Current Therapies and Future Options for Breast Cancer Treatment: An Interview With Yolanda Bryce, MD

Dr Bryce spoke with IO Learning about current breast cancer treatments and future options for the 1 in 8 women who will ultimately face breast cancer in their lifetime. 

What contributes to your ability to treat breast cancer percutaneously?

For locoregional therapy when we’re dealing with primary breast cancer, there are a few things that have opened the door to the possibility of percutaneous treatment. The first is screening. Breast cancer screening has made it possible for us to catch breast cancer at a smaller size. We’re finding cancers that are <2 cm, and a lot of times <1 cm. The surgeons have also tailored their surgeries so they don’t need to do these large surgeries anymore. Surgeons went from radical mastectomy all the way down to a lumpectomy, which is removing only the tumor and a little bit of a margin. There has also been an evolution in the way we assess margins. In the past, we wanted a large margin (about 1 cm). Currently, when dealing with invasive breast cancer, we make sure the tumor is not touching the inked margin, whereas we want a little more (about 2 mm) with non-invasive breast cancer (ductal carcinoma in situ). The goal of surgery is now to do a smaller surgery with better cosmesis. We’re looking at those entities, and asking, why can’t we go even smaller? Why not do a percutaneous ablation? There are some studies that have shown that when we’re dealing with small tumors, we can obtain a 100% ablation. 

Regarding oligometastasis, there have been some retrospective trials, but not really any prospective data. The retrospective trials are showing that patients with oligometastasis seem to have a better prognosis than other metastatic breast cancer patients. In interventional oncology (IO), we have borrowed data from other types of cancer and other fields to explore how we can manage oligometastatic breast cancer. For example, we look at how primary liver cancer is treated as far as the tumor size, location, number, and so forth, and how that responds to ablation. In addition, we look at how patients have responded to locoregional therapy using external beam radiation. Once we look at these data, we try to extrapolate them into treating oligometastasis from breast cancer. There is some success in treating oligometastatic breast cancer, but overall survival needs to be demonstrated. On the other hand, when a patient presents for IO intervention with diffuse metastatic disease in the liver, sadly, these patients have undergone at least two lines of chemotherapy (and usually more). Their liver has already taken a beating, so the patient no longer has a normal liver. When these patients are treated with either radioembolization or another kind of liver-directed therapy, the liver is already sick and is then bombarded with another treatment. A lot of work must be done to define which patients are good candidates for liver-directed therapy, and to determine the optimal timing of the liver-directed therapy. Maybe we shouldn’t wait until the patient has had multiple lines of chemotherapy; maybe liver-directed therapy should be done a little earlier.

Are there any particular studies underway that are looking at these areas?

My colleague, Amy Deipolyi, MD, PhD, at Sloan Kettering, is studying radioembolization of breast cancer metastasis, and she is looking at two different entities. The first is simply the basic outcome of radioembolization in the breast cancer metastatic setting, and the second is the abscopal effect, because there is some suggestion that radioembolization could produce a more systemic response.

Tell us more about locoregional therapy with ablative techniques — are they effective?

There are many different kinds of ablation techniques in primary breast cancer. In the United States, radiofrequency ablation (RFA) and cryoablation are most common. In Europe, a lot of high-intensity focused ultrasound (HIFU) is utilized. I don’t have any clinical experience with HIFU, so my preference is cryoablation of breast cancer. RFA is faster than cryoblation; however, you can see the treatment zone better with cryoablation than with RFA, so potentially you can control any complications. Also, forming the ice ball in cryoablation is analgesic, meaning that it deadens the pain. RFA, on the other hand, can be very painful, so these patients sometimes need anesthesia. Cryoablation is not painful. In my practice, the patients I treat tend to be those who do not want surgery or who are not surgical candidates. I can’t do a procedure that requires heavy sedation, because the patient is not eligible for it.

Is most of the locoregional therapy offered palliative?

Sometimes it is palliative, but I try to treat with curative intent. Sometimes a patient has a 5 cm tumor that is invading the skin. Obviously, I can’t cure that. Otherwise, I do intend to cure the patient.

There are some patients who cannot undergo surgery, so locoregional therapy of primary breast cancer may be effective for them. We are trying to move toward locoregional therapy for all patients with small breast cancers, whether or not they can undergo surgery. These patients have options. I get satisfaction from doing locoregional therapy on patients with small tumors because I don’t think it’s necessary to do a surgery for such a small tumor and I know locoregional therapy in this setting is curative. However, the median survival for breast cancer in the localized stage is already high — approximately 99% at 5 years. Therefore, innovation is needed elsewhere, again, in the metastatic setting.

Is oligometastasis to the lung common? 

The order of things for breast cancer seems to be that bone is the most common, with the liver and lung probably the next most common areas.

Are there areas more or less receptive to different techniques?

The success of the technique has a lot to do with tumor size. Obviously, location is important as well. Sometimes tumors are very central and the procedure is more difficult, but usually the size is the issue. A good ablation result is usually possible in tumors that are <2 cm. The problem is that the tumors undergoing treatment are only those large enough to be seen. It’s a systemic disease most of the time. One lesion could be treated with ablation because it’s visible, but down the line, others appear. Should we keep ablating all of the lesions or switch to another chemotherapy? It’s difficult to know whether or not to continue with chemotherapy, because even if the disease is no longer visible, it’s impossible to know whether the tumor is becoming resistant to the chemotherapy with repeated doses. Breast cancer in the metastatic setting needs significant research. 

You mentioned radioembolization and the case of a woman that you treated to complete health in your CIO presentation. Could you elaborate?

A woman had undergone previous lines of chemotherapy and her performance status was ECOG 1, so she wasn’t at a normal baseline of ECOG 0, but she was still very active. Total bilirubin was 1.4, which is not prohibitive to liver-directed therapy, but it demonstrated that her liver was not normal. I did the case and had a beautiful, complete response. All of the tumors in the liver, which was initially completely diffuse, had a great response. I did the right side and I waited 2 months before I did the left side. The patient did well initially, but a few months later, there was a decline in her liver function. Ascites were visible on her imaging and she died of liver failure about 8 months after the second treatment. It would be a positive if we could find some kind of therapies that target the tumors more and the normal parenchyma less. There is work in abscopal effects, trying to treat one tumor and then using immunotherapy to address all the other tumors. There are things that people are doing in other fields. I have a colleague who is looking at pancreatic cancer, injecting a virus and seeing abscopal events elsewhere. We need to find a therapy that is more targeted than just blasting, especially when we’re talking about the liver, because patients with metastases to the liver are the patients who are actually dying. We need something that not only takes care of their liver tumors, but also preserves the liver. I have some interest in immunotherapy work and I’m hoping that we’re able to find a more targeted therapy for these individuals rather than compromising the whole liver.

Any final thoughts?

Breast cancer is something that is very prevalent. It affects 1 out of 8 women. There are so many advancements in one little section of breast cancer (primary breast cancer) and that’s great, but there’s a whole other section that needs our attention (metastatic breast cancer), and it must be a multidisciplinary approach. It can’t only be IO. It must be IO combined with our medical oncologist partners, our surgeons, and our radiation oncologist colleagues. We need a multidisciplinary approach, and we need to define better criteria for who will respond to certain therapies. We have to move beyond how we’ve done things in the past. We need to be more creative in how we approach this population.

Disclosures: None.

Address for correspondence: Yolanda Bryce, MD, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. Email: brycey@mskcc.org