390例原发乳腺癌远处转移与分子分型关联性的10年回顾性分析

背景与目的：根据肿瘤的分子标志物不同,乳腺癌可以被分为几种亚型。不同亚型转移模式的区别对患者治疗方式的选择有很大临床意义,但目前探讨较少。该研究探讨了不同分子亚型的乳腺癌易首发转移的部位以及时间。方法：1998—2004年间在中山市人民医院接受手术治疗的早期原发性浸润性乳腺癌患者共390例纳入该研究。肿瘤分为Luminal A、Luminal B、HER-2过表达型和三阴性型4种亚型。随访这些患者,记录初次远处转移部位及时间,采用Kaplan-Meier法进行生存分析。结果：390例患者中,Luminal A型215例(55.1%)、三阴性型80例(20.5%)、HER-2型52例(13.3%)、Luminal B型43例(11.0%)。中位随访118个月(11～163个月), 72例(18.5%)出现远处转移：其中Luminal A型37例,Luminal B型8例,HER-2过表达型10例和三阴性型17例。骨是最常见的首次转移部位(39/72,54.2%),其次是肺(25/72,34.7%)、肝(22/72,30.6%)、脑(7/72,9.7%)。Luminal型(Luminal A型70.2%,Luminal B型50.0%)患者的骨转移比例显著高于HER-2过表达型(30.0%)及三阴性型(35.3%)乳腺癌(P=0.03)。Luminal B型(37.5%)和三阴性(17.6%)乳腺癌的脑转移比例显著高于Luminal A型和HER-2过表达型(P＝0.01)。生存分析显示不同亚型乳腺癌的9年无远处转移生存率差异无统计学意义,但是HER-2过表达型和三阴性型乳腺癌转移出现显著早于Luminal型乳腺癌。结论：不同亚型乳腺癌的初次远处转移模式不同。Luminal型转移出现较早、易发生骨转移;三阴性乳腺癌和Luminal B型乳腺癌转移出现较晚,并易发生脑转移。     

新疆地区1006例不同分子分型乳腺癌的临床病理特征及预后

目的 探讨新疆地区不同分子分型乳腺癌的临床病理特征和预后。方法 收集2008年1月至2010年12月新疆医科大学附属肿瘤医院行手术治疗的1006例女性乳腺癌患者的临床病历资料,根据雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体-2（HER-2）和Ki-67的状态,将乳腺癌分为：Luminal A型、Luminal B型、HER-2过表达型及Basal like型,对比分析不同分子分型乳腺癌患者的临床病理特征、复发转移及预后情况。结果 Luminal A型551例（54.8％）,Luminal B型182例（18.1％）,HER-2过表达型77例（7.7％）,Basal-like型196例（19.4％）。不同分子分型乳腺癌在肿块大小、淋巴结转移数目、临床分期、组织学分级、民族及内分泌治疗的差异均具有统计学意义（P＜0.05）。获得随访的971例患者中,HER-2过表达型的局部复发率（12.3％）及远处转移率（27.4％）均高于其他分型（P＜0.05）。Luminal A型、Luminal B型、HER-2过表达型及Basal-like型6年无病生存率分别为86.8％、75.8％、58.9％、79.1％（P＜0.05）;6年生存率分别为92.1％、83.1％、67.1％、88.0％（P＜0.05）。Cox多因素回归分析显示,淋巴结转移数目、组织学分级、内分泌治疗及分子分型是影响新疆地区乳腺癌总生存时间（OS）和无病生存时间（DFS）的独立因素,民族亦是影响该地区乳腺癌患者DFS的独立因素。结论 新疆地区Luminal A型乳腺癌最常见,预后最好,HER-2过表达型比例最低,预后最差。乳腺癌预后与淋巴结转移数目、组织学分级、内分泌治疗及分子分型有关,民族是影响乳腺癌患者DFS的重要因素。     

新疆喀什维吾尔族与汉族乳腺癌患者分子分型的研究

  目的   比较维族与汉族乳腺癌患者分子分型特点,用以指导临床。   方法   采用2011年《St.Gallen早期乳腺癌初始治疗国际专家共识》提出的乳腺癌分子分型方法对喀什地区第一人民医院369例有病理诊断的维、汉族乳腺癌患者进行分子分型,比较两者特点。   结果   284例维族乳腺癌患者的Luminal A型、Luminal B伴HER-2阴性亚型、Luminal B伴HER-2阳性亚型、HER-2过表达型和三阴型乳腺癌比例分别为12.67%（36/284）、34.51%（98/284）、20.07%（57/284）、14.79%（42/284）和17.96%（51/284）;85例汉族患者相应分子分型比例分别为16.47%（14/85）、37.65%（32/85）、10.59%（9/85）、10.59%（9/85）和24.71%（21/85）;维族和汉族HER-2阳性率分别为34.86%（99/284）和21.18%（18/85）;维族乳腺癌患者Luminal B伴HER-2阳性亚型比例高于汉族（P=0.045）,维族乳腺癌患者HER-2阳性率高于汉族（P=0.030）。   结论   与汉族患者比较,维族乳腺癌患者有较高的Luminal B伴HER-2阳性亚型比例和较高的HER-2阳性率,针对HER-2的靶向治疗在维族乳腺癌患者中显得更重要。      

Clinicopathological Features of Indonesian Breast Cancers with Different Molecular Subtypes

Background: Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. They are classified into luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes. Most of breast cancers reported in Indonesia are already large size, with high grade or late stage but the clinicopathological features of different molecular subtypes are still unclear. They need to be better clarified to determine proper treatment and prognosis. Aim: To elaborate the clinicopathological features of molecular subtypes of breast cancers in Indonesian women. Materials and Methods: A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast cancer samples from Dr. Sardjito General Hospital in Central Java,Indonesia was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The relation of clinicopathological features of breast cancers with molecular subtypes of luminal A, luminal B, Her-2 and triple negative/basal-like were analyzed usingPearson`s Chi-Square test. A p-value of <0.05 was considered statistically significant. Results: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal-like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant difference was found in breast cancer molecular subtypes in regard to age, histological grade, lymph node status and staging. However it showed insignificant result in regard to tumor size. Luminal A subtype of breast cancer was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09), negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the difference was insignificant, luminal A subtype breast cancer was mostly found in small size breast cancer (p:0.129). Her-2+ subtype breastcancer was more commonly diagnosed with large size, positive lymph node metastasis and poor grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old women. Conclusions: This study suggeststhat immunohistochemistry-based subtyping is essential to classify breast carcinoma into subtypes that vary in clinicopathological features, implying different therapeutic options and prognosis for each subtype.     

可手术的不同分子亚型乳腺癌的临床特征和生存分析

目的 分析Luminal A型、Luminal B型、人表皮生长因子受体2(HER-2)型和Basal-like型4种乳腺癌亚型的临床特征和生存状况,探讨乳腺癌个体化综合治疗的理论基础.方法 回顾性分析经手术治疗、资料完整、免疫组化方法能明确判定受体状况的乳腺癌患者408例,比较各型乳腺癌的临床特征、复发转移及生存情况.结果 Luminal A型248例,占60.8%;Luminal B型32例,占7.8%;HER-2型51例,占12.5%;Basal-like型77例,占18.9%.HER-2型乳腺癌≤45岁者明显少于其他亚型,Basal-like型乳腺痛发生腋窝淋巴结转移者的比例低于其他亚型,Luminal B型晚期病例多于其他亚型,而HER-2型早期病例多于其他亚型.获得随访的243例患者中,复发或转移58例,死亡51例.Luminal A型的复发转移率明显低于Luminal B型和Basal-like型(均P<0.05).Luminal A型、Luminal B型、HER-2型和Basal-like型的5年生存率分别为89.83%、86.15%、86.70%和79.85%,Luminal A型高于Basal-like型(P=0.008).Luminal A型、Luminal B型、HER-2型和Basal-like型的5年无病生存率分别为83.52%、68.88%、75.83%和71.66%,Luminal A型高于Luminal B型和Basal-like型(P=0.0481和P=0.0306).结论 中国人各亚型乳腺癌的构成比与欧美国家接近,Luminal A型是最常见的乳腺癌亚型,预后较好,Basal-like型和Luminal B型所占比例较小,但预后较差.     

新疆乳腺癌分子分型的临床病理学意义

目的:回顾性分析新疆维吾尔自治区人民医院病理科确诊的乳腺癌病理资料,探讨新疆地区不同分子分型乳腺癌的临床病理意义.方法:收集2011 年 1 月至2014 年 12 月就诊于新疆维吾尔自治区人民医院并行改良根治手术的 406 例乳腺癌患者的临床病理资料,根据雌激素受体ER、孕激素受体PR、人表皮生长因子受体-2 (HER-2)和 Ki-67 增殖指数进行分子分型,比较不同分子亚型乳腺癌患者的临床病理特征.结果:luminal A型中组织学分级I级最常见,luminal B型发病年龄较luminal A型年轻、但组织学分级更高,淋巴结转移更常见,HER-2过表达型淋巴结转移率最高,三阴性型组织学分级III级比例最高.不同分子分型乳腺癌在肿块大小、组织学分级方面的差异均显示统计学意义(P<0.05).结论:新疆地区luminal B 型乳腺癌更常见,HER-2 过表达型比例最低.联合组织学分类和分子分型,更有助于指导乳腺癌的诊断和治疗.     

Breast cancer subtypes identified by the ER, PR and HER-2 status in Thai women

Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2+), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, χ2). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, χ2). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, χ2). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.     

Molecular Profiling of Breast Carcinoma in Almadinah,KSA: Immunophenotyping and Clinicopathological Correlation

Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basallike) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p< 0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p< 0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.     

Relationships between Reproductive Risk Factors for Breast Cancer and Tumor Molecular Subtypes

Background: Due to wide clinical differences in the various pathological types of breast cancer and also closeassociations between disease prognosis and molecular subtypes, relationships of the latter with traditional risk factorshave been suggested. Hence, the present study aimed to assess any associations. Methods: This bi-center cross-sectionalstudy was performed on 800 consecutive women with known breast cancer referred to two Comprehensive Cancer Centersin Tehran between 2006 and 2016. Baseline information related to reproductive risk profiles as well as pathologicaltumor diagnosis and molecular subtypes determined using immunohistochemical analysis by immune-staining forER, PR, and HER2 molecules were collected by reviewing hospital records. Results: Of 800 samples included forimmunohistochemical analysis, 314 (39.3%) were diagnosed as of Luminal A subtype, 107 (13.4%) as Luminal Bsubtype, 153 (19.1%) as HER-2 over-expressing, and 226 (28.3%) as triple negative. Among all reproductive riskfactors initially assessed, young age was associated with HER-2 over-expression, greater tumor size and a history ofabortion with the luminal B subtype, lower age at pregnancy with the luminal A subtype, and lower gravidity anda shorter duration of breastfeeding with the triple negative subtype. Conclusion: Each molecular subtype of breastcancer in our population may be associated with specific reproductive risk factors.     

Association of Poor Prognosis Subtypes of Breast Cancer with Estrogen Receptor Alpha Methylation in Iranian Women

Breast cancer is a prevalent heterogeneous malignant disease. Gene expression profiling by DNA microarraycan classify breast tumors into five different molecular subtypes: luminal A, luminal B, HER-2, basal and normallikewhich have differing prognosis. Recently it has been shown that immunohistochemistry (IHC) markersincluding estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2(Her2), can divide tumors to main subtypes: luminal A (ER+; PR+/-; HER-2-), luminal B (ER+;PR+/-; HER-2+),basal-like (ER-;PR-;HER2-) and Her2+ (ER-; PR-; HER-2+). Some subtypes such as basal-like subtype have beencharacterized by poor prognosis and reduced overall survival. Due to the importance of the ER signaling pathwayin mammary cell proliferation; it appears that epigenetic changes in the ERα gene as a central component of thispathway, may contribute to prognostic prediction. Thus this study aimed to clarify the correlation of differentIHC-based subtypes of breast tumors with ERα methylation in Iranian breast cancer patients. For this purposeone hundred fresh breast tumors obtained by surgical resection underwent DNA extraction for assessedment oftheir ER methylation status by methylation specific PCR (MSP). These tumors were classified into main subtypesaccording to IHC markers and data were collected on pathological features of the patients. ERα methylation wasfound in 25 of 28 (89.3%) basal tumors, 21 of 24 (87.5%) Her2+ tumors, 18 of 34 (52.9%) luminal A tumors and7 of 14 (50%) luminal B tumors. A strong correlation was found between ERα methylation and poor prognosistumor subtypes (basal and Her2+) in patients (P<0.001). Our findings show that ERα methylation is correlatedwith poor prognosis subtypes of breast tumors in Iranian patients and may play an important role in pathogenesisof the more aggressive breast tumors.     

不同分子亚型乳腺浸润性导管癌的临床特征与预后分析

目的 探讨不同分子亚型乳腺浸润性导管癌的临床病理特征及预后情况,并分析影响乳腺浸润性导管癌预后的因素。方法 收集西安交通大学医学院第一附属医院2000年1月至2012年12月收治的具有完整临床病理和随访资料的乳腺浸润性导管癌822例,基于免疫组化检测结果将乳腺癌分为4个基本分子亚型,即Luminal A型、Luminal B型、HER-2过表达型和三阴性乳腺癌,分析不同分子亚型乳腺浸润性导管癌患者在年龄、肿瘤大小、腋窝淋巴结转移、临床分期和预后方面的差异及影响预后的因素。结果 至随访截止日期,822例乳腺癌患者中有54例出现局部复发和转移,46例死亡,死亡率5.6％。不同分子亚型乳腺浸润性导管癌在发病年龄、肿瘤大小及临床分期中的差异有统计学意义（P＜0.05）,而在腋窝淋巴结转移中的差异无统计学意义（P＞0.05）。单因素生存分析显示不同的发病年龄、临床分期、肿瘤大小、腋窝淋巴结转移状态以及分子亚型与乳腺癌预后相关（P＜0.05）。Cox多因素分析显示分子亚型及腋窝淋巴结转移状态为乳腺浸润性导管癌的独立预后因素,HER 2过表达型乳腺癌在各个分子亚型中预后最差。 结论 乳腺癌分子分型对于预测乳腺癌的预后具有重要意义,需进一步研究以在临床上指导乳腺癌患者的个体化治疗。     

青年乳腺癌及其分子亚型的临床特征分析

目的探讨青年乳腺癌及其分子亚型的临床病理特点及预后情况。方法回顾性分析2003年5月至2009年12月期间南京医科大学第一附属医院乳腺外科收治的77例青年乳腺癌患者（≤35岁）的临床资料,将其中69例浸润性癌,按照ER、PR和HER-2的表达情况分成4种分子亚型,即Luminal A型、luminal B型、HER-2过表达型和三阴性乳腺癌,并分析各亚型的临床病理特点及预后情况。定量资料的比较采用单因素方差分析,定性资料的比较采用非参数检验或Fisher确切概率检验。结果全组青年乳腺癌患者占同期乳腺癌的7．2％（77／1065）,其中T3期（〉5cm）38例（49．4％,38／77）,淋巴结转移37例,转移率为48．1％（37／77）。临床分期Ⅱ、Ⅲ期的患者分别占42．9％（33／77）和35．1％（27／77）。77例患者中浸润性癌69例,其中luminal A型34例（49．3％,34／69）,luminal B型8例（11．6％,8／69）,HER-2过表达型12例（17．4％,12／69）,三阴性乳腺癌15例（21．7％,15／69）。各亚型乳腺癌在年龄、肿瘤直径、淋巴结转移、临床分期、脉管浸润、肿瘤分级及p53分布的差异均无统计学意义（P〉0．050）。结论青年乳腺癌患者临床分期比较晚,但不同分子亚型乳腺癌的临床病理特点无差别,分子分型是否有利于指导青年乳腺癌患者的个体化治疗有待于进一步研究。     

Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women

Purpose

Breast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes.

Methods

We investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2?) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype.

Results

We found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype.

Conclusions

The results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.     

Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients

Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. However, its clinical significance remains to be established. In this study, the main aims were to discover whether reclassification of breast cancer into molecular subtypes provides more precise information regarding outcome compared to conventional histopathological grading and to study breast cancer-specific survival in the different molecular subtypes. Cases of breast cancer occurring in a cohort of women born between 1886 and 1928 with long-term follow-up were included in the study. Tissue microarrays were constructed from archival formalin-fixed, paraffin-embedded tissue from 909 cases. Using immunohistochemistry and in situ hybridisation as surrogates for gene expression analyses, all cases were reclassified into the following molecular subtypes: Luminal A; Luminal B (HER2?); Luminal B (HER2+); HER2 subtype; Basal phenotype; and five negative phenotype. Kaplan–Meier survival curves and Cox proportional hazards models were used in the analyses. During the first 5 years after diagnosis, there were significant differences in prognosis according to molecular subtypes with the best survival for the Luminal A subtype and the worst for HER2 and five negative phenotype. In this historic cohort of women with breast cancer, differences in breast cancer-specific survival according to subtype occur almost exclusively amongst the histopathological grade 2 tumours. From 5 years after time of diagnosis until the end of follow-up, there appears to be no difference in survival according to molecular subtype or histopathological grade.     

乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用

目的:探讨乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用.方法:收集漯河市中心医院收治的236例接受新辅助化疗患者的临床病理资料,分为Luminal A、Luminal B、Her-2阳性和三阴乳腺癌4种分子分型,分析分子分型与临床病理因素、新辅助化疗疗效及 5 年生存率的相关性.结果:236例患者中,107例(45.3%)为Luminal A亚型,47例(19.9%)为Luminal B亚型,27例(11.4%)为Her-2阳性亚型,55例(23.3%)为三阴乳腺癌亚型.Her-2阳性(25.9%)及三阴乳腺癌亚型(30.9%)的病理完全缓解(pCR)率明显高于Luminal亚型(Luminal A亚型 4.7%及Luminal B亚型 8.5%),差异有统计学意义(P<0.05).与Luminal亚型相比,Her-2阳性及三阴乳腺癌亚型具有更差的5年无病生存和总生存(P<0.01);获得pCR的乳腺癌患者的5年无病生存和总生存明显高于化疗后仍有癌残留的患者(P<0.05).结论:相对于Luminal亚型,Her-2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是Her-2阳性和三阴乳腺癌亚型预后反而更差.     

Clinicopathologic Features and Molecular Subtypes of Breast Cancer in Young Women (Age ≤35)

Introduction: Breast cancer in young women is a relatively rare disease; however it tends to be more aggressive and is the leading cause of cancer death in this population. The aim of this study is to investigate the clinical and biological features of breast cancer arising in young Turkish breast cancer patients. Materials and Methods: Patients with breast cancer aged 35 or less (≤35 years) were selected for the study. In total 211 cases were included. Pathologic features; histologic subtypes, grade, lymphovascular invasion, axillary involvement, and stage were recorded for each. Results: The most common subtype was luminal B (36.5%), followed by luminal A (30.8%), triple negative (23.2%) and HER2+(9.5%) subtypes. Twelve percent of the patients had stage 4, 32.7% had stage 3, 46.4% had stage 2, and 6.2% had stage 1 disease at the time of diagnosis. Mean tumour diameter was 3.87 cm (range 0.3-13 cm). The axillary lymph nodes were positive in 74.4% of the patients, while lympho-vascular invasion was seen in 56.4%. Some 9.5% of patients had grade 1, 51.2% had grade 2, and 31.8% had grade 3tumors. Conclusions: Young women with breast cancer in Turkey are more likely to present with luminal B subtype. Tumors in young women are more likely to present with advanced disease, to be high grade and and to have more lymphovascular invasion. Further research should focus on whether we need new treatment strategies for young patients with breast carcinoma.     

Differential Distribution of microRNAs in Breast Cancer Grouped by Clinicopathological Subtypes

Background: microRNAs (miRNAs) that regulate proliferation, invasion and metastasis are considered to bethe principal molecular basis of tumor heterogeneity. Breast cancer is not a homogeneous tissue. Thus, it is veryimportant to perform microarray-based miRNA screening of tumors at different sites. Methods: Breast tissuesamples from the centers and edges of tumors of 30 patients were classified into 5 clinicopathological subtypes.In each group, 6 specimens were examined by microRNA array. All differential miRNAs were analyzed betweenthe edges and centers of the tumors. Results: Seventeen kinds of miRNAs were heterogeneously distributedin the tumors from different clinicopathological subtypes that included 1 kind of miRNA in Luminal A andLuminal B Her2+ subtypes, 4 kinds in Luminal A and Her2 overexpression subtypes, 6 kinds in Luminal BKi67+ and Luminal B Her2+ subtypes, 2 kinds between Luminal B Ki67+ and triple-negative breast cancer(TNBC) subtypes, 2 kinds between Luminal B Her2+ and TNBC subtypes, and 2 kinds between Luminal BKi67+, Luminal B Her2+, and TNBC subtypes. Twenty kinds of miRNAs were homogenously distributed in thetumors from different clinicopathological subtypes that included 6 kinds of miRNAs in Luminal B Ki67+ andLuminal B Her2+ subtypes, 1 kind in Luminal B Ki67+ and Her2 overexpression subtypes, 10 kinds betweenLuminal B Ki67+ and TNBC subtypes, 2 kinds in Luminal B Her2+ and TNBC subtypes, and 1 kind betweenLuminal B Ki67+, Luminal B Her2+, and TNBC subtypes. Conclusions: A total of 37 miRNAs were significantlydistributed in tumors from the centers to edges, and in all clinicopathological subtypes.     

Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy

PurposeTo determine whether tumor grade, molecular subtype and hypoxia predict response to hypofractionated versus standard radiotherapy (RT) following breast-conserving surgery (BCS) for node-negative breast cancer in a randomized controlled trial (RCT).Patients and methodsFormalin-fixed paraffin-embedded (FFPE) tumor blocks were available on 989 of 1234 patients enrolled in the Hypofractionation Whole Breast Irradiation (HWBI) Trial. A central pathology review and assessment of tumor grade using the Nottingham grading system was carried out. Tumors were classified by molecular subtype as luminal A, luminal B, HER2 enriched, basal-like or unclassified using a six-biomarker panel; ER, PR, HER-2, Ki67, CK5/6 and EGFR. Tumors were also classified as hypoxic based on the expression of HIF1α, CAIX or GLUT-1. The primary end point was local recurrence (LR).ResultsMedian follow-up was 12 years. In the multivariable Cox model, molecular subtype was the only factor predictive of LR, the 10-year cumulative incidence was 4.5% for luminal A and basal-like, 7.9% for luminal B and 16.9% for HER-2 enriched tumors (P < 0.01). Tumor grade, molecular subtype or hypoxia did not predict response to hypofractionation.ConclusionsIn women enrolled in the HWBI trial following BCS tumor molecular subtype predicted LR. However tumor grade, molecular subtype and hypoxia did not predict response to hypofractionation suggesting that patients with node-negative breast tumors of all grades and molecular subtypes may be safely treated with hypofractionated RT regimens.     

Distribution, clinicopathologic features and survival of breast cancer subtypes in Southern China

Breast cancer research and treatment by different subtypes is an inevitable trend. We investigated the clinicopathologic features and outcomes of different breast cancer subtypes in Southern China. A total of 5809 patients with invasive ductal carcinomas were identified. Immunohistochemical (IHC) markers for estrogen receptor (ER), progesterone receptor (PR), Her2/neu, and Ki‐67 proliferation index were used to classify cases into five molecular subtypes. Clinicopathologic characteristics and survival rates were analyzed retrospectively. Of all patients, 31.1% were luminal A subtype, 30.4% luminal B (high Ki‐67), 13.1% luminal B (Her2/neu+), 9.0% Her2/neu and 16.5% triple negative subtype. Luminal B (high Ki‐67) presented primarily in premenopausal patients with the lowest average age (43.0 years). Her2/neu positive tumors were more closely associated with aggressive features including increased tumor size, positive lymph node status and lymphvascular invasion (LVI). Triple negative subtype was characterized by poorer histologic grade. Her2/neu positive cases had presented the worst 5‐year disease‐free survival (DFS) and overall survival (OS). Multivariate analyses of OS and DFS suggested that there were different negative prognostic factors for the five subtypes. The benefit of the cyclophosphamide, methotrexate, and 5‐fluorouracil (5FU) (CMF) regimen was equal to that of anthracycline‐based and Taxane‐based regimens for patients with luminal A subtype and triple negative subtype, but inferior to anthracycline‐based and Taxane‐based regimens for those with two luminal B subtypes and Her2/neu subtype. The prognostic significance of traditional markers may differ among subtypes. This study revealed the distinct clinicopathologic characteristics, systemic therapy benefits, prognostic factors and survival rate among different breast cancer subtypes.     

不同分子分型乳腺癌的临床病理特征及预后的关系

目的 探讨乳腺癌分子分型与临床病理特征及预后的关系.方法 选择126例乳腺癌患者,按孕激素受体(PR)、雌激素受体(ER)和人类表皮生长因子受体-2(HER-2)的状态分为Luminal A型、Luminal B型、HER-2过度表达型和Basal-like型,比较不同分子分型乳腺癌患者的临床病理特征、复发转移及预后情况.结果 156例乳腺癌患者中,Luminal A型68例(54.0%)、Luminal B型22例(17.5%)、HER-2过度表达型9例(7.1%)、Basal-like型27例(21.4%).乳腺癌不同分子分型间绝经状态、肿瘤直径、淋巴结转移数目、临床分期及组织学分级的差异均有统计学意义(P<0.05).HER-2过度表达型与Basal-like型的局部复发率分别为33.3%和14.8%,远处转移率分别为55.6%和40.7%,均高于其他2种亚型,差异均有统计学意义(P<0.05).4组中位无瘤生存时间的差异有统计学意义(χ2=8.002,P<0.05),HER-2过度表达型与Basal-like型的MPFS较短.结论 HER-2过表达型和Basal-like型乳腺癌的病理学特征较差,且预后不良;而Luminal A型预后较好.