Navigating Personalized Approaches With Radiation Therapy for Early-Stage Breast Cancer

We sat down with Robert W. Mutter, MD, at the 2024 ACRO Summit to get an inside look at his presentation on partial breast irradiation in early-stage breast cancer.

In the interview, Mutter emphasized the importance of considering each patient's unique perspective, priorities, and risk-benefit evaluations regarding treatment options using radiation therapy and endocrine therapy, and highlighted research into de-intensifying surgery and the omission of certain treatments, and urged the use of multidisciplinary approaches to inform treatment decision-making.

He underscored the significance of long-term follow-up data from clinical trials, particularly in understanding the benefits and drawbacks of radiation therapy and endocrine therapy, to better counsel patients. Mutter previously provided further insights into the evolving treatment paradigm of early-stage breast cancer. Mutter is the chair of research in the Department of Radiation Oncology, as well as an associate professor of radiation oncology and an associate professor of pharmacology at the Mayo Clinic in Rochester, Minnesota.

OncLive: What is the benefit of a personalized treatment approach for patients with early-stage breast cancer?

Mutter: When I speak with patients, each one is different. They all have their individual evaluation of the risks and benefits of treatment, and how one [patient] prioritizes local control might be different from another patient who prioritizes minimizing all AEs. We're trying to encourage [the consideration of] the patient perspective in the context of research and in discussing these various treatment options.

It's important that patients be aware of the option of radiation therapy, as well as the option of omission of radiotherapy. Similarly, with endocrine therapy, there are several different endocrine therapy approaches, and in some patients, it may be reasonable to omit endocrine therapy altogether as well, just like radiation therapy, especially in older populations.

There is a lot of research ongoing now in terms of de-intensifying surgery, such as the omission of central lymph node biopsy in these patients. We're encouraging multidisciplinary care and making patients aware of all their treatment options so that they can make the best decision for themselves.

What should your colleagues be aware of when treating patients who are candidates for partial breast irradiation?

I want colleagues to be aware of the long-term benefits of radiation. There has been a lot of research into ways to omit radiation. What I really want colleagues to be aware of now that we have long-term follow-up from clinical trials like the [randomized] CALGB 9343 study, as well as the phase 3 PRIME II study [ISRCTN95889329], I want colleagues to see the whole picture of the pros and cons of radiation therapy. It's important to help them counsel patients going forward.

Similarly, with endocrine therapy, I want them to be aware of both the AEs, as well as some of the adherence issues, so that we can better counsel patients for all the treatment options available to them.

What dosing regimens do you use in your own practice for this type of treatment approach?

Now that we have the long-term results of several randomized trials, which have used various partial breast irradiation techniques, as well as various dosing regimens, the question arises about which regimen is best for each patient. One of the things I proposed in my talk [at the 2024 ACRO Summit] is that a regimen of 26 Gy in 5 fractions should be considered a great option for partial breast irradiation delivery.

Even though [this regimen] has not been studied independently in the context of a partial breast irradiation trial, we know that this regimen is non-inferior to 3 weeks of whole breast radiation in the phase 3 FAST-Forward trial [ISRCTN19906132]; it was non-inferior in terms of disease control and in terms of AEs. It’s very reasonable to extrapolate from that data and offer that regimen for partial breast irradiation because it was so effective in the context of whole breast irradiation.

We also know from the phase 3 IMPORT LOW trial (ISRCTN12852634) that with the 3-week regimen for whole breast irradiation, we can tighten the volumes to have equivocal local control by giving that regimen with a partial breast technique. Extrapolating for both these trials, the IMPORT LOW and FAST-Forward trials—one being a partial breast study and one a whole breast study—even though that 26 Gy in 5 fractions regimen has not been studied directly in the context of partial breast irradiation, that option of a mini-tangent technique is a great one for patients to consider.

How would you approach the use of radiation in patients with higher-risk disease?

For higher-risk patients, those where we might consider boosting the lumpectomy cavity, if we're treating with whole breast irradiation, some doctors may prefer to administer a higher dose. We know that 40 Gy in 15 fractions is biologically equivalent to that dose of 26 Gy in 5 fractions. For patients that we might consider boosting in the context of that 40 Gy in 15 fractions regimen, a good option is to administer 6 Gy in 5 fractions.

That regimen comes from the randomized phase 3 APBI-IMRT-Florence trial [NCT02104895] of partial breast irradiation randomized trial. Six Gy in 5 fractions is a great option for patients with higher-risk features who we might normally consider a boost dose for partial breast delivery. However, if they have favorable features, such as patients who were enrolled into the IMPORT LOW trial—meaning tumors that are 2 cm or smaller, grade I to II, and hormone receptor–positive, node-negative disease—those patients probably don't need that aggressive 30-Gy dosing. We just give 26 Gy in 5 fractions, and that will likely lead to the least risk for the patient in the long-term in terms of AEs.

Reference

Mutter RW. Partial breast irradiation and early-stage breast cancer: known knowns, known unknowns and unknown unknowns. Presented at: 2024 ACRO Summit; March 13-16, 2024; Orlando, FL.