The ways in which patients with breast cancer respond to neoadjuvant chemotherapy will give practitioners a clue as to how they will benefit from radiation therapy (RT), Welela Tereffe, MD, explained during the 2017 OncLive®
State of the Science Summit on Breast Cancer.
This topic is being explored in the ongoing phase III NSABP B-51 trial, which is looking at standard or comprehensive RT in patients with early-stage breast cancer who have undergone surgery and received prior chemotherapy (NCT01872975). Specifically, researchers will evaluate postmastectomy chest wall and regional nodal RT and postlumpectomy regional nodal RT in patients with positive axillary nodes before neoadjuvant chemotherapy, who convert to pathologically negative axillary nodes after the treatment.
Tereffe, who is an associate professor in the Department of Radiation Oncology at The University of Texas MD Anderson Cancer Center, discussed the current state of RT in breast cancer and emphasized the importance of a multidisciplinary approach.
OncLive: Could you provide an overview of your presentation on RT at this State of the Science Summit?
: I reviewed the role of RT in patients who received neoadjuvant chemotherapy, noting that response to neoadjuvant chemotherapy can risk-stratify patients into 2 groups. One group has a low risk of local regional recurrence and would sustain a relatively small benefit from either postmastectomy radiation or—in the breast-conserved setting—from the addition of regional nodal irradiation to the standard whole breast treatment. The other group is a high-risk group that would benefit from escalated radiation to reduce local regional recurrence, metastases, and death from breast cancer.
The primary way that patients are stratified is by nodal response. Patients with a complete response in the lymph nodes are generally at lower risk. However, there are interactions by subtype, and it appears that patients who have triple-negative, estrogen receptor (ER)–negative, or HER2-positive disease have relatively higher rates of local regional recurrence both with and without a complete response to chemotherapy. They are the most likely to be targeted for escalated treatment, even with a good response to chemotherapy.
What should community oncologists take away from your lecture and apply to clinical practice?
The first thing that I would emphasize is that patients who will receive neoadjuvant chemotherapy must be treated in a multidisciplinary fashion that starts at the time of diagnosis. It is important to assure that the staging workup is sufficient for the subsequent decision-making that will flow to the surgeons and the radiation oncologist. Additionally, this is to make sure that there is serial follow-up of patients receiving neoadjuvant chemotherapy to assess response.
Then, a multidisciplinary, collaborative decision-making process for both the type of surgery that will be performed—in terms of the breast surgery and axillary surgery—and the role of RT can follow.
Secondly, for any patient who was initially node-positive prior to neoadjuvant chemotherapy, a referral to a radiation oncologist is appropriate. In addition, for any patient that remains node-positive after neoadjuvant chemotherapy, RT is absolutely indicated.
It seems that the importance of a multidisciplinary approach has been emphasized in recent years. How does this better serve the patient?
Coordinated care results in better outcomes, so having everyone who will have an impact on the patient's care involved in the process is beneficial. This includes having the diagnostic imaging specialist, the pathologist, the radiation oncologist, the medical oncologist, the surgeon, and the plastic surgeon involved from the beginning to assure that the patient gets the most rational, coordinated treatment possible. As a general principle, this is a good approach to follow. In patients who receive neoadjuvant chemotherapy, it is of critical importance because significant information is lost without multidisciplinary evaluation from the beginning. Inappropriate or inadequate neoadjuvant chemotherapy is actually worse than upfront surgery.
In the worst-case scenario, patients who are either lost to follow-up or received a truncated course of chemotherapy, and don't subsequently complete that treatment after surgery, are probably worse off than if they had received upfront surgery and at least had their definitive treatment.
What do you envision for the role of RT in this field moving forward?
Much like how systemic therapy is being targeted to the right patients, we can escalate treatment in those patients who both need and would benefit from RT. We de-escalate treatment in patients who don’t need or wouldn’t benefit from it. Then we’ll focus our clinical trials on patients who clearly need escalated therapy but don't benefit from what is currently available.
That is the schema that we will see in radiation therapy, as well: escalated treatment for high-risk patients who are likely to benefit and de-escalation or complete omission of RT for patients who are sufficiently treated with surgery or endocrine therapy. Then, we give some form of combined, multimodality novel therapy for these patients who have poor outcomes, but for whom escalation of standard systemic therapy or radiation is unlikely to be effective.
For example, patients with triple-negative disease who are poor responders to chemotherapy can be treated with high-dose RT, and yet their outcomes will still be poor. We could treat them with third-line chemotherapy and, yet again, their outcomes would still be poor. They need novel, systemic therapy—possibly in conjunction with chemotherapy such as immunotherapy—which has shown great promise for patients with intact tumors.
The combination of RT and immunotherapy has a synergistic effect—radiation releases immune cells and causes cell death, which exposes elements of the cell that can increase the immune response. When that treatment is given in conjunction with immunotherapy, the outcomes are synergistically improved. Strategies like that are likely to be more effective for patients with high-risk disease who don’t respond to standard treatment.
Are there ongoing trials in this space that you are excited about?
I am certainly excited about the NSABP B-51 trial, which randomizes patients with T1 to T3, N1 disease who have had complete response in the lymph nodes to neoadjuvant chemotherapy, to receive more or less radiation therapy.
Similarly, I am excited about the ALLIANCE trial, which is a companion trial of sorts to this study. It randomizes patients with residual lymph node disease to axillary dissection followed by RT or no axillary dissection followed by RT to a field that also includes that axilla. Both of these approaches have the promise of helping us figure out in whom we can appropriately escalate or de-escalate treatment.
There are several prospective studies ongoing worldwide that either randomly assign or prospectively observe patients who are ER-positive with early-stage disease who undergo breast-conserving surgery, to omission of RT if they also have a low Oncotype
score, or some other molecular test that suggests that they are at low risk of recurrence.
What else is important for radiation oncologists to know right now?
Our multidisciplinary colleagues and the general public need to know that the short- and long-term toxicities of RT are very manageable in the modern era. A lot of what we know—or what we think we know—about radiation effects are from very outdated trials conducted in the 1960s and 1970s, when the radiation modalities and the treatment planning were downright barbaric compared with what we have today.
Even comprehensive RT for patients with left-sided tumors can be administered in a way that safely protects the lung and the heart; it is associated with a relatively low risk of lymphedema and relatively high satisfaction rates with cosmesis. Those are all very hopeful things for patients who do actually need comprehensive RT.