Prognostic factors for survival in metastatic breast cancer by hormone receptor status通过激素受体状态判断转移性乳腺癌患者生存预后因素AbstractHormone receptor (HR) status is an important prognostic factor for patients with metastatic breast cancer (MBC) and is also correlated with other prognostic factors, such as initial lymph node status, HER2-Neu status and age. The prognostic value of these other factors, however, is unknown when stratified by HR positive versus HR negative patients. The aim of this study was to evaluate prognostic factors for MBC survival in relation to HR status. Dutch women diagnosed with breast cancer in2003–2006 treated with curative intent who developed MBC within 5 years offollow-up were selected from the Netherlands cancer registry (N = 2,001). Independent prognostic factors for survival after metastatic occurrence were determined by multivariable Cox survival analyses stratified by HR status. Interactions between HR status and prognostic factors were determined. Median survival for MBC patients with HR negative (HR−) tumours was 8 months, compared to 19 months for HR positive (HR+) patients. The prognostic value of lymph node status, HER2-Neu status, adjuvant endocrine treatment and first-line palliative chemotherapy was dependent on HR status. Initial lymph node status was independently associated with survival in HR− patients, but not in HR+ patients. HER2-Neu positive status was associated with better survival in both HR+ and HR− patients, although the association was stronger in HR− patients. Similarly, patients treated with first-line palliative chemotherapy fared better, especially HR− patients. HR+ patients had worse survival if they had received adjuvant endocrine treatment. This study shows that the prognostic value of various factors depends on HR status in MBC. This information may help physicians to determine individual prognostic profiles and therapeutic strategies for MBC patients.对有转移的乳腺癌患者来说，激素受体状态是一个很重要的预后因素，并且和其它的预后因素相关；例如最初的淋巴结状态、HER2和年龄；当HR（+）和HR （—）区分时，这些其它因素的预后价值，然而，并不清楚；这篇研究的目的是评估有转移的乳腺癌患者的生存与HR状态相关的预后因素。

在2003-2006年间，从荷兰癌症登记处挑选的是2100个被诊断为乳腺癌并接受过根治性手术的荷兰女性患者，而且在随访中5年内发生乳腺癌转移。

对发生远处转移的乳腺癌患者，独立的预后因素被多个变量所决定。

COX生存分析由HR的状态所决定。

HR的状态和预后因素的相互作用被决定；与HR（+）的有转移的乳腺癌患者的中位生存时间是19个月相比，HR（—）阴性的中位生存时间是8个月；淋巴结状态、HER-2状态、辅助内分泌治疗和一线姑息性化疗的预后价值取决于HR的状态；第一站淋巴结状态和HR（—）患者的生存情况密切相关，但和HR（+）的患者并无密切相关。

HER-2阳性状态在HR（—）和HR（+）患者中都有更好的生存率，尽管和HR（+)的相关性要强于HR（—）者；同样的，接受一线姑息性化疗的患者预后更好，尤其是HR（—）患者；HR（+）患者如果已经接受辅助内分泌治疗会有更差的生存率。

这项研究表明有远处转移的乳腺癌患者，各种因素的预后价值取决于HR状态。

这个信息可能帮助内科医生对有远处转移的乳腺癌患者确定个人预后资料和治疗计划。

p53 Family Members Regulate Phenotypic Response to Aurora Kinase A Inhibition in Triple-Negative Breast CancerAbstractTriple-negative breast cancer (TNBC) is an aggressive disease with a poor prognosis. Advances in the treatment of TNBC have been hampered by the lack of novel targeted therapies. The primary goal of this study was to evaluate the efficacy of targeting Aurora kinase A (AurA), a key regulator of mitosis, in TNBC models. A secondary objective was to determine the role of the p53 family of transcriptional regulators, commonly mutated in TNBC, in determining the phenotypic response to AurA inhibitor alisertib (MLN8237). Alisertib exhibited potent antiproliferative and proapototic activity in a subset of TNBC models. The induction of apoptosis in response to alisertib exposure was dependent on p53 and p73 activity. In the absence functional p53 or p73, there was a shift in the phenotypic response following alisertib exposure from apoptosis to cellular senescence. Additionally, senescence wasin patient-derived tumor xenografts with acquired resistance to alisertib treatment. AurA inhibitors are a promising class of novel therapeutics in TNBC. The role of p53 and p73 in mediating the phenotypic response to anti-mitotic agents in TNBC may be harnessed to develop an effective biomarker selection strategy in this difficult to disease.三阴性乳腺癌是一种预后差的侵袭性疾病。

三阴性乳腺癌治疗的提高被阻断因为缺乏创新有效的靶向治疗；这篇研究的主要目的是评估靶向激酶A的有效性——有丝分裂的关键的调控，在三阴性乳腺癌模型中；第二个目的是确定P53家族在转录调节中的作用，通常发生突变；AbstractWe aim to describe trends in net survival (NS) and to assess the prognostic factors among women with de novo metastatic breast cancer (MBC) according to human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status. Data on women suffering from de novo MBC and diagnosed from 1998 to 2009 were provided by the Côte-d'Or breast cancer registry. NS was described using the Pohar Perme estimator and prognostic factors were investigated in a generalised linear model. We identified 232 patients (mean age = 64.7). Median NS was 29.2 months, 1- and 5-year NS were 76% and 26% respectively. The survival trend in patients with HER2-positive tumours who did not receive trastuzumab was similar to that in women with triple-negative tumours. A higher relative excess risk of death by cancer was observed for high-grade tumours [RER, relative excess rates = 1.76 (95% CI,confidence intervals: 1.17-2.62) for Scarff Bloom Richardson grade 3 vs. 1 + 2], while a lower risk was observed for luminal tumours [RER = 0.49 (95% CI:0.27-0.89)] and HER2-positive tumours treated with trastuzumab [RER = 0.28 (95% CI: 0.14-0.59)], both compared with triple-negative tumours. Surgery of the primary tumour was associated with better survival [RER = 0.43 (95% CI: 0.28-0.68)]. With half of the women dead before 29 months, stage IV breast cancer still has a bleak outlook. Progress should continue with new target therapies for both HR and HER2 receptors.© 2015 John Wiley & Sons Ltd.Locoregional and distant recurrences after breast conserving therapy in patients with triple-negative breast cancer: ameta-analysis.Mammographic tumour appearance and triple-negative breast cancer associated with long-term prognosis of breast cancer death: A Swedish Cohort StudyHighlightsA Bayesian approach was conducted to capture the evolution of tumour attributes.Casting and architecture distortion contribute 10- and 4-fold risk for TNBCand NTN.The effect of triple-negative was noted only in casting and architecturedistortion.Abstract BackgroundNumerous studies have paid attention to the role of the triple-negative marker in the prognosis of breast cancer, but very few studies have combined mammographic phenotypes with the triple-negative marker to assess their relevance to the long-term prognosis of breast cancer. The current study aims to assess the respective contributions of both mammographic tumour appearance and the triple-negative marker, and their possible interactions, on the long-term survival of breast cancer, taking into account the prognostic factors already established.MethodsA retrospective cohort of 498 breast cancer patients was enrolled at Falun Central Hospital, Sweden, between 1996 and 1998, and information on immunohistochemical markers and histological tumour distribution in these patients was collected. This cohort – together with prior information on conventional tumour attributes and mammographic tumour features from 1968 to 1995 – was formed by the Bayesian method and was followed over time until the end of 2011.ResultsAfter considering tumour attributes, histological tumour distribution, andtriple-negative cancer, two mammographic tumour features – casting type (adjusted hazard ratio, aHR = 3.47, 2.21–5.53) and architectural distortion (aHR = 4.43,2.02–9.50) – had poorer survival compared to other types (stellate, circular,crushed-stone-like, and powdery mass). Triple-negative status conferred an independent 1.95-fold (1.06–3.52) higher risk for death from breast cancer thannon-triple-negative status. Stratified by mammographic tumour features, the impact of triple-negative status on the prognosis of breast cancer was statistically significantly greater for the casting and architecturally distorted types (aHR = 5.40, 1.40–20.59) but was not statistically significant for other types of mammographic appearance (aHR = 1.75, 0.75–4.21). Stratified by the triple-negative feature, the effect of casting type and architectural distortion versus other tumour types on the risk of breast cancer death was statistically significant not only among triple-negative breast cancers (aHR = 9.67, 2.74–29.54) but also among non-triple-negative cancers (aHR = 4.11,1.88–8.68).ConclusionIn addition to demonstrating mammographic appearance and the triple-negative feature as two independent prognostic factors, the most novel finding of this study is that the triple-negative feature played a more important role among breast tumours with the mammographic appearance of casting and architectural distortion than among tumours with other types of mammographic appearance. The risk stratification of long-term prognosis of breast cancer in the light of multi-attribute information in chronological order (mammographic tumour appearance first and then thetriple-negative test) may aid clinicians in developing a customised schedule of surveillance and in optimising treatment and adjuvant therapy.Exercise and dietary advice intervention for survivors oftriple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile.Abstract PURPOSE:Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been tested specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associatedwith breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile.METHODS:Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy-Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin).RESULTS:Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p < 0.05) than the control group. The intervention group also improved quality of life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p < 0.05).CONCLUSIONS:Exercise and dietary counseling led to loss of body fat and improved quality of life in survivors of triple-negative breast cancer. BMI was associated with favorable changes in leptin and adiponectin which may reflect a change in adiposity with intervention. Exercise and healthy eating may be equally effective in this high-risk population as in other breast cancer survivors and should be encouraged as a part of a cancer survivorship program.。