HER-2 Status and Prognosis in Breast Cancer Patients with Brain Metastases
HER-2 Status and Prognosis in Breast Cancer Patients with Brain Metastases
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: A retrospective analysis of newly-diagnosed brain metastases in patients with breast cancer revealed that those with HER-2 positive disease had more favorable survival than those who were HER-2 negative. Compared to those with "triple negative" disease (median survival 4.0 months) those who had HER-2 positive disease survived 17.1 months. Furthermore, the median survival of the entire cohort was modestly improved compared with historical controls from the 1980s and 1990s.
Source: Eichler AF, et al. Survival in patients with rain metastases from breast cancer. The importance of HER-2 status. Cancer. 2008;112:2359-2367.
Over the past two decades there has been a 24% decrease in breast cancer mortality rates, attributable primarily to early recognition and effective adjuvant therapy.1 Nonetheless, for those with metastatic disease, the disease remains lethal and is the second leading cause of cancer-related death in women. Metastatic disease to the brain is an important cause of morbidity and mortality occurring in approximately one in five of those patients with metastatic disease and confers a very poor prognosis. Death can be the result of progressive disease within the brain, or because of progressive disease systemically, or both, and typically survival is measured in months after the diagnosis of CNS involvement.
Previous reports examining prognostic factors that might influence survival in patients with brain metastases had not included HER-2 status. To this end, Eichler and colleagues performed a single-institution, retrospective cohort study of all breast cancer patients with newly diagnosed brain metastases over the most recent 5 years.
There were 83 patients with breast cancer and newly diagnosed brain metastases between January 1, 2001, and December 31, 2005 treated at their institution (Massachusetts General Hospital). Survival was estimated using the Kaplan-Meier method and curves were compared using the log-rank test. A Cox proportional hazards model was used to determine independent predictors of survival.
The median overall survival from the time of BM was 8.3 months. On univariate analysis, HER-2-positive patients were found to have prolonged survival compared with HER-2-negative patients (17.1 months vs 5.2 months). Patients with triple negative disease (estrogen receptor, progesterone receptor and HER-2) had a median survival of 4.0 months, compared with 11.2 months for all other patients. Additional predictors of improved survival on univariate analysis included £ 3 foci of brain metastases, controlled or absent systemic disease, and controlled local disease. On multivariate analysis, only HER-2 status, number of brain metastases, and local disease status remained independent predictors of survival.
Commentary
The survival of breast cancer patients with brain metastases appears to be improving. For a subset who present with a single brain lesion, surgical resection or stereotactic radiosurgery combined with whole brain radiotherapy has improved neurologic progression-free and overall survival by 2-6 months over whole brain radiotherapy alone.2-4 Another factor, no doubt, is the improvement in systemic therapy, including the introduction of specific therapy for those with HER-2 positive tumors.5
The reasons behind the improved survival for those with HER-2 positive disease and brain metastases compared to those who are HER-2 negative is unclear, but it may just reflect improved systemic control related to trastuzumab therapy. Also possible is that the biology of HER-2 positive disease is different and more responsive to cranial radiotherapy or that there is some control of CNS lesions by penetration of the blood brain barrier by trastuzumab.
For whatever reason, it is apparent that HER-2 status is a strong predictor of survival after the diagnosis of brain metastases. This was a retrospective study, limited in size, and perhaps biased because the age/functional status, etc of patients referred to a tertiary center such as theirs might not reflect the general population of breast cancer patients, but it is difficult to refute their conclusion that better understanding of both the predictors of brain recurrence and the delayed effects of treatment is needed to properly counsel patients regarding the risk-benefit ratio of various treatment modalities.
References
1. Jatoi I, et al. Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol. 2007;25(13):1683-1690.
2. Andrews DW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363(9422):1665-1672.
3. Patchell RA, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494-500.
4. Vecht CJ, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol. 1993;33(6):583-590.
5. Slamon DJ, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-792.
A retrospective analysis of newly-diagnosed brain metastases in patients with breast cancer revealed that those with HER-2 positive disease had more favorable survival than those who were HER-2 negative. Compared to those with "triple negative" disease (median survival 4.0 months) those who had HER-2 positive disease survived 17.1 months.Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.