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Radiation After Breast-Conserving Surgery Cuts Recurrence

Janis C. Kelly

October 20, 2011 — Long-term data from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) confirm initial reports that radiotherapy can halve recurrence risk and substantially reduce the risk for cancer death in women with breast cancer treated with breast-conserving surgery.

The updated EBCTCG report was published online today in theLancet.

Lead author Sarah C. Darby, MD, from the Clinical Trials Service Unit at the University of Oxford, United Kingdom, told Medscape Medical News that the new data confirm and extend the conclusions from earlier studies. “The substantial reduction in mortality conferred by radiotherapy is an important confirmation of previous results,” Dr. Darby said.

“At the moment, most protocols specify that radiotherapy should be given to all patients after breast-conserving surgery,” she explained. “However, for some time, doctors have been wondering whether it is really necessary for all women. These findings will enable both doctors and patients to have a better idea of the benefit that is likely to be gained from radiotherapy on a patient-by-patient basis. Thus, it is likely that as a result of this paper, some women will be given radiotherapy who would not otherwise have had it; it is also likely that some women will not be irradiated who would otherwise have been. In due course, the findings may be reflected in treatment protocols.”

Ian H. Kunkler, MD, from the Department of Clinical Oncology at the University of Edinburgh, Scotland, reviewed the study for Medscape Medical News. He was principal investigator on a different trial of postoperative radiotherapy in breast cancer (the PRIME II study).

“The implication from this EBCTCG study for clinical practice is that it confirms current consensus that there is no group of patients from whom radiotherapy can omitted after breast-conserving surgery, although the absolute benefit in low-risk older patients treated with tamoxifen after breast-conserving surgery is very small,” Dr. Kunkler said.

The analysis involved 10,801 women who participated in 17 trials of radiotherapy after breast-conserving surgery that have been carried out worldwide. These included trials of lumpectomy and of sector resection or quadrantectomy. Median follow-up was 9.5 years, and 25% of the patients were followed for more than 10 years.

The reduction in cancer recurrence became apparent in the first year after radiotherapy, and was sustained throughout the first decade. Ten years after a breast cancer diagnosis, 35% of the women who did not have radiotherapy had a recurrence, compared with only 19% of the women who had radiotherapy — an absolute risk reduction of 15.7% (P < .0001).

First recurrences were locoregional in half of the women who received radiotherapy but in nearly three quarters of the women who did not receive radiotherapy.

The 15-year absolute risk reduction for breast cancer death was 3.8% with radiotherapy (P = .00005), which suggests that on average 1 breast cancer death is avoided for every 4 recurrences avoided by radiotherapy, the authors write. In addition, radiotherapy did not increase the 15-year risk for death from causes other than breast cancer.

“The overall findings from these trials show that radiotherapy after breast-conserving surgery not only substantially reduces the risk of recurrence, but also moderately reduces the risk of death from breast cancer. These results suggest that killing microscopic tumour foci in the conserved breast with radiotherapy reduces the potential for both local recurrence and distant metastasis,” the authors conclude.

According to Dr. Darby, one surprise was that radiotherapy greatly improved 10-year recurrence risk even in young women with high-grade estrogen-receptor-positive tumors and even if they were taking tamoxifen.

In an accompanying comment, Thomas A. Buchholz, MD, head of the division of radiation oncology at the University of Texas M.D. Anderson Cancer Center in Houston, writes: “The data from many thousands of clinical trial patients reviewed by the EBCTCG investigators continue to provide us with crucially important insights. The data reinforce the important role that radiotherapy has in management of breast cancer, and the fact that the benefits of radiation are complementary to the advances in both surgery and systemic treatment is particularly rewarding. The incremental benefits of each component of treatment contribute to the ongoing success in reduction of breast cancer mortality rates.”

Dr. Kunkler noted that “the latest Oxford overview provides important longer-term data, confirming the impact of locoregional radiotherapy after breast-conserving surgery on reducing recurrence and breast cancer mortality. The benefit of radiotherapy exceeds that of adjuvant chemotherapy alone or hormonal therapy alone.”

He explained that because the study includes few patients older than 70 years, the generalizability of the data to this low-risk subgroup of women is limited. “Indeed, the events per woman-year in the 70 or older group without radiotherapy are relatively low (2.1%). This older group also has the competing risk of nonbreast cancer mortality (mainly vascular),” he said.

Dr. Kunkler also pointed out that the paper reports no data on HER2 status. “An international priority is to identify the molecular characteristics of a very-low-risk older population that could be spared the burden and toxicity of several weeks of adjuvant radiotherapy after breast-conserving surgery and tamoxifen,” he said.

Dr. Darby, Dr. Buchholz, and Dr. Kunkler have disclosed no relevant financial relationships.