Oncology NEWS International.
Focus on Breast Cancer
ASCO studies pose question: Do brain metastases in patients with HER2+ breast ca affect overall survival?
September 1, 2007
It is possible that certain patients are predisposed to developing CNS metastases, according to research from Baylor College of Medicine (abstract 1019). In a genetic analysis that compared breast cancer patients with CNS metastases and those without, Yee-Lu Tham, MD, and colleagues identified 354 genes that were more highly expressed in primary breast tumors from patients who developed brain metastasis.
No effect of early diagnosis
Polish researchers showed that early diagnosis of these brain metastases does not improve survival, even when patients receive treatment before symptoms are present (abstract 1015). Anna Niwinska, PhD, and colleagues from The Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, screened 80 metastatic HER2-positive patients with MRI of the brain every 3 months and detected occult metastases in 29, who were treated with whole brain radiotherapy. These patients were compared with 48 who were treated for symptomatic brain metastases.
Median overall survival was the same in both groups: 53 months for the asymptomatic patients vs 52 months for the symptomatic patients. Median survival after the diagnosis of brain metastases was also the same: 9 months vs 9.3 months. However, brain lesions as the cause of death was significantly higher in the patients treated only after symptoms developed: 48% vs 16% for those with asymptomatic brain lesions. Patients treated before symptoms developed also had improved quality of life due to a lower rate of neurological complications. "Early treatment of asymptomatic disease reduced cerebral deaths but not overall deaths," Dr. Niwinska concluded.
HER2 status and brain mets: Time to take an interest
MINESH MEHTA, MD Oncologists should take an interest in the relationship between HER2-positive breast cancer and the development of CNS metastases since breast cancer is the second most common cause of brain metastasis, said Dr. Mehta, of the University of Wisconsin Medical School, in his discussion of the posters on that topic at ASCO 2007.
"There are more cases of brain metastases from breast cancer than there are cases of gliomas," he noted.
Based on epidemiologic studies, Dr. Mehta said, the risk for brain metastasis in breast cancer patients is associated with younger age, presence of visceral metastasis, hormone-receptor negativity, and HER2 overexpression. Patients with HER2-positive tumors have a 10-fold increased risk of the brain being the first site of relapse.
At ASCO, Pinder et al (abstract 1018) found that patients receiving trastuzumab have a risk for CNS metastasis that is nearly three times higher than that of HER2-positive patients who do not receive trastuzumab.
There are two possible explanations, Dr. Mehta said: Treatment with trastuzumab controls the disease well enough to give brain metastasis time to emerge, and trastuzumab may select out clones with an affinity for the CNS. The latter concept is investigated in the study by Tham et al (abstract 1019), which identified 354 genes that were overexpressed in patients developing brain metastases.
"There may be a set of genes predisposing patients to the development of CNS metastases," Dr. Mehta observed. "We need to evaluate patients after exposure to trastuzumab to see if the drug is selecting out these clones. This work is being planned." Interestingly, he said, while HER2-positive patients were found to have a greater risk of developing brain metastases, compared to HER2-negative patients, their overall survival was actually better than that of HER2-negative patients who developed brain metastases (Sawrie et al, abstract 1016). "These are very intriguing findings, and imply that the more aggressive treatment that HER2-positive patients receive [trastuzumab] may prolong their survival," Dr. Mehta said. "Women who develop brain metastases from HER2-positive breast cancer and are treated with trastuzumab may have the same risk of dying as those who do not develop brain metastases."
Dr. Mehta then posed this question: "Knowing that HER2-positive patients are at an increased risk for brain metastases, should we screen for this?" He answered no, because based on the study from Poland (abstract 1015), screening and early treatment do not make a difference in overall survival.
• Even though HER2-positive breast cancer patients are at increased risk of brain metastases, the development of CNS disease in these patients does not affect overall survival.
• Screening for brain mets isn't necessary, since screening and early treatment do not increase overall survival, according to studies presented at ASCO.