As many as 60,000 American women each year are told they have a very early stage of breast cancer — Stage 0, as it is commonly known — a possible precursor to what could be a deadly tumor. And almost every one of the women has either a lumpectomy or a mastectomy, and often a double mastectomy, removing a healthy breast as well.
Yet it now appears that treatment may make no difference in their outcomes. Patients with this condition had close to the same likelihood of dying of breast cancer as women in the general population, and the few who died did so despite treatment, not for lack of it, researchers reported Thursday in JAMA Oncology.
Their conclusions were based on the most extensive collection of data ever analyzed on the condition, known as ductal carcinoma in situ, or D.C.I.S.: 100,000 women followed for 20 years. The findings are likely to fan debate about whether tens of thousands of patients are undergoing unnecessary and sometimes disfiguring treatments for premalignant conditions that are unlikely to develop into life-threatening cancers.
Diagnoses of D.C.I.S., involving abnormal cells confined to the milk ducts of the breast, have soared in recent decades. They now account for as much as a quarter of cancer diagnoses made with mammography, as radiologists find smaller and smaller lesions. But the new data on outcomes raises provocative questions: Is D.C.I.S. cancer, a precursor to the disease or just a risk factor for some women? Is there any reason for most patients with the diagnosis to receive brutal therapies? If treatment does not make a difference, should women even be told they have the condition?
Such questions are unlikely to be resolved by the new study. Some doctors, including the chief breast cancer surgeon at Memorial Sloan Kettering Cancer Center, said they did not see reason to change the current approach.
The new data are helpful, said Dr. Barnett S. Kramer, director of the division of cancer prevention at the National Cancer Institute, and are consistent with other data pointing in the same direction. The new study, he added, provides, “the type of evidence that builds the justification for less morbid treatment.”
Dr. Otis W. Brawley, chief medical officer at the American Cancer Society, said he was not ready to abandon treatment until a large clinical trial is done that randomly assigns women to receive mastectomies, lumpectomies or no treatment for D.C.I.S., and that shows treatment is unnecessary for most patients. But Dr. Brawley, who was not involved in the study, also said he had no doubt that treatment had been excessive.
“In medicine, we have a tendency to get too enthusiastic about a technique and overuse it,” Dr. Brawley said. “This has happened with the treatment of D.C.I.S.”
A majority of the 100,000 patients in the database the researchers used, from a national cancer registry, had lumpectomies, and nearly all the rest had mastectomies, the new study found. Their chance of dying of breast cancer in the two decades after treatment was 3.3 percent, no matter which procedure they had, about the same as an average woman’s chance of dying of breast cancer, said Dr. Laura J. Esserman, a breast cancer surgeon and researcher at the University of California, San Francisco, who wrote an editorial accompanying the study.
The data showed that some patients were at higher risk: those younger than 40, black women and those whose abnormal cells had molecular markers found in advanced cancers with poorer prognoses.
D.C.I.S. has long been regarded as a precursor to potentially deadly invasive cancers, analogous to colon polyps that can turn into colon cancer, said Dr. Steven A. Narod, the lead author of the paper and a researcher at Women’s College Research Institute in Toronto. The treatment strategy has been to get rid of the tiny specks of abnormal breast cells, just as doctors get rid of colon polyps when they see them in a colonoscopy.
But if that understanding of the condition had played out as expected, women who had an entire breast removed, or even both breasts as a sort of double precaution, should have been protected from invasive breast cancer. Instead, the findings showed, they had the same risk as those who had a lumpectomy. Almost no women went untreated, so it is not clear if as a group they did worse.
But some women who died of breast cancer ended up with the disease throughout their body without ever having it recur in their breast — many, in fact, had no breast because they had had a mastectomy. Those very rare fatal cases of D.C.I.S. followed by fatal breast cancer, Dr. Narod concluded, had most likely already spread at the time of detection. As for the rest, he said, they were never going to spread anyway.
Dr. Esserman said that if deadly breast cancers started out as D.C.I.S., the incidence of invasive breast cancers should have plummeted with rising detection rates. That has not happened, even though in the pre-mammography era, before about 1980, the number of women found to have D.C.I.S. was only in the hundreds. Nearly 240,000 women receive diagnoses of invasive breast cancer each year.
Those facts lead Dr. Narod to a blunt view. After a surgeon has removed the aberrant cells for the biopsy, he said, “I think the best way to treat D.C.I.S. is to do nothing.”
Others drew back from that advice.
Dr. Monica Morrow, chief breast cancer surgeon at Memorial Sloan Kettering Cancer Center, said it made more sense to view D.C.I.S. as a cancer precursor that should be treated the way it is now, with a lumpectomy or mastectomy. She questioned whether those women who were treated and ended up dying of breast cancer anyway had been misdiagnosed.
In some cases, pathologists look at only a small amount of tumor, Dr. Morrow said, and could have missed areas of invasive cancer. Even the best mastectomy leaves cells behind, she added, which could explain why a small number of women with D.C.I.S. who had mastectomies, even double mastectomies, died of breast cancer.
Dr. Brawley said the new study, by showing which D.C.I.S. patients were at highest risk, would help enormously in defining who might benefit from treatment. It could not show that the high-risk women — young, black or with tumors with ominous molecular markers — were helped by treatment because there were too few of them, and pretty much every one of them was treated. But Dr. Brawley said he would like to see clinical trials that addressed that question, as well as whether the rest of the women with D.C.I.S., 80 percent of them, would be fine without treatment or with anti-estrogen drugs like tamoxifen or raloxifene that can reduce overall breast cancer risk.
The notion that most women with D.C.I.S. might not need mastectomies or lumpectomies can be agonizing for those, like Therese Taylor of Mississauga, Ontario, who have already gone through such treatment. Four years ago, when she was 51, a doctor sent her for a mammogram, telling her he felt a lump in her right breast. That breast was fine, but it turned out she had D.C.I.S. in her left breast. A surgeon, she said, told her that “it was consistent with cancer” and that she should have a mastectomy.
“I went into a state of shock and fear,” Ms. Taylor said. She had the surgery.
She regrets it. “It takes away your feeling of attractiveness,” she said. “Compared to women who really have cancer, it is nothing. But the mastectomy was for no reason, and that’s why it bothers me.”
But if D.C.I.S. is actually a risk factor for invasive cancer, rather than a precursor, it might be possible to help women reduce their risk, perhaps with hormonal or immunological therapies to change the breast environment, making it less hospitable to cancer cells, Dr. Esserman said.
“As we learn more, that gives us the courage to try something different,” she said.
The stakes in this debate are high. Karuna Jaggar, executive director of Breast Cancer Action, an education and activist organization, said women tended not to appreciate the harms of overtreatment and often overestimated their risk of dying of cancer, making them react with terror.
“Treatment comes with short- and long-term impacts,” Ms. Jaggar said, noting that women who get cancer treatment are less likely to be employed several years later and tend to earn less than before. There are emotional tolls and strains on relationships. And there can be complications from breast cancer surgery, including lymphedema, a permanent pooling of lymphatic fluid in the arm.
“These are not theoretical harms,” Ms. Jaggar said.