Take Carcinoma Out of DCIS and Ease Off Treatment

Nick Mulcahy

January 21, 2010

January 21, 2010 — The term carcinoma in the phrase ductal carcinoma in situ (DCIS) is misleading and troubling and ought to be dropped, or at least its dropping should be considered, suggest some recent editorials in major journals.

Both editorials also suggest that DCIS is a possible candidate for management by active surveillance, a treatment strategy of growing importance in prostate cancer in which low-risk patients do not receive radiotherapy or surgery unless they progress to higher risk.

However, unlike in prostate cancer, where active surveillance and a revised sense of what is acceptable management in low-risk patients have been gaining strength for a number of years at multiple North American centers, these potential changes for DCIS are still at an early stage. And, at this point, much of the push for DCIS changes — proposed and actual — appears to be emanating from 1 center in particular, the University of California in San Francisco (UCSF).

The prospect of changing terminology and treatment options in DCIS is complicated in the United States by what 2 different experts described as "hysteria" surrounding breast cancer.

Nevertheless, investigators at UCSF have gone ahead and are investigating what has been called "an important first step in the direction" of active surveillance for DCIS.

Dr. Laura Esserman (courtesy of University of California, San Francisco)

The UCSF pilot study involves 40 women with estrogen-receptor-positiveDCIS who received hormonal therapy for 3 months before surgery.The outcomes include change in tumor volume during thisperiod and the identification of cellular components that are predictive of clinical response to therapy.

From preliminary results from 23 women (BMC Cancer. 2009;9:285), the UCSF investigators concluded that "further work is needed to identify which women may be the best candidates for such treatment for DCIS and whether best responders may safely avoid surgical intervention."

We should be demanding change.

However, the pilot study is a step in the direction of active surveillance, because the investigators' "ultimate goal is to identifynonsurgical means of treatment to prevent DCIS progression toinvasive cancer, as pointed out in an editorial in the Journal of the National Cancer Institute (2008;100:228-229).

Regardless of the final findings of this pilot study, Laura Esserman, MD, MBA, professor of surgery and radiology at UCSF and an investigator in the study, thinks the time is now to discuss a change in the approach to DCIS. "We should be demanding change," she told Medscape Oncology.

One Editorial, 1 Forceful Call for Change

Dr. Esserman, who is also director of the Carol Franc Buck Breast Care Center at UCSF, recently made a forceful call for change in the naming and management of minimal-risk cancers and conditions, including DCIS, in an essay that she cowrote with colleagues for the Journal of the American Medical Association (JAMA. 2009;302:1685-1692).

Minimal-risk lesions should not be called cancer

"Minimal-risk lesions should not be called cancer," they write.

The JAMA editorial received widespread media coverage after the chief medical officer of the American Cancer Society made controversial remarks about breast and prostate cancer screening related to the editorial.

Lost in the media swirl was much of the substance of Dr. Esserman's essay. In it, she and her coauthors propose another term for DCIS and other low-risk lesions.

"A more appropriate term, such asindolent lesions of epithelial origin (IDLE) tumors, would helpfocus on systematically studying how to reduce or eliminatetherapeutic interventions while achieving a good outcome," they write.

"Methods exist to identifylow- and high-risk cancers. Tests for prognosis andpredictionof breast cancer are available and provide betterdiscriminatory information than clinical features alone," write Dr. Esserman and colleagues.

With DCIS, the "bulk of what we find is not high grade" Dr. Esserman explained to Medscape Oncology in an interview. She noted that only high-grade DCIS is likely to progress to invasive breast cancer.

If it doesn't look like high-grade DCIS, we should leave it alone.

"If it doesn't look like high-grade DCIS, we should leave it alone. We would eliminate two thirds of all biopsies if we did," Dr. Esserman said.

She also said that currently "there are sufficient data to stop and rethink the entire approach to DCIS."

Less than 5% of DCIS turns out to be "something else," including invasive cancer, said Dr. Esserman. Because a vast amount of DCIS is overtreated, a new approach to management is required. This has historical precedent, she said. "It's the story of every medical intervention — you treat a condition to the maximum extent and then you must re-evaluate your approach."

James Olson, PhD, distinguished professor of history at Sam Houston State University in Huntsville, Texas, and author of Making Cancer History: The University of Texas M.D. Anderson Cancer Center (Johns Hopkins University Press, 2009), corroborated Dr. Esserman's comments with regard to cancer.

"A key dynamic in the history of cancer treatment has been steady increases in the aggressiveness of treatments in the search for a cure, until a plateau is reached in terms of survival rates, after which there has been a search for less aggressive therapies while preserving existing survival rates," he told Medscape Oncology.

DCIS Was Rare Before Mammography

In the case of DCIS, there is a lack of convincing data that early treatment reduces mortality, Dr. Esserman said. Furthermore, finding DCIS has not led to a decrease in invasive breast cancer rates, she added.

"There are now 60,000 new cases a year of DCIS in the United States. But we haven't seen any drop in invasive cancers, despite treatment of DCIS as if it were early cancer," she explained.

In arguing for a change of approach to DCIS, Dr. Esserman said that screening for precancerous tissue works in some other cancers — it has led to a decrease in cervical cancer — but evidently not in breast cancer.

The burgeoning problem of DCIS is a result of mammography screening, said Dr. Esserman. In the days before widespread mammography, DCIS was rare. In the United States, DCIS incidence has risen from 1.87 per 100,000 in 1973 to 1975 to 32.5 in 2004, according to a recent report published online January 13 in the Journal of the National Cancer Institute by Beth Virnig, PhD, and colleagues. Dr. Virnig is professor of public health at the University of Minnesota School of Public Health in Minneapolis.

Dr. Esserman asked a basic question about breast cancer screening: "Is the purpose of mammography screening to look for DCIS? No," she answered.

"Maybe we shouldn't try so hard to find it — particularly low- and intermediate-grade DCIS. We need to take them out of the screening agenda," she added.

A Second Editorial, Less Forceful

Another call for removing the term carcinoma from DCIScomes from Carmen Allegra, MD, chief of hematology and oncology at the Shands Cancer Center of University of Florida in Gainesville.

Writing in a commentary also published online January 13 in the Journal of the National Cancer Institute, Dr. Allegra says that "strong consideration" should be given to changing the phrase DCIS to eliminate the "anxiety-producing" term carcinoma.

Dr. Allegra also writes that, with improved risk stratification, a watchful-waiting-type approach might be a good strategy for some women with DCIS, a subset "who can be monitored after biopsy in lieu of surgery or other therapies."

Dr. Allegra's proposals are especially notable because they appear in her commentary about a recent national DCIS conference. Dr. Allegra was chair of the conference — the State of the Science Conference on the Diagnosis and Management of DCIS — which was sponsored by the National Cancer Institute and National Institutes of Health.

Dr. Ann Partridge (courtesy of Sam Ogden)

Ann Partridge, MD, MPH, from the Dana-Farber Cancer Institute in Boston, Massachusetts, who was approached for an independent comment, agrees that the term DCIS is "confusing." Dr. Partridge is the lead author of a study that indicated that women treated for DCIS greatly overestimate the likelihood of recurrence and their risk for invasive breast cancer (J Natl Cancer Inst. 2008;100:243-251).

"Cancer implies that it can spread and be uncontrolled and kill you," she told Medscape Oncology.

" 'This is not a life-threatening problem' — that's the first thing I tell patients," she said.

Dr. Partridge agreed that DCIS is overtreated, but she noted that there is uncertainty about which patients are at highest risk of progressing to invasive breast cancer. "There are ways to risk-stratify, but they aren't great," she said.

Hysteria and Breast Cancer

Until better prognostic and predictive markers come along, overtreatment of DCIS continues. Reports that patients with DCIS are increasingly choosing bilateral mastectomy as their treatment may be the "major clinical dilemma in DCIS today," notes a recent commentary in the Journal of Clinical Oncology (2009;27:5303-5305), as reported by Medscape Oncology.

There's a hysteria around breast cancer.

The extremism that sometimes comes into play in DCIS treatment decision making is a "cultural problem," said Dr. Partridge. "There's a hysteria around breast cancer," she added.

That "hysteria" is one of the main reasons that the strategy of active surveillance, now advancing in prostate cancer, is currently not a viable option for DCIS, said Dr. Esserman.

However, Dr. Partridge noted that men, in general, have more to potentially lose from adverse effects with radical treatments for low-risk prostate cancer than women do with the treatment for DCIS. "There is a big difference between incontinence and impotence and [removing] a piece of breast or a even whole breast," she observed. Thus men, as a group, may be more willing to watch and wait for a time to see if their condition worsens, she suggested.

The researchers have disclosed no relevant financial relationships.

J Natl Cancer Inst. 2010;102:1-9, 170-178. Abstract, Abstract


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