乳腺癌骨转移患者预后相关因素

乳腺癌是世界范围内女性最常见的恶性肿瘤,高达75%的患者最终会发生骨转移。骨转移发生风险与肿瘤分子分 型、组织病理和患者生理阶段等密切相关,骨转移合并其他部位转移、发生骨相关事件、骨转移灶的特点等都可影响患者的预后。 目前临床广泛应用的骨转移治疗方法包括全身应用抗肿瘤药物和骨改良药物、局部行骨转移灶放疗和骨转移灶手术。除抗肿瘤 药物外的其他治疗手段都有望改善患者预后。近年来发展的骨转移治疗新手段,如对乳腺癌原发灶的处理、放射性物质镭、骨转 移关键信号分子抑制剂和某些新技术应用在提高患者生存方面都有良好的前景。本文就乳腺癌骨转移患者的预后相关因素作 简要综述。     

70例乳腺癌骨转移的临床病理因素分析

目的:分析探讨乳腺癌骨转移的临床病理特点.方法:回顾性分析我院收治的乳腺癌骨转移患者的临床病理资料并用COX比例风险模型进行乳腺癌骨转移预后因素分析.结果:乳腺癌骨转移好发部位依次为椎体、骨盆、肋骨、胸骨等;乳腺癌术后前3年骨转移发生率较高,为62.9%.COX比例风险模型分析显示乳腺癌术后腋窝淋巴结阳性数目、雌孕激素受体状况、HER-2表达、术后辅助化疗情况是乳腺癌术后骨转移的独立影响因素.结论:腋窝淋巴结阳性数目、雌孕激素受体状况、HER-2表达、术后辅助化疗情况都是乳腺癌术后骨转移的独立影响因素.对乳腺癌骨转移的发生规律的认识有助于临床早期诊断和治疗.     

乳腺癌骨转移放射治疗临床分析（附32例报告）

目的：探讨乳腺癌骨转移的临床特点及放射治疗效果。方法：回顾分析32例乳腺癌骨转移资源，转移灶单发10例，多发22例，共68处病灶，其中脊柱占27．9％，骨盆占22．1％，肋骨占13．2％，股骨占10．3％，其余依次为肱骨，颅骨，肩胛骨，胫骨，锁骨。22例行放射治疗，放疗前中度疼痛17例，重度疼痛5例，6例功能障碍。结果：22例治疗后完全 缓解16例，部分缓解6例，卡氏评分有所改善，功能障碍均恢复，治疗后的1、2、3卸生存率分别为59．1％，22．7％，4．5％，中位生存期15月，而未治组10例的中位生存期为4．5月（P＜0．01）。结论：乳腺癌骨转移行放射治疗，止痛作用快而持久，提高了患的生存质量，是一种简单有效的治疗方法。     

首发单纯骨转移乳腺癌患者的临床病理特征及预后分析

  目的  探讨乳腺癌首发单纯骨转移（bone-only metastasis, BOM）患者的临床病理学特征及预后特点。  方法  回顾性分析2009年1月至2016年12月967例于天津医科大学肿瘤医院治疗的转移性乳腺癌患者的临床病理资料。分为180例BOM组与787例非BOM组, 对BOM组患者的预后因素行单因素分析和Cox回归模型多因素分析, 并根据激素受体（hormone receptor, HR）状态、转移数目及治疗方式行亚组分析。  结果  BOM组与非BOM组患者的中位无进展生存（progression-free survival, PFS）时间分别为19.4个月与10.0个月, BOM组中位总生存（overall survival, OS）时间为45.6个月。BOM组与非BOM组HR阳性患者分别占81.7%（147/180）与64.7%（509/787）（P < 0.001）。Cox回归模型多因素分析显示HR状态、转移位置、转移数目和治疗方式是BOM患者预后的独立影响因素。BOM组的HR阳性患者内分泌治疗（P=0.004）或联合治疗（P < 0.001）较单独化疗的预后更佳。影响BOM组HR阳性患者预后的主要因素为骨转移数目和内分泌治疗。单部位骨转移患者行内分泌治疗（P=0.004）或联合治疗（P= 0.002）较单独化疗的预后更佳, 多部位骨转移患者行联合治疗较单独化疗（P < 0.001）或内分泌治疗（P=0.04）的预后更佳。  结论  对于HR阳性BOM尤其是单部位骨转移患者, 单纯内分泌治疗可获得较为满意的疗效, 而对于多部位BOM则应考虑行联合治疗。      

老年乳腺癌的临床特点及预后因素

目的：探讨老年乳腺癌的临床特点及影响其预后的相关因素。方法：从我院1979年1月至1998年12月20年间收治的819例女性乳腺癌患中,收集整理≥60岁的女性乳腺癌176例,并其进行分析。结果：本组176例老年乳腺癌患年龄67．6岁,其中60岁－70岁占82．9％。平均病程是19．94月。TNM分期Ⅲ、Ⅳ期43例（24．43）％,伴有合并症87例（49．43％）,腋下淋巴结有转移80例（45．45％）,5年生存率65．34％。结论：（1）病程长,但病期相对并不晚。（2）老年乳腺癌发展慢。（3）老年乳腺癌病人多伴有合并症。（4）其预后与患的合并症,组织学恶性程度,雌激素水平等有关,给予适当合理的治疗能明显改善其预后。     

乳腺癌骨转移的临床病程

目的 探讨乳腺癌骨转移的临床病程和规律。方法 回顾性分析345例乳腺癌患骨转移好发部位、病灶特点、发生时间、激素受体分布情况及预后等规律。结果 乳腺癌骨转移好发部位依次是腰椎、胸椎、骨盆、肋骨和股骨；几乎全部是溶骨性病灶；中位发生骨转移时间是术后33个月；88．7％患就诊时有相应症状；骨转移患中激素受体阳性比例较高；首发骨转移的预后介于软组织和内脏之间；延缓骨转移与内脏转移的间隔时间有利于生存期的改善。结论 对乳腺癌骨转移规律的认识有助于临床诊断和治疗。     

33 例乳腺癌骨转移放射治疗临床分析

 引言 对我科自1994 年1 月～2001 年12月收治的33 例乳腺癌患者术后骨转移作一临床分析。     

33例乳腺癌骨转移的临床分析

目的 33例乳腺癌发生骨转移临床分析。方法 回顾分析了33例乳腺癌发生骨转移的年龄、病理分型、术前临床分期、转移部位、术后辅助性化疗情况及骨转移部位。结果 本组33例乳腺癌发生骨转移的中位年龄为45岁,病理均为乳腺浸润性非特殊型癌,ER阳性13例,阴性20例。术前临床分期:Ⅲ期15例(45.5％),术后辅助性化疗不规范。发生骨转移的部位以椎骨最多11例(33.3％),其次为盆骨8例(24.2％)。结论 对年龄轻、病理分型差、临床分期较晚的乳腺癌病人应进行正规治疗降低骨转移发生率。     

首诊Ⅳ期乳腺癌骨转移患者的临床病理特征及预后分析

  目的  探讨首诊Ⅳ期乳腺癌骨转移（initially diagnosed stage Ⅳ breast cancer bone metastasis,IDBCBM）患者的临床病理特征、治疗和预后的关系。  方法  回顾性分析2007年3月至2016年11月天津医科大学肿瘤医院收治的74例IDBCBM患者的临床资料,并行单因素分析和采用Cox回归模型进行多因素分析。  结果  患者的中位年龄为53.3岁。中位总生存时间（overall survival,OS）为34.3个月,3年和5年的生存率分别为37.8%和12.2%。首发转移模式仅为骨转移的患者预后较好,中位生存时间为41.7个月,3年和5年的总生存率分别为54.5%和20.4%。在单因素分析中,分子亚型、激素受体状态、HER-2表达情况、淋巴结状态、Ki-67指数、骨转移数目（number of bone metastasis,NBM）、初始转移模式、药物治疗模式及局部治疗与预后相关;74例IDBCBM患者的Cox回归模型多因素分析显示首发骨转移模式,NBM,药物治疗模式,Ki-67均是影响患者OS的独立预后因素（均P < 0.05）。  结论  Ki-67的高表达、单一的药物治疗模式、NBM较多、骨合并内脏转移均与患者预后较差相关,但局部的手术和放疗是否获益尚无定论。      

Assessment of prognostic scores in brain metastases from breast cancer

Background

Breast cancer (BC) is the second most common cause of brain metastases (BM). Optimal management of BM from BC is still debated. In an attempt to provide appropriate treatment and to assist with optimal patient selection, several specific prognostic classifications for BM from BC have been established. We evaluated the prognostic value and validity of the 6 proposed scoring systems in an independent population of BC patients with BM.

Methods

We retrospectively reviewed all consecutive BC patients referred to our institution for newly diagnosed BM between October 1995 and July 2011 (n = 149). Each of the 6 scores proposed for BM from BC (Sperduto, Niwinska, Park, Nieder, Le Scodan, and Claude) was applied to this population. The discriminative ability of each score was assessed using the Brier score and the C-index. Individual prognostic values of clinical and histological factors were analyzed using uni- and multivariate analyses.

Results

Median overall survival was 15.1 months (95% CI,11.5–18.7). Sperduto-GPA (P < .001), Nieder (P < .001), Park (P < .001), Claude (P < .001), Niwinska (P < .001), and Le Scodan (P = .034) scores all showed significant prognostic value. The Nieder score showed the best discriminative ability (C-index, 0.672; Brier score error reduction, 16.1%).

Conclusion

The majority of prognostic scores were relevant for patients with BM from BC in our independent population, and the Nieder score seems to present the best predictive value but showed a relatively low positive predictive value. Thus, these results remain insufficient and challenge the routine use of these scoring systems.     

Prognostic factors for patients with liver metastases from breast cancer

Summary Background The prognosis of patients with liver metastases from breast cancer is commonly poor. After initial diagnosis of hepatic metastases, a median survival time of 1–20 months can be expected. The definition of prognostic factors for such patients may influence therapeutic decisions. In particular, the characterization of patients who can expect long-term survival could assist in optimizing treatment. Methods We retrospectively studied n=350 patients with liver metastases from breast cancer. All patients were stratified following their survival after occurrence of liver metastases. Kaplan–Meier studies were performed, as well as univariate and multivariate analyses of several clinical, histopathological and therapeutic factors. Results Median survival time was 14 months. N=66 (18.9%) patients survived longer than 36 months after the primary diagnosis. Multivariate analysis showed prognostic relevance for the time interval between the primary diagnosis of breast cancer and the initial diagnosis of hepatic metastases (p<0.05). Furthermore, prognostic relevance was found for the pattern of metastasization (p<0.05) and for signs of hepatic dysfunction (ascites, jaundice, p<0.005). Univariate analysis showed a prognostic benefit for patients with an expression of Ki-67<20%, p53<50% and a positive hormonal receptor status. Patients who received a regional therapy survived on average longer than patients who were only treated systemically (33 versus 11 months, p<0.001). Conclusions Consideration of prognostic implications of the described parameters may help to find the most appropriate treatment for patients with liver metastases from breast cancer. The possibility of local therapeutic interventions should be considered in a defined subgroup.     

Prognostic factors for patients with hepatic metastases from breast cancer

Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan-Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16-51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml(-1) and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients.British Journal of Cancer (2003) 89, 284-290. doi:10.1038/sj.bjc.6601038 www.bjcancer.com     

Brain metastases in breast cancer: prognostic factors and management

Background The purpose of this retrospective study was to analyze the overall survival of patients with brain metastases due to breast cancer and to identify prognostic factors that affect clinical outcome. Methods Of the 7,872 breast cancer patients histologically diagnosed with breast cancer between January 1990 and July 2006 at the Asan Medical Center, 198 patients with solitary or multiple brain metastases were included in this retrospective study. Central nervous system (CNS) lesions were diagnosed by computed tomography (CT) or magnetic resonance imaging (MRI). Patients with leptomeningeal or dural metastases without co-existent parenchymal metastatic lesions were excluded in this study. We reviewed the medical records and pathologic data of these 198 patients to characterize the clinical features and outcomes. Results The median age of the patients at the diagnosis of brain metastases was 45 years (range 26–78 years). Fifty-five patients (28%) had a single brain metastasis, whereas 143 (72%) had more than two metastases. A total of 157 (79.2%) patients received whole-brain radiation therapy (WBRT). A total of 7 (3.6%) patients underwent resection of solitary brain metastases, 22 (11%) patients underwent gamma-knife surgery, three patients underwent intrathecal chemotherapy (1.5%) and 9 (4.6%) patients received no treatment. The overall median survival time was 5.6 months (95% confidence interval (CI), 4.7–6.5 months) and 23.1% of the patients survived for more than 1 year. The median overall survival time was 5.4 months for patients treated with WBRT, 14.9 months for patients treated with surgery or gamma-knife surgery only, and 2.1 months for patients who received no treatment (P < 0.001). Multivariate analysis demonstrated that Eastern Cooperative Oncology Group (ECOG) performance status (relative risk (RR) = 0.704, 95% CI 0.482–1.028, P = 0.069), number of brain metastases (RR = 0.682, 95% CI 0.459–1.014, P = 0.058), treatment modalities (RR = 1.686, 95% CI 1.022–2.781, P = 0.041), and systemic chemotherapy after brain metastases (RR = 1.871, 95% CI 1.353–2.586, P < 0.001) were independent factors associated with survival. Conclusion Although survival of breast cancer patients with brain metastases was generally short, the performance status, number of brain metastases, treatment modalities and systemic chemotherapy after brain metastases were significantly associated with survival. Patients with single-brain metastasis and good performance status deserve aggressive treatment. The characteristics of initial primary breast lesions did not affect survival after brain metastasis.     

Incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases

ER, PgR and HER-2 status are the cornerstones of choosing systemic therapy for breast cancer, but can change during the disease course. Guidelines recommended the biopsy of the metastatic tumor to reassess receptor status. Bone is the most frequent metastatic site of breast cancer but remained technically difficult to biopsy. Our study aimed to evaluate the incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases. One hundred and fifty-five breast cancer patients were diagnosed with pathology-confirmed bone metastasis at Fudan University Shanghai Cancer Center. Ninety-three patients with receptor status available on both primary tumor and bone metastases were included in our study. ER, PgR and HER-2 status converted from positive to negative in 10.8% (10/93), 28.0% (26/93) and 8.6% (8/93) of the patients, while ER, PgR and HER-2 status converted from negative to positive in 3.2% (3/93), 4.3% (4/93) and 1.1% (1/93) of the patients, respectively. 40.4% (17/42) of the HER2-0 tumors converted to HER2-low, which enabled them to receive the treatment of new antibody-drug conjugates (ADCs). Prior endocrine and anti-HER2 therapy were the independent risk factors for receptor conversion. Loss of HR expression in bone metastases was significantly associated with worse first-line PFS (adjusted hazard ratio = 3.271, P-value = .039) and OS (adjusted hazard ratio = 6.09, P-value = .011). In conclusion, our study confirmed that patients may experience receptor conversion between primary breast cancer and bone metastases, possibly influenced by prior treatments, which significantly influenced prognosis. The rebiopsy of bone metastases in patients with primary HER2-0 tumors may benefit from the new ADC drugs.     

Analyzing prognostic factors in breast cancer using a multistate model

In breast cancer clinical research, an important goal is to analyze how factors are seen to affect the disease process. Meanwhile, the disease progression is not fully modelled using standard analysis since transitions between intermediate events such as local-regional recurrences (LRR) or metachronous contralateral breast cancer (MCBC) are not considered. In the present study, the progression of disease was modelled using a multistate model. By this approach, we assessed transitions during the course of the disease and studied prognostic factors for each transition. The model was applied to 6,185 patients with unilateral ductal invasive breast cancer, clinical stage I through III, treated between 1981 and 1988 at the Curie Institute.At first diagnosis, high clinical stage, high histological grade, positive lymph nodes, and age less than 40 years were associated with increased risks of LRR, metastases, or death. Except age, the same factors remained predictive for metastases or death following LRR. Chemotherapy for the first cancer was associated with a decreased risk for developing MCBC. As the time interval from diagnosis of the primary tumor to that of a local or contralateral recurrence increased, the risk of metastases or death decreased. Nodal status for the first tumor and clinical stage for the contralateral tumor increased the risk of metastases or death following MCBC. Conversely, the risk decreased for patients who received adjuvant hormone therapy following MCBC. In conclusion, the multistate model offers us a much more appropriate way to study prognostic factors for each transition in breast cancer disease.     

145例乳腺癌骨转移临床病理分析

目的：探讨乳腺癌骨转移的相关因素及处理对策。方法：本文对１９５４年１月～１９７７年１２月我院收治的２８０３例原发乳腺癌术后发生骨转移的１４５例患者临床资料进行回顾性分析。结果：乳腺癌术后骨转移发生率５．１％,骨转移部位分布较广泛,多数出现在脊柱,术后前５年发生率占７６．４％,腋淋巴结阳性患者较阴性患者较早发生转移。出现转移后经治疗患者较未治疗患者生存期有显著性差异。结论：乳腺癌术后骨转移出现时间与其分布有其规律,综合治疗后乳腺癌患者可延缓出现转移的时间。出现骨转移后,积极治疗,可达到延长生存期改善生存质量的目的。     

Cost effectiveness of bisphosphonates in the management of breast cancer patients with bone metastases.

BACKGROUND: Bisphosphonates are recommended to prevent skeletal related events (SREs) in patients with breast cancer and bone metastases (BCBM). However, their clinical and economic profiles vary from one agent to the other. MATERIALS AND METHODS: Using modeling techniques, we simulated from the perspective of the UK's National Health Service (NHS) the cost and quality adjusted survival (QALY) associated with five commonly-used bisphosphonates or no therapy in this patient population. The simulation followed patients into several health states (i.e. alive or dead, experiencing an SRE or no SRE, and receiving first or second line therapy). Drugs costs, infusion costs, SREs costs, and utility values were estimated from published sources. Utilities were applied to time with and without SREs to capture the impact on quality of life. RESULTS: Compared to no therapy, all bisphosphonates are either cost saving or highly cost-effective (with a cost per QALY < or = 6126 pounds sterlings). Within this evaluation, zoledronic acid was more effective and less expensive than all other options. CONCLUSIONS: Based on our model, the use of bisphosphonates in breast cancer patients with bone metastases should lead to improved patient outcomes and cost savings to the NHS and possibly other similar entities.     

Bone metastases from breast carcinoma: histopathological - radiological correlations and prognostic features

The aim of this study was to identify factors that may be associated with the development of bone metastases in patients with metastatic breast carcinoma and to see if any of these factors had a bearing on subsequent survival. In total, 492 patients presented to the Nottingham City Hospital with metastatic breast carcinoma between July 1997 and December 2001. Of these, 267 patients had bone metastases at presentation with metastatic disease, 91 patients in this group had bone as their only site of metastatic disease. Sites of first presentation of metastatic disease were prospectively recorded, as were histological features of the primary tumour (tumour type, histological grade, lymph node stage, tumour size and oestrogen receptor (ER) status). The radiological features of the bone metastases, the metastasis-free interval and serological tumour marker levels at presentation with metastases were all recorded. There was a significant association between the development of bone metastases and lower grade tumours (P=0.019), ER-positive tumours (P<0.0001) and the lymph node stage of the primary tumour (P=0.047). A multivariate analysis found that metastasis-free interval, additional sites of metastatic disease other than bone, ER status and serological tumour marker levels all independently contributed to survival from time of presentation with bone metastases.