Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG).

BACKGROUND: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified. PATIENTS AND METHODS: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time. RESULTS: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%). CONCLUSION: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.     

Primary breast cancer phenotypes associated with propensity for central nervous system metastases

BACKGROUND: There is anecdotal evidence that the incidence of central nervous system (CNS) metastases in breast cancer patients is increasing. It is unclear whether specific tumor biological properties or the use of systemic therapies influence this risk. METHODS: Using a database of 10,782 patients, 2685 patients were identified who experienced recurrence distantly. Clinical and biological features were analyzed in 2 ways: (1) patients who ever had versus those who never had CNS metastases, and (2) CNS metastases as the first site of recurrence versus those who had other sites. Correlations of survival after CNS metastasis with clinical and biologic features were also analyzed. RESULTS: In the ever versus never analysis, CNS metastases were significantly associated with younger age, premenopausal status, infiltrating ductal carcinoma histology (IDC), estrogen receptor (ER) and progesterone receptor (PR) negativity, low Bcl-2, high S-phase, aneuploidy, and altered p53. Tumor size, lymph node status, and use of adjuvant systemic therapy played little role. HER-2 overexpression was not associated with an increased risk in these patients (none of whom were treated with trastuzumab) (P = .91). However, epidermal growth factor receptor (EGFR) overexpression was associated with increased risk (P = .02). A multivariate analysis revealed ER negativity (odds ratio [OR] 2.8, P < .001), IDC histology (OR 2.5, P = .02), and young age (P < .001) as independent factors for CNS metastases. The clinical and biologic profiles of primary tumors with CNS metastases at first recurrence did not differ from those with CNS metastases after recurrence to other sites, except for HER-2 status. HER-2-positive tumors were not more likely to undergo recurrence initially in the CNS (P =.04). The median survival after CNS metastases was 5.5 months and HER-2-positive patients had a shorter survival. CONCLUSIONS: Younger patients with hormone receptor-negative, highly proliferative, genomically unstable, and p53-altered tumors were at increased relative risk for CNS metastases. HER-2 expression and adjuvant systemic therapies did not increase this risk.     

Central nervous system metastases in a cohort of metastatic breast cancer patients treated with trastuzumab

Background  Several analyses suggest an increase of brain metastases in HER2 over-expressing breast cancers treated with trastuzumab as compared to historical series of unselected patients. Patients and methods  We analyzed the incidence of central nervous system (CNS) metastases in 78 patients with HER2 over-expressing breast cancer treated with trastuzumab between July 2000 and June 2006 at the Oncology Department of University Federico II in Naples. We also characterized and compared patients with and without CNS involvement. Results  The median follow-up was 35.3 months (95%CI 26.3–44); median overall survival was 56 months (95%CIs 46-nr); 5 patients showed CNS involvement before trastuzumab therapy while 31 developed CNS metastases during trastuzumab treatment. The median overall survival after CNS metastases was 25.4 months (95%CIs 15.2-nr); patients with CNS lesions showed worse overall survival than patients without CNS lesions (39.1 vs. 75 months, p = 0.005). Conclusion  CNS metastases are common events in patients with metastatic HER2 over-expressing breast cancer treated with trastuzumab; the impact on survival is detrimental even if survival after CNS metastases is longer than historical reports. Appropriate investigation of the role of CNS imaging screening and the prophylactic treatment strategies for CNS represents a priority research in this setting. E. Montagna and G. Cancello have contributed equally to this work.     

Central nervous system metastases in women after multimodality therapy for high risk breast cancer

Background: Central nervous system (CNS) relapse is increasing in breast cancer. This increase may reflect altered failure patterns from adjuvant therapy, more effective systemic therapy with improved control in non-CNS sites, or a resistant breast cancer subtype.Methods: To determine the factors associated with clinical CNS relapse, we examined response to neoadjuvant chemotherapy (chemosensitivity), time to relapse and sites of relapse in a cohort of 140 patients without evidence of metastasis at presentation.Results: At 5 years (interquartile range 3–6 years), 44 (31%) patients developed distant metastases, including 13 with CNS metastases. CNS relapse was early (median 24 months after diagnosis) and associated with relapse in bone and liver, suggesting hematogenous dissemination. Those with CNS relapse were younger at diagnosis (40 versus 49 years) and more likely to have lymphovascular invasion in the primary tumor compared with non-CNS metastases. Response to neoadjuvant chemotherapy was not different (69% versus 73% response rate) between the two groups. Extent of residual disease after chemotherapy was strongly associated with relapse outside the CNS but not CNS relapses. The CNS was an isolated or dominant site of metastasis in 8 of 13. Despite treatment, most patients with CNS involvement died of neurologic causes a median of 6 months later.Conclusion: Breast cancers that develop CNS metastases differ from those that develop metastases elsewhere. Both tumor behavior and reduced chemotherapy accessibility to the CNS may contribute to increased CNS involvement in breast cancer patients treated with multimodality therapy.     

Predictors of nodal metastasis in salivary gland cancer

OBJECTIVES: This study was conducted to determine clinical and histologic factors that would predict nodal metastasis in patients with major salivary gland cancer. METHODS: A retrospective study of 40 patients who underwent surgery, including neck dissection, for major salivary gland cancer between 1975 and 1997 was performed. Patient charts were reviewed, and clinical and pathologic data were extracted along with outcome. Predictive factors were identified and survival curves were obtained. RESULTS: Neck dissections were performed in 40 patients, which revealed histologic evidence of tumor in lymph nodes in 15 cases. Histologically proven metastasis was found in 16% of specimens from elective and 73% of specimens from therapeutic neck dissection. Five-year overall and locoregional disease-free survival rates for histologically positive and negative groups were 40% versus 63% (P < 0.05) and 67% versus 69% (P = 0.59), respectively. Univariate analysis of the factors revealed that clinical evidence of nodal metastasis (P < 0.001) and high-grade cancer (P < 0.033) predicted histologic nodal involvement. Multivariate analysis revealed that only a positive neck examination was a significant predictive factor (OR = 31, 95%CI = 2.99-312). CONCLUSIONS: Our results suggest that clinical neck examination is a reliable predictor of regional metastasis in patients with major salivary gland cancer. In view of the low frequency of occult metastases, routine elective treatment of the neck is not recommended.     

Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases

BACKGROUND: The purpose of the current study was to characterize the outcomes of patients with metastatic triple-negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) recurrence. METHODS: Using pharmacy and pathology records, a study group of 116 patients who were treated for metastatic triple-negative breast cancer at Dana-Farber Cancer Institute between January 2000 and June 2006 was identified. RESULTS: The median survival from time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were diagnosed with CNS involvement at the time of initial metastatic diagnosis; overall, 46% of patients were diagnosed with CNS metastases before death. The median survival after a diagnosis of CNS metastasis was 4.9 months. The age-adjusted and race-adjusted rate of death for patients whose first presentation included a CNS metastasis was 3.4 times (95% confidence interval, 1.9-6.1 times) that of patients without a CNS lesion at the time of first metastatic presentation. Of the 53 patients who developed brain metastases, only 3 patients were judged to have stable or responsive systemic disease in the face of progressive CNS disease at the last follow-up before death. CONCLUSIONS: Triple-negative breast cancer is associated with poor survival after recurrence. CNS recurrence is common, but death as a direct consequence of CNS progression in the setting of controlled systemic disease is uncommon. Thus, it does not appear that the high rate of CNS involvement is because of a sanctuary effect, but rather is due to the lack of effective therapies in general for this aggressive subtype of breast cancer. New treatment strategies are needed.     

Clinical Significance of Occult Micrometastases in Axillary Lymph Nodes in "Node-negative" Breast Cancer Patients

The most important subgroup of breast cancer patients for whom reliable prognostic indicators are needed is women without axillary lymph node metastases. We evaluated the clinical significance of occult micrometastases in axillary lymph nodes in 148 consecutive "node-negative" breast cancer patients. The median age of the patients at surgery was 52 years and the median follow-up period after surgery was 98.5 months. Occult micrometastases were detected in 21 of 148 patients (14.2%) by means of immunohistochemical analysis using AE1/3 antibody and a single unstained section after routine histopathological examination. Log-rank tests indicated that the 7–year disease-free survival (DFS) and overall survival (OS) rates by Kaplan-Meier methods were significantly better in patients without occult micrometastases than in patients with occult micrometastases [DFS, 93% versus 71% ( P =0.0009); OS, 96% versus 76% ( P =0.0001)]. According to Cox's multivariate analysis, the presence of occult micrometastases had the most significant effect on DFS ( P =0.0053) and OS ( P =0.0035). These findings suggest that the presence of occult micrometastases is an independent and significant predictor of clinical outcome, and that their immunohistochemical detection after routine histopathological examination is useful for selecting the "node-negative" breast cancer patient subgroup at high risk for relapse and death.     

Routine Neuroimaging in Patients with Stage IV Non-Small Cell Lung Cancer: A Single Center Experience

Background: There is a lack of consensus in current practice guidelines regarding routine neuroimaging in patients with stage IV non-small cell lung cancer (NSCLC) without neurologic symptoms, and there is a paucity of data on the impact of such imaging on overall survival (OS). Methods: This retrospective study included 257 patients with stage IV NSCLC without neurologic symptoms diagnosed between January 1, 2013 and December 31, 2016 at Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). The primary objective of this study was to compare the evolution of patients with stage IV NSCLC who had baseline brain imaging versus with who did not. Secondary objectives were to determine the proportion of patients who underwent brain imaging in their initial investigation and the proportion of patients who developed metachronous central nervous system (CNS) metastasis. Results: CNS imaging, mainly with computed tomography (CT), was performed at diagnosis in 56% of patients, and the prevalence of synchronous CNS metastasis among these patients was 32%. There was no difference in median OS between patients who underwent initial CNS imaging and those who did not, but we did show a tendency for a higher cumulative incidence of metachronous CNS metastasis in patients without baseline imaging. These metachronous metastases were symptomatic and were more often not treated when compared to synchronous metastases. Conclusions: In this small, unicentric retrospective study, there was no benefit with routine neuroimaging in terms of median OS in stage IV NSCLC patients without neurologic symptoms.     

The effect of prior adjuvant chemotherapy on survival in metastatic breast cancer

Some adjuvantly treated patients develop recurrent breast cancer and little is known about the effect of prior adjuvant chemotherapy on subsequent response rates to systemic therapy or on overall survival. We describe our retrospective comparison of 179 patients who received doxorubicin containing adjuvant chemotherapy and developed recurrent breast cancer on University of Arizona Cancer Center clinical trials with 202 non-adjuvantly treated patients entered onto clinical protocols for recurrent or metastatic breast cancer during the same period. Adjuvant failures had a shorter median survival from the date of onset of recurrent disease (18 months versus 28 months, P less than 0.001), a lower response rate to initial combination chemotherapy (38% versus 69%, P = 0.001), and a high incidence of CNS involvement at the time of relapse (11%). In patients having recurrent or metastatic breast cancer, a history of prior adjuvant chemotherapy appears to identify a subgroup who will have a higher incidence of CNS involvement, a lower response rate to chemotherapy and a shorter survival with metastatic disease. These findings may help explain the failure of improved relapse free survival seen in many adjuvant chemotherapy trials to result in improved overall survival.     

Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors

BACKGROUND: A higher incidence of central nervous system (CNS) metastases in HER-2-positive metastatic breast cancer (MBC) has recently been reported. MATERIALS AND METHODS: Aims of this observational study were to evaluate the incidence of CNS metastases in HER-2-positive MBC patients, to define the outcome of patients with CNS metastases, and to identify the risk factors for CNS relapse. RESULTS: Between April 1999 and June 2005 we treated 122 consecutive HER-2-positive MBC patients with chemotherapy and trastuzumab. At a median follow-up of 28 months from the occurrence of metastatic disease, 43 patients (35.2%) developed CNS metastases. The median time to death from the diagnosis of CNS metastases was 23.46 months. At multivariate analysis we found that only premenopausal status at diagnosis of breast cancer and visceral metastases as the dominant site at relapse were significantly associated with a higher risk for CNS metastases. CONCLUSION: The CNS metastasis incidence is very high in HER-2-positive MBC, but the survival after CNS relapse in these patients is longer than in patients unselected for HER-2 status, because of the better control of extracranial disease obtained by trastuzumab. The identified risk factors for CNS relapse could allow us to select a subgroup of HER-2-positive MBC patients as candidates for active surveillance for CNS progression (by computed tomography or magnetic resonance imaging) and/or as candidates for accrual in trials of prevention of CNS relapse.     

Clinical significance of occult micrometastases in axillary lymph nodes in "node-negative" breast cancer patients.

The most important subgroup of breast cancer patients for whom reliable prognostic indicators are needed is women without axillary lymph node metastases. We evaluated the clinical significance of occult micrometastases in axillary lymph nodes in 148 consecutive "node-negative" breast cancer patients. The median age of the patients at surgery was 52 years and the median follow-up period after surgery was 98.5 months. Occult micrometastases were detected in 21 of 148 patients (14.2%) by means of immunohistochemical analysis using AE1 / 3 antibody and a single unstained section after routine histopathological examination. Log-rank tests indicated that the 7-year disease-free survival (DFS) and overall survival (OS) rates by Kaplan-Meier methods were significantly better in patients without occult micrometastases than in patients with occult micrometastases [DFS, 93% versus 71% (P = 0.0009); OS, 96% versus 76% (P = 0.0001)]. According to Cox's multivariate analysis, the presence of occult micrometastases had the most significant effect on DFS (P = 0.0053) and OS (P = 0.0035). These findings suggest that the presence of occult micrometastases is an independent and significant predictor of clinical outcome, and that their immunohistochemical detection after routine histopathological examination is useful for selecting the "node-negative" breast cancer patient subgroup at high risk for relapse and death.     

Central nervous system metastases in patients with high-risk breast carcinoma after multimodality treatment

BACKGROUND: The current study was performed to determine the incidence of central nervous system (CNS) metastases and to examine associated disease characteristics in a group of patients with locally advanced breast carcinoma (LABC) or inflammatory breast carcinoma (IBC) treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX). METHODS: Seven hundred sixty-eight patients treated with multimodality therapy between 1982 and 2000 in any of 6 neoadjuvant trials were eligible for the current study. Five hundred ninety-two patients (77%) had LABC, and 176 (23%) had IBC. CNS disease was defined as the presence of brain metastases or leptomeningeal disease. Time to detection of CNS disease and overall survival were estimated using the Kaplan-Meier product-limit method, and differences were evaluated using log-rank tests. RESULTS: The median patient age was 48 years. Most tumors were classified as T4 lesions (58%) and exhibited lymph node involvement (78%). Fifty-one percent of all tumors had positive hormone receptor status. At a median follow-up duration of 9.5 years, 61 patients (8%) had developed CNS metastases, with the CNS representing the first site of recurrence for 38 of these 61 (63%). Characteristics associated with the development of CNS metastases over time included negative hormone receptor status (P = 0.03), Grade 3 disease (P = 0.01), and larger tumor size (P = 0.02). The median time to detection of CNS metastases was 2.3 years. Ten patients (16%) remained alive after treatment for CNS metastases. The median survival from the time of diagnosis of CNS metastases was 8 months. CONCLUSIONS: CNS metastases from breast carcinoma were relatively uncommon and were strongly associated with more aggressive clinical presentation. Survival from the time of diagnosis of such metastases generally was short.     

Clinical outcome of breast cancer patients with liver metastases alone in the anthracycline-taxane era: a retrospective analysis of two prospective, randomised metastatic breast cancer trials

Liver metastases have long been known to indicate an unfavourable disease course in breast cancer (BC). However, a small subset of patients with liver metastases alone who were treated with pre-taxane chemotherapy regimens was reported to have longer survival compared with patients with liver and metastases at other sites. In the present study, we examined the clinical outcome of breast cancer patients with liver metastases alone in the context of two phase III European Organisation for Research and Treatment of Cancer (EORTC) trials which compared the efficacy of doxorubicin (A) versus paclitaxel (T) (trial 10923) and of AC (cyclophosphamide) versus AT (trial 10961), given as first-line chemotherapy in metastatic BC patients. The median follow-up for the patients with liver metastases was 90.5 months in trial 10923 and 56.6 months in trial 10961. Patients with liver metastases alone comprised 18% of all patients with liver metastases, in both the 10923 and 10961 trials. The median survival of patients with liver metastases alone and liver plus other sites of metastases were 22.7 and 14.2 months (log rank test, P=0.002) in trial 10923 and 27.1 and 16.8 months (log rank test, P=0.19) in trial 10961. The median TTP (time to progression) for patients with liver metastases alone was also longer compared with the liver plus other sites of metastases group in both trials: 10.2 versus 8.8 months (log rank test, P=0.02) in trial 10923 and 8.3 versus 6.7 months (log rank test, P=0.37) in trial 10961. Most patients with liver metastases alone have progression of their disease in their liver again (96 and 60% of patients in trials 10923 and 10961, respectively). Given the high prevalence of breast cancer, improved detection of liver metastases, encouraging survival achieved with currently available cytotoxic agents and the fact that a significant portion of patients with liver metastases alone have progression of their tumour in the liver again, a more aggressive multimodality treatment approach through prospective clinical trials seems worth exploring in this specific subset of women.     

Leptomeningeal metastases from breast cancer: intrinsic subtypes may affect unique clinical manifestations

Leptomeningeal metastasis (LM) usually occurs late during the course of breast cancer. The aim of this study was to characterize the clinical features and outcomes of LM based on breast cancer subtypes in conjunction with brain parenchymal metastases. A retrospective study was performed of breast cancer patients with LM, who received palliative management at Samsung Medical Center between 1995 and 2008. Among the 272 metastatic breast cancer patients with central nervous system (CNS) involvement, 68 patients with LM were identified. The median age was 46 years (range, 24-72 years). The median survival duration from LM to death (LM-OS) was 4.5 months (range, 0.2-26.4 months). Patients surviving for 12 or more months were rarer among triple negative (TN) patients compared to other subtypes (21.7% for HR + ve vs. 27.8% for HER2 + ve vs. 72.7% for TN, P = 0.217). Death caused by CNS involvement appeared to be much more common in TN than in other subtypes (0% for HR + ve vs. 36% for HER2 + ve vs. 64% for TN, P = 0.060). Median survival time from distant metastasis was significantly different among the three groups (28.3 vs. 29.1 vs. 11.8 months, P < 0.0001). However, median survival time from LM did not differ (4.1 vs. 5.9 vs. 3.8 months, P = 0.226). Characteristic manifestations and treatment outcomes of LM may be affected by the unique biology of breast cancer intrinsic subtypes. The different roles of active combined treatment modalities including both systemic chemotherapy and local treatment modalities should be considered to improve outcomes.     

Pattern of tumor recurrence in initially nonmetastatic breast cancer patients: distribution and frequency of metastases at unusual sites

BACKGROUND: Breast cancer is likely to have systemic involvement. However, to the authors' knowledge there are few reports to date regarding clinically detected patterns of metastasis, meticulously studied in regard to the natural history of breast cancer, including unusual sites of metastasis. METHODS: Patients treated for invasive breast cancer from April 1983 to May 2007 were retrospectively analyzed. Patterns of clinically apparent tumor recurrence, focusing especially on unusual metastases, were studied as well as possible risk factors for unusual metastases and their influence on survival. RESULTS: Overall, 3783 patients were eligible for the current analysis. The median duration of follow-up was 5.0 years (range, 0.6 years-20.4 years). Cumulative 5-year and 10-year survival rates were 89.7% and 81.5%, respectively. "Unusual metastasis" was defined as systemic failure with a frequency of < or =1%; in the current series; it was observed in 85 (2.2%) patients %. Of those, 70 (82%) had preceding metastasis in the usual sites. The median duration until the development of usual and unusual metastasis was 2.3 years and 3.6 years, respectively (P < .0001). Among 764 patients with distant metastasis, the 5-year cumulative overall survival rate in those with or without unusual metastasis was 53.5% and 53.4 years, respectively (P = .33). No risk factors for unusual metastasis were identified. CONCLUSIONS: This retrospective study examined the frequency of unusual metastases in a large number of Japanese patients with initially nonmetastatic breast cancer. The prognosis of patients with unusual metastases was found to be similar to that of patients with metastasis only at more usual sites.     

Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy.

PURPOSE: The aim of this study was to characterize the prevalence and predictors of central nervous system (CNS) metastasis among women with HER2-overexpressing metastatic breast cancer receiving trastuzumab-based therapy. METHODS: The frequency and time course of isolated CNS progression were characterized among women with HER2-positive metastatic breast cancer, receiving chemotherapy with or without trastuzumab as first-line treatment for metastatic disease in two clinical trials. The first trial was a multicenter randomized phase III study of chemotherapy (doxorubicin/cyclophosphamide or paclitaxel) +/- trastuzumab, and the second was a multicenter phase II trial of vinorelbine + trastuzumab. All patients had measurable disease and were free of symptomatic CNS disease at initiation of study treatment. RESULTS: Nearly 10% of patients receiving trastuzumab in combination with chemotherapy developed isolated CNS metastases as first site of tumor progression. Progression in the CNS tended to be a later event than progression at other sites among women receiving trastuzumab-based therapy. Trastuzumab-based treatment did not substantially delay onset of CNS metastases as initial site of progression. Following diagnosis with primary breast cancer, tumors with HER2 gene amplification tend to be associated with greater risk of isolated CNS progression compared with those lacking gene amplification. CONCLUSIONS: Patients with HER2-overexpressing metastatic breast cancer are at risk for isolated CNS progression, reflecting improved peripheral tumor control and patient survival through use of trastuzumab-based therapy, and a relative lack of CNS activity with trastuzumab. Clinicians should be aware of this association. Better treatments for CNS recurrences are needed.     

Clinical outcome of central nervous system metastases from breast cancer: differences in survival depending on systemic treatment

Central nerve system (CNS) metastases are a feared complication of breast cancer and are associated with poor prognosis. The purpose of this study is to investigate the clinical characteristics of CNS metastases and to clarify the prognostic factors after CNS metastases in breast cancer at a single institution over a long time period. We retrospectively reviewed the medical records of breast cancer patients diagnosed at Seoul National University Hospital from 1981 to 2009 and identified the patients who experienced CNS metastases. We collected the data, including demographics, clinico-pathologic characteristics, dates of diagnosis of original breast cancer and subsequent metastases, and date of death, and correlated the findings with the clinical outcome. A total of 400 patients were identified, of whom 17 (4.3%) were diagnosed with CNS metastases and primary breast cancer concurrently and 383 (95.7%) experienced CNS metastases subsequent to the diagnosis of primary breast cancer. Further, 318 patients (79.5%) had only brain parenchymal metastases, 30 (7.5%) had only leptomeningeal metastases, and 52 (13%) had both. After the diagnosis of CNS metastasis, 170 patients (42.5%) received systemic chemotherapy (CTx) and 143 (35.8%) received CTx after whole brain radiation therapy (WBRT). The patients with good performance status (PS), initial CNS metastasis as recurrence, absence of extracranial metastases, non-visceral extracranial metastases, longer interval from the date of primary breast cancer to the date of CNS metastasis, and CTx after WBRT and gamma-knife surgery (GKS), had better outcomes in univariate analyses. In multivariate analysis, good PS, systemic CTx after WBRT, GKS, and longer interval to CNS metastasis, were independent prognostic factors for overall survival after CNS metastases. Our results suggest that appropriate palliative systemic therapy after WBRT or GKS, and adequate palliative treatment via combined modalities are helpful for breast cancer patients, even after the detection of CNS metastases.     

单中心25例隐匿性乳腺癌的临床病理特征及预后分析

目的： 回顾性分析隐匿性乳腺癌(occult breast cancer，OBC )患者的资料，初步探讨其临床病理特征及影响患者预后的因素。方法：收集四川大学华西医院肿瘤中心2001年10月至2016年6月收治的25例隐匿性乳腺癌的临床病理及治疗资料，采用Kaplan Meier法计算生存率并绘制生存曲线，log rank检验及COX回归分别进行单因素及多因素生存分析。结果：本组患者5年总生存率（overall survival,OS）为57.8%。雌激素受体（estrogen receptor，ER）阳性率48%，孕激素受体（progesterone receptor，PR）阳性率52%，人表皮生长因子受体2(human epithelial growth factor receptor 2, HER2)阳性率32%。单因素分析结果显示：PR状态、放疗、内分泌治疗及远处转移是可能影响预后的因素。多因素分析结果显示远处转移是唯一影响预后的因素，降低了患者总生存率（HR=0.131；95%CI，0.020~0.835；P=0.031）。结论：隐匿性乳腺癌发病率低，诊断困难，远处转移是影响预后的重要因素。手术、化疗、放疗、内分泌治疗和靶向治疗的综合治疗是提高隐匿性乳腺癌患者生存率的重要措施。     

Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis

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.     

CNS metastases in breast cancer.

As systemic therapy of metastatic breast cancer improves, CNS involvement is becoming a more widespread problem. This article summarizes the current knowledge regarding the incidence, clinical presentation, diagnosis, prognosis, and treatment of CNS metastases in patients with breast cancer. When available, studies specific to breast cancer are presented; in studies in which many solid tumors were evaluated together, the proportion of patients with breast cancer is noted. On the basis of data from randomized trials and retrospective series, neurosurgery and stereotactic radiosurgery (SRS) may prolong survival in patients with single brain metastases. The treatment of multiple metastases remains controversial, as does the routine use of whole-brain radiotherapy (WBRT) after either surgery or SRS. Although it is widely assumed that chemotherapy is of limited benefit, data from case series and case reports suggest otherwise. WBRT, neurosurgery, SRS, and medical therapy each have a role in the treatment of CNS metastases; however, neurologic symptoms frequently are not fully reversible, even with appropriate therapy. Studies specifically targeted toward this group of patients are needed.