Post-lumpectomy radiotherapy reduces long-term recurrence in younger breast cancer patients

Samson, Kurt

Oncology Times UK:
doi: 10.1097/01.OTU.0000393796.62725.a1

    A study presented at the Meeting's plenary session – the largest analysis of all randomised control trials to date in breast-conserving surgery – showed that a short course of radiation after lumpectomy significantly reduced absolute risk of recurrence within 10 years and mortality – but only in younger women.

    A short course of radiation after younger women underwent lumpectomy for breast cancer significantly reduced both their absolute risk of recurrence within 10 years and mortality from the disease, regardless of whether cancer was localised or had spread to adjacent tissue, according to a large review of clinical trial data by British researchers.

    Presented during the plenary session of the American Society for Radiation Oncology Annual Meeting, the study analysis of data on some 10,000 patients showed that adding radiation to breast-conserving surgery in women with node-negative cancer lowered the 10-year absolute risk of recurrence by 14.5%, and 15-year mortality from breast cancer by 3.2%, but the benefit depended on age, tumour grade, and tamoxifen use.

    In women with node-positive disease, the 10-year recurrence risk was reduced by 17.7%, and the 15-year death risk, by 7.8%.

    The findings, by the Early Breast Cancer Triallists’ Collaborative Group (EBCTCG), at Oxford University, add to a growing body of evidence that the addition of radiation can benefit breast cancer patients in mid-life.

    ‘These studies confirm that after a lumpectomy, radiation therapy reduces a woman's risk of her breast cancer returning and her chances of dying of the disease’, said lead author Dr Sarah Darby, professor of medical statistics at the Clinical Trial Service Unit and Epidemiological Studies Unit at the Nuffield Department of Clinical Medicine, Oxford, during a news briefing at the Meeting.

    “We are now able to determine which women will have substantial benefit…and which women will have only a modest benefit. For those who receive substantial benefit, radiation is really life-saving, and reduced the risk of dying from breast cancer considerably.

    ‘For other women, radiation can still decrease the chance of dying by a small amount. I think that all women undergoing lumpectomy would benefit from considering adjuvant radiotherapy.’

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    Early Breast Cancer Triallists’ Collaborative Group

    The EBCTCG reviewed the medical records of 10,906 women who participated in 17 randomised trials of radiation after breast-conserving lumpectomy with a median follow-up of 9.5 years.

    In women with node-negative cancer, radiation therapy reduced the absolute risk of recurrence by nearly 14.5% over 10 years, and absolute mortality after 15 years by 3.2%.

    Some women derived greater benefit from radiotherapy after their breast-conserving surgery than did others, the team found; factors involved included age, tumour grade, the extent of surgery, and tamoxifen use.

    Among women with oestrogen receptor (ER)-positive tumours in trials that included tamoxifen, radiotherapy reduced the 10-year recurrence for women under the age of 40 with high-grade tumours by about 35%, and those with ER-poor tumours by 23%. In women over age 70 with low-grade tumours, treatment reduced the 10-year recurrence risk by about 5%.

    Radiotherapy was also effective in the 1,108 subjects with node-positive disease, reducing the 10-year risk of recurrence by 18%, and the 15-year risk of death by nearly 8% (51.2% to 43.4%).

    Among the 1,108 women with pathologically node-positive disease, radiation reduced the 10-year risk of isolated locoregional recurrence by 30.8%; however the reduction in 10-year risk of any recurrence was 17.7%, primarily because a higher percentage of node-positive women had distant recurrence or contralateral breast cancer as their first event by year 10.

    In the node-positive group, no single factor was independently predictive of the 10-year gain in recurrence risk, Dr Darby said.

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    Only in younger women

    Dr Kevin S Hughes, co-director of the Avon Comprehensive Breast Evaluation Center and medical director of the Bermuda Cancer Genetics and Risk Assessment Clinic at Massachusetts General Hospital, said the paper represented a major step forward, although more work is still needed.

    ‘This is a very important study, and is a major contribution in that it confirms that radiation therapy will increase survival in younger women who have a lumpectomy’, he said.

    However, the headlines that the study has generated have missed the important difference between the ages of women who received survival benefit from the treatment and those who did not, he said in a telephone interview: ‘Most of the headlines have missed the fact that the survival benefits are significant only in younger women. They don't apply to women over 70 with Stage I breast cancer.’

    Although the practice of giving a short course of radiation after breast-conserving lumpectomy is already widespread in the United States, the new data emphasise the survival benefits of this approach in younger women.

    ‘Finding that radiation decreases local recurrence is well accepted. More importantly, this study confirms what radiation has an impact on overall survival for younger women or women with more aggressive cancers. It won't change what most of us are already doing. There is no evidence that we need to change our approach of - avoiding radiation after lumpectomy in older women, but we do need additional research in this specific area’, Dr Hughes said.

    ‘We still need to find out which women over 70, if any, might benefit from radiation. In my opinion, adding radiation to lumpectomy is not always necessary and is a mixed bag in older patients – we simply need to know more.’

    Dr Gary M Freedman, professor of radiation oncology in the Women's Cancer Program and director of the Radiation Oncology Residency and Fellowship at Fox Chase Cancer Center, agreed that the study makes an important contribution to the current treatment milieu.

    ‘Even though the study confirms what is already known – that radiation therapy after lumpectomy reduces the risk of recurrence in the breast by a significant amount in most patients, it represents the largest and best designed analysis of all of the prospective randomised trials on this subject, so it is less subject to bias or undue - influence from any single study’, he explained.

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    Similar to adding endocrine therapy?

    Dr Freedman noted that the survival benefit from adding radiation in node-negative women of about 3% is comparable to what could be expected from adding endocrine therapy in these women.

    ‘This makes radiation of equal importance in most patients; however, the survival benefit from radiation is even greater in higher-risk women with younger age, high grade, or node positive status’, Dr Freedman said.

    The study confirms findings of several earlier single trials, such as one by Dr Hughes and colleagues, published in the New England Journal of Medicine in 2004, that indicated that in some carefully selected women, the benefit of radiation exists, but only in a clinically smaller group.

    Careful selection is based upon older age and node-negative and ER-positive status when endocrine therapy is planned, so that those women may have more of a choice in their treatment whether to ‘opt out’ of radiation, he noted.

    ‘With long-term follow-up, the new study shows that radiation therapy using techniques from the era of the 80s and 90s did not have significant late cardiac effects that reduced the long-term benefits of radiation, as occurred in earlier analyses of radiation from the 60s and 70s, and it is likely that radiation techniques in most places today are superior to those of the 90s’, he said.

    © 2011 Lippincott Williams & Wilkins, Inc.