Wednesday, June 23, 2004

A Debate on How to Treat Precancerous Breast Disease from the New York Times

The first time Jane Leffingwell was told that she had a precancerous lesion of the breast, she received the least aggressive treatment available: breast-conserving surgery, or lumpectomy.

She was 46, and her lesion, called ductal carcinoma in situ, or D.C.I.S., was deemed low grade, with a low likelihood of recurring.

But two years later, in 2001, a follow-up mammogram revealed that the lesion had returned. This time, her surgeon recommended a mastectomy, even though the recurrence did not increase her extremely low risk of dying of breast cancer.

"A mastectomy was obviously something I needed to think about," said Ms. Leffingwell, of Greenland, N.H.

The diagnosis of ductal carcinoma in situ, a noninvasive lesion of the lining of the milk ducts, has increased markedly in recent years, as a result of the widespread use of mammography. In 1983, the condition was diagnosed in 4,800 women. Two decades later, that number has soared to more than 50,000, with the vast majority of the lesions detected as microcalcifications on mammograms. D.C.I.S. is too small to be detected as a lump by a woman or her doctor.

But there is a mounting debate among experts over how aggressively to treat the disease, which has a 10-year mortality rate hovering around 1 percent. Studies, including a recent review published in The Journal of the National Cancer Institute, indicate that treatment varies widely across the country and that the form of treatment a woman receives appears to make little or no difference in survival rates.

D.C.I.S. has traditionally been treated aggressively, with mastectomy and lymph node biopsies to test for spread of the disease. But many experts now recommend the less-aggressive lumpectomy plus radiation, and some argue that women with low-grade D.C.I.S., who make up as much as 25 percent of cases, do not need radiation at all.

My partner, who does breast surgery only under extreme duress, points out the illogical treatment of breast disease by stating, "For invasive cancer you conserve the breast but for pre-invasive disease you remove it?" Much of this has to do with the potential for DCIS to return, and uncertainties concerning the biologic behavior of the disease. Treatment does seem to be moving to a more breast-conservation oriented approach:

The National Cancer Institute review, by Dr. Nancy N. Baxter, an assistant professor of surgery at the University of Minnesota in Minneapolis, found a trend in 1999 toward less aggressive therapy. For example, mastectomy was performed in 28 percent of cases, compared with 43 percent in 1992; lymph node biopsies dropped to 15 percent from 34 percent in the same period.

At the same time, the use of radiation therapy after lumpectomy has increased, rising to 54 percent in 1999 from 45 percent in 1992.

So the question remains, what to do? DCIS can be low-grade or very aggressive. Surgical margins are very important in determining need for mastectomy or radiation. As expected recurrence rates vary with treatment modality:

With lumpectomy alone, the risk of recurrence of D.C.I.S. is 30 percent over 10 years, studies have shown. Half of the recurrences are invasive breast cancer, the other half recur in the same precancerous form. Radiation, according to three large randomized clinical trials, reduces the 10-year risk of invasive breast cancer by half, to about 7 percent. Giving tamoxifen, a hormonal treatment, after radiation drops the risk to 3.5 percent. With mastectomy, the 10-year recurrence rate is 1 percent.

In a study published last year in The American Journal of Surgery, Dr. Silverstein followed women with D.C.I.S. who had characteristics suggesting they were at low risk for recurrence. Their tumors were small, they had wide margins (the space between the outermost precancerous cells and the edge of the specimen that was surgically removed), and they were of a low-grade, non-comedo type. The patients were older, so there was less time for recurrence.

After 10 years, Dr. Silverstein found the patients in the low-risk group who had lumpectomy alone had a recurrence rate of 4 percent, a rate so low that radiation would not be indicated, he said.

This study relied on the application of the Van Nuys Prognostic Index, a score based on tumor size, margins, and histologic grade. The new modification now adds the age of the patient. Each factor is assigned a numeric value and they are added together. The abstract:

The original Van Nuys prognostic index (VNPI) was introduced in 1996 as an aid to the complex treatment decision-making process for patients with ductal carcinoma in situ (DCIS) of the breast. This update adds patient age to the previous predictors of local recurrence in breast preservation patients. METHODS: A prospective database consisting of 706 conservatively patients with DCIS was examined using multivariate analysis. Four independent predictors of local recurrence (tumor size, margin width, pathologic classification, and age) were used to derive a new formula for the University of Southern California (USC)/VNPI. RESULTS: In all, 706 patients with pure DCIS were treated with breast preservation. There was no statistical difference in the 12-year local recurrence-free survival in patients with USC/VNPI scores of 4, 5, or 6, regardless of whether or not radiation therapy was used (P = not significant). Patients with USC/VNPI scores of 7, 8, or 9 received a statistically significant average 12% to 15% local recurrence-free survival benefit when treated with radiation therapy (P = 0.03). Patients with scores of 10, 11, or 12, although showing the greatest absolute benefit from radiation therapy, experienced local recurrence rates of almost 50% at 5 years. CONCLUSIONS: Ductal carcinoma in situ patients with USC/VNPI scores of 4, 5 or 6 can be considered for treatment with excision only. Patients with intermediate scores (7, 8, or 9) should be considered for treatment with radiation therapy or be reexcised if margin width is less than 10 mm and cosmetically feasible. Patients with USC/VNPI scores of 10, 11, or 12 exhibit extremely high local recurrence rates, regardless of irradiation, and should be considered for mastectomy, generally with immediate reconstruction or reexcision if technically possible.

A randomized trial is currently underway to examine if radiation can be eliminated from the treatment regimen.
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