SABCS: One-Third of HER2-Positive Breast Tumors Metastasize to Brain

Michael Smith
SAN ANTONIO, Dec. 17 -- In about a third of women with HER2-positive breast cancer, the disease will metastasize to the brain, a researcher said here.
Action Points --->
Explain to interested patients that the spread of breast cancer to the brain is relatively common but the natural history of the metastasis has not been clear.
Note that this study suggests that about a third of patients with HER2-positive disease will develop brain metastases, often fairly quickly after diagnosis.
These studies were published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
The brain is the first metastatic target of the HER2-positive cells in about 50% of patients, rather than a late occurrence, Denise Yardley, M.D., of the Sarah Cannon Cancer Center in Nashville, reported at the San Antonio Breast Cancer Symposium.
On the other hand, treatment with trastuzumab (Herceptin) appears to extend survival in women with brain metastases, even though the drug does not cross the blood-brain barrier, Dr. Yardley said.
The data emerged from the 1,000-patient registHER observational prospective study and has begun to clarify the natural history of HER2-positive metastatic disease, Dr. Yardley said.
Brain metastases are known to be increased in women with HER2-positive tumors, she said, but it hadn't been clear how many occur, when they take place, nor how long women can expect to survive after the spread is detected.
Analysis of 768 patients in the registry -- those diagnosed before July 1, 2005 -- showed:
30.7% developed brain metastases, 23.9% after their initial diagnosis with breast cancer and entry into the registry.
The brain was the first and only site of disease spread in 36.9% of those who developed metastases after diagnosis and the first site of several in 11.9%.
The brain metastases developed early in the course of the disease, at a median of 12.1 months after diagnosis.
Median survival was 13.9 months for all patients.
The median survival time is considerably higher than would be expected, Dr. Yardley said, because survival after brain metastases in other forms of cancer is usually between four and six months.
Because many of the patients in the study were being treated with trastuzumab, the finding may indicate some disruption of the blood-brain barrier that allows the molecule to attack the brain lesion, Dr. Yardley speculated.
She added that many patients with brain metastases are now switching to lapatinib (Tykerb), an EGFR/HER2 tyrosine kinase inhibitor, which is small enough to cross the blood-brain barrier.
Indeed, researchers are increasingly concerned about brain metastases in HER2-positive cancer and seeking to enhance the action of lapatinib, according to Nancy Lin, M.D., of the Dana-Farber Cancer Center in Boston.
Dr. Lin presented exploratory data on the combination of lapatinib and capecitabine (Xeloda), used to treat 49 women with brain metastases who had progressed despite treatment with lapatinib alone.
The goal of therapy was to produce an objective response of more than a 50% reduction in volume of the targeted lesion, Dr. Lin said.
Because of the small size of the study and lack of randomization, she said, "it's hard to be completely definitive about the conclusions. But what we observe is that the response rate is higher with the combination than with single-agent lapatinib -- 20% versus 6%."
Dr. Yardley's data "will become the reference for that kind of information," commented Charles Geyer, M.D., of Allegheny General Hospital in Pittsburgh, who was not involved in either study.
He said earlier estimates have been based mainly on retrospective series, and prospective data is likely to be "a more accurate reflection of things."
"It really does appear that trastuzumab -- being an antibody -- doesn't get adequate CNS penetration," he said, and the potential advantage of lapatinib is better access to the brain and nervous system.
In Dr. Lin's study, he said, "basically, they are seeing some activity in these patients."
The studies were supported by Genentech and GlaxoSmithKline. Dr. Lin reported financial links with both companies. Dr. Yardley reported links with Lilly, Pfizer, Genentech, Abraxis, and Novartis.
Primary source: Breast Cancer Research and TreatmentSource reference:Lin NU, et al "Lapatinib and capecitabine for the treatment of brain metastases in patients with HER2+ breast cancer: an updated analysis from EGF105084" Breast Cancer Res Treat 2007; 106 (Supp1): Abstract 6076. Additional source: Breast Cancer Research and TreatmentSource reference: Yardley DA, et al "registHER: patient characteristics and time course of CNS metastases in patients with HER2-positive metastatic breast cancer" Breast Cancer Res Treat 2007; 106 (Supp1): Abstract 6049.