Is there a clear role for hormonal therapy in metastatic breast cancer?

Reporting from the MBCC, ONCOLOGY spoke with Eric P. Winer, MD, Director, Breast Oncology Center; Chief, Division of Women's Cancers; Thompson Senior Investigator in Breast Cancer Research, Dana-Farber Cancer Institute. At this year’s conference, Dr. Winer presented two lectures, “Strategies for Patients with Refractory HER2-Positive Breast Cancer,” and “Addressing Menopausal Symptoms and Fertility in Breast Cancer.

ONCOLOGY: Is there a clinical role for hormonal therapy in the metastatic breast cancer setting?

DR. WINER: Yes, in patients with HER2+ and ER+ disease, there is a role for at least a trial of hormonal therapy.  Increasingly, I tend to use hormonal therapy, when I administer it to patients with HER2+ disease, in conjunction with chemotherapy.  I tend not to use hormonal therapy as the initial treatment for patients with HER2+ disease unless their disease is quite indolent, as the likelihood of obtaining a response is substantially less than with chemotherapy plus (trastuzumab (Herceptin).

ONCOLOGY: What does this mean for clinicians?

DR. WINER: In terms of treatment for the practicing clinician, we increasingly use trastuzumab through multiple lines of therapy and there is now evidence to support that approach. It also makes sense to incorporate lapatinib (Tykerb) into at least one of the treatment regimens.  In general, after disease progression on the first or second trastuzumab-based regimen, it is very reasonable to consider a regimen such as lapatinib and capecitabine (Xeloda).

ONCOLOGY: Have we made any progress in brain metastases associated with advanced disease?

DR. WINER: Brain metastases affect as many as 40% of patients with HER2+ metastatic breast cancer.  There is no clear evidence that screening for brain metastases improves outcome, but prompt treatment of initial symptoms is important. The initial therapy usually involves radiation, either whole brain radiation, whole brain irradiation with the addition of stereotactic radio-surgery, or radio-surgery alone.  For patients who have a limited number of lesions that appear to be resectable, neurosurgery is also a consideration.

After disease progression, if additional local therapy cannot be given, we usually consider systemic therapies that have the greatest chance of penetrating the CNS.  There are a variety of ongoing trials.  Outside of a trial, I would tend to favor a combination of capecitabine and lapatinib.

ONCOLOGY: From what you’ve seen at the MBCC and in your work, any hint that there might be a next generation of Herceptin in the pipeline?

DR. WINER: I don't know that there is a next better Herceptin on the way, but there are multiple agents in development all of which demonstrate clear activity against trastuzumab-resistant breast cancer.  Among the most promising agents are T-DM1, neratinib, pertuzimab, and the HSP-90 inhibitors.