Barbara Nickles, of Selden, N.Y., had a double mastectomy after she was diagnosed with ductal carcinoma in situ — a condition that some doctors consider pre-cancer and others view as the disease itself. (Jackie Molloy)

Barbara Nickles and Ligia Toro de Stefani are both women in their early 60s who were diagnosed with abnormal cells in a breast, or Stage 0 breast cancer, as it’s sometimes labeled. Nickles decided to have a double mastectomy. Toro de Stefani opted for “active surveillance” and a twice-yearly battery of tests.

“I wish I had breasts, but I am also happy they are gone so that I don’t have to worry so much about breast cancer,” says Nickles, whose grandmother had the disease.

“Quality of life is the most important thing to me,” says Toro de Stefani, an avid traveler and scuba diver.

The two illustrate the vexing questions facing the 60,000 women a year diagnosed in this country with ductal carcinoma in situ (DCIS), a condition in which cancerous-looking cells are found in the breast duct. What exactly is it — a pre-cancer, cancer or more a risk factor? How much treatment is too much? Too little? Which women can safely skip surgery? What about those who want more treatment than their doctors recommend?

The DCIS conundrum is sparking increasingly heated debate among physicians as well. Most say the condition, while not cancer, needs aggressive treatment because 20 percent to 30 percent of cases will spread to surrounding tissue and become invasive cancer if left alone. To date, that has meant surgery for DCIS patients; most have lumpectomies, often followed by radiation, but some undergo mastectomies. Some women also end up taking an anti-cancer drug — such as tamoxifen — for several years.

Breast surgeon Shelley Hwang of the Duke Cancer Center is leading a new natioductal carcinoma in situ. (Shawn Rocco/Duke Health)

But a growing group of oncologists, worried about overtreatment, is stepping up efforts to add another approach — active surveillance — to the anti-DCIS arsenal. Proponents are launching COMET, the nation’s first prospective, randomized clinical trial to test whether such close monitoring is safe and effective for many women.

If the answer is yes, backers say, it could spare thousands the pain, trauma and cost of intrusive therapies.

“This is a trial whose time has come,” said Otis Brawley, chief medical officer of the American Cancer Society. “Many of us have felt for two decades that this study needed to be done, but we needed to get doctors and patients to the right point emotionally where it could go forward.”

About 255,200 women will be diagnosed with breast cancer this year, with about 1 in 4 of those with DCIS — a condition that was rarely identified before mammograms became widespread in the 1980s. Almost all women with DCIS survive over the long term, regardless of whether they get lumpectomies or mastectomies, studies have shown.

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The opening of the new trial parallels greater interest in surveillance for a variety of pre- and early-stage cancers. In recent years, the proportion of U.S. men with low-risk prostate cancers being monitored rather than removed has surged to more than 40 percent. Last fall, a study by Memorial Sloan Kettering Cancer Center in New York found that active surveillance may be a suitable approach for some thyroid cancer patients.

Shelley Hwang, chief of breast surgery at the Duke Cancer Institute, said COMET reflects the growing realization that DCIS, like breast cancer itself, represents a range of subtypes of abnormal cells and that treatments need to be tailored to individual risks. High-grade DCIS has a fast rate of cell division and is more likely to become invasive cancer, for example, while the low-grade kind has a slower proliferation rate and is much less risky.

Barbara Nickles inside her home. (Jackie Molloy/for The Washington Post)

But current screening can’t differentiate between harmless and worrisome cases.

“You are going to catch both the sharks and the minnows with the wide net of screening,” said Hwang, the principal investigator of the trial. “We are working to identify and treat just the sharks.”

Only women who are at least 40 years old and have low-risk DCIS are eligible for COMET. Patients have to agree to be randomly assigned to either active surveillance or standard therapy, including surgery. Women in the surveillance group will see their doctors and get mammograms every six months. Those who develop invasive cancer will be able to switch immediately to the treatment group for surgery and other therapy — which should assure them a high chance of complete recovery, Hwang said.

Both groups will be offered tamoxifen or other drugs to reduce the risk of recurrence.

A key aspect of the trial, which aims to enroll 900 participants at 100 medical centers nationwide, will focus on psychological factors: Do women in the surveillance group experience more anxiety because they aren’t moving forcefully against their DCIS? Or do they benefit from a restrained approach?

The impulse to reduce overtreatment is part of a longer-term effort by physicians to “first, do no harm,” said Steven Katz, an internist at the University of Michigan who researches how medical decisions are made. And from the reduced use of antibiotics to the dialing back of radiation and chemotherapy for breast cancer, “there’s a sea change going on.”

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Yet while physicians and breast surgeons generally support testing surveillance in a trial, many say that, in practice, the approach has a long way to go. In about 20 percent of DCIS cases, biopsies miss invasive cancers that are found only when surgeons remove the entire affected area.

Part of the problem is that doctors don’t know enough about DCIS to predict when it will remain indolent or become invasive. “If we knew which DCIS was purely DCIS and would stay DCIS, we would never have to treat it,” said Monica Morrow, chief of breast surgery at Memorial Sloan Kettering. “Understanding the biology is the fundamental issue, but that remains elusive.”

A far bigger overtreatment issue, she argues, is the sharp increase in women requesting double mastectomies when they have DCIS or early-stage cancer in one breast. “They say, ‘We want it anyway for peace of mind.’ ”

COMET supporters say the trial could offer a way to discourage such surgeries. “If we can get to the point where we say, ‘This is not cancer, but a marker of risk,’ maybe we can reduce that number,” said Deanna Attai, a breast surgeon at the University of California at Los Angeles.

Fewer than 2,000 women with DCIS are getting active surveillance in the United States, according to cancer experts. Most physicians don’t offer it because they say there is not enough data to support it and because the current standard of care is so successful. However, some doctors will oversee surveillance if a patient has already decided against surgery.

In Toro de Stefani’s case, “she was coming to me for affirmation that this was a good alternative for her,” said Alastair Thompson, a COMET co-principal investigator at the MD Anderson Cancer Center in Houston, along with Ann Partridge at Dana-Farber Cancer Institute in Boston.

Toro de Stefani, 62, sees Thompson twice a year when she drives the six hours from her home in South Texas for her next mammogram and round of testing. And while confident of the course she chose after her 2016 diagnosis, the retired cardiovascular researcher also is prepared to take more aggressive action if needed.

“I’m not going to die of this,” she declared.

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In Selden, N.Y., Nickles faced several challenges when she was diagnosed in 2013. Her doctor said she needed a mastectomy rather than a lumpectomy because her DCIS was “diffuse” — spread throughout the milk ducts of her right breast.

Moreover, because she had large breasts, her doctor said the plastic surgeon would have to operate on her healthy one to reduce its size as part of the reconstruction procedure. Nickles, who administers echocardiograms at local health facilities, instead chose to have a double mastectomy, followed by reconstruction with implants.

“It was a no-brainer,” said Nickles, 61, who responded to a Washington Post inquiry placed through the health-care social network Inspire.

She was relieved that she would no longer have to worry about her family’s history of cancer, but she didn’t bargain for the ensuing complications. In late January, more than three years after her reconstructive surgery, she began having night sweats and fevers. Within days, her right breast had swollen to twice its normal size because of fluid buildup. She ultimately had both implants removed.

Even so, Nickles said she wouldn’t have chosen active surveillance: “I’m still feeling relieved that my cancer was removed and doesn’t require ongoing vigilance.”

Desiree Basila, a math and science teacher in San Francisco, had a different reaction a decade ago after learning she had DCIS. When she met with her first surgeon, the doctor slapped down her imaging scans, brusquely said she had cancer and immediately talked about doing a mastectomy the following week.

Basila ended up seeing Hwang, who was then at the University of California at San Francisco and working closely with Laura Esserman, a longtime proponent of active surveillance. After Hwang ran through the standard surgical treatments, Basila responded, “What if I decided to just do nothing?”

She entered a small clinical trial testing whether tamoxifen could shrink tumors before breast surgery, later deciding she didn’t want the drug or the operation. She has since been followed through active surveillance and now, at 62, is working as a patient advocate for the COMET trial.

“People hear ‘active surveillance,’ and they tend to think it means the patients are doing nothing,” Basila said. “But it isn’t doing nothing. It’s a real commitment by patients and physicians to watch carefully. I don’t think doing these brutally aggressive treatments are necessarily what’s needed to have the longest and happiest lives. It’s driven by blind fear.”

It will probably take six to 10 years to get definitive answers from COMET, which stands for Comparison of Operative to Medical Endocrine Therapy. At some point, the findings will likely be combined with those of two European trials, called LORIS and LORD. All will be collecting and assessing tissue, blood and imaging results to determine which characteristics make DCIS mild or menacing.

Hwang thinks the long wait will be time well spent. Only hard data will bring about the treatment changes she believes will help many women.

“People are very anxious about embarking on a de-escalation of treatment,” she said. “That’s the problem with our intervention-focused culture. Taking something away is very scary, and we will need evidence to bring about change.”