Brain metastases in patients with breast cancer: new horizons

Brain metastases occur in as many as one third of patients with disseminated breast cancer. In this article, we discuss various presentations of brain metastases from breast cancer and review evidence that supports different treatment options. Because no prospective, randomized, controlled studies, to our knowledge, have focused solely on patients with brain metastases from breast cancer, we will first review retrospective studies of patients with brain metastases from breast cancer. Randomized studies of patients with brain metastases caused by multiple primary cancers will also be examined, and the conclusions from these studies will be extrapolated to patients with breast cancer. Because brain metastases from breast cancer occur in a variety of different clinical settings, ranging from a single metastasis without extensive extracranial disease to multiple brain metastases with widespread extracranial disease, treatment approaches must be tailored to the specific circumstances of each patient. For different clinical scenarios, neurosurgical resection, radiosurgery, and/or whole-brain radiation therapy may be appropriate treatment options. For patients with brain metastases from breast cancer that overexpresses HER2/neu, trastuzumab could alter the natural history of the non-central nervous system (CNS) disease. Therefore, HER2 status could also influence the treatment of brain metastases from breast cancer. Given the prevalence of brain metastases in patients with metastatic breast cancer in contemporary series, the rationale for clinical trials of CNS screening and prophylactic cranial irradiation will be discussed.     

Brain metastases: the HER2 paradigm.

Between 100,000 and 170,000 patients with cancer develop central nervous system (CNS) metastases each year in the U.S., of which approximately 20% carry a primary diagnosis of breast cancer. As a consequence of improvements in systemic therapy, which have allowed patients to live longer with advanced cancer, CNS metastases are emerging as an important sanctuary site, and the incidence may be increasing in patients with particular tumor subtypes. Unless there are improvements in the treatment of CNS disease, a growing proportion of patients may be at risk of experiencing both morbidity and mortality as a result of uncontrolled CNS progression, often at a time when their extra-CNS disease is apparently under control. This article reviews changes in the epidemiology and natural history of women with brain metastases from HER2-positive breast cancer over the last decade and presents the therapeutic challenges and opportunities that have arisen in this setting. First, the apparent increase in CNS disease among women with HER2-positive breast cancer, relative to historical controls, is discussed, followed by consideration of potential causes of this observation. Next, the implications of CNS disease, in terms of prognosis and the potential development of preventive strategies are considered. Finally, new developments in systemic approaches to the treatment of CNS disease, including cytotoxic chemotherapy and targeted therapy, are explored.     

Central nervous system metastases in women with HER-2 positive metastatic breast cancer after treatment with trastuzumab

Background: Historically, central nervous system (CNS) metastases have been reported to occur in 10–16% of women with metastatic breast cancer (MBC) with a median survival of less than 1 year after diagnosis of CNS disease. A higher rate of CNS metastases has been described in women with metastatic breast cancer (MBC) over‐expressing HER‐2 who receive trastuzumab therapy. Aims: The aim of this study was to examine the frequency of and potential risk factors for CNS metastases in these women. Our a priori hypotheses were that in MBC patients treated with trastuzumab, CNS metastases occurred (i) more frequently than historical controls, and (ii) in women with controlled systemic disease. Methods: A retrospective cohort study of 28 consecutive patients with MBC over‐expressing HER‐2 and treated with trastuzumab and chemotherapy was performed. Results: A total of 22/25 (88%) patients who initially responded to trastuzumab had progressed within a median of 11.2 months after starting trastuzumab therapy. Central nervous system metastases occurred in 11/28 (39%) patients and the remaining 11 patients had progressed elsewhere. At diagnosis of CNS metastases, 9/11 (82%) had controlled systemic disease (CR = 2, PR = 6, SD = 1). There were trends for patients with CNS metastases to have greater than one site of metastatic disease at the commencement of trastuzumab therapy (P = 0.06), and to be hormone receptor negative at initial diagnosis (P = 0.14). The median time to diagnosis of CNS metastases after the commencement of trastuzumab therapy was 12 months (range 6–19 months). The median survival after diagnosis of CNS metastases was 12 months (range 2–22 months). Conclusions: This study demonstrates a high rate of CNS metastases (39%) in HER‐2 positive MBC patients treated with trastuzumab. At CNS metastases most patients had controlled systemic disease and the median survival after CNS relapse was 1 year. We suggest aggressive management of CNS disease in this population. Additional strategies to decrease the incidence of CNS metastases in these patients may include prophylactic whole brain irradiation and the development of novel pharmacological agents with successful CNS penetration.     

Treatment of Breast Cancer Brain Metastases

Approximately 10% to 15% of women with metastatic breast cancer will develop brain metastases. Treatment options for these women remain limited, particularly at the time of central nervous system (CNS) relapse following completion of initial CNS-directed therapy. Historically, prior studies have broadly examined systemic treatments for breast cancer brain metastases with mixed, but overall disappointing, results. More recently, studies have increasingly selected patients based on breast cancer subtype and have examined novel, targeted agents that have preclinical suggestion of blood–brain barrier penetration. Correlative science objectives, with both tissue-based and novel imaging endpoints, are more frequently incorporated into trials of this nature, with the goal of enhancing our understanding of possible predictors of response. This review summarizes the current and emerging data on systemic therapy for breast cancer brain metastases and provides a framework for future directions in treating this clinically-challenging entity.     

The prognostic analysis of clinical breast cancer subtypes among patients with liver metastases from breast cancer

Background

To determine whether the inferior outcome noted with triple-negative breast cancer (TNBC) reflects a higher risk population among patients with breast cancer liver metastases.

Methods

A total of 123 patients with breast cancer liver metastases diagnosed at Tianjin Medical University Cancer Hospital were included in this study. Breast cancer subtype was assigned using immunohistochemistry or fluorescence in situ hybridization: hormone receptor (HR) positive (+)/human epidermal growth factor receptor 2 (HER2) negative (?), HR+/HER2+, HR?/HER2+ and triple-negative subtype. Clinical features and survival were evaluated in different subtypes.

Results

The median age at breast cancer diagnosis was 47 years (range, 23–67 years). Breast cancer subtype was confirmed in all patients (39.8% with HR+/HER2?, 24.4% with HR+/HER2+, 15.3% with HR?/HER2+ and 20.3% with TNBC). The median overall survival after liver metastases was 29 months (range, 4–89 months), and the overall 1-, 2- and 3-year survival rate was 68.3, 48.0 and 34.1%, respectively. Survival was found to be impacted by breast cancer subtype (P = 0.001), and was shortest for patients with TNBC. Time to liver metastases (TTLM) less than 24 months and liver metastasis lesions ≥3 were found to be important predictors of poor survival after liver metastases (P = 0.009 and 0.001, respectively).

Conclusions

The results indicate that clinical breast cancer subtype remains an independent prognostic predictor among patients with breast cancer liver metastases. Liver metastases arising from TNBC confers the worst prognosis, and novel agents capable of controlling intrahepatic and extrahepatic TNBC are needed.     

Bevacizumab and Paclitaxel for Breast Cancer Patients with Central Nervous System Metastases: A Case Series

Central nervous system (CNS) metastases are a major concern in patients with stage IV breast cancer. Recent studies have shown the efficacy of anti–vascular endothelial growth factor drugs on brain tumors, in particular glioblastoma, but none has explored their efficacy and tolerance in breast cancer patients with CNS metastases. We report 4 cases of patients with CNS metastases treated with bevacizumab and paclitaxel. All but 1 had previous whole-brain radiation therapy, performance status 0–2, and radiographic evidence of progressive CNS metastases. Patients received paclitaxel 80 mg/m² on days 1, 8, and 15, and bevacizumab 10 mg/kg on days 1 and 15. Response was evaluated according to the World Health Organization criteria. Three patients had brain metastases, and 1 had meningeal lesions. Only 1 patient was chemotherapynaive. Significant antitumor activity was observed, with 1 complete response and 3 partial responses in the CNS metastases. With a mean follow-up of 9 months, duration of response was 11, 10, 8, and 6 months. No patient had extra-CNS progression. This observed antitumor activity suggests efficiency of the combination of bevacizumab and paclitaxel and warrants further evaluation of this combination as an alternative option for the treatment of multiple CNS metastases in breast cancer.     

Paget’s disease of the nipple

The widespread use of trastuzumab in the past decade has led to a significant and measureable improvement in the survival of patients with human epidermal growth factor receptor-2 (HER2) overexpressing breast cancer, and in many ways has redefined the natural history of this aggressive breast cancer subtype. Historically, survival in patients with HER2-positive disease was dictated by the systemic disease course, and what appears to be the central nervous system (CNS) tropism associated with HER2-amplified tumors was not clinically evident. With improved systemic control and prolonged survival, the incidence of brain metastases has increased, and CNS disease, often in the setting of well-controlled extracranial disease, is proving to be an increasingly important and clinically challenging cause of morbidity and mortality in patients with HER2-positive advanced breast cancer. This review summarizes the known clinical data for the systemic treatment of HER2-positive CNS metastases and includes information about ongoing clinical trials of novel therapies as well as emerging strategies for early detection and prevention.     

Prognostic Factors and Survival According to Tumor Subtype in Women With Breast Cancer Brain Metastases

Breast cancer (BC) is the second most cause of central nervous system (CNS) metastases. Studies report that almost one third of patients (pts) with triple-negative, one-third with human epidermal growth factor receptor 2 (HER2)-positive and 15% of those with hormone receptor-positive, HER2-negative metastatic breast cancer will develop brain metastases. It is known that the development of symptomatic brain metastases in women with advanced breast cancer is associated with poor prognosis, irrespective of local and systemic treatments. In the present study, we aim to determine the association between BC subtypes and CNS metastases occurrence and prognosis. Retrospective analysis of 309 BC patients with CNS metastases, confirmed by pathological and/or radiological methods, treated in a Cancer Center between 2003 and 2021, was obtained to identify clinicopathologic factors associated with early onset of brain metastases and survival outcomes. For analysis purposes, 3 BC subtypes were considered according to hormone receptor status and HER-2 expression: ER and/or PR positive, HER-2 positive and triple negative. The median time between diagnosis of BC and detection of CNS metastases was 43 months, and it was significantly shorter in triple negative group (8 months). Twenty-one patients (6,8%) had CNS metastases at BC diagnosis, with CNS being the first site of recurrence in 35,3%, mainly in HER2 positive. Most of the patients had parenchymal metastases (n = 245) and 37 (12%) had leptomeningeal (LM) disease, with predominance in ER and/or PR positive subtype (70,3%). In patients submitted to CNS surgery, the concordance between primary tumor and metastases subtype was higher in triple negative (76,9%) compared to 63,2% in HER-2 positive and 38,9% in ER and/or PR positive group (P < 0.05). After CNS involvement, 25,4% (n = 34) of patients with triple negative disease did not receive any systemic therapy, compared to 30,6% (n = 41) in HER-2 positive and 44% (n = 59) in ER and/or PR positive groups (P = 0.05). Median survival after CNS metastases was 9 months, but significantly longer in HER-2 positive group (16 months) and in patients submitted to surgical resection of CNS metastases, irrespectively of subtype (22 months vs 5 months in other treatment modalities). In multivariate Cox regression analysis, having HER-2 positive tumor was an independent prognostic factor for increasing survival after CNS metastases (HR 0.60, 95% CI: 0.41-0.87, P = 0.007), regardless the therapeutic strategy. Clinical behavior and prognosis of CNS metastases varies according to BC subtype. The association between LM disease and ER and/or PR positive tumors should be explored in upcoming studies. Also, these patients’ prognosis depends on the availability of specific treatment options, therefore, innovative and effective therapeutic approaches are needed, in order to improve survival and quality of life of these patients.     

Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer

BACKGROUND.

Molecular profiling studies have identified subtypes of breast cancer that can be approximately classified by estrogen receptor (ER), progesterone receptor (PR), and HER‐2/neu (HER‐2) expression. These molecular subtypes are prognostically significant, but to the authors' knowledge, differences in their etiologic profiles have not been established. Reproductive factors may plausibly be differentially correlated with the risk of different breast cancer subtypes because these factors are presumed to impact exposure to endogenous sex hormones.

METHODS.

The authors pooled 2 population‐based, case–control studies of breast cancer in women ages 55 to 79 years for an analysis including 1476 controls and 1023 cases of luminal breast cancer, 39 cases of HER‐2‐overexpressing breast cancer, and 78 cases of triple‐negative breast cancer. Polytomous logistic regression was used to compare each case group with controls.

RESULTS.

Associations varied by molecular subtype. Early age at menarche was only found to be associated with risk of HER‐2‐overexpressing disease (odds ratio [OR] of 2.7; 95% confidence interval [95% CI], 1.4‐5.5), whereas breastfeeding for ≥6 months was only found to be protective for luminal and triple‐negative disease (OR of 0.8 [95% CI, 0.6‐1.0] and OR of 0.5 [95% CI, 0.3‐0.9], respectively). Both late age at menopause and the use of estrogen plus progestin hormone therapy were only found to be associated with risk of luminal disease (OR of 1.6 [95% CI, 1.1‐2.2] and OR of 1.7 [95% CI, 1.3‐2.1], respectively). No differences in risks associated with parity or age at first live birth were observed by subtype.

CONCLUSIONS.

Certain reproductive factors may have a greater impact on the risk of certain molecular subtypes of disease compared with others. Future studies that further define the etiology of breast cancer subtypes will add to the biologic understanding of this disease. Cancer 2008. © 2008 American Cancer Society.     

Breast cancer statistics, 2013

In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 232,340 new cases of invasive breast cancer and 39,620 breast cancer deaths are expected to occur among US women in 2013. One in 8 women in the United States will develop breast cancer in her lifetime. Breast cancer incidence rates increased slightly among African American women; decreased among Hispanic women; and were stable among whites, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives from 2006 to 2010. Historically, white women have had the highest breast cancer incidence rates among women aged 40 years and older; however, incidence rates are converging among white and African American women, particularly among women aged 50 years to 59 years. Incidence rates increased for estrogen receptor‐positive breast cancers in the youngest white women, Hispanic women aged 60 years to 69 years, and all but the oldest African American women. In contrast, estrogen receptor‐negative breast cancers declined among most age and racial/ethnic groups. These divergent trends may reflect etiologic heterogeneity and the differing effects of some factors, such as obesity and parity, on risk by tumor subtype. Since 1990, breast cancer death rates have dropped by 34% and this decrease was evident in all racial/ethnic groups except American Indians/Alaska Natives. Nevertheless, survival disparities persist by race/ethnicity, with African American women having the poorest breast cancer survival of any racial/ethnic group. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high‐quality screening, diagnosis, and treatment to all segments of the population. CA Cancer J Clin 2014;64:52–62. ^© 2013 American Cancer Society, Inc.     

Prognostic factors of survival in the trastuzumab era among women with breast cancer and brain metastases who receive whole brain radiotherapy

BACKGROUND:

The objective of this study was to review the outcome of women with breast cancer with known receptor status who were treated with whole brain radiotherapy for brain metastases and to determine factors that impact survival.

METHODS:

A total of 223 women with breast cancer and brain metastases, who received whole brain radiotherapy, were identified. All women with HER‐2–positive disease had received trastuzumab. Kaplan‐Meier product limit method was used to determine overall survival (OS) estimates. Cox proportional hazards models were then fitted to explore the association of OS with various patient and tumor characteristics.

RESULTS:

Median age at brain metastases diagnosis was 50 years. Sixty‐seven (30.2%) patients had hormone receptor‐positive/HER‐2–negative disease, 101 (45.50%) had HER‐2–positive disease, and 54 (24.3%) had triple receptor‐negative disease. Median OS from brain metastases was 6 months, with 1‐year survival of 30% (95% confidence interval [CI], 23%‐36%). Women with hormone receptor‐positive/HER‐2–negative, HER‐2–positive, and triple‐negative tumors had median survivals of 5, 9, and 5 months, respectively (P = .0069). In the multivariate model, women with HER‐2–positive disease had a significantly decreased risk of death compared with women with hormone receptor‐positive/HER‐2–negative disease (hazard ratio, 0.63; 95%CI, 0.42‐0.94; P = .02). The risk of death among women with triple‐negative disease compared with hormone receptor‐positive/HER‐2–negative disease was not significantly different (P = .54). Lower recursive partitioning analysis class and ≥30‐gray brain radiation dose were also significantly associated with a decreased risk of death.

CONCLUSIONS:

Breast tumor subtype has a significant prognostic role among women with breast cancer and brain metastases. In addition, in the trastuzumab era factors such as recursive partitioning analysis and adequate radiation dose continue to be important prognostic factors. Cancer 2010. © 2010 American Cancer Society.     

Defining prognosis for women with breast cancer and CNS metastases by HER2 status

BackgroundThe purpose of this retrospective study was to determine, in a cohort of patients with breast cancer and central nervous system (CNS) metastases, the effect of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive disease and to compare this with that of patients with HER2-negative disease.MethodsFive hundred and ninety-eight patients with invasive breast cancer, CNS metastases and known HER2 status were identified. Time to CNS metastases and survival after CNS metastases were estimated by the Kaplan–Meier method, and Cox models were fitted to determine the association between HER2 status, trastuzumab treatment and outcomes after adjustment for other patient characteristics.ResultsIn the multivariable model, patients with HER2-negative disease [Hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.15–1.95, P = 0.003] and patients with HER2-positive disease who did not receive trastuzumab (HR 2.13, 95% CI 1.51–3.00, P < 0.0001) had shorter times to CNS metastases compared with patients with HER2-positive disease who had received trastuzumab as first-line therapy for metastases. Furthermore, patients with HER2-negative disease (HR 1.66, 95% CI 1.31–2.12, P < 0.0001) and patients with HER2-positive disease who had never received trastuzumab (HR 1.34, 95% CI 0.78–2.30, P = 0.28) had an increased hazard of death compared with patients with HER2-positive disease who had received trastuzumab before or at the time of CNS metastases diagnosis.ConclusionIn our cohort of patients with breast cancer and CNS metastases, patients with HER2-positive disease treated with trastuzumab had longer times to development of and better survival from CNS metastases compared with patients with HER2-positive disease who had never received trastuzumab and patients with HER2-negative breast cancer.     

Multifactorial central nervous system recurrence susceptibility in patients with HER2-positive breast cancer: epidemiological and clinical data from a population-based cancer registry study

BACKGROUND:

A series of retrospective studies have reported that patients with human epidermal growth factor receptor 2(HER2)‐positive breast cancer are at a greater risk of central nervous system (CNS) metastases. Trastuzumab, which does not cross the blood‐brain barrier, has been associated with this increased risk.

METHODS:

The authors evaluated incidence, survival, and risk factors for CNS metastases in the incident breast cancer population systematically collected by the Parma Province Cancer Registry over the 4‐year period between 2004 and 2007.

RESULTS:

A total of 1458 patients with a diagnosis of stage I to III invasive breast cancer were analyzed for study purposes. At a median follow‐up of 4.1 years, CNS events were observed in 1.3% and 5% of HER2‐negative patients and HER2‐positive patients, respectively (P < .0001). The administration of trastuzumab either as adjuvant therapy or for metastatic disease was associated with a significantly increased risk of CNS involvement at first disease recurrence and after first extracranial recurrence, respectively. According to multivariate analysis, HER2‐positive status and trastuzumab treatment, high Ki‐67 index, and hormone receptor negativity remained independent risk factors for the development of CNS metastasis.

CONCLUSIONS:

To the authors' knowledge, this is the first population‐based cancer registry study analyzing factors associated with CNS recurrence in a general population of newly diagnosed breast cancer patients with known HER2 status. The data from the current study provide evidence that patients with HER2‐positive breast cancer have a significantly higher incidence of CNS metastasis after treatment with trastuzumab. Improvements in systemic control and overall survival associated with trastuzumab‐based therapy may lead to an “unmasking” of CNS disease recurrence that would otherwise remain clinically silent before a patient's death. Cancer 2011. © 2010 American Cancer Society.     

Alcohol consumption and risk of breast cancer by molecular subtype: Prospective analysis of the nurses' health study after 26 years of follow‐up

Alcohol consumption is a consistent risk factor for breast cancer, although it is unclear whether the association varies by breast cancer molecular subtype. We investigated associations between cumulative average alcohol intake and risk of breast cancer by molecular subtype among 105,972 women in the prospective Nurses' Health Study cohort, followed from 1980 to 2006. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6, and epidermal growth factor status from immunostained tumor microarrays in combination with histologic grade. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Competing risk analyses were used to assess heterogeneity by subtype. We observed suggestive heterogeneity in associations between alcohol and breast cancer by subtype (p_het = 0.06). Alcohol consumers had an increased risk of luminal A breast cancers [n = 1,628 cases, per 10 g/day increment HR (95%CI) = 1.10(1.05–1.15)], and an increased risk that was suggestively stronger for HER2‐type breast cancer [n = 160 cases, HR (95%CI) = 1.16(1.02–1.33)]. We did not observe statistically significant associations between alcohol and risk of luminal B [n = 631 cases, HR (95%CI) = 1.08(0.99–1.16)], basal‐like [n = 254 cases, HR (95%CI) = 0.90(0.77–1.04)], or unclassified [n = 87 cases, HR (95%CI) = 0.90(0.71–1.14)] breast cancer. Alcohol consumption was associated with increased risk of luminal A and HER2‐type breast cancer, but not significantly associated with other subtypes. Given that ERs are expressed in luminal A but not in HER2‐type tumors, our findings suggest that other mechanisms may play a role in the association between alcohol and breast cancer.     

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.     

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and breast cancer risk

The World Cancer Research Fund/American Association for Cancer Research (WCRF/AICR) has published eight nutrition‐related recommendations for the prevention of cancer. However, few prospective studies have examined these recommendations by breast cancer hormone receptor subtype and only one case–control study has included the dietary supplements recommendation in their evaluation. We investigated whether adherence to the WCRF/AICR cancer prevention recommendations was associated with breast cancer incidence, overall and by hormone receptor subtype, in the Swedish Mammography Cohort. Among 31,514 primarily postmenopausal women diet and lifestyle factors were assessed with a self‐administered food frequency questionnaire. A score was constructed based on adherence to the recommendations for body fatness, physical activity, energy density, plant foods, animal foods, alcoholic drinks and dietary supplements (score range 0–7). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow‐up 1,388 cases of breast cancer were identified. Women who met six to seven recommendations had a 51% decreased risk of breast cancer compared to women meeting only zero to two recommendations (95% CI = 0.35–0.70). The association between each additional recommendation met and breast cancer risk was strongest for the ER‐positive/PR‐positive subtype (HR = 0.86; 95% CI = 0.79–0.94), while for the ER‐negative/PR‐negative subtype the individual recommendations regarding plant and animal foods were most strongly associated with reduced risk. Our findings support that adherence to the WCRF/AICR recommendations reduces breast cancer risk in a population of primarily postmenopausal women. Promoting these recommendations to the public could help reduce breast cancer incidence.     

luminal B 型晚期乳腺癌临床病理特征及预后分析

  目的  探讨luminal B型晚期乳腺癌患者的临床病理特征及预后因素。  方法  收集2008年6月至2013年6月天津医科大学肿瘤医院收治的206例luminal B型晚期乳腺癌患者的临床资料,回顾性分析其临床病理特征及影响预后的因素。  结果  206例患者中HER-2阳性型54例（26.2%）,HER-2阴性型152例（73.8%）。其中HER-2阳性型患者中Ki-67＞30%为57.4%（31/54）,较HER-2阴性型的55.9%（85/152）高,差异具有统计学意义（P<0.01）;HER-2阳性型患者中无病生存期（disease free survival,DFS）<36个月为79.6%（43/54）,较HER-2阴性型的65.1%（99/152）高,差异具有统计学意义（P<0.05）。206例患者的中位生存期为25（2.1～85.0）个月,是否合并内脏转移、一线解救化疗疗效、是否行解救内分泌治疗是luminal B型晚期乳腺癌患者的独立预后因素（P<0.05）。  结论  luminal B型晚期乳腺癌患者中,HER-2阳性型中的Ki-67指数比HER-2阴性型更高,且更易在3年内发生复发、转移。合并内脏转移、一线解救化疗时病情进展、未行解救内分泌治疗是影响luminal B型晚期乳腺癌患者不良预后的独立因素。      

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.