重组人血管内皮抑素联合NP方案治疗晚期NSCLC随机、双盲、对照、多中心Ⅲ期临床研究

  目的   对比重组人血管内皮抑素(YH-16)联合GP方案与GP方案在治疗转移性三阴性乳腺癌中的有效性和安全性。   方法  55例转移性乳腺癌患者既往均经病理学诊断为三阴性浸润性导管癌, 均接受过紫杉类及蒽环类药物治疗。随机分为观察组及对照组, 其中观察组27例, 给予重组人血管内皮抑素联合GP方案治疗(重组人血管内皮抑素15 mg静脉滴注d1~14, 吉西他滨1 000mg/m²静脉滴注d1, 8;顺铂40mg/m²静脉滴注d1, 2);对照组28例, 仅给予GP方案化疗, 每3周为1个周期, 每2个周期评价疗效。   结果   55例患者均可评价疗效, 观察组(27例): 完全缓解(CR)3例(11.1%), 部分缓解(PR)9例(33.3%), 客观有效率(CR+PR)44.4%;对照组(28例): CR 1例(3.5%), PR 9例(32.1%), 客观有效率(CR+PR)35.7%。两组中位疾病进展时间分别为7.0、5.2个月, 无疾病进展生存比较有显著性差异(P=0.001)。不良反应主要为胃肠道反应及骨髓抑制, 两组比较无显著性差异(P > gt; 0.05)。   结论   重组人血管内皮抑素联合GP方案治疗转移性三阴性乳腺癌具有协同作用, 未增加不良反应, 可延长中位疾病进展时间, 值得进一步研究。     

Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry

BACKGROUND: Tumor markers are becoming increasingly important in breast cancer research because of their impact on prognosis, treatment, and survival, and because of their relation to breast cancer subtypes. The triple-negative phenotype is important because of its relation to the basal-like subtype of breast cancer. METHODS: Using the population-based California Cancer Registry data, we identified women diagnosed with triple-negative breast cancer between 1999 and 2003. We examined differences between triple-negative breast cancers compared with other breast cancers in relation to age, race/ethnicity, socioeconomic status (SES), stage at diagnosis, tumor grade, and relative survival. RESULTS: A total of 6370 women were identified as having triple-negative breast cancer and were compared with the 44,704 women with other breast cancers. Women with triple-negative breast cancers were significantly more likely to be under age 40 (odds ratio [OR], 1.53), and non-Hispanic black (OR, 1.77) or Hispanic (OR, 1.23). Regardless of stage at diagnosis, women with triple-negative breast cancers had poorer survival than those with other breast cancers, and non-Hispanic black women with late-stage triple-negative cancer had the poorest survival, with a 5-year relative survival of only 14%. CONCLUSIONS: Triple-negative breast cancers affect younger, non-Hispanic black and Hispanic women in areas of low SES. The tumors were diagnosed at later stage and were more aggressive, and these women had poorer survival regardless of stage. In addition, non-Hispanic black women with late-stage triple-negative breast cancer had the poorest survival of any comparable group.     

Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer

Neoadjuvant chemotherapy (NAC) for breast cancer is evolving and subsequent adjuvant systemic treatment is mainly based on the presence of the Estrogen (ER) receptor, Progesterone (PR) receptor and Human Epidermal growth factor Receptor 2 (HER2) status on the core needle biopsy prior to treatment. It is not well known whether these biomarkers change after NAC, requiring a change in further adjuvant systemic treatment. A review of the literature (PubMed search) revealed 32 relevant studies that investigated the concordance of the hormone receptors (ER and/or PR) and HER2 after NAC with or without trastuzumab. Discordance of the hormone receptor status was reported in four out of eight studies in 8-33% of the patients. About half of the studies that tested the ER and PR receptor status separately reported discordances of 2.5-17% and 5.9-51.7% respectively. Studies that concluded that ER and/or PR receptor remained stable after NAC were performed with evidently lower number of patients compared to studies that reported a change. Good concordance of the HER2 amplification tested with FISH was reported, although the HER2 expression measured with immunohistochemistry was more discordant. A switch to a negative HER2 receptor in up to 43% of the patients was reported when NAC was combined with trastuzumab.Until more comparable studies are being published, retesting the receptor status of the residual tumor after NAC should be considered in order to improve future tailored adjuvant therapies.     

A functional polymorphism of TGFBR2 is associated with risk of breast cancer with ER(+), PR(+), ER(+)PR(+) and HER2(-) expression in women

Little is known about the correlation between TGFBR2 G-875A and breast cancer risk. Moreover, the associations of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) in breast cancer tissues with the TGFB1 C-509T, T+29C and TGFBR2 G-875A polymorphisms remain to be determined. In this study, we genotyped for TGFB1 C-509T, T+29C and TGFBR2 G-875A in fresh surgically resected tissues (n=82) and archived paraffin-embedded specimens (n=88) from 170 patients with breast cancer, as well as peripheral blood samples from 178 cancer-free female individuals. Evaluation of ER, PR and HER2 expression was performed using immunohistochemical staining. Logistic regression analysis was carried out to determine the risk of breast cancer by calculating the odds ratios (ORs) and their 95% confidence intervals (CIs). As a result, no difference was observed in the TGFB1 C-509T, T+29C genotype and allele frequencies between patients and controls. However, the frequency of the TGFBR2 -875A allele was marginally higher in cancer-free female individuals than that of women with breast cancer (24.2 vs. 17.9%, P=0.05). Notably, when stratification was performed by ER, PR and HER2 expression, the TGFBR2 -875A allele was found to correlate significantly to a decreased risk of breast cancer with ER(+) (OR=0.57, 95% CI 0.35-0.92), PR(+) (OR=0.54, 95% CI 0.34-0.88), ER(+)PR(+) (OR=0.55, 95% CI 0.33-0.92) and HER2(-) (OR=0.55, 95% CI 0.34-0.88) under a dominant genetic model. In conclusion, this is the first study to suggest that the TGFBR2 -875A allele modifies predisposition to breast cancer with an expression of ER(+), PR(+), ER(+)PR(+) and HER2(-).     

Discordances in ER,PR, and HER2 between primary breast cancer and brain metastasis

When distant metastases are discovered, it is important to determine receptor profiles of these lesions through histologic examination. However, brain metastasis sites are difficult to reach to be routinely biopsied. The purpose of this study was to determine expression profiles of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer brain metastasis (BCBM) and the existence of discordance between primary breast cancer and brain metastasis. A total of 37 patients who underwent craniotomies for metastatic brain tumors arising from breast cancer at National Cancer Center (NCC) of Korea between 2002 and 2014 were retrospectively reviewed. Clinicopathologic data were collected from electronic medical records. Receptor profiles of primary breast cancer and brain metastasis in each patient were identified. Data of ER, PR, and HER2 expression in brain metastasis were available in electronic medical records for 21 (56.8%) of 37 cases. Results of ER, PR, and HER2 expression were positive in 47.6, 42.9, and 38.1% of patients with brain metastasis, respectively. Receptor conversion occurred in 11 (52.4%) of 21 patients (for ER, 9.5%; for PR, 38.1%; for HER2, 23.8%). Overall survival was longer in patients with concordant receptor expression patterns between primary breast cancer and brain lesion compared to that in patients with discordant patterns. However, such difference was not statistically significant (discordant vs. concordant median survival: 19.2 versus 31.1 months, p?=?0.181). Receptor conversion in BCBMs was observed in over 50% of Korean patients used in this study. HER2 conversion was observed in 23.8% of patients in this study. Therefore, if resistance to anti-HER2 treatment is suspected in patients with BCBM, biopsy is needed to determine receptor profiles of brain lesion.     

Use of ER/PR/HER2 subtypes in conjunction with the 2007 St Gallen Consensus Statement for early breast cancer

Background  

The 2007 St Gallen international expert consensus statement describes three risk categories and provides recommendations for treatment of early breast cancer. The set of recommendations on how to best treat primary breast cancer is recognized and used by clinicians worldwide. We now examine the variability of five-year survival of the 2007 St Gallen Risk Classifications utilizing the ER/PR/HER2 subtypes.     

Prognostic factors in Luminal B-like HER2-negative breast cancer tumors

BackgroundMolecular and genomic platforms can classify breast cancer intrinsic subtypeswith precision, however these are not widespread and immunohistochemical (IHC) classification is still used globally. This study aimed to evaluate the main clinical and pathologic prognostic factors for Luminal B-like HER2-negative breast cancer in our clinical setting.MethodsA retrospective review of early Luminal B-like HER2-negative breast cancer patients diagnosed in 2017 in our center was conducted. The main prognostic factors for relapse were evaluated, including patient's characteristics such as age, menopausal status, comorbidity index, personal and family history of breast cancer and obesity; tumor features such as size, histology and grade, oestrogen and progesterone receptor (PgR) status, HER2 status, Ki67 index and nodal involvement; and the given treatment. Cancer relapse during five years of follow-upwas considered the main outcome.ResultsFifty-six patients with early Luminal B-like HER2-negative breast cancer were included. Seven patients relapsed within five years of follow-up. Lymph node involvement at diagnosis and postoperatively were significantly associated with relapse (24,5% vs 71,43%p = 0.022; 38,8% vs 83,3%p = 0.004, respectively),although the number of pathologic positive lymph nodes was not associated with relapse occurrence (mean 1.5 in no-relapse group vs 0.8 in relapse group; p = 0.308).Other possible risk factors such as young age, premenopausal status, self-history of breast cancer, tumor size, histologic grade, PgR, or Ki 67 were not significantly associated with relapse. Additionally, the distribution of the number of positive nodes among relapse and no relapse groups(2,1 vs 1,8; p = 0.082) was not significant.ConclusionsLymph node involvement was the only prognostic factor in Luminal B-like HER2-negative breast cancer identified in this study, independently of the number of affected nodes.     

Palbociclib in highly pretreated metastatic ER-positive HER2-negative breast cancer

Purpose

We aimed to investigate the role of palbociclib, a first-in-class cyclin-dependent kinase 4 and 6 inhibitor, in postmenopausal women with highly pretreated endocrine therapy-resistant metastatic breast cancer (MBC).

Methods

Between 28 September 2015 and 14 March 2017, a compassionate use program was established in the University Hospitals Leuven in which 82 postmenopausal women with estrogen receptor-positive, HER2-negative MBC were included after at least four lines of systemic treatment. The efficacy and safety analysis was performed in 82 patients who had received at least one dose of palbociclib and who had at least 6-month follow-up at the data cut-off point. The primary objective was the evaluation of efficacy of the combination of palbociclib and endocrine therapy with clinical benefit as primary endpoint, defined as the absence of progressive disease and being on treatment for at least 6 months. Secondary objectives were the evaluation of toxicity and the identification of potential predictors for clinical benefit.

Results

The median age of the patients was 67.1 years (range 34.8–85.9) at the time of inclusion. The average duration of treatment was 5.6 months (range 1–19), with a median progression-free survival of 3.17 (95% CI 2.76–4.70) months. At the data cut-off point, 10 patients were still on treatment with palbociclib. In this highly pretreated setting, 34 patients experienced no progressive disease within 6 months, resulting in an overall clinical benefit rate (CBR) of 41.5%. 20.7% (17/82) showed stable disease for ≥?9 months and 13.4% for ≥?12 months. None of the investigated predicting factors were significantly associated with clinical benefit at 6 months. For 43.9% of the patients, treatment delay or dose reduction was indicated.

Conclusions

Palbociclib in combination with endocrine therapy shows an unexpectedly high CBR and favorable safety profile in heavily pretreated endocrine-resistant estrogen receptor-positive, HER2-negative MBC patients.

     

ER/PR+和HER2-型乳腺癌患者免疫组化指标的列线图预后模型

目的：探讨改良雌激素受体（estrogen receptor,ER)/孕激素受体(progesterone receptor,PR)阳性（+）及人类表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）阴性（-）（ER/PR+、HER2-）型乳腺癌患者的传统预后模型,满足目前的临床实际需求。方法：选取了2009 年1 月至2009 年12 月上海市黄浦区中心医院乳腺外科收治的335 例ER/PR+、HER2-型乳腺癌患者。将97 个变量纳入模型,采用SCAD变量选择的方法,在充分考虑协变量是否存在对数线性关系、非对数线性关系（分段线性关系）临界值的合理确定、共线问题后,构建一个新的ER/PR+、HER2-型乳腺癌患者传统免疫组化指标的Cox回归预后模型,并进一步建立其列线图模型;在此基础上建立了术后1、3 和5 年生存概率的列线图;并通过比较模型的区分度（discrimination）和校准度（calibration）来评价模型的预测能力。结果：通过乳腺癌预后建立Cox 回归模型结果显示,患者的预后与组织级别、淋巴结转移、Ki67、PR和年龄等因素有关;其中组织级别和淋巴结转移对风险比的影响呈对数线性关系,Ki67、PR和年龄对风险比的影响呈非对数线性关系,其合理临界值分别为Ki67（60%）、PR（20%）和年龄（55 岁）。该模型术后1、3 和5 年的ROC曲线下面积（AUC值）均高于0.85,说明该Cox 回归模型具有较高的区分度。该模型Gr?nnesby-Borgan 拟合优度检验统计量值为1.37、对应的P值为0.5,说明该Cox回归模型有较好的校准度。结论：通过改良ER/PR+和HER2-型乳腺癌患者的传统预后模型,建立患者术后1、3 和5年生存概率的列线图,能准确、直观、有效地预测患者的生存概率,对乳腺癌患者临床治疗有较好的指导意义。     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.