三阴性乳腺癌

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

Abstract

Hormone 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 in

2003–2006 treated with curative intent who developed MBC within 5 years of

follow-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 Cancer

Abstract

Triple-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 was

in 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；

Abstract

We 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,