August 2, 2002
DCIS: A breast cancer dilemma
When a woman hears "breast cancer," no matter how small or treatable her disease, the words pack a wallop. Last year, a biopsy revealed that Lois Tibbetts, a 52-year-old woman from Scituate, Mass., had a form of breast cancer called ductal carcinoma in situ, or DCIS. It is a very early form of breast cancer confined to the milk ducts in which it formed. With proper treatment, the chances of curing DCIS are nearly 100 percent. Still, Tibbetts panicked.
Lois Tibbetts
"It's scary when you hear the word 'cancer'," she says. A close friend of hers had died of breast cancer at age 47. "I remember thinking, 'I'm not going to make it. I'm going to be a statistic.'"
But Tibbetts did not become a statistic, at least not in the way she had feared. "I made it, beautifully," she says, following surgery and radiation. She was one of 47,100 American women diagnosed with DCIS in 2001. Because it's biologically different and less dangerous, DCIS is categorized separately from invasive breast cancer, which is more common and was diagnosed in about 192,000 women that same year, according to the American Cancer Society.
Not an invasive tumor, a DCIS lesion is a collection of cancer cells inside the branching milk ducts of the breast, where 90 percent of breast cancers form. The cancer is termed "in situ" because the cells haven't escaped beyond the walls of the milk ducts to invade other tissues, or metastasize to other parts of the body.
DCIS often is diagnosed in a biopsy performed because a mammogram showed suspicious flecks called microcalcifications. (Only a minority of microcalcifications are a signal of DCIS.) Until the 1980s, when mammography use expanded widely, DCIS was rarely found at all, and then only after it was large enough to be felt by the fingers, or when its presence was betrayed by an abnormal nipple discharge. In addition, some DCIS lesions were found only after they had turned into invasive cancers.
Ann Partridge, MD, MPH; Lois Tibbetts; and Julia Wong, MD
Tibbetts, who calmed down after the initial shock, was referred to the Gillette Center for Women's Cancers, within the Women's Cancers Program, at Dana-Farber, where doctors say frightened reactions like hers are very common. "Research shows that many women with DCIS overestimate their chances of having a recurrence," says Ann Partridge, MD, MPH, a medical oncologist at the center who often counsels DCIS patients about their treatment options.
"We do a lot of education here." Many women are not familiar with DCIS. If they are, they also know it is a disease surrounded by controversy because of uncertainty about its treatment. Many DCIS lesions never turn into invasive cancer and remain harmless for a lifetime. But a substantial number do escape the milk ducts and become invasive, possibly life-threatening cancers. Because doctors can't reliably predict how dangerous a woman's DCIS will be, some women may decide they have no choice but to undergo a mastectomy. Some may even choose to have a preventive mastectomy of the other breast, just to be on the safe side. There are many points of decision along the DCIS trail.
"It's hard for patients to understand why we don't know the exact right thing to do," says Julia Wong, MD, of Dana-Farber's Radiation Oncology Department. "But the good thing is that no matter what we end up choosing, you're very, very likely to be cured of this disease."
Still, ensuring that the woman is cured exacts a cost. In some cases, it is the loss of a breast or the need for radiation treatment. Therapy might also include taking a hormonal treatment, the drug tamoxifen, which may cause unpleasant and, rarely, dangerous side effects. "These cases take a lot of discussion time," adds Jay Harris, MD, chair of Radiation Oncology, "because we try to weigh the options and not just enumerate the risks and benefits. Getting the patients involved in this decision-making process is very important to their long-term satisfaction. We try not to steer them very much at all."
Eric Winer, MD, director of the Gillette Center for Women's Cancers, and Nancy Borstelmann, MS, LICSW, a social worker, studied the different ways women react to a DCIS diagnosis. In earlier work, says Dr. Winer, they found that "some women have no difficulty in understanding that this is not likely to be life threatening, while others are more anxious and much more worried about a recurrence." Some women may insist on a mastectomy because of fear.
The aim of treatment is to prevent a recurrence, either in the form of another DCIS or an invasive cancer. The largest and most aggressive-looking DCIS lesions are treated with a mastectomy, like some small invasive cancers. But unlike with the latter, mastectomies for DCIS generally don't involve dissecting lymph nodes or undergoing chemotherapy. If the surgeon can perform a "lumpectomy" — removing the DCIS surrounded by a clear margin of cancer-free tissue — the breast can be conserved. After a lumpectomy, many patients undergo radiation because it has been shown to further reduce the risk of a relapse.
Some of the smallest and least-abnormal-looking DCIS lesions are being treated simply with lumpectomy and no radiation — but the jury's not yet in on how safe this is. Dr. Wong heads a Dana-Farber study testing this no-radiation strategy following a lumpectomy. About 150 patients have been treated so far, but there are no data yet on the rate of recurrences in these women.
Tibbetts came to the Dana-Farber Breast Oncology Center on the advice of family friends who are doctors. When told of her options, she said, "I wanted the least amount of surgery I could have" to conserve her breast. An initial lumpectomy performed by Dirk Iglehart, MD, director of the Women's Cancers Program, didn't remove all the cancer, but a second surgery resulted in clear margins of cancer-free tissue. Then she had six weeks of radiation — 33 treatments in all — at a center near her home.
In addition, Tibbetts is taking tamoxifen, an estrogen-blocking drug that has been shown to prevent recurrences of invasive breast cancers, and which is now approved for women with DCIS to lower their recurrence risk.
In one study, says Dr. Partridge, the rate of recurrence after a lumpectomy and radiation therapy for DCIS was approximately 13 percent among women who didn't take tamoxifen, and 8 percent for those who did. Although this represents a statistically significant reduction in risk, she says, the risk is low to begin with.
Because tamoxifen may cause or worsen hot flashes and other menopausal symptoms, in addition to raising the risk of rarer but more serious side effects, such as blood clots and endometrial cancer, Dr. Partridge says a woman must carefully weigh its risks and benefits.
"I don't make any judgments," she says. "I tell them, 'there is no right answer, and the decision should be what makes you most comfortable.'"
The quandary of DCIS — which is being diagnosed at about eight times the rate it was two decades ago — has accompanied the surge in mammography and the message to women about catching breast cancers early while they are small. Yet scientists continue to debate whether mammograms are detecting dangerous cancers early enough — especially in younger women — to make a difference in survival.
In 2001, the issue roiled the waters as two Danish scientists said their review of past mammography studies failed to show that annual screening resulted in longer life. However, several medical organizations, including the American Cancer Society, maintain that mammograms do save lives and advise women to have annual mammography screening beginning around age 40.
Nevertheless, some women now are wondering whether they should get mammograms, all the more so because of the uncertainties over what DCIS really means. "Once you find it, you're kind of stuck doing something about it — and what do you do?" asks Dr. Wong. That's the question that Dana-Farber scientists are intensively pursuing, and their answers hopefully will not be long in coming.
Ideally, more precise biological "markers" will be found to help scientists differentiate between types of DCIS that have greater or lesser degrees of risk. (A marker is some kind of biological difference between cells that can help in distinguishing them.) "Markers are important for identifying patients at high risk, and finding markers could help clinical management," says Kornelia Polyak, MD, PhD, a researcher in the Adult Oncology Department.
Using a gene-hunting technique called SAGE, Polyak has been searching for genetic differences between normal breast cells, DCIS cells, and invasive breast cancer cells, with the idea that these differences could serve as markers. The most dramatic difference she has uncovered so far is a gene called HIN-1, which is very active in normal breast cells but is entirely silent in DCIS cells. She and her colleagues concluded that HIN-1 must have an important role in the normal cell. When she took normal copies of HIN-1 and put them into breast cancer cells, the added gene somehow squelched the malignant growth of the cancer cells. It's only a laboratory test, but Dr. Polyak told the American Association of Cancer Research in April that HIN-1 may have potential to be both a diagnostic tool and a treatment.
Until leads like this bear fruit, women will face uncertainty as they decide how to treat their DCIS. Valerie Ferris of Newburyport, Mass., a very active 45-year-old mom, learned last February that she had microcalcifications scattered through large areas of both breasts; those in her right breast were cancerous. She and her doctors decided that even though calcifications in her left breast were benign, she would have that breast removed as well to eliminate any uncertainty in the future.
"My doctors told me that if I had a bilateral mastectomy, the cure rate was over 98 percent, and it would be over and done," says Ferris. As she thought about it, the threat of cancer was more disturbing than facing the operation. Had she decided against it, "I would have been constantly concerned, and I would have worried myself sick."
Instead, she underwent the mastectomy, which was performed by Carolyn Kaelin, MD, a breast surgeon in the Gillette Center. "Now," says Ferris, who is currently undergoing breast reconstruction, "I have no regrets. I feel I have really made the right choice for me and my life, especially when the oncologist told me I was now cancer-free!"
