Radiation Therapy Helps Prevent DCIS Recurrence After Breast-Conserving Surgery

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Radiation Therapy Helps Prevent DCIS Recurrence After Breast-Conserving Surgery

Key Words
Breast cancer, ductal carcinoma in situ (DCIS), breast-conserving surgery, radiation therapy.

Summary
The addition of radiation therapy to breast-conserving surgery halves the risk of a tumor recurrence compared with surgery alone in women with noninvasive breast tumors, according to a pooled analysis of results from four randomized clinical trials.

Source
Cochrane Database of Systematic Reviews, Issue 1, January 21, 2009 (see the journal abstract).

Background
Ductal carcinoma in situ (DCIS) is a condition in which abnormal cells are found in the lining of a breast duct. DCIS is considered a noninvasive tumor because the abnormal cells have not spread outside the duct to other tissues in the breast. ("In situ" means "in place.") DCIS may also be called intraductal carcinoma or Stage 0 breast cancer. It is the most common noninvasive tumor of the breast.

Most often, DCIS is discovered during a routine mammogram. Very few patients who are diagnosed with DCIS have a lump in the breast that can be felt. DCIS accounts for about one in five cases of breast cancer that are detected by mammography.

DCIS may become invasive cancer and spread to other tissues. It is also a risk factor for developing cancer elsewhere in the same or opposite breast. Although not all DCIS will progress to invasive disease, doctors currently cannot reliably tell which tumors are likely to progress and which are not.

The outlook for women who are treated for DCIS is generally very good. The most commonly used treatment is breast-conserving surgery (BCS; also known as lumpectomy), frequently followed by radiation therapy (RT, or radiotherapy). Because conventional RT exposes both normal and cancerous tissue to radiation, it may have long-term complications, including an increased risk of other cancers. It has not been entirely clear whether, for women with DCIS, the benefit of RT in reducing the risk of invasive breast cancer outweighed the risk of long-term complications.

The Study
To determine the balance between the benefits and risks of RT for women with DCIS, researchers in Australia searched the published literature for randomized controlled trials that compared BCS alone to BCS plus RT in patients with DCIS. They identified four trials that met the selection criteria--one conducted in the United States, one in the United Kingdom and Australia, and two in Europe.

Together, these trials enrolled more than 3,900 women with DCIS between 1986 and 1999. Most of the women had DCIS that could not be felt and had been diagnosed by a routine mammogram. In each trial, women were assigned at random to be treated with either BCS alone or BCS plus RT. Patients were followed for a median of 4.4 to 10.5 years. The women's median age at diagnosis was about 50.

The principal investigator for the study was Annabel Goodwin, M.D., of Westmead Hospital in Australia.


Results
The pooled analysis of the four trials showed that, overall, 10.9 percent of women treated with BCS plus RT had a recurrence of DCIS or invasive breast cancer in the same breast, compared with 22.9 percent of women treated with BCS alone. This amounted to a 51 percent lower risk of recurrence of DCIS or invasive breast cancer for women treated with BCS plus RT. In all four trials, survival was more than 90 percent for women in both treatment groups. The researchers found no evidence that complications of RT caused any excess deaths.

Comments
"This result confirms the benefit of radiotherapy following [BCS] for DCIS and supports its use for all women," the authors conclude. They also concluded that longer follow-up would be required to show whether RT causes long-term harm. Newer techniques for delivering RT, developed over the past 10 years since patients were treated in these four trials, decrease the exposure of normal tissue to radiation and may further reduce the risk of long-term complications, they add.

The findings of this pooled analysis confirm the value of RT following BCS in women with DCIS, comments Worta McCaskill-Stevens, M.D., of the National Cancer Institute's Division of Cancer Prevention.

A good deal of confusion currently surrounds the question of whether DCIS is cancer or not, adds McCaskill-Stevens. Furthermore, in the United States disparities exist in both recommendations for and treatment of DCIS. These issues will be the focus of a National Institutes of Health state-of the-science conferenceon the diagnosis and management of DCIS to be held in September 2009.

Limitations
In three of the four trials included in this pooled analysis, participants were not tested to find out whether their tumors contained receptors for the female hormones estrogen and progesterone. When these receptors are present, the tumor is said to be hormone receptor positive. These trials were conducted before it became standard practice to test for hormone receptor status in all women diagnosed with breast cancer. Today, for women with DCIS whose tumors are hormone receptor positive, the drug tamoxifen should be considered. Additional hormonal drugs are currently being tested in clinical trials for hormone receptor-positive DCIS.