Lani
11-03-2007, 01:10 AM
Cancer. 2007 Oct 25; [Epub ahead of print]
Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis.
Altundag K, Bondy ML, Mirza NQ, Kau SW, Broglio K, Hortobagyi GN, Rivera E.
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
BACKGROUND.: Breast cancer is the second most common cause of central nervous system (CNS) metastases. Several risk factors for CNS metastases have been reported. The objective of the current study was to describe clinicopathologic characteristics and prognostic factors in breast cancer patients with CNS metastases. METHODS.: The authors retrospectively evaluated clinical data from 420 patients who had been diagnosed with breast cancer and CNS metastasis between 1994 and 2004 at the University of Texas M. D. Anderson Cancer Center. RESULTS.: The median age of the patients at the time of diagnosis of breast cancer was 45 years (range, 25-77 years). Premenopausal and postmenopausal patients were distributed equally. Most patients had invasive ductal histology (91.2%), grade 3 tumors (81.4%) (using the modified Black nuclear grading system), T2 tumor classification (40.1%), and N1 lymph node status (59.7%) diagnosis. Forty percent of patients had estrogen receptor (ER)-positive disease, and 34% had progesterone receptor-positive disease. HER-2/neu status was recorded for only 248 patients, and 39% of the patients in that group had HER-2/neu-positive disease. The most common sites of first metastasis were liver, bone, and lung. CNS metastasis was the site of first recurrence in 53 patients (12%). In total, 329 patients had received either neoadjuvant treatment (113 patients) or adjuvant chemotherapy (216 patients). The majority of those patients (74.4%) had received anthracycline-based regimens. Metastasis was solitary in 111 patients (26.4%), and 29 patients had only leptomeningeal metastases. The median time from breast cancer diagnosis to CNS metastasis was 30.9 months (range, from -5 months to 216.7 months). The median follow-up after a diagnosis of CNS metastasis was 6 months (range, 7-95.9 months). In all, 359 patients died, and the overall median survival was 6.8 months. Only age at diagnosis and ER status were associated significantly with overall survival in the multivariate analysis. CONCLUSIONS.: The current results indicated that the prognosis remains patients with breast cancer metastatic to the CNS. More effective treatment approaches are needed for patients with CNS metastases, even for those with favorable prognostic factors, such as ER-positive tumors or younger age. Cancer 2007. (c) 2007 American Cancer Society.
PMID: 17960791 [PubMed - as supplied by publisher]
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Patients Who Survived for >18 Months
Eighty-two patients (19.5%) were alive at least 18 months after diagnosis of CNS metastasis. Of these 82 patients, 25 patients (30%) had HER-2-positive breast cancer. Furthermore, 18 patients (4.2%) were alive at least 60 months after this diagnosis. The median age of these relatively longer surviving patients was 42 years. Most of these patients had tumors of the ductal histologic type, tumors classified as T1 or T2, lymph node status N0 or N1, and a metastatic status of M0 at diagnosis. Approximately 50% of these patients had ER-positive or PR-positive disease, and 73% had grade 3 disease. Forty-six percent of these patients had a single CNS metastasis.
Compared with the median age of all breast cancer patients, the median age of patients with CNS metastases in our series was younger. Moreover, our cohort comprised more patients with ER-negative tumors than with ER-positive tumors. These data support previous reports indicating that patients with ER-negative tumors and younger age had a greater tendency to develop CNS metastases.[1][9][10]
Authors of a previous study reported that prior lung metastases predicted brain metastases in patients with breast cancer.[21] This also was true for our study cohort, in which 84 patients had lung as the primary metastatic site. Moreover, the median time from first metastatic site to CNS metastasis was shorter for patients who had lung as the first metastatic site than for patients who had bone as the first metastatic site. This may be explained partly by the assumption that metastatic breast cancer cells lodged in lung parenchyma can go more readily to the brain than those lodged in other sites.[22] The results from our multivariate analysis indicated that age and ER status were 2 independent factors for overall survival. Patients aged <50 years are expected to have better a performance status, resulting in better tolerance to therapy and longer overall survival. Similarly, Patients with ER-negative tumors tended to have a worse prognosis than patients with ER-positive tumors.
Among 248 patients with known HER-2 status in our study, 97 patients with breast cancer (39%) had HER-2-positive disease. This information supports the broad perception that positive HER-2 status is a risk factor for CNS metastases. Furthermore, several studies have reported improved survival from the time of diagnosis of CNS metastases diagnosed in patients who had HER-2-positive disease compared with patients who had HER-2-negative disease.[23][24] In our study, patients who had HER-2/neu-positive disease also lived longer compared with patients who had HER-2/neu-negative disease (11 months vs 6 months; P = .005). Improvements in survival largely can be attributed to the control of other sites of visceral metastases by the use of trastuzumab.
Although the survival outlook for patients with breast cancer metastatic to CNS is generally poor, there were some long-term survivors. Eighty-two patients (19.5%) survived for >18 months. The median age of these patients was 42 years. Compared with an unselected series of breast cancer patients, this longer surviving population was younger and predominantly was premenopausal. This group also included a higher proportion of patients with a single metastatic lesion and with CNS as the first metastatic site. Compared with unselected breast cancer patients, these patients had a higher percentage of ER-positive tumors. Any or all of these characteristics may explain their potential for prolonged survival.
Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis.
Altundag K, Bondy ML, Mirza NQ, Kau SW, Broglio K, Hortobagyi GN, Rivera E.
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
BACKGROUND.: Breast cancer is the second most common cause of central nervous system (CNS) metastases. Several risk factors for CNS metastases have been reported. The objective of the current study was to describe clinicopathologic characteristics and prognostic factors in breast cancer patients with CNS metastases. METHODS.: The authors retrospectively evaluated clinical data from 420 patients who had been diagnosed with breast cancer and CNS metastasis between 1994 and 2004 at the University of Texas M. D. Anderson Cancer Center. RESULTS.: The median age of the patients at the time of diagnosis of breast cancer was 45 years (range, 25-77 years). Premenopausal and postmenopausal patients were distributed equally. Most patients had invasive ductal histology (91.2%), grade 3 tumors (81.4%) (using the modified Black nuclear grading system), T2 tumor classification (40.1%), and N1 lymph node status (59.7%) diagnosis. Forty percent of patients had estrogen receptor (ER)-positive disease, and 34% had progesterone receptor-positive disease. HER-2/neu status was recorded for only 248 patients, and 39% of the patients in that group had HER-2/neu-positive disease. The most common sites of first metastasis were liver, bone, and lung. CNS metastasis was the site of first recurrence in 53 patients (12%). In total, 329 patients had received either neoadjuvant treatment (113 patients) or adjuvant chemotherapy (216 patients). The majority of those patients (74.4%) had received anthracycline-based regimens. Metastasis was solitary in 111 patients (26.4%), and 29 patients had only leptomeningeal metastases. The median time from breast cancer diagnosis to CNS metastasis was 30.9 months (range, from -5 months to 216.7 months). The median follow-up after a diagnosis of CNS metastasis was 6 months (range, 7-95.9 months). In all, 359 patients died, and the overall median survival was 6.8 months. Only age at diagnosis and ER status were associated significantly with overall survival in the multivariate analysis. CONCLUSIONS.: The current results indicated that the prognosis remains patients with breast cancer metastatic to the CNS. More effective treatment approaches are needed for patients with CNS metastases, even for those with favorable prognostic factors, such as ER-positive tumors or younger age. Cancer 2007. (c) 2007 American Cancer Society.
PMID: 17960791 [PubMed - as supplied by publisher]
^^^^^^^^^^^^^^^^^^^
Patients Who Survived for >18 Months
Eighty-two patients (19.5%) were alive at least 18 months after diagnosis of CNS metastasis. Of these 82 patients, 25 patients (30%) had HER-2-positive breast cancer. Furthermore, 18 patients (4.2%) were alive at least 60 months after this diagnosis. The median age of these relatively longer surviving patients was 42 years. Most of these patients had tumors of the ductal histologic type, tumors classified as T1 or T2, lymph node status N0 or N1, and a metastatic status of M0 at diagnosis. Approximately 50% of these patients had ER-positive or PR-positive disease, and 73% had grade 3 disease. Forty-six percent of these patients had a single CNS metastasis.
Compared with the median age of all breast cancer patients, the median age of patients with CNS metastases in our series was younger. Moreover, our cohort comprised more patients with ER-negative tumors than with ER-positive tumors. These data support previous reports indicating that patients with ER-negative tumors and younger age had a greater tendency to develop CNS metastases.[1][9][10]
Authors of a previous study reported that prior lung metastases predicted brain metastases in patients with breast cancer.[21] This also was true for our study cohort, in which 84 patients had lung as the primary metastatic site. Moreover, the median time from first metastatic site to CNS metastasis was shorter for patients who had lung as the first metastatic site than for patients who had bone as the first metastatic site. This may be explained partly by the assumption that metastatic breast cancer cells lodged in lung parenchyma can go more readily to the brain than those lodged in other sites.[22] The results from our multivariate analysis indicated that age and ER status were 2 independent factors for overall survival. Patients aged <50 years are expected to have better a performance status, resulting in better tolerance to therapy and longer overall survival. Similarly, Patients with ER-negative tumors tended to have a worse prognosis than patients with ER-positive tumors.
Among 248 patients with known HER-2 status in our study, 97 patients with breast cancer (39%) had HER-2-positive disease. This information supports the broad perception that positive HER-2 status is a risk factor for CNS metastases. Furthermore, several studies have reported improved survival from the time of diagnosis of CNS metastases diagnosed in patients who had HER-2-positive disease compared with patients who had HER-2-negative disease.[23][24] In our study, patients who had HER-2/neu-positive disease also lived longer compared with patients who had HER-2/neu-negative disease (11 months vs 6 months; P = .005). Improvements in survival largely can be attributed to the control of other sites of visceral metastases by the use of trastuzumab.
Although the survival outlook for patients with breast cancer metastatic to CNS is generally poor, there were some long-term survivors. Eighty-two patients (19.5%) survived for >18 months. The median age of these patients was 42 years. Compared with an unselected series of breast cancer patients, this longer surviving population was younger and predominantly was premenopausal. This group also included a higher proportion of patients with a single metastatic lesion and with CNS as the first metastatic site. Compared with unselected breast cancer patients, these patients had a higher percentage of ER-positive tumors. Any or all of these characteristics may explain their potential for prolonged survival.