Neuro-Oncology Care

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Specialized Neuro-Oncology Care

 

by Jonathan Berkowitz, MD, PhD

medical oncology, neuro-oncology, hematology

 

 

As a part of the cancer center of Santa Barbara with Sansum clinic, we have developed a neuro-oncology clinic with the goal of providing highly specialized care, including access to clinical trials for patients with brain tumors and brain metastases from other malignancies.

 

We are fortunate to be a member of a research network with the UCLA Jonsson Comprehensive Cancer Center, through which we have opened a clinical trial that ad- dresses this goal for women with breast cancer metastatic to the brain.

 

 

This year, the American Cancer Society estimates that more than 226,000 women will be diagnosed with invasive breast cancer and that more than 39,000 will die of this disease. In 25 percent of breast cancer cases, the human epidermal growth factor receptor 2 (HER-2) is overexpressed. Historically, this has been associated with a relatively poor prognosis. Over the last decade, the addition of trastuzumab, (Herceptin®, Roche), an antibody against HER-2, to chemotherapy has significantly improved survival of these patients, especially in those with localized disease.

 

While women with HER-2 positive metastatic breast cancer derive benefit from trastuzumab, this drug does not appear to have efficacy in the brain. This has become more important as breast cancer is the second most common cause of brain metastases. In one study, one third of women treated with trastuzumab for metastatic cancer developed brain metastases. In 50 percent of patients, the cause of death was progressive CNS disease. Another FDA-approved agent for treating HER2- positive metastatic breast cancer, lapatinib (Tykerb®, GlaxoSmithKline), showed a low response rate in patients with brain metastases after trastuzumab and radiation. Pertuzumab (Perjeta®, Roche) is the newest approved agent in this setting, but the study that led to its approval excluded patients with brain metastases.

 

Therefore, breast cancer with brain metastases represents a highly unmet medical need, for which novel targeted therapies are needed. This led to a study using afatinib, a small molecule, irreversible inhibitor of HER-2 as well as two other related proteins (HER-1 and HER-4); these may be important proteins to block to prevent resistance to HER-2 inhibition. In patients with HER2- positive metastatic breast cancer, who progressed after trastuzumab therapy, nearly half of the patients appeared to benefit from taking afatinib. In addition, in one lung cancer study with afatinib, a patient with brain metastases had a sustained response, and in another lung cancer study, those with or without brain metastases achieved comparable outcomes on afatinib.

 

The purpose of this study is to investigate whether afatinib alone or in combination with vinorelbine has any effect on HER2-positive breast cancer with brain metastases after failure of prior trastuzumab or lapatinib. In this study, patients will be randomized to receive afatinib, afatinib + vinorelbine chemotherapy; or investigator's choice of medical treatment approved for metastatic breast cancer. This study is currently accepting new patients in our Santa Barbara and Solvang offices.

 

We are also planning to have studies in the near future for patients with primary brain tumors, such as glioblastoma. Please contact us with any questions at (805) 563-5800.

 


 

Case Report

 

Breast Cancer Metastatic to the Brain


The patient is a 42-year-old woman who was diagnosed with right-sided breast cancer in 2008. She had noted then that for the prior two months of breastfeeding, her daughter was not getting any milk from the right breast, where she had previously had mastitis. She was seen by her obstetrician, and a mass was felt in the right breast.

 

A mammogram showed an area of increased density encompassing a huge region of the upper outer quadrant of the right breast correlating to the hard mass. An ultrasound- guided biopsy of a 2.6cm mass in the right breast revealed invasive carcinoma with mixed ductal and lobular features. It was estrogen-receptor and progesterone-receptor positive, and HER2 was overexpressed.

 

An MRI of the breasts showed a 7.3cm x 4.3cm mass in the right breast primarily upper outer quadrant with extension to the nipple, sub-areolar region, anteriorly to the lower inner quadrant, with no contralateral disease, asymmetric lymph nodes more prominent on the right than the left. A PET scan demonstrated multifocal tumor in the right breast and multiple areas of abnormal nodal activity in the right axilla suggestive of metastatic disease, but negative for any other sites of disease.

 

The patient then underwent alternative medicine treatments and returned one year later, at which time she was found to have metastases to multiple skeletal regions and the lungs. She was then treated with docetaxel, carboplatin and trastuzumab for five of six planned cycles with an excellent response. She discontinued chemotherapy early because of toxicity.

 

She was maintained on trastuzumab and tamoxifen, which was well-tolerated. The patient was on these therapies for nearly two years until she complained of significant headaches with associated blurry vision and nausea. An MRI of the brain showed multiple lesions in the brainstem and both cerebral and cerebellar hemispheres, with significant edema.

 

The patient then received whole brain radiotherapy, and continued trastuzumab, with the addition of nanoparticle albumin-bound (nab) paclitaxel. After fifteen months of therapy, a brain MRI showed a right cerebellar nodule had grown from 4mm to 9mm. This was then treated with stereotactic radiosurgery, and lapatinib was added to her treatment regimen in January of this year.

 

Soon after, the nab-paclitaxel was discontinued and by June her brain metastases had progressed again. Lupron and tamoxifen were added at that time, but in November of this year her brain metastases had once again progressed. Fortunately, she is eligible for a clinical trial designed for patients with HER2 positive metastatic to the brain using a new agent called afatinib. She enrolled on the trial and was randomized to receive afatinib, and she has just recently started this medicine.

 


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