what is even more precious.

  But people are complex and contain multitudes. Cancer patients or BRCA patients are neither simply martyrs nor warriors. In some form, both narratives imbue each mastectomy. Patients are actors in their own fate, and acted upon by modern medicine. With this in mind, I’d like to look at two sorts of mastectomies, separated by untold medical advances, an ocean, and more than a century of time. The first, performed on the novelist Frances Burney in 1811, treated her cancer. The second ones, performed on my mother’s cousin Kathy in 1979, and Lisa, in 1983, were done to lower their risk of cancer and occurred thanks to the empowerment of the women’s liberation movement of the 1970s. Ironically, between 1811 and 1979, the treatments for cancer and cancer risk took opposite paths. Surgery for actual cancer became less draconian, shrinking from removal of the entire breast to simple removal of the tumor. As scientists learned to pinpoint cancer risk with increasing accuracy, treatment for high-risk patients took the opposite path, culminating in the prophylactic mastectomy.

  The novelist Frances Burney’s account of her own mastectomy—one of the few patient-written narratives passed down from history—lays bare the underlying brutality of the operation. Her description in a letter to a friend nine months later is one of the most visceral, horrifying, death-metal things I’ve ever read. But if she could endure it, we should be able to read about it, no? (If you are squeamish, you may wish to jump to p. 144.)

  In 1810, she developed a lump in her breast. Cancer. Napoleon’s surgeon, Baron Dominique Jean Larrey, vowed to operate. She didn’t want to spend months dreading her operation, so she asked the surgeons to give her only a few hours’ notice. One morning, a letter came. The surgeons would arrive at ten o’clock that day—in two hours. So she tried to prepare herself, even though she “had to disguise my sensations and intentions” from Mr. Frances Burney, who was not keen on the procedure, and whom Fanny wanted to protect from watching her suffer. She had to get him out of the house, so she asked her son Alex to contact a colleague of her husband’s and to tell him to make the supposed business urgent and important enough to keep her husband out of the house the whole day. “Speechless & appalled, off went Alex, &, as I have since heard, was forced to sit down & sob in executing his commission,” she wrote.

  Then she told the doctors she needed a few more hours—until 1:00 PM—to get ready. She fixed up a room for her husband to stay in while she recovered. And with that in order, she was ready to face the dread procedure—but one of the attending doctors was running late and couldn’t show up until 3:00 PM. The suspense was awful. “This, indeed, was a dreadful interval,” she wrote. “I had no longer anything to do—I had only to think—TWO Hours thus spent seemed never-ending.” I feel you, Frances. She stumbled into the salon, where the sight of the bandages, compresses, sponges, and other surgical materials made her feel a little sick.

  In case she died during the operation, she wrote notes to her husband and son. Then she drank a single wine cordial—I hope she’s underestimating her consumption for propriety’s sake, because if I knew what was coming next I’d get drunk off my gourd—and seven men in black entered her room without even knocking. As it turns out, this emotional nightmare—the contemplation of her own death, the dreadful anticipation of the operation, the tears of her son—would take a distant second to the physical nightmare that was about to begin.

  They asked her to mount the bed in the middle of the living room but she couldn’t move, locked in a moment of horror. “I stood suspended, for a moment, whether I should
not abruptly escape—I looked at the door, the windows—I felt desperate.” But of course, there is no escape from cancer, except the purifying fire of surgery. After a moment, “my reason then took the command, & my fears & feelings struggled vainly against it.” Her maid wept by the door, and her two nurses stood “transfixed.” The doctors tried to send the women away, but Fanny resisted them. “No, I cried, let them stay!” Two of the women broke and ran off, but one defiantly remained.

  The women weren’t the only ones afraid. The doctors stammered at Frances. One of them tore paper into tiny bits; another had a face “pale as ashes.”

  And screw anesthesia. Anesthesia is for pansies—or for operations conducted at least thirty years later. They placed an ordinary cambric handkerchief over her face and called it a day. It was quite thin; she still could see the squadron of doctors and “the glitter of polished Steel” through it. They uncovered her breast, and one of them made a circle in the air with his finger, indicating that they would take the whole thing off. This freaked her out, so she ripped the handkerchief off her face and sat up, explaining that all her pain radiated from a single point in her breast. But the doctors told her again that it must all come off, and firmly put the cloth back over her face.

  Then they started sawing off her breast while she watched them through the handkerchief. Here’s how that felt:

  When the dreadful steel was plunged into the breast—cutting through veins—arteries—flesh—nerves—I needed no injunctions not to restrain my cries. I began a scream that lasted unintermittingly during the whole time of the incision—& I almost marvel that it rings not in my Ears still! so excruciating was the agony. When the wound was made, & the instrument was withdrawn, the pain seemed undiminished, for the air that suddenly rushed into those delicate parts felt like a mass of minute but sharp & forked poniards, that were tearing the edges of the wound—but when again I felt the instrument—describing a curve—cutting against the grain, if I may so say, while the flesh resisted in a manner so forcible as to oppose & tire the hand of the operator, who was forced to change from the right to the left—then, indeed, I thought I must have expired.

 

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