Tailored RT Approaches Poised to Alter Treatment in Early-Stage Breast Cancer

Jean Wright, MD

Jean Wright, MD

In an era of precision medicine in oncology, individualized approaches with radiation therapy may spare patients with early-stage breast cancer from intensive or unnecessary treatment, said Jean Wright, MD.

"In breast cancer, we no longer view radiation decisions as a one-size-fits-all [approach]," explained Wright. "There is a lot of nuance in terms of deciding the optimal dose, fields that should be treated, and length of treatment, as well as whether or not the patients need radiation at all."

In an interview during the 2020 OncLive^® State of the Science Summit™ on Breast Cancer, Wright, director of the Breast Cancer Program and associate professor of radiation oncology and molecular radiation sciences at Johns Hopkins Medicine, discussed the evolution of radiation oncology in early-stage breast cancer and how novel radiation modalities are poised to transform the field.

OncLive: How has radiation oncology evolved in breast cancer?

Wright: When you look at the era before 2000, there were so many landmark trials that established the role of radiation oncology in the management of curable breast cancer. The role of postoperative radiation therapy in women who have lumpectomy, and the role of postmastectomy radiation for higher-risk patients who have undergone mastectomy, were defined.

At the end of those trials, we ended up with a broad recommendation that if a patient had a lumpectomy, radiation was automatically a component of her [treatment]. If a patient had certain features following mastectomy, she would automatically be recommended for postmastectomy radiation.

In the first 2 decades of the 2000s, a number of key studies posed the question, "Do we have to do things the same for [all patients]?" In the early 2000s, partial breast radiation became an option outside of clinical trials based on published [data]. There was even a national guideline about it. That looked at reducing the dose and minimizing the tissue exposed to radiation treatment.

Another important innovation at that time was hypofractionation. In the early studies, radiation was almost always done in a relatively slow fashion, with a standardized dose per treatment that would take between 6 and 7.5 weeks to deliver.

Some early studies looked at shorter-course radiation with a lower total dose, but a higher dose per treatment. They demonstrated equivalent oncologic outcomes with that shorter course, with less acute and late toxicity. It was another major shift [that informed radiation oncologists] that not all patients need a protracted course.

What are some of the key strategies in current radiation treatment in early-stage breast cancer?

The first theme is further tailoring [radiation], which means looking to reduce the radiation dose and radiation fields. We have a lot of trials trying to refine when [radiation] is safe and appropriate, and for which patients we can further tailor those recommendations.

The second theme is [understanding] in which patients can omit radiation all together. We have a defined subset of low-risk patients who may not need radiation therapy after lumpectomy. Those women are older than 70 years old with low-risk features. The coming decade is looking to identify younger patients who have equally low risk of recurrence. How do we find those women? What types of tests do we need to do to determine who they are?

The third theme is looking at the response to preoperative systemic therapies to guide radiation decisions. In the early studies, [it was thought] that any woman with a certain number of positive lymph nodes should receive radiation. Now, we have a study that asks, "If a patient has lymph node—positive disease, but a good response to preoperative systemic therapy, can [she be spared] postmastectomy radiation or regional lymph node radiation? Can response to chemotherapy help us tailor decisions in that setting?”

Lastly, looking at the ways we use technology to reduce morbidity in breast cancer radiation is an important theme in breast cancer. Protons, for example, is something that everyone is very excited about in radiation oncology.

Could you expand on proton therapy?

Protons have been available in radiation oncology for quite a few decades now, but they have recently garnered a lot of attention. There started off being 2 radiation oncology centers that had protons, but now there are well over 20—and that number is growing.

In breast cancer, the main potential benefit of proton therapy is reducing the radiation exposure to the heart and lungs compared with photon-based techniques. In select cases, the way the radiation dose is delivered confers a lower radiation exposure to the heart and lungs.

There is a large study open at all or almost all of the proton centers across the United States comparing photons and protons for women who need internal mammary lymph node radiation. That subset of patients can have higher cardiac exposure.

For women who do not need lymph node radiation, we are often able to avoid the heart in a way that there is no meaningful difference between photon and proton radiation.

The large study will look at the risk of major coronary events [in patients] over the next 5 to 10 years, with the hypothesis that proton radiation will be associated with a lower risk of cardiac sequelae. It is interesting that a randomized radiation oncology study has a toxicity endpoint rather than an efficacy endpoint.

What data have emerged on this topic?

There have been 2 major studies comparing whole-breast irradiation to partial breast irradiation. One is a Canadian study called RAPID, and the second is the NSABP B-39/RTOG 0413 study from the United States. Both trials utilized a similar approach to compare the therapies.

It requires a lot of nuance to go into detail, but the take-home message, from my perspective, is that whole- and partial breast irradiation appear to be efficacious. The risk of recurrence seems to be roughly equivalent between the 2 approaches. Depending on the subset of patient, partial breast irradiation may have slightly lower efficacy, but that is expected since less tissue is being radiated. The differences are clinically very small, and I don't believe they are meaningful.

These trials lay the groundwork of treating the lumpectomy cavity as opposed to the whole breast. Partial breast irradiation should be considered an absolute standard of care option for many patients. One of those studies showed a slightly inferior cosmetic outcome with partial breast irradiation compared with whole-breast irradiation.

How did the IMPORT LOW study differ from those 2 studies?

The IMPORT LOW study also compared whole-breast irradiation with partial breast irradiation, but it used the same fractionation for the 2 approaches as opposed to RAPID and NSABP B-39/RTOG 0413, which used completely different fractionations. The cosmetic results were far better with partial breast irradiation in this study.

Partial breast irradiation is here and ready for primetime, but questions regarding the appropriate dose and fractionation need to be answered.

The RAPID and NSABP B-39/RTOG 0413 trials used accelerated partial breast irradiation, which is radiation given twice daily over 1 week. It was a condensed course, but it was a very intensive, high-dose treatment. In IMPORT LOW, the treatment was a 3-week course of radiation, similar to what we may do when radiating the whole breast.

There are smaller ongoing studies looking at different dose fractionations to try to define the optimal regimen. Yes, partial breast irradiation is here; yes, it is acceptable, but we need to fine-tune it a bit.

What is your take-home message?

While some of these ongoing trials may not be available at every center, many centers may have 1 or 2 trials available to enroll patients on. We should be considering [clinical trials] for our patients to help us move remaining questions forward.