New Era of Personalization in Breast Radiation: A Conversation With Dr. Wendy Woodward

For years, the "daily grind" of breast cancer treatment meant six weeks of hospital visits — a significant burden on a patient's time, finances and emotional well-being. However, the tide is turning. In this interview, Dr. Wendy Woodward, a radiation oncologist at The University of Texas MD Anderson Cancer Center, discussed the transformative rise of hypofractionated radiation, which is condensing treatment into just one to three weeks for many patients.

While the trend toward de-escalation offers newfound freedom, Woodward emphasized that shorter is not always better. For those with aggressive T4 tumors or inflammatory breast cancer (IBC), the tried and true conventional schedules remain the gold standard for cure. From leveraging cholesterol metabolism as a future biomarker to "throwing the kitchen sink" at stage 4 disease, Woodward explored how the field is balancing the convenience of modern technology with the precision required to save lives.

Woodward is a Professor and the Chair, ad interim of the department of Breast Radiation Oncology at The University of Texas MD Anderson Cancer Center.

CURE: One of the biggest burdens for patients has historically been the daily grind of several weeks of treatment. With the rise of hypofractionated radiation, how has the typical patient experience changed recently? And are there specific patients who still benefit from a more traditional schedule?

Woodword: Shorter courses make things easier. It's cheaper, it's less time away from your life, it's less burden. So patients, even those who are eligible to omit radiation, will often now choose it because five fractions seems very doable and they'd rather not give up a little bit of benefit in reducing risk when it's pretty easy to get it. The vast majority of patients need their regional nodes treated, so patients who have more advanced-stage breast cancer, can now be treated with three to four weeks of radiation instead of five to six.

So, I think overall, things have gotten easier, and that trend continues. There's an active study in whether or not four (weeks) can be three and three can be two, and just trying to really continue to demonstrate what is the fastest, safest, equally effective option. So I think that's all been really well received by patients.

There are patients who still benefit from conventional fractionation at the end of the day. Patients are not looking for you to offer them something easy that isn't as good. They come wanting the confidence that we're going to do everything we can to cure their cancer, and for things that are more aggressive, patients who have what are called T4 breast cancers — meaning that they involve the skin or the chest wall — or patients who have disease in advanced lymph nodes that need additional radiation dose because they're not going to be removed by surgery, the vast majority of data that we have for efficacy in that space is still with conventional fractionation.

There is one randomized trial which demonstrates equivalent efficacy for hypofractionation in patients who had more advanced disease. It's a Chinese randomized study, and it looks to be completely equivalent, but it's worth noting that the dose they used is a little bit higher to make it equivalent to that five-to-six-week radiation, and that's not the standard hypofractionated dose. So, I think there may be strategies to make even the more complicated breast cancer courses a little bit shorter, but it's not one size fits all. It really deserves some careful attention and maybe some more data.

I think one of the things that came as a surprise is that one of the randomized studies, the Scoggins study, presented outcome data for the first time at one of the meetings in the past year, and demonstrated that the outcome wasn't as good, and it was a little hard to understand why all of the pieces didn't really point in a clear direction. It didn't halt the progress of hypofractionation, but it does remind you that we are still collecting outcome data, and we want to be as direct and transparent about what we know and what we don't know and where it really has been well tested and where it's still a little bit emerging.

For a patient sitting in your office today, how close are we to using biological markers like tumor microenvironment and cholesterol metabolism to personalize radiation dose and perhaps give less to some and more to others?

I would say we do a lot of personalization in thinking about biology of tumors. So, the biomarkers we use today are based on receptor status. They're based on genomic tests like oncotype and other measures of patient-specific tumor that have been shown to correlate with outcome and can help you to understand is this more aggressive or less aggressive tumor, and should I do more or less here? So, I think that kind of nuance and personalization happens all the time.

My lab is particularly interested in cholesterol and its role in breast cancer and breast cancer recurrence. It is not something that today we have robust clinical data to say, “Oh, we should give more dose or less dose based on cholesterol specifically,” but there's certainly lots of active use of biomarkers in how we personalize radiation and lots of interesting things to come.

What is the most promising advancement in radiation for inflammatory breast cancer (IBC) patients right now, particularly regarding the use of pre-operative radiation or dose escalation for those with residual disease?

I think one of the things that has been really transformative for inflammatory breast cancer is understanding the value of the newest systemic therapies. So for example, we were able to partner with one of the other big IBC clinics in the country and demonstrate that the standard of care KEYNOTE-522 regimen for triple-negative breast cancer is affording those patients around a 30% to 35% pathologic complete response rate, which is better than anything that had been seen historically and gives us a new bar to advance.

Similarly, with the HER2-positive patients, we are working on data right now that demonstrates that the de novo stage 4 HER2-positive patients who have already progressed to stage 4 at the time they're diagnose, can actually have really long no evidence of disease status, and may even be curable with the remarkable HER2-targeted therapies in combination with surgery and radiation.

So there's a trial that's about to open that's been run by SWOG that'll be asking this question in de novo stage 4 breast cancer of all subtypes, which is, should you be throwing the kitchen sink at these patients? Are they curable with these modern agents combined with surgery and radiation, which we don't standardly offer to stage 4 patients, but might be value added in the setting of really effective systemic therapy? So, I think that's a space that's really making an outcome difference for patients. I think we continue to see that because the agents are so good, it's worthwhile to give appropriate standard fractionation radiation for inflammatory breast cancer, because at the point that you've had a pathologic complete response to these great drugs, you're in the best position possible to be cured of your breast cancer. And the last thing you want to do is waste that, don't leave it on the table. So I think in this setting of de-escalation, we've got to be really careful to be giving patients the right treatment for them; absolutely de-escalate everywhere where it's safe and appropriate, but don't de-escalate because the wave is going that way — de-escalate because it's the right thing for that patient.

Transcript has been edited for clarity and conciseness.

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