Challenges Remain in Treating Patients With Phyllodes Breast Tumors

Andrea V. Barrio, MD

Although phyllodes tumors represent approximately 1% of breast cancers and can be primarily treated with surgery, there are challenges with managing the disease if it metastasizes, according to Andrea V. Barrio, MD.

Phyllodes tumors are classified within 3 subtypes—benign, borderline, or malignant—based on their histologic features. These subtypes are able to better predict the prognosis of the patient, Barrio explained.

These malignant tumors, which are considered a sarcoma, are primarily treated by surgery and can recur locally. However, local recurrence in phyllodes tumors has been linked to margin status. Patients with a positive margin have a much higher rate of recurrence and correlated with a higher risk of metastases as opposed to those with a negative margin, which has a lower risk of metastasizing. Malignant tumors in particular are at highest risk of metastases.

“The problem is once it metastasizes, these tumors are uniformly fatal,” Barrio noted. “And we don’t have very good treatments.”

Barrio added that it is imperative to closely observe the margin since it plays such an important role in management. If a positive margin is detected, it should be resected before moving forward.

Since these tumors are malignant in a small subset of patients, it is difficult to collect data and perform larger-size trials, said Barrio.

OncLive: Could you provide some background on phyllodes tumors?

In an interview with OncLive during the 20th Annual Lynn Sage Breast Cancer Symposium, Barrio, a breast surgeon at Memorial Sloan Kettering Cancer Center, discussed the challenges with phyllodes tumors of the breast and how to manage this disease moving forward.Barrio: Phyllodes tumors are rare tumors in the breast. They probably represent about 1% of all the breast tumors we see. They are classified into different histologic subtypes based on their grade. We grade them as benign, borderline, or malignant based on a variety of histologic features. Based on that, that tells us a little bit about prognosis. We know these tumors are treated primarily with surgeries, so we remove them with either a local incision or mastectomy, depending on the tumor size. Really, there is no other additional treatment other than surgery for these tumors.

They are capable of recurring locally and we know that local recurrence is linked to the margin status. If you have a positive margin, there is a much higher rate of recurrence, so we try to achieve a negative margin when we remove these. The likelihood that the tumor will metastasize is a much lower risk.

Could you elaborate more on the challenges seen with these tumors?

To characterize which tumors might have the highest risk of metastases, we know malignant tumors are at higher risk, but we recently analyzed our experience with malignant phyllodes tumors and we found that patients who had uniformly poor features in their tumors were at the highest risk for spread of their tumor.The challenge with the tumor is that they are so rare. It’s hard to understand prognosis. When patients come to see you, patients want to know, “What is the likelihood that this tumor is going to come back or spread? What additional treatments can you give me?” Unfortunately, there aren’t really any additional treatments.

The rates of local recurrence are really variable in the literature; however, for the most part, their risk of local recurrence at 10 years is anywhere from 10% to 15%—not astronomically high. The risk of spread of the tumor is not very high either, and is very limited to the subset of patients who have malignant phyllodes tumors. That risk of spread is less than 2%.

What data do we currently have for these tumors?

What are the key points oncologists should take away from your presentation?

It’s hard to know how to monitor these patients going forward because they want to know what types of scans they should get, and [whether or not they should be monitored]. There is no good answer to that because there are no data. The biggest challenge is the lack of data guiding us on how we should monitor these patients after surgery.As a rare tumor, it is very hard to do any prospective studies, but I have just finished an analysis of 125 malignant and borderline phyllodes tumors of the breast to better understand prognosis, and again to identify that those patients with uniformly poor pathologic features have the highest risk of spread. That paper was submitted for publication and is still pending in terms of acceptance.The key point, in terms of local recurrence, is that margins matter. You don’t want to leave a positive margin, you want to make sure you take the patient back and resect it. Alternative to that, the optimal negative margin with when you take that out is not really known. The National Comprehensive Cancer Network recommends a margin of 1 cm, but I think that is probably too much. You could have a low risk of local recurrence with a margin of 1 mm or a little more than that.

What does the future look like for phyllodes tumor treatment?

We try to caution people not to take these really large margins because there are not really any data to support that. The other thing I hope they take home is that they understand that the likelihood of distant recurrence is rare and that we really, again, limit that to those with phyllodes tumors with the worst prognostic features.One of the things that will be interesting going forward is understanding and correlating prognosis with genetic alterations. Our pathology group at Memorial Sloan Kettering Cancer Center has done some genetic sequencing of the tumors and understand that the pathways by which these develop can be very different. One of the things I spoke to one of our pathologists about was correlating outcome in patients with genetic alterations to see and identify certain genetic features of the tumors that might predict worse prognosis.

View more from the 2018 Lynn Sage Breast Cancer Symposium