Postoperative Radiation in Breast Cancer Now a Personalized Process

Susan A. McCloskey, MD

Postoperative radiation in breast cancer has become a personalized process, even enabling physicians to identify patients with ductal carcinoma in situ (DCIS) who have smaller incremental benefits and can potentially omit radiotherapy, says Susan A. McCloskey, MD.

Two studies published in the New England Journal of Medicine (NEJM) that addressed the use of postoperative radiation in patients with breast cancer have been instrumental to the implementation of this personalized approach.

The first trial randomized women with early-stage breast cancer to whole-breast or thoracic-wall irradiation and regional nodal irradiation or whole-breast or thoracic-wall irradiation alone. Approximately 4000 patients enrolled on the trial, 76.1% of whom received breast-conserving surgery. Following mastectomy, 73.4% of patients in both arms received chest-wall irradiation. Ten-year follow up showed overall survival of 82.3% and 80.7% in the nodal-irradiation arm and control arms, respectively. Additionally, disease-free survival (DFS) was 72.1% and 69.1% in the nodal-irradiation group and control group, respectively (HR, 0.89; 95% CI, 0.80-1.00; P = .04).¹

A second trial similarly randomized women with early-stage breast cancer to whole-breast irradiation and regional nodal irradiation or whole-breast irradiation alone. A total of 1832 women participated in the study. Neither arm showed a significant difference in survival, and 10-year follow-up showed respective DFS rates of 82.0% in the nodal-irradiation group and 77.0% in the control arm (HR, 0.76; 95% CI, 0.61-0.94; P = .01).²

OncLive: Please provide an overview of your presentation.

Can you elaborate on some of these data?

In an interview during the 2018 OncLive^® State of the Science Summit^TM on Breast Cancer, McCloskey, assistant professor of radiation oncology, University of California, Los Angeles (UCLA), Jonsson Comprehensive Cancer Center, discussed the use of postoperative radiation in patients with breast cancer.McCloskey: Postoperative radiation is a large topic, and we use radiation in different clinical circumstances—be it after lumpectomy, mastectomy for DCIS, or for more locally advanced invasive disease. I wanted to cover a little bit about all of those clinical scenarios to inform the audience of situations in which radiation is appropriate to consider, when it may be appropriate to forego, and how we can tailor our radiation recommendations to the population at hand. I also spoke about some technological advances that make radiation a much better experience than it has historically been for women.The thing that is striking to me is that there have been many recent advances, across the spectrum of clinical scenarios, in which we give radiation. Physicians have identified the subsets of women with early-stage disease with DCIS who have smaller incremental benefits and can potentially benefit from the omission of radiation therapy.

Physicians have come a long way in informing postmastectomy radiation recommendations. If anything, physicians are using radiation a bit more commonly, but they are also aiming to tailor it more to risk factors, individualized decision making, and patient preferences so that we can inform our patients, help them weigh the pros and cons, and come to a decision.

Several studies have helped tailor recommendations. Two NEJM articles were published looking at regional nodal radiation. It's unusual for us; we are a small field, so to make it into NEJM and have those articles come out has helped physicians tailor how much radiation to give and which areas are treated; it’s been a big advance. Technologically, there have been so many advances.

How have the NCCN guidelines impacted practice?

Which patients are most likely to benefit from postoperative radiation?

I published a study [recently] where we interviewed women who had been through radiation therapy [for breast cancer]. We asked about baseline fears and expectations and then interviewed them about 6 months or longer out from their experience to ask whether or not their fears lived up to reality. There were such beautiful data in terms of women saying, “Sure, if women knew the truth they would be less fearful,” and, “I had much fewer short- and long-term side effects than I anticipated.” I've gotten great feedback from women that hearing from other women who have been through the process has helped alleviate their fears.We all reference NCCN guidelines, so these various trials that I've spoken about that are helping to hone our indications for radiation. They then get represented in guidelines to help us make decisions.Women who have early-stage invasive breast cancer who are under the age of at least 65, if not 70. Women who are younger certainly benefit tremendously from radiation. Radiation remains the standard of care to complete breast conservation after lumpectomy for all women with invasive breast cancer; it’s a circumstance that's widely accepted. Women with higher-grade DCIS, or larger-volume DCIS certainly benefit from radiation [as well].

Can you speak to the use of accelerated partial breast irradiation?

Women who have larger primary tumors or node-positive breast cancers after mastectomy certainly benefit. There are indications across the board. We use radiation in the metastatic setting, as well for palliation and increasingly to try to be part of definitive therapy. All stages and presentations seem to benefit from radiation in those select subsets I mentioned before that we can try to start to forego radiation in, [so that we don’t have to] unnecessarily subject them to it.In accelerated partial breast irradiation, there was a change in the guidelines. The updated guidelines [have enabled us] to apply accelerated partial breast irradiation to a larger population of women than [we could] previously. Prior ASTRO consensus guidelines recommended that it be used specifically in women over the age of 60. Women with DCIS were in a cautionary category. Now, women over the age of 50 are eligible.

Are there any other potentially transformative clinical trials examining the use of radiation?

Is there anything else you would like to emphasize?

There are clearly other criteria, in which they have to have node-negative breast cancer, small tumor size, and favorable overall disease. Now that the age criteria have changed, women with small, lower, intermediate-grade DCIS are also candidates for accelerated partial breast irradiation per the guidelines; it’s certainly evolving. We are still waiting on the large randomized trial that will help influence and decide this once and for all.There have been less practice-changing phase III randomized trials in the postmastectomy setting. Some of [the information] that has helped us hone our radiation recommendations is meta-analysis. There will definitely be randomized trials looking at women with low- or intermediate-grade DCIS that is of small volume, or T1, node-negative invasive breast cancer in women over the age of 70 with estrogen receptor—expressing disease that demonstrates a benefit to radiation. However, there is a small overall incremental benefit. It's those subsets where we think we can start to forego radiation safely with informed decision making with the patient.The study that we did has been truly informative for me to see just how much fear and misinformation there is in the general population about radiation. In our study, 60% of women said they were not at all familiar with radiation, but 50% of women were worried about the harmful adverse events (AEs) of radiation. To see those numbers and then see women [report] having a better experience than [anticipated] is attributable to tremendous technological advances.

I spoke on ways we can protect organs from radiation and homogenize or make the dose even to temper skin reactions and acute AEs. Damage to normal organs and skin reactions were the number 1 and 2 fears that women reported. Technological advances have helped us so much. As the guidelines evolve and we know who benefits from radiation, we can give [patients] the best and most tailored, most AE-reducing, convenient treatment courses of radiation.

References

1. Poortmans P, Collette S, Kirkove C, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;373:317-327. doi: 10.1056/NEJMoa1415369.
2. Whelan T, Olivotto I, Parulekar W, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307-316. doi: 10.1056/NEJMoa1415340.