MIAMI BEACH – Adding radiotherapy and tamoxifen to breast-conserving surgery significantly reduces the local recurrence rate and the breast cancer–specific death rate in women with ductal carcinoma in situ, according to a systematic review and meta-analysis.

The review of 22 studies with a minimum of 10-year follow-up data showed that surgery plus radiation therapy nearly halved the rate of ipsilateral local recurrence from 23.5% with surgery alone to 13.5%, and the addition of tamoxifen cut the rate even further, to 9.2%.

The addition of tamoxifen to surgery and radiation also reduced breast cancer death rates from 3.1% without the drug to 1.5% with it, reported Dr. Kirsty Stuart of the Westmead Breast Cancer Institute at Westmead Hospital in Sydney, Australia.

"DCIS [ductal carcinoma in situ] treatment, however, will ultimately depend on the individual patient, their general condition, their tumor, and their fears," she told attendees at the annual meeting of the American Society for Radiation Oncology.

Dr. Stuart and colleagues conducted a meta-analysis of published randomized or nonrandomized trials of long-term outcomes in DCIS to determine the benefits of adjuvant radiotherapy and tamoxifen, a selective estrogen receptor modulator. The subjects all had pure DCIS with a minimum of 10-years’ follow-up, with data on treatment type and local recurrence. All studies were peer reviewed.

The investigators defined local recurrence as subsequent ipsilateral breast or chest wall disease (DCIS or invasive), and calculated the breast cancer death rate as the number of deaths from breast cancer divided by the total number of DCIS cases.

They identified a total of 22 qualifying studies dating from 1974 through 2011 with 6,167 patients. In all, 4.9% of patients had mastectomies, 51.8% had conservative surgery plus radiation, 41.2% had conservative surgery alone, and 2.1% had biopsy alone.

Among all cases, ipsilateral local recurrence was seen in 3.3% of mastectomy patients, 13.5% of patients who had surgery and radiation, 23.5% of surgery only patients, and 35.1% of biopsy only patients. Between-treatment comparisons showed that mastectomy was significantly better than each of the forms of therapy, both at preventing all cases of ipsilateral local recurrences and all cases of invasive local recurrence.

Looking at the addition of tamoxifen to surgery with or without radiation, the authors found that the drug significantly reduced the rate of local recurrence, from 24.1% with surgery alone to 19.8% with surgery and tamoxifen, and from 14.9% for the surgery/radiation combination to 9.2% for the two modalities plus tamoxifen.

Between-treatment comparisons showed that adding tamoxifen to radiation and surgery significantly improved recurrence rates over surgery plus radiation (P = .037), surgery plus tamoxifen (P = .0086), or surgery alone (P less than .000001). Compared with surgery only, the relative risk for invasive local recurrence was 0.71 for surgery plus tamoxifen, 0.63 for surgery plus radiotherapy, and 0.35 for all three treatments.

Invasive breast cancer death rates were also significantly lower when tamoxifen was added to surgery and radiation, decreasing from 8.4% without the drug to 4.3% with it.

"From the pooled data, conservative surgery alone for DCIS has a high recurrence rate that is partly reduced with tamoxifen," Dr. Stuart said.

"DCIS treatment will ultimately depend on the individual patient, their general condition, their tumor, and their fears."

"Conservative surgery plus radiation therapy almost halves the ipsilateral recurrence rate, and has a breast cancer death rate that is equivalent to that of the mastectomy population.

"Conservative surgery and radiation therapy plus tamoxifen halves the invasive local recurrence rate, from 8% to 4%, and halves the breast cancer death rate, from 3% to 1.5%."

In a separate study Dr. Julia Wong of the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, both in Boston, presented 8-year follow-up data on wide-area excision alone in 132 patients treated for DCIS. The investigators found that 19 patients had a local recurrence. The cumulative 8-year local recurrence rate was 14.4%. A total of 13 of the recurrences were DCIS, and 6 were invasive disease. All but one of the recurrences was detectable by mammogram, and one was palpable.

A total of 14 of the recurrences were in the same quadrant as the original tumor, and 5 were elsewhere in the same breast. Of the six patients with invasive disease, none had axillary involvement, and no patients developed distant metastases.

Other events seen in the study included 13 contralateral breast cancers (4 DCIS, 9 invasive), 1 other cancer, and 3 deaths from other causes.

"Even in this highly selected group of patients with small grade 1 or 2 DCIS treated with wide excision alone and margins 1 cm or greater, there is a substantial local recurrence rate, especially in the same quadrant," Dr. Wong said.

The meta-analysis was internally funded. Dr. Stuart reported having no relevant financial disclosures. Dr. Wong’s study was funded by participating institutions. Dr. Wong reported no other relevant financial disclosures.

Multimodal DCIS Therapy, Tamoxifen Cuts Breast Cancer Deaths