In the early 20th century, in a lab at Johns Hopkins Hospital in Baltimore, a surgeon named Joseph Colt Bloodgood made a series of medical observations that have influenced how doctors treat breast cancer to this day. Bloodgood argued that a biopsy could show “a pre-existing local defect which is benign and in which later there may be a cancerous development” and was the first to describe, in a 1934 paper, “precancerous” lesions of the breast. In other words, abnormal cells (the “local defect”) could exist without turning into cancer. There may be a cancerous development.
What Bloodgood described 85 years ago as precancerous tissue of the breast is what doctors now call DCIS, ductal carcinoma in situ, or breast cancer that originates in the milk ducts and stays there without spreading. (Cancer, by definition, must be invasive.) Doctors have been diagnosing DCIS ever since the American Cancer Society first recommended regular mammography in 1976, and the organization estimates that there were 63,000 new cases of DCIS in 2017. The condition accounts for one in every four new cases of breast cancer each year.
Recently, doctors began to refer to DCIS as “stage zero” breast cancer, a term that has created problems far greater than semantics within the medical community. Most experts agree that 70 to 80 percent of DCIS doesn’t become invasive. However, current guidelines from the American Cancer Society state that the ultimate goal in treating DCIS is to prevent it from becoming invasive cancer, and until new guidelines are established, the standard of care for treating DCIS will continue to be surgery—lumpectomies or mastectomies, along with, for some women, radiation or chemotherapy. Physicians, it seems, are increasingly divided on surgery versus no surgery.
“There are a lot of people out there who say we overtreat DCIS,” says Elizabeth Feldman, a breast surgeon at Reston Breast Care Specialists, whose concern isn’t the 70 to 80 percent who won’t develop invasive cancer but the 20 to 30 percent who will. “The problem is we don’t know in whom we should under-treat. A certain percentage will go on to develop invasive disease, and you don’t want to leave disease in someone that will potentially cause them morbidity, or even mortality.” Feldman adds that in the past ten years, she has seen an increase in the rate of women in their twenties and thirties being diagnosed with DCIS, mirroring an overall national increase in the incidence of breast cancer in women under 40.
On a mammogram, DCIS looks like grains of sand. Because it usually can’t be felt, women have no way of finding it during a self-exam, nor would an ob-gyn be able to feel it during an annual checkup. DCIS is categorized by grade: Low-grade DCIS moves slowly, with cells that look similar to normal breast cells, and is unlikely to recur after surgery. Moderate-grade DCIS grows more rapidly and starts to fill up the ducts, while high-grade DCIS grows so rapidly that it can be seen dividing under a microscope.
All three have potential to spill out of the duct and become invasive. “The dilemma is that we don’t know which intraductal ‘cancers’ will progress to invasive lesions,” says breast-cancer surgeon Marc E. Boisvert, who directs the MedStar Regional Breast Health Program at Washington Hospital Center. “But we are sure that most of them, especially the low-grade ones, don’t.”
Boisvert is leading MedStar’s efforts as part of a study called COMET (Comparison of Operative to Monitoring and Endocrine Therapy for low-risk DCIS). The clinical trial was launched at Duke University in 2016 and now comprises more than 100 clinical sites nationwide. The study puts forth the belief that DCIS is being overdiagnosed and overtreated due to greater screening—a notion Bloodgood might applaud were he alive today. It states that false-positive mammograms and overdiagnosis create health-care expenditures estimated to approach $4 billion annually—and that much of this financial “burden” comes from treating DCIS specifically.
To be included in the COMET study, women must be at least 40 years old with low- or mid-grade DCIS. The prospective, randomized clinical trial places them in two groups: a “no-surgery” group, which tests the approach known as “active surveillance,” and a “surgery” group, which follows the current standard of care, surgery plus therapy. With active surveillance—a method popularized for its success in prostate cancer—women are closely monitored with frequent follow-ups and mammograms. The belief is that watching and waiting will do less harm to the patient than would surgery and associated therapy. Those whose DCIS has turned invasive will be able to switch immediately to the surgery group.
The study ultimately will measure the number of women who receive standard-of-care treatment and develop invasive cancer after two years compared with the number who are placed on active surveillance.
COMET aims to enroll about 1,200 women nationwide. MedStar currently has six and hopes to increase that number to 90. When the study concludes in 2021, Boisvert says, “I expect to see that these patients who are on observation will do just as well from a cancer point of view as those who get standard-of-care treatment.”
Along with learning more about the behavior of DCIS, Boisvert explains, a big part of the research goal is understanding how quality of life is affected for women in both groups. The study’s overarching hypothesis is that active surveillance doesn’t yield lower quality of life when com-pared with the surgery group, taking into account measures such as depression, anxiety, and coping.
Until the COMET study is complete and the data mined, which Boisvert estimates will take until 2025, doctors will continue to follow the standard of care for treating DCIS—surgery.
Feldman is cautiously optimistic: “I think that once the studies that have gathered this information are complete, it will be a lot better. Because at least we’ll have scientific, prospectively gathered data upon which to make recommendations. Right now, we don’t have that.”
For more information on participating in the COMET study at MedStar Washington Hospital Center, contact oncology-research manager Hiwot Guebre-Xabiner at 202-877-9386.
This article appears in the February 2019 issue of Washingtonian.