Tailor DCIS Treatment to Cancer Recurrence Risk

OB/GYN News,  March 15, 2000  by Bruce Jancin

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SAN ANTONIO -- The emerging trend in management of ductal carcinoma in situ is to tailor treatment intensity to the level of an individual's recurrence risk, Dr. Monica Morrow said at a breast cancer symposium sponsored by the San Antonio Cancer Institute.

"What we're beginning to see with DCIS is, I think, a picture similar to what we now have with invasive breast carcinoma," said Dr. Morrow, professor of surgery and director of the Lynn Sage Comprehensive Breast Cancer Program at Northwestern University, Chicago.

"DCIS is a continuum of diseases with different levels of risk," she noted. "So it doesn't make any more sense to assume that all DCIS can be treated with excision alone, or that all DCIS must be treated with excision, radiation, and tamoxifen, any more than it would make sense to say that all patients with invasive breast carcinoma must be treated with mastectomy, chemotherapy, and tamoxifen."

Dr. Morrow also outlined her current management approach to another extremely common premalignant breast lesion, atypical hyperplasia. She emphatically favors tamoxifen over prophylactic mastectomy as a means of reducing risk in women who find their calculated risk of invasive breast cancer unacceptable.

With regard to DCIS, everyone wants to know this: Do all women with mammographically detected lesions benefit from adjunctive radiotherapy to the ipsilateral breast, as suggested by National Surgical Adjuvant Breast and Bowel Project study [NSABP] B-17, or is excision and observation sufficient in a subset of patients?

A recently updated subset analysis of B-17 provides useful guidance on this score, the surgeon continued.

In NSABP B-17, 818 women with DCIS underwent lesion excision to a negative margin and were then randomly assigned to radiotherapy or no treatment. At the 8-year follow-up, those who received radiation had significantly lower rates of both invasive and noninvasive breast carcinoma.

The subset analysis showed that the only independent predictor of ipsilateral breast tumor risk during follow-up was comedo necrosis; nonirradiated patients with moderate to marked comedo necrosis had a far greater risk than those with slight to no comedo necrosis (Cancer 86[3]:429-38, 1999).

Dr. Morrow uses the B-17 data in counseling patients. She informs those with minimal or no comedo necrosis and negative surgical margins that by undergoing postoperative radiotherapy they can expect only a small further reduction in risk of recurrence: an absolute 7% decrease at 8 years, as indicated by the B-17 trial results. Some patients consider that benefit worth the cost of radiation therapy; others do not.

The other important patient decision in DCIS involves whether to go on tamoxifen. Here the 1,804-patient NSABP B-24 trial is helpful. Following DCIS excision and ipsilateral breast radiotherapy, those who were randomly assigned to 5 years of tamoxifen had an 8.2% rate of all breast cancer events, compared with 13.5% in those who received placebo (Lancet 353[9169]:1986-87, 1999).

The relative reduction in recurrence rate associated with tamoxifen was equal in younger and older patients, but women under age 50 had a larger absolute benefit because their recurrence rate without tamoxifen was higher: 33 events per 1,000 patients per year, compared with 13 events per 1,000 patients per year in women age 50 or older.

Several studies have shown that tamoxifen blunts the sharply elevated risk of local failure present in women who have positive tumor margins following excision.

Consultants have been fielding numerous questions lately from patients and physicians about a widely publicized report by Dr. Melvin J. Silverstein of the University of Southern California. It concluded that postoperative radiotherapy is of no benefit in lowering the recurrence rate in patients whose DCIS is excised with margins of 10 mm or more (N. Engl. J. Med. 340[19]:1455-61, 1999).

Dr. Morrow said that this report hasn't affected her management strategy for two reasons. First, margins greater than 10 mm aren't cosmetically feasible in many patients; with a 15-mm DCIS, for example, surgeons would have to take out a piece of breast tissue at least 35 mm in diameter.

Second, the Silverstein study is neither randomized nor prospective; rather, it's a series of patients collected at two centers over 20 years. As such, the findings can only be regarded as exploratory, she said.

Turning to atypical hyperplasia, Dr. Morrow said that the first order of business is for a physician to use the Gail formula to calculate an affected woman's 5-year and lifetime breast cancer risks based upon the known major risk factors.

If the patient finds her calculated risk level unacceptable, one option is prophylactic mastectomy But Dr. Morrow considers that too extreme. "We virtually never suggest prophylactic mastectomy to someone with atypical hyperplasia unless they have multiple other risk factors."

Instead, she directs patients to consider the NSABP P-1 trial, which included roughly 1,100 women with atypical hyperplasia. Randomization to 5 years of tamoxifen reduced their breast cancer risk by roughly 85%. "For the high-risk patient, this is an excellent and certainly less morbid alternative to prophylactic mastectomy," she said.

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