Managing Patients With Stage 1 HER2-Positive Breast Cancer

In this expert roundtable series, Reshma Mahtani, DO, Miami Cancer Institute, Florida, leads a 4-part discussion on the management of early-stage HER2-positive breast cancer. Participating in the discussion are Terry Mamounas, MD, Orlando Health Cancer Institute, Florida, and Jane Meisel, MD, Winship Cancer Institute, Atlanta, Georgia.

In this video, our experts discuss the management of patients with stage 1, HER2-positive tumors, sharing data from several trials in this space, including the APT, ADEPT, and ATEMPT 2.0 trials.

Watch episode 3 on optimizing therapy for patients with high-risk HER2-positive breast cancer.

Transcript:

Dr Reshma Mahtani: With that, let's move to the second part of our conversation today where we'll focus on management of stage 1, HER2-positive disease. And I think here we have a few trials that have been reported, and we have long-term follow-up for example, the APT trial with paclitaxel and trastuzumab. Jane, maybe you can take us through your approach to these small, stage 1, HER2-positive tumors and some of the data with the APT trial.

Dr Jane Meisel: Yes, absolutely. The APT trial was a really, in my mind, fantastic trial. It was an adjuvant trial that looked at patients who had tumors less than 3 cm—although the vast majority of patients on this trial had tumors less than 2 cm and node negative—and gave them essentially a de-escalated adjuvant approach, using weekly paclitaxel for 12 weeks plus trastuzumab, and then completing a year of trastuzumab-based therapy. Just 2 drugs, only 12 weeks of chemotherapy, and that was what they received. We now have the 10-year invasive disease-free survival outcomes on those patients: 91.3% of patients are disease free at 10 years.

This data­­—even before we had the information looking out that far—had become a standard of care for a lot of smaller, node-negative tumors. It is something I put into play in my clinic. I would say for patients who have tumors less than 1 cm, I'm using this almost universally, and for those that are between 1 and 2 cm, like we discussed in the prior section, I'm using a combined approach. For patients who may be older or frailer and have tumors closer to 1 cm, I definitely use this as well. For those that are maybe younger and have more aggressive-looking tumor biology or have tumors closer to 2 cm based on imaging, I will sometimes go with a modified neoadjuvant approach. But this has been a great study that has changed, in many ways, the way we treat these patients with smaller tumors, and probably has allowed us to overtreat far fewer of them.

And then there are studies looking to potentially take this further. There's one called the ADEPT trial that's under the development by the same folks who developed the APT trial, Dr [Sara] Delaney and her colleagues at Dana-Farber [Cancer Institute]. And this is a trial for ER-positive, HER2-positive patients, looking at a combination of HP [trastuzumab and pertuzumab] plus endocrine therapy with no chemotherapy. Another very novel concept, but for those patients who have small tumors who would really like to avoid chemotherapy entirely, and do so in a controlled setting, I found that trial, which we've had open here at Emory as well, has been very well received by patients. We'll see what the outcomes look like, but I think it's great that we're able to study these things.

Dr Reshma Mahtani: Yes, and another important trial in this setting is the ATEMPT 2.0 study, where the same investigators again are looking to assess 6 cycles of treatment with T-DM1 followed by treatment with trastuzumab for the remainder of the year. Hopefully we'll see that a shorter duration of T-DM1 is equally effective, but hopefully can reduce discontinuation rates. We saw in ATEMPT 1.0 there were a fair percentage of patients that weren't able to complete the whole year of T-DM1.

Terry, you brought this up in the last section: as we think of these tumors that are on the larger side stage 1, so T1c, there are certain factors that might push us in favor of upfront surgery, in terms of how these patients have done long term. But then T1c and 0 patients were actually eligible for the KATHERINE trial. How do you make a decision for these T1c patients? How do you perceive the value of upfront systemic therapy versus upfront surgery in those patients?

Dr Terry Mamounas: Yes, for patients that have on the lower end of the T1c, closer to 1 cm, less than 1.5 cm, and also for patients that have some comorbidities, that are older and they try to avoid the more intense regimens, doing surgery first, making sure their nodes are negative and then treating them with a regimen such as TH [paclitaxel plus trastuzumab] or even TCH [docetaxel, carboplatin, and trastuzumab] if they can tolerated, is a very reasonable approach for patients that are fit to receive more therapy. For those that have potentially 1.5 cm to 2 cm tumors, our bias is to use neoadjuvant therapy, if possible, for the reasons that I alluded to earlier. But again, we don't use the dual antibodies. We just use either TH or TCH with [docetaxel] as was back in this BCIRG study for 6 cycles. These are options that you can explore. But again, our bias is sometimes to use this best in the neoadjuvant setting, not in the adjuvant setting.

Now, for a small tumor that you survey the axilla, the nodes look normal on the ultrasound, and you're pretty certain that hopefully they will be negative, I think either/or approach is fine. But sometimes there could also be some clinical involvement of the nodes and when you do the surgery and you find out that the patient had positive node, you go, “Darn, I wish I would like have given them in the neoadjuvant setting” because then you can capitalize on the downstaging effect.

That's usually how we approach them. There is not one size fits all here, but it's more of the art of oncology to select the appropriate patient for the appropriate candidates. It’s great that we have these options because we can safely tell the patient, “you can do surgery upfront and you do fine based on the APT and the ATEMPT, and also you can do neoadjuvant chemotherapy with the same regimen.” If you are one of the few patients that potentially would have residual disease for the triple-positive patients, then it is almost about a 50% pCR. And that's with TCH, right? With TH, would maybe be even less than that. There are some patients that may still have residual disease, which we like to know about.

Dr Reshma Mahtani: That's an important point that you brought up, about patients who go on to have surgery and are found to have pathological nodal disease at the time of surgery. Would you have a sense of how often that would happen, based on the literature? Are you routinely making sure that all these patients have an axillary ultrasound?

Dr Terry Mamounas: Yes, we do, particularly if we're going to base our treatment on the premise that they are going to be T1c or T1b and T0. Obviously T1a and T1b, the rate of nodal lymphoma is much lower, for T1c is probably higher. I would probably estimate it in about 20% to 25%. It's always intriguing when you go back to an all the old studies, the NSABP Protocol B-18, that was before axillary ultrasound, just the fingers of the surgeon looking at the axilla. And for patients who were clinically node-negative and went to the arm that had surgery, first 48% of those patients had involvement with the axilla. For those that had neoadjuvant chemotherapy, 33% ended up having positive nodes because they were downstaged.

That was sobering back in the days before axillary ultrasound and bigger tumors. Although the B-18 didn't have a lot of big tumors, most of were like 2 or 3 cm tumors, but that always brings it back. But today is different. And if we can survey the axilla, we can rule at least a lot of disease for the majority of the patients. You know, we can never predict for sure that you're not going to have 1 mm or 2 mm disease in the nodes. But we almost routinely survey these patients before we position them to therapy.

Dr Reshma Mahtani: Jane, has that been your approach as well at your institution?

Dr Jane Meisel: It really has been. I think that it's great that we have more data to guide all of our decisions now, but I do think some of the areas that are still a little bit gray allow us to still put all of that shared decision making into practice. But it's good to have, I think we can have more comfortable conversations with people because we have more data to guide each potential decision point.

Dr Terry Mamounas: And if I may add, like what I said before, now we have another incentive to know if they are node-positive and give neoadjuvant chemotherapy because we can potentially downstage them and minimize their original nodal radiation based on the results of the B-51, that were presented in San Antonio. Before, after neoadjuvant chemotherapy, if your nodes were positive before, we still give you neoadjuvant therapy now. Knowing if a patient has a positive node that converts to negative, that's important.

Dr Jane Meisel: Yes, and you made a really good point, that particularly after B-51 was presented, that becomes even more important because for many patients, the option to do less radiation, which can have long-term effects, you know, that impact them physically every day is, is very meaningful.