Patient Selection Key When De-Escalating Radiation in Breast Cancer

Jonathan B. Strauss, MD, MBA

Over the past several years, several clinical trials have evaluated the role of radiation in the treatment of patients with breast cancer and whether doses can be reduced. Although de-escalation is possible, patient selection is key, according to Jonathan B. Strauss, MD, MBA.

“Selecting the right patients for de-escalation is key. Right now, we are using these clinical variables in combination with the discussion and the thought process of that patient’s health and lifespan in order to select the right person,” said Strauss. “We then have the discussion with that woman to make sure she’s comfortable with the residual risk she would have without radiation.”

Data from several clinical trials have shown that hypofractionation is comparable to conventional methods in the oncologic space in terms of efficacy, although the former appears to be easier on the patient, in terms of cosmetics, added Strauss, vice chair for Education, Department of Radiation Oncology, and associate professor of Radiation Oncology, at Northwestern University. As such, hypofractionation is currently the preferred approach in this setting for women receiving treatment to the whole breast.

In patients receiving partial-breast radiation, however, choosing between hypofractionation and conventional fractionation is more difficult, as available data in this patient population are mixed.

“We continue to explore when we can use hypofractionation instead of our conventional fractionation of radiotherapy, when it’s reasonable to do partial radiation instead of whole breast radiation, and how we can potentially continue to push the envelope on shortening courses of radiotherapy,” said Strauss.

In an interview with OncLive at the 21st Annual Lynn Sage Breast Cancer Symposium, Strauss discussed the role of hypofractionated radiotherapy in patients with breast cancer, offered advice on treatment selection, and highlighted the different radiotherapy approaches available to patients with ductal carcinoma in situ (DCIS).

OncLive: Could you discuss the methods for de-escalating radiotherapy in patients with breast cancer?

Strauss: For the intact breast, we’ve had many trials come out over the past few years that are really upending how we consider delivering radiotherapy. Most notably, we now have 5 randomized trials comparing a hypofractionated whole-breast regimen with a conventional fractionated regimen. In every 1 of these trials, we see that these 2 regimens are totally equivalent oncologically, so [patients] do just as well with hypofractionation. In some of these trials, hypofractionation appears to be gentler cosmetically, while in others they look equivalent. Regardless, in every trial, hypofractionation appears to be at least as good as conventional fractionation. For women treated to the breast alone, we are really not doing conventional fractionation any longer. All of these women [are] receiving a hypofractionation approach.

With regard to accelerated partial-breast radiation, the picture is slightly more [unclear]. We’ve had several trials exploring external beam techniques that look quite good [in terms] of cancer control. We’ve had some trials where we may have pushed the envelope a little bit too far with regard to treating a large volume of the breast; doses were relatively high, given twice a day, and may have resulted in some compromising cosmetic outcomes. On the other hand, we have regimens where our cosmetics look very good with a somewhat gentler partial-breast radiation technique. We also have some trials where we may have treated too small of a volume and we might not have been achieved an equivalent cancer control. I believe we are seeing this in the intraoperative radiation trials, where we are still waiting for updates, and potentially, the balloon-based techniques. We saw in a presentation that it may be the women who received MammoSite that appear to have a higher risk of breast recurrence than those who used external beam radiation, but we are still waiting on the publication of that manuscript to see if each of these patients were equally matched in regard to prognostic factors.

What is your rationale when making these treatment decisions?

For me, it’s relatively straightforward. If I am treating the breast and regional lymph nodes, I always use conventional fractionation off-study because we don’t yet have great trial data [supporting the] use hypofractionation in that setting. If I am only treating the breast, I always use a hypofractionated regimen. Some of these women will receive a boost and some will not, and we have some series now suggesting that we can identify some subsets of women at such low risk for recurrence that it doesn’t make sense to do dose-escalation with the boost when their recurrence risks are so good. In other women with a somewhat higher rate of breast recurrence risk, it makes sense to push the dose higher. I tailor the use of a boost to the risk of recurrence. I am starting to use partial-breast techniques, and I tend to apply the IMPORT LOW regimen to a relatively large volume of the breast in lower-risk women, and that looks oncologically equivalent and slightly better cosmetically.

How do you select between partial- versus whole-breast radiation?

Right now, I am restricting partial-breast radiation to relatively lower-risk women. For instance, [I would use this approach in] those over the age of 50 with estrogen receptor positivity, HER2-negative, grade 1/2 tumors that are negative for LBI with negative nodes and negative margins. Right now, those are the women I find probably best qualified, or women of a similar age with very low-risk, grade 1/2 DCIS. Those are the women for which I feel comfortable with stopping [treatment] early and [for whom] a large volume breast technique like the IMPORT LOW trial seem quite wise. I deliver this in conjunction with other heart-sparing techniques, like in the prone position or using deep inspiration breath-hold.

What is your advice for treating patients with DCIS?

The management of DCIS remains controversial; it has been for decades. However, we are starting to get more and more information about how to select patients most appropriately for those who need radiotherapy and those who will be able to omit radiotherapy in consultation with their physicians. What we are learning is there are fairly clear prognostic factors associated with the risk of recurrence. These [factors] include age, where younger age is associated with a higher risk, size of DCIS, and margin status; where clearly negative margin status is better; and having a 2 mm margin is better for women receiving whole-breast radiation, and for women who are planning to omit radiation, an even wider margin is helpful. It is fairly clear that women with grade 1/2 DCIS, at the very least, have a slower rate of recurrence and probably also have a lower rate of DCIS recurrence.

We can look at these factors such as age, size, margin status, grade, and also whether they plan to take endocrine therapy. We can sum these factors, either by applying the data from randomized trials for which a patient might be eligible or we can use the Memorial Sloan Kettering Cancer Center online nomogram to assess the risk of recurrence, and for patients in which that risk is quite low, we can discuss whether they want to pursue radiotherapy. Radiotherapy always seems to work and always seems to reduce the risk of breast recurrence, but when that risk is very low to begin with, then the absolute benefit of radiotherapy becomes very small. For those women, after discussion, sometimes omission of radiotherapy is the right answer; it depends on how the patient values that potential risk and what her risk threshold is.

Additionally, when we treat these women, it’s imperative that we treat them as safely as possible because the benefits of radiation that we view are reproducible and relatively modest, so we have to make sure that the radiation isn’t harmful.

Where should future research focus?

Looking toward the future, the question is whether molecular biomarkers may exist that we could add to those clinical variables to further improve stratification. In that front, we have more work to do to validate those markers that are out right now before shifting them into widespread clinical usage.

<<< View more from the 2019 Lynn Sage Breast Cancer Symposium