Phase 1 Study of Erlotinib and Metformin in Metastatic Triple-Negative Breast Cancer

BackgroundEpidermal growth factor receptor (EGFR) is frequently overexpressed in metastatic triple-negative breast cancer (mTNBC). One strategy for overcoming resistance to EGFR inhibition is concomitant inhibition of downstream signaling. The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. We evaluated the combination of erlotinib and metformin in a phase 1 study of patients with mTNBC.Patients and MethodsPatients with mTNBC who had received at least one prior line of therapy for metastatic disease were eligible. Erlotinib dose was fixed at 150 mg daily. Metformin dose escalation was planned according to a 3 + 3 design. Dose-limiting toxicities (DLT) were assessed during the first 5 weeks of therapy. The primary objective was to determine the maximum tolerated dose of metformin with fixed-dose erlotinib. Secondary endpoints were response rate, stable disease rate, and progression-free survival.ResultsEight patients were enrolled. The median number of prior therapies for metastatic disease was 2.5 (range, 1-6). No DLT events were reported during the DLT assessment period. Most adverse events were grade 1/2. Grade 3 diarrhea despite maximum supportive care required dose reduction of metformin in one patient. Grade 3 rash led to study withdrawal in one patient. No grade 4 adverse events were reported. The best observed response was stable disease in 2 patients (25%). Median progression-free survival was 60 days (range, 36-61 days).ConclusionErlotinib and metformin were well tolerated in a population of pretreated mTNBC patients but did not demonstrate efficacy in this population.     

Risk communication in a patient decision aid for radiotherapy in breast cancer: How to deal with uncertainty?

Background and aimPatient decision aids for oncological treatment options, provide information on the effect on recurrence rates and/or survival benefit, and on side-effects and/or burden of different treatment options. However, often uncertainty exists around the probability estimates for recurrence/survival and side-effects which is too relevant to be ignored. Evidence is lacking on the best way to communicate these uncertainties. The aim of this study is to develop a method to incorporate uncertainties in a patient decision aid for breast cancer patients to support their decision on radiotherapy.MethodsFirstly, qualitative interviews were held with patients and health care professionals. Secondly, in the development phase, thinking aloud sessions were organized with four patients and 12 health care professionals, individual and group-wise.ResultsConsensus was reached on a pictograph illustrating the whole range of uncertainty for local recurrence risks, in combination with textual explanation that a more exact personalized risk would be given by their own physician. The pictograph consisted of 100 female icons in a 10 x 10 array. Icons with a stepwise gradient color indicated the uncertainty margin. The prevalence and severity of possible side-effects were explained using verbal labels.ConclusionsWe developed a novel way of visualizing uncertainties in recurrence rates in a patient decision aid. The effect of this way of communicating risk uncertainty is currently being tested in the BRASA study (NCT03375801).     

AXL表达与乳腺癌预后及临床病理特征关系的Meta分析

目的 探讨受体酪氨酸激酶AXL蛋白的表达对乳腺癌患者预后及临床病理特征的意义。方法 在中国知网(CNKI)、万方医学网(Wanfang Data)、 Cochrane Library、Embase、PubMed和Medline数据库中,搜索国内外公开发表的有关AXL与乳腺癌预后关系的文献,检索时限均为从建库至2019年10月。2位研究者按纳入和排除标准独立筛选文献、提取资料和评价纳入研究的偏倚风险,并进行Meta分析。结果 共纳入7篇文献,包括933例乳腺癌患者。AXL高表达组的乳腺癌患者总生存期(overall survival,OS)明显低于低表达组(HR=2.36,95%CI 1.60~3.46,P<0.000 1),但其表达在无复发生存期(relapse free survival,RFS)和无疾病生存期(disease free survival,DFS)中差异无统计学意义,且与乳腺癌的年龄、临床分期、组织分级、淋巴结转移及受体表达的相关性分析无统计学意义。结论 AXL的阳性表达与乳腺癌患者预后不良有关,是乳腺癌个体化治疗的潜在分子标志物。     

乳腺癌21基因检测的研究进展

乳腺癌是一类具有异质性的肿瘤，不同患者的治疗方法和疗效都不相同。尽管目前仍在努力为激素受体（hormone receptor，HR）阳性（+）、人表皮生长因子受体2（human epidermal growth factor receptor 2,HER-2）阴性（-）、淋巴结（axillary lymph node，ALN）阴性（-）的早期乳腺癌患者寻找合适的治疗方法，但其术后是否需要化疗仍然是肿瘤科医生面临的一个难题。以往治疗主要依赖于经典的组织病理学和免疫组织化学技术，随着精准医疗时代的到来，我们需要更定量的诊断方法和合理的个体化治疗。虽然化疗可降低疾病复发风险并提高生存率，但它带来的不良反应事件会降低患者的生活质量，尤其低复发风险（recurrence risk,RS)有可能超过化疗益处。21基因检测不仅可以预测这类早期乳腺癌化疗疗效及评估预后，还可提供精准的个体化治疗方案指导用药，为患者增添信心。本文就乳腺癌21基因检测的研究进展进行综述。     

乳腺癌X线表现分析

目的分析乳腺癌典型及不典型X线征象,提高对乳腺癌不典型X线表现的认识。方法对61例经手术病理证实的乳腺癌资料进行回顾性分析。结果61例乳腺癌主要X线征象:肿块39例;微小钙化30例;不伴肿块及微小钙化的乳腺局部结构紊乱4例、星芒征3例、非对称性密度增高3例。结论肿块及微小钙化是乳腺癌最主要、最直接的X线征象,但部分乳腺癌X线上缺乏上述2种表现,单纯以结构紊乱、非对称性密度增高或星芒征为主要表现。提高对此类乳腺癌不典型X线表现的认识,有利于防止误、漏诊。     

X线及MRI对聚丙烯酰胺凝胶隆胸后乳腺病变诊断价值的评价与比较

目的对聚丙烯酰胺凝胶(PAG)注射式隆胸术后,出现并发症或合并乳腺其他病变的X线与MRI的诊断价值进行评估。方法回顾性分析26例PAG隆胸术后钼靶X线与MRI的影像表现。结果钼靶X线及MRI能显示充填物位置、形态,合并乳腺病变4例,X线全部漏诊,MRI能检出病灶。结论钼靶X线是PAG隆胸术后普查、随访的首选方法,但出现并发症或者合并乳腺病变时,MRI具有无法比拟的优越性,在临床诊断与治疗中发挥了重要作用。     

Eating to beat breast cancer: Potential role for soy supplements

Background: The study reviews the anticancer properties of naturalisoflavones which occur in especially high concentration in soybeans. Itconsiders the suitability of soybean products for clinical trials aiming toreduce the progression of breast cancer.Methods: Evidence is reviewed that plant isoflavones such asgenistein show cytostatic activity against human mammary cancer cell linesin vitro and can also suppress carcinogen-induced mammary cancer inyoung and mature rats.Results: Plant isoflavones are converted in the bowel to compoundswith potential antioestrogenic and antioxidative properties. These compoundsshow cytostatic activity for both oestrogen receptor-positive and negativehuman mammary cancer cell lines, and also inhibit growth and progress of therat mammary cancer model. The high content of soybean products in the diet ofAsian women has been postulated as one reason for their relatively low breastcancer incidence.Conclusion: Preclinical studies suggest that soybean products begiven priority for clinical trials in breast cancer protection. A pilot studycould test soy protein supplements as long-term adjuvant dietary treatmentafter primary surgery for early breast cancer, looking for a decrease in therisk of recurrence or of second primary tumours.     

Aesthetic refinements in prophylactic mastectomy with immediate reconstruction

Immediate reconstruction of more than 1000 breasts was performed on high-risk patients on whom a prophylactic mastectomy was done. The mastectomy removes as much breast tissue as possible while leaving sufficient skin, and possibly the nipple-areola complex, to enable immediate reconstruction. The creation of symmetrical, well-balanced muscle pockets for the implant is the most important factor in producing satisfactory results in these cases.     

MMP-9和TIMP-1表达失衡与乳腺癌浸润、转移的相关性

目的 研究乳腺癌组织中基质金属蛋白酶（MMP－9）和金属蛋白酶组织抑制因子（TIMP－1）的表达变化与乳腺癌生物学行为及淋巴结转移的关系。方法 应用SP免疫组织化学方法检测85例乳腺癌组织MMP－9，TIMP－1及细胞增殖核抗原ki-67的表达情况。结果 MMP-9阳性染色率90．59％，MMP－9阳性表达与肿瘤浸润，淋巴结转移，ki-67指数及TNM分期呈正相关（Pearson列联系数分别为P=0.03,P=0.02,P=0.004和P＝0．0000，P＜0．05，0．01。TIMP－1阳性染色率为78．82％，TIMP－1阳性表达与肿瘤浸润，淋巴结转移及TNM分期浸润，转移及ki-67指数显著相关（P＜0．05，P＜0．01，P＜0．001）。结论 MMP－9和TIMP－1表达失衡与乳腺癌浸润及淋巴结转移密切相关。