Yttrium-90 Therapy for Hepatic Breast Cancer Metastases: An Interview With Robert J. Lewandowski, MD, FSIR

At the 39th Society for Interventional Radiology (SIR) Annual Scientific Meeting in San Diego, Robert J. Lewandowski, MD, FSIR, presented results from a study of yttrium-90 radioembolization for breast cancer metastases in the liver. The study reviewed treatment outcomes of 75 women ages 26 to 82 with chemotherapy-resistant breast cancer liver metastases that were too large or too numerous to treat with other therapies. Results showed the therapy was safe and provided disease stabilization in 98.5% of the treated liver tumors, and 24 patients had 30% reduction in tumor size. Interventional Oncology 360 spoke with Dr. Lewandowski, an interventional radiologist who is also chair of SIR’s Interventional Oncology Service Line, about the study and its results. 

View video of this interview.

Q: What was the need for the study of Y-90 in patients with breast cancer metastases in the liver? 

A: Breast cancer is a huge worldwide health problem. Many women suffer from breast cancer, with over a million new cases diagnosed annually. Most of these patients will develop metastases or disease outside of the breast. And half of those patients with metastases will develop disease in the liver. There are several chemotherapies and other treatment options for patients with metastatic breast cancer but ultimately those therapies either stop working or patients suffer toxicities and are unable to continue. A patient’s prognosis worsens once there is cancer in the liver. The liver can stretch and patients experience pain. In addition, liver function declines as the hepatic tumor burden increases and some patients are unable to receive chemotherapy. By controlling the disease in the liver, we can ameliorate symptoms, make these patients candidates for other therapies, and potentially help them live longer. 

Q: What were the methods for the study?

A: When we see patients with breast cancer that has spread to the liver, they have typically progressed on many different types of chemotherapy. We see patients that are very late in the disease process. In this current study, we reviewed 75 women with metastatic breast cancer. With a mean age in their 50s, more than 85% of these patients had multiple tumors in their liver. Seventy-seven percent of the patients also had cancer outside of the liver. But in these patients that we treated with radioembolization — having a large disease burden, having been heavily treated with chemotherapies, and having limited treatment options —we were able to safely perform a procedure. This therapy is performed in an outpatient setting and involves gaining access through the artery in the groin in order to deliver radiation directly to the liver tumors. Patients come in to the hospital, have the procedure, and go home the same day in a safe, effective manner. The radioembolization procedure controlled the disease in 98.5% of patients. Only 1 of the 75 patients had disease progression following our therapy and 84% of the tumors that we treated decreased in size. 

Q: Could you describe the results further and share what you thought were the most remarkable results?

A: There was a very high disease control rate of 98% (including stable disease and tumors that were decreased in size) for this safe outpatient procedure. We determined toxicities first from a clinical standpoint, evaluating how patients were feeling following radioembolization. The majority of the patients had some self-resolving fatigue that lasted a few days or weeks. In terms of significant adverse effects, about 5% of patients had abdominal pain that required pain medication. We also looked at biochemical toxicities, specifically the effect of radioembolization on liver function. Less than 5% of these patients had any significant liver function abnormalities from a laboratory standpoint. The therapy was safe, well tolerated, and effective. 

One of the interesting things about our study is that we looked at the granular details on which patients are going to do well on our therapy. With other types of cancers, we have identified several different prognosticators that help us determine which patient will do well with radioembolization. In these patients, we found that women who had normal liver functions and less than 25% of their liver burdened by tumor did the best in terms of how long they were going to live after this procedure.

Q: Could you describe how you think this might affect future care for these breast cancer metastasis patients in interventional oncology?

A: Intra-arterial therapies such as chemoembolization and radioembolization have been typically employed for primary liver cancer such as hepatocellular carcinoma, and recently there has been a lot of enthusiasm for these therapies, especially radioembolization, in metastatic colon cancer to the liver. What we found is that radioembolization has been very effective in metastatic colon cancer to the liver in the salvage setting; we explored that here in the case of metastases from breast cancer. The overall survival and response rates for radioembolization of colon cancer for patients who have failed the first two lines of chemotherapy is far better than that of those patients who receive third-line chemotherapies. Because of that, we are now looking at moving radioembolization up in the treatment paradigm. There are 2 high-level studies being sponsored by industry looking at radioembolization with chemotherapy in first- and second-line therapies for colon cancer. Results from those studies could further influence a change in the treatment paradigm. I think we can envision the same shift for breast cancer: those women who have liver-dominant or liver-only metastases would receive radioembolization earlier in the course of their disease and potentially receive radioembolization combined with systemic therapy. 

Another interesting point from our study is that a few of the patients were also treated with capecitabine (Xeloda), an oral chemotherapy agent that is FDA approved for breast cancer. We recently published a separate study in which we treated patients with liver-only metastases from a variety of cancers, who received whole-liver radioembolization while on full-dose capecitabine. This was a dose-escalation study; all patients were given full-dose capecitabine, and we escalated the dose of radiation. Some of those patients had breast cancer and we saw a very good signs in terms of response and tolerability in those patients. This would be a very interesting way to move radioembolization earlier into the course of therapy by combining it with proven breast cancer systemic agents. This combination might prove to have a synergistic effect because capecitabine is a radiosensitizer, which has the ability to potentiate the effects of the radiation that we deliver.

Q: Could you talk a little more about the importance of patient selection?

A: Patient selection for any intervention, whether that intervention be medication, surgery, or intra-arterial therapy like radioembolization, is of utmost importance. If you don’t select the appropriate patients, they will not tolerate the therapy. So we look at certain things when we’re doing these procedures, and this approach is not unlike how a medical oncologist or a surgeon would approach patients. If a medical oncologist or surgeon saw a patient who did not meet the criteria for their intervention, then they would not be offering the therapy. One of the most important things is performance status, because you want to know to what degree the cancer is limiting these patients’ lives. One of the easy ways that we do this is to ask whether patients are up and out of their bed over half the day. If so, those patients typically will tolerate therapy. Many studies have shown across different cancer types that if you have absolutely no symptoms from your cancer, you tend to have better results than if patients have symptoms. We also look at the liver function, because as I mentioned, we’re delivering high-dose radiation to these tumors in the liver, so we want to make sure the liver is going to tolerate it. Lastly, you have to understand the disease burden. If they have a small spot in the liver and they have disease everywhere else in the body it doesn’t make sense to go after that little spot in the liver. You have to make sure that treating the liver disease is going to have a positive impact on the patient. 

Q: Anything else you want to point out to IO clinicians?

A: These image-guided minimally invasive therapies, such as chemoembolization and radioembolization, have been primary employed for hepatocellular carcinoma. Many interventional oncologists now use these therapies to treat patients with metastatic tumors, such as neuroendocrine and colon cancer. 

Now the majority of providers performing transcatheter intra-arterial procedures are treating a variety of types of tumors that have spread to the liver. Additional meaningful data are needed. Registries or multi-institutional studies are needed that combine data for cancers other than HCC, because it seems that high-dose radiation is going to be able to safely stabilize disease across different tumor types. The potential of image-guided therapies needs to be explored more. We’ve seen radioembolization used successfully for ocular melanoma that has spread to the liver as well as for cholangiocarcinoma. We’ve seen benefits described when treating patients with sarcomas, breast cancer, gastric cancer, lung cancer, prostate cancer, pancreatic cancer, cervical cancer, and ovarian cancer. Again, many people have treated a wide variety of cancer types – and we see such a heterogeneous patient population that it’s difficult to get meaningful data at this point in time.

Editor's Note: Disclosure: Dr. Lewandowski reports consultancy for Cook Medical and advisory board membership with Boston Scientific and BTG. 

Suggested citation: Ford J. Yttrium-90 therapy for hepatic breast cancer metastases: an interview with Robert J. Lewandowski, MD, FSIR. Intervent Oncol 360. 2014;2(6):E53-56.