Radiotherapy for Early Breast Cancer and 1 to 3 Positive Nodes

Zosia Chustecka

March 19, 2014

GLASGOW, Scotland — For women with early breast cancer who undergo mastectomy and axillary dissection, radiotherapy is recommended for those who are found to have 4 or more positive lymph nodes, but is not usually given to women who are found to be node-negative.

However, for the women who fall into the gray area in between, who are found to have 1 to 3 positive axillary nodes, there has been insufficient evidence to make a recommendation one way or another.

Now there are data to show that radiation is also beneficial in this group.

The results were presented March 19 here at the 9th European Breast Cancer Conference, and published online simultaneously in the Lancet.

The finding comes from a meta-analysis of individual data for a total of 8135 women participating in clinical trials who were followed for an average of 11 years; 1314 of these women were found to have 1 to 3 positive nodes.

The results for this subgroup of women showed that postmastectomy radiotherapy significantly reduced both recurrence and breast cancer mortality, even when systemic therapy was given.

The meta-analysis was conducted by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG), and presented at the meeting by Paul McGale, PhD, senior statistician at the University of Oxford, United Kingdom.

In women who had 1 to 3 positive nodes, postmastectomy radiotherapy reduced the recurrence rate by 32% and reduced the breast cancer mortality rate by 20%. The benefit was similar whether women had only 1 positive node or whether they had 2 or 3 positive nodes.

"Giving radiotherapy to these women led to nearly 12 fewer recurrences per 100 women after 10 years and 8 fewer deaths per 100 women after 20 years," Dr. McGale said in a statement.

The results from the meta-analysis also confirmed previous findings of benefit from radiotherapy for women with 4 or more positive nodes, and the lack of benefit for women with node-negative disease.

For women with 4 or more positive nodes (n = 1772), the meta-analysis showed that radiotherapy reduced overall recurrence by 21% and breast cancer mortality by 13%. In other words, radiotherapy for these women led to 9 fewer recurrences per 100 women after 10 years, and 9 fewer breast cancer deaths per 100 women after 20 years.

These results are statistically similar to those found for the subgroup of women with 1 to 3 positive nodes, commented coauthor Carolyn Taylor, FRCR, a clinical oncologist at Oxford University Hospitals and a clinical research fellow at the University of Oxford. She noted that the women with more positive nodes would be at a higher risk for recurrence, but the proportional reduction in risk was similar to that seen in women with fewer positive nodes.

In this meta-analysis, a total of 5821 women had node-positive disease; of these, 3131 (54%) had axillary dissection (defined as removal of axillary lymph nodes in at least levels I and II) and 2541 (44%) had axillary sampling (less extensive axillary surgery), while for 149 (2%), the extent of axillary surgery was unknown.

The meta-analysis also confirmed that there was no significant benefit from radiotherapy for women who were found to be node-negative (n = 700). "There was no evidence that radiotherapy provided any benefit" in this group, the researchers write.

Benefit Seen Regardless of Chemotherapy

"Another result from our study is that the proportional benefits of radiotherapy were similar in women regardless of whether or not they had also received chemotherapy or hormonal therapy," Dr. McGale said. The most common chemotherapy used in the trials was cyclophosphamide, methotrexate, and fluorouracil, and the most common hormonal therapy used was tamoxifen

"This is important because most women today receive these therapies. Our results suggest that women being treated today are likely also to benefit from radiotherapy if they have any positive lymph nodes," he added.

The meta-analysis included trials that were conducted between 1964 and 1986.

"Since the time when the women in these trials were randomized, there have been advances in radiotherapy and also in breast screening, surgery, lymph node staging, and systemic therapy," Dr. McGale commented. "So the absolute benefits from postmastectomy radiotherapy today may be smaller than those we have reported here. But the proportional benefits from radiotherapy are likely to be at least as big."

The same point was highlighted by Dr. Taylor. "In recent years, larger numbers of women with just a few positive lymph nodes have received chemotherapy, and the types of chemotherapy have changed. Also, the vast majority of women with hormone-sensitive tumors are now given hormonal therapy."

In addition, radiotherapy techniques have improved in the past few decades, and women today receive better coverage of target areas, and doses to normal tissues are likely to be lower, the researchers point out.

"We will have to wait for results from new trials to observe directly the long-term effects of modern radiotherapy in women who are given modern chemotherapy and hormonal therapy," Dr. Taylor said.

"However, it is likely that the percentage reductions in disease recurrence and breast cancer mortality from today's radiotherapy will be at least as big as the benefits seen here," Dr. Taylor commented.

Best Guide Currently Available?

Until the new trials are completed, these data from the meta-analysis "might be the best guide that is currently available to help estimate the likely absolute benefits from radiotherapy in women today," the authors write.

These data are likely to apply to women being treated today.

In an interview with Medscape Medical News, Dr. Taylor emphasized that the new finding was for women with 1 to 3 positive nodes, a subgroup for which there had been little information about previously. The results from the meta-analysis show that the proportional reduction in both breast cancer recurrence and mortality did not vary according to whether or not the women received chemotherapy and/or hormonal therapy, and also it did not vary according to the number of nodes that were positive. "So these data are likely to apply to women being treated today," she said.

"What will be different is the absolute risk reduction, because women today get better detection with screening and better treatment with chemotherapy and local targeted agents, so their absolute risks of recurrence are likely to be much less than was seen in the women participating in these trials," she explained. "But we can apply those proportional benefits to work out the absolute gains for women who are being considered for postmastectomy radiotherapy," she added.

When asked whether postmastectomy radiotherapy should now be recommended for all women with 1 to 3 positive nodes, Dr. Taylor emphasized the need to assess each patient individually.

The benefit that an individual woman will get will depend on what her risk for recurrence is in the absence of radiotherapy, she said. "So, for example, for a woman with 3 positive nodes and a large high-grade tumor, her risk of recurrence is high and she would be likely benefit from radiotherapy. But for a woman with 1 positive node and a lower risk of recurrence, I as a clinician would need to work out her risk of recurrence in the absence of radiotherapy, and then I would use the proportional reduction in risk from this study to work out her gain from radiotherapy, because as a clinician I am always balancing up the risks of the treatment versus the benefits."

Each clinician would need to similarly weigh the risk and benefit for the patient that is facing them, she said, but the results from this meta-analysis would suggest that most women with 1 to 3 positive nodes would benefit from radiotherapy.

The study was funded by Cancer Research UK, the British Heart Foundation, and the UK Medical Research Council.

Lancet. Published online March 19, 2014. Abstract

9th European Breast Cancer Conference (EBCC-9): Abstract o-202. Presented March 19, 2014.


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