Radiotherapy for Hormone-Positive Breast Cancer Patients Over 65

Today we are discussing the role of radiotherapy as treatment for women aged 65 and older with hormone-positive breast cancer. We are joined by Dr. Ian Kunkler, professor of clinical oncology at the Edinburgh Cancer Research Center at the University of Edinburgh, United Kingdom. Dr. Kunkler presented data from the PRIME 2 trial which tested whether women with axillary node-negative, hormone receptor–positive breast cancer who are treated with hormone therapy following breast-conserving surgery, benefit from additional radiotherapy. Dr. Kunkler presented results from this trial at the annual San Antonio Breast Cancer Symposium.

-Interviewed by Anna Azvolinsky, PhD

Cancer Network: Could you describe the rationale and the design of the PRIME 2 study?

Dr. Kunkler: Post-operative radiotherapy has really been the standard of care for all patients after breast-conserving surgery and hormone therapy irrespective of age and risk, but now older patients represent a significant proportion of patients presenting in the clinic. Over 50% are now over the age of 65 and in many of those patients, breast cancer has a relatively benign cause, and in some of those patients at low risk, radiotherapy may represent overtreatment. We have relatively sparse evidence of the role of radiotherapy in older patients. We have a tendency to extrapolate results from younger patients. The role of the trial was to assess the impact of radiotherapy in a low-risk, older population. Those who were eligible for the study were 65 or older, had breast-conserving surgery with clear margins, were either estrogen receptor– or progesterone receptor–positive, were receiving adjuvant endocrine therapy, and were histologically node negative. We excluded patients who were under 65 or who had a combination of grade 3 histology and vascular invasion.

Cancer Network: What did the results of this study show?

Dr. Kunkler: What we presented were the 5-year actuarial local recurrence at 5 years, which showed that in the group without radiotherapy there was a risk of recurrence of 4.1% compared to 1.3% in the irradiated group. We also carried out a subset analysis according to estrogen receptor status, which showed that the benefits of radiotherapy were even smaller in those with estrogen receptor–rich tumors. So we had a local recurrence rate in the no radiotherapy group of 3.2% compared with 0.8% in the radiotherapy group, an absolute difference that is quite modest, of 2.4%. What we also observed was that in the group of low estrogen-receptor status, category 2 to 6, there was a relatively high number of recurrences in the no-radiotherapy group (11% in all, representing 20% of all events in the trial), suggesting that that is a group with low estrogen receptor from which radiotherapy should not be omitted.

Cancer Network: In your opinion, what is the impact to clinical practice as a result of this study?

Dr. Kunkler: I think that what it suggests is that there is a low-risk group of patients for which now the omission of radiotherapy is an option. I think it will be up to clinicians to decide whether the absolute benefits are sufficient to justify the continuation of radiotherapy in that subgroup.

Cancer Network: Are there differences in the use of radiotherapy in the United Kingdom compared with the United States?

Dr. Kunkler: Broadly, practice is the same in the United States and in the United Kingdom, and at the moment there is no specific subgroup from which radiotherapy has been systematically omitted. This might be a study that acts as the tipping point to change practice.

Cancer Network: Are there follow-up studies now that are ongoing or being planned that will further address the role of radiotherapy in treating women with any type of breast cancer?

Dr. Kunkler: Clearly, one of the important things is to see whether we can develop a molecular signature to identify patients who are genuinely low risk, and a trial like the PRIME trial may be one in which such a molecular signature could be tested.

Cancer Network: Thank you so much for joining us today, Dr. Kunkler.

Dr. Kunkler: A pleasure.