分子分型对乳腺癌新辅助化疗后肿瘤退缩模式的影响

  目的  探讨乳腺癌新辅助化疗（neoadjuvant chemotherapy,NAC）后不同分子分型的乳腺原发病灶退缩模式。  方法  选取2008年7月至2017年10月山东大学附属山东省肿瘤医院收治的108例ⅡA~ⅢC期乳腺浸润性导管癌行新辅助化疗后手术患者的临床病理资料,手术标本制作次连续病理大切片,电子显微镜下勾画残余肿瘤范围,三维重建残余肿瘤,评价新辅助化疗后原发肿瘤临床病理退缩模式。  结果  108例患者新辅助化疗后向心性退缩（concentric shrinkage mode,CSM）与非向心性退缩（nonconcentric shrinkage mode,NCSM）中Luminal A型分别占47.4%（9/19）与52.6%（10/19）,Luminal B HER-2阴性型、HER-2阳性型分别占53.6%（15/28）、72.7%（16/22）与46.4%（13/28）、27.3%（6/22）,HER-2阳性型分别占84.6%（11/13）与15.4%（2/13）,三阴性乳腺癌分别占80.8%（21/26）与19.2%（5/26）。  结论  Luminal B HER-2阳性型、HER-2阳性型及三阴性乳腺癌的原发肿瘤更易出现CSM,Luminal A型、Luminal B型HER-2阴性型的原发肿瘤临床病理退缩模式无显著性差异。分子分型可用于预测乳腺癌新辅助化疗后原发肿瘤的临床病理退缩模式,有助于选择新辅助化疗后适合保乳治疗的患者、降低局部复发率。      

分子分型与乳腺癌新辅助化疗疗效的相关性

目的:探讨乳腺癌分子分型与新辅助化疗疗效的相关性.方法:回顾性分析81例原发乳腺癌患者,分子分型分为HER-2阳性型和三阴型、Luminal A型、Luminal B1型、 Luminal B2型,并评估其与乳腺癌新辅助化疗疗效的关系.结果:新辅助化疗疗效与各分子分型之间的相关性无统计学意义,但新辅助化疗有效率达到pCR+tpCR(%)以三阴型最高(25%),其次是HER-2阳性型(23.1%),而达到CR+PR(%)为HER-2阳性型最高(84.6%).结论:乳腺癌新辅助化疗可有效控制肿瘤,分子分型能作为乳腺癌新辅助化疗疗效的缓解独立预测因子.     

乳腺癌分子分型在新辅助化疗疗效和预后中的预测作用

[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]对接受新辅助化疗方案治疗的157例乳腺癌患者进行回顾性分析.依据免疫组化雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(Her2)表达水平将乳腺癌分为Luminal A、Luminal B、Her2阳性和三阴性4个分子分型,分析4个分子分型与临床病理因素、新辅助化疗疗效及3年生存率的相关性.[结果] 157例患者中,分子分型与肿瘤大小、淋巴结转移相关,T3～4期的三阴性型的比例高于T1～2期(P=0.003);N0、N1、N2、N3期的三阴性型的比例分别为44.4％、23.8％、25.6％和22.2％ (P=0.014).不同分子分型间新辅助化疗有效率无明显差异(P=0.632),而T分期(P=0.014)、N分期(P=0.031)与有效率明显相关.不同分子分型间新辅助化疗3年生存率有明显差异,Luminal A型最高,三阴性型最低(P=0.049).乳腺癌预后影响因素Cox回归模型分析提示分子分型(P=0.003)、年龄(P=0.007)、T分期(P=0.013)、N分期(P=0.000)是乳腺癌患者的独立预后因素.[结论]乳腺癌分子分型与肿瘤大小、淋巴结转移状态相关,能作为新辅助化疗远期疗效的独立预测因子.     

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.     

Ki-67与分子亚型预测乳腺癌新辅助化疗敏感性的研究

目的:探讨Ki-67表达与乳腺癌不同分子亚型预测乳腺癌新辅助化疗的敏感性.方法:收集广东省妇幼保健院乳腺中心2007-01-2011-05接受新辅助化疗的55例局部晚期乳腺癌患者的临床资料,分析Ki-67表达、乳腺癌分子亚型与新辅助化疗临床有效率及病理完全缓解之间的关系.结果:55例患者新辅助化疗后总有效率(RR)为78.2％(43/55),其中有20.0％(11/55)病例达临床完全缓解(CR),9.1％(5/55)的病例达病理完全缓解(pCR),58.2％(32/55)病例达临床部分缓解(PR),21.8％(12/55)的病例为病情稳定(SD),无患者获得疾病进展(PD).Ki-67高表达组(Ki-67≥14％)新辅助化疗临床有效率优于Ki-67低表达组(Ki-67＜14％),x2=7.004,P=0.018;但两组的肿瘤原发灶的病理完全缓解(pCR)差异无统计学意义,x2=0.008,P=1.000.在Ki-67低表达组内,不同分子亚型的乳腺癌新辅助化疗疗效,差异有统计学意义,x2 =8.306,P=0.040;三阴型乳腺癌的有效率优于Luminal A型,x2=10.617,P=0.009;三阴型、Luminal B型与HER-2过表达型的新辅助化疗有效率,差异无统计学意义,x2=5.091,P=0.078;Luminal A型、Luminal B型与HER-2过表达型的新辅助化疗有效率,差异无统计学意义,x2=0.417,P=0.812.在Ki-67高表达组内,不同分子亚型的乳腺癌新辅助化疗疗效,差异无统计学意义,x2 =2.921,P=0.404.不同分子亚型的乳腺癌新辅助化疗临床疗效,差异有统计学意义,x2=14.068,P=0.003;三阴型、Luminal B型和HER-2过表达型乳腺癌新辅助化疗的临床疗效优于Luminal A型;三阴型、Luminal B型与HER-2过表达型的新辅助化疗临床疗效差异无统计学意义,x2 =2.074,P=0.354.而这4型乳腺癌新辅助化疗的病理完全缓解(pCR)差异无统计学意义,x2=7.335,P=0.062.结论:Ki-67表达和乳腺癌分子亚型可预测新辅助化疗的疗效,Ki-67高表达和三阴型乳腺癌的患者从新辅助化疗中获益更多.     

乳腺癌分子分型在新辅助化疗疗效和预后中的预测作用

目的探讨乳腺癌分子分型在乳腺癌新辅助化疗疗效和预后中的预测作用。方法选取2012年9月至2015年8月间广西玉林市红十字会医院接受新辅助化疗的乳腺癌患者68例,采用免疫组化法进行乳腺癌分子分型,分为HER-2过表达组(11例),Luminal A组(22例),Luminal B组(23例)和三阴性组(12例)。观察4组患者的新辅助化疗疗效,化疗后均随访12个月,统计四组患者的无病生存率。结果三阴性组患者新辅助化疗有效率为83.4%,与HER-2过表达组患者的72.7%比较,差异无统计学意义(P>0.05),但两组均明显高于Luminal A组和Luminal B组患者,差异均有统计学意义(P<0.05)。Luminal A组和Luminal B组患者新辅助化疗有效率分别为68.2%和69.6%,两组比较差异无统计学意义(P>0.05)。随访12个月,Luminal A组和Luminal B组患者的无病生存率均较HER-2过表达组和三阴性组患者高,差异均有统计学意义(P<0.05),其中Luminal A组患者的无病生存率最高,三阴性组患者无病生存率最低。结论不同分子分型乳腺癌患者的新辅助化疗疗效和预后均有自身的特征,临床可将乳腺癌患者的分子分型作为预测新辅助化疗疗效和预后的参考指标之一。     

腋窝淋巴结阴性浸润性乳腺癌的分子分型及预后观察

目的探讨腋窝淋巴结阴性浸润性乳腺癌患者的分子分型及其预后情况。方法回顾性分析2006年12月至2009年6月间180例腋窝淋巴结阴性浸润性乳腺癌的临床病理资料,并按照雌激素受体(ER)、孕激素受体(PR)及人类表皮生长因子受体-2(HER-2)的检测结果将其分为管腔上皮(Luminal)型、基底样(Basal-like)型及HER-2过表达(over-expression)型,观察不同分型乳腺癌在不同年龄、肿瘤大小及分期中的表达及预后情况。结果 180例腋窝淋巴结阴性浸润性乳腺癌患者中,Luminal型、Basal-like型、HER-2过表达型分别占54.4%(98/180)、27.8%(50/180)和17.8%(32/180)。Luminal型、Basal-like型、HER-2过表达型在不同年龄、肿瘤大小及临床分期中的表达差异无统计学意义(P>0.05)。Basal-like型患者术后36和60个月的转移率分别为14.0%和36.0%,高于Luminal型的3.1%、20.4%及HER-2过表达型的6.3%、21.9%,差异有统计学意义(P<0.05)。Basal-like型患者术后60个月的死亡率为24.0%,高于Luminal型(10.2%)及HER-2过表达型(15.6%),HER-2过表达型患者术后60个月的死亡率高于Luminal型,差异有统计学意义(P<0.05)。结论腋窝淋巴结阴性浸润性乳腺癌的分子分型以Lumina1型最为常见,Basal-like型与HER-2过表达型构成比较低,其中Basal-like型患者预后较差,其次为HER-2过表达型患者。     

乳腺癌的磁共振强化方式与新辅助化疗后退缩模式间的相关性及其临床意义

  目的  探讨乳腺癌的磁共振强化方式与新辅助化疗后退缩模式间的相关性,及其指导制定手术方案的临床意义。  方法  55例局部进展期乳腺癌患者分别于新辅助化疗前及全程化疗后手术前,行乳腺磁共振动态增强扫描,观察化疗前肿瘤的磁共振强化方式和化疗后肿瘤退缩模式,分析两者之间的相关性。  结果  55例患者中54例为单乳病变、1例为双乳病变,共56处病灶。肿块样强化为24处(43%),其中23处呈向心性退缩、1处呈环形退缩(P < 0.01);多灶肿块样强化为13处(23%),其中2处为单一肿块呈向心性退缩、11处退缩后仍呈多灶肿块(P < 0.01);肿块伴周边非肿块样强化为8处(14%),其中4处呈向心性退缩、4处呈蜂窝状多灶退缩(P>0.05);非肿块样强化为11处(20%),其中4处呈向心性退缩、7处呈蜂窝状多灶退缩(P < 0.01)。  结论  新辅助化疗后肿瘤的退缩模式是保乳手术选择的关键因素之一,根据乳腺癌在新辅助化疗前的磁共振动态增强强化方式,可在一定程度上预测其在化疗后的退缩模式,进而预测患者保乳手术的可行性,为临床医生选择个体化的后续治疗方案提高患者生存质量提供参考。      

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.     

乳腺癌分子分型对多西他赛联合表阿霉素新辅助化疗疗效和预后的预测价值

目的探讨乳腺癌分子分型对多西他赛+表阿霉素新辅助化疗的临床疗效及预后的预测价值。方法对126例行多西他赛+表阿霉素新辅助化疗的老年乳腺癌患者的肿瘤组织行免疫组织化学检测,依据雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(HER2)表达情况及Ki67水平,将乳腺癌分三阴型、HER2过表达型、Luminal A型、Luminal B型,分析不同分子分型患者病理完全缓解率(p CR)的差异,比较不同分子分型患者术后无病生存时间(DFS)和总生存时间(OS)。结果乳腺癌分子分型各组p CR依次为三阴型(42.1%)、HER2过表达型(30.8%)、Luminal A型(13.2%)和Luminal B型(4.7%),三阴型和HER2过表达型者的临床总有效率分别为94.7%和80.8%,高于Luminal A型的63.7%和Luminal B型的55.9%(P<0.05)。Cox回归分析显示,分子亚型为影响乳腺癌临床疗效的独立因素,以三阴型为对照,Luminal A型、Luminal B型的OR值分别为1.885和2.317。Luminal A型患者的OS、DFS均高于三阴型(χ~2=3.176,P=0.032;χ~2=3.743,P=0.029)。结论以ER、PR、HER2、Ki67为依据的乳腺癌分子分型可能是老年乳腺癌多西他赛+表阿霉素新辅助化疗后p CR、OS、DFS的预测指标。     

Carcinoma of the axillary breast

A review of the world literature regarding carcinoma of ectopic breast tissue along with the addition of one cases is reported. A total of 90 cases of carcinoma of ectopic breast tissue were found, 64 of which occurred in the axilla. The combined survival beyond the 4-year post-treatment period was 9.4%. No survival advantage was found for radical or modified radical mastectomy over that of local excision combined with axillary dissection or radiation. The addition of radiation therapy to either type of mastectomy provided no additional benefit. The correct preoperative diagnosis was rarely made. Outcome was reported in 42 cases; 28 survived longer than 1 year, with 12 recurrences at the time of reporting, and 6 were alive with no evidence of disease at 4 years or longer. Improved prognosis requires diagnostic suspicion and early biopsy of unidentified lesions of the axilla or embryonic milk line.     

Prospective analysis of the long-term effect of teaching breast self-examination and breast awareness

Breast cancer is the most common cancer in women in the industrialized world and a leading cause of death. Breast self-examination (BSE) is one of the methods for an early detection of breast cancer. In the present study the effectiveness of a campaign promoting BSE and breast awareness was analysed. Seminars were conducted in 2003 in Lower Saxony, Germany by a female gynaecologist and a social pedagogue and included a lecture, an individual training in BSE in a separate room and a talk about the importance of regular BSEs. Questionnaires were handed out immediately after the seminar and were sent by post 1 year later. Attendance of the seminar resulted in a significantly higher percentage of monthly BSEs (21.4% before vs. 61.9% after the teaching). Furthermore, 92.1% of the women who did not perform a monthly BSE stated that at least they examined their breasts more frequently after attending the seminar. The data demonstrate that the seminars in BSE had profound effects on the compliance of women in carrying out BSE regularly and correctly, without influence of age or education.     

The anatomy of the arteries and veins of the breast

Textbook accounts of this subject are inadequate. This review considers the work of Cooper and Salmon and reproduces some of their figures. Applications in the diagnosis and treatment of cancer are discussed. The largest mammary arteries are the lateral (from the axillary) and the anterior medial and posterior medial (from the internal thoracic). The branches of these arteries do not follow the duct system, but instead form a plexus in the anterior fat layer. Normally there are no hypervascular or hypovascular areas. The contribution of the mammary branches of the posterior (aortic) intercostal arteries is minor. There are superficial and deep sets of veins, the latter associated with arteries. Mammary vessels of living women are demonstrated by infrared photography, thermography, and mammography. In the diagnostic use of these methods there is a tendency to rely upon the concept of normal vascular symmetry, but this is a fallacy.     

Trends in the management of breast cancer

Responses of general surgeons to a questionnaire on breast cancer were analyzed to determine the current trends in the management of this disease. A 21-item questionnaire was mailed to members of the New Jersey Chapter of the American College of Surgeons in 1982 and the responses, received on noncoded, anonymous answer sheets, were analyzed for frequency distribution. These responses were compared to previously recorded responses to the same questions for 1971 and 1977. Seventy-six percent of the respondents in 1982 performed needle aspirations often or always, compared to 36% in 1971 and 80% in 1977. The use of routine mammography has increased from 16% in 1971 and 20% in 1977 to 38% in 1982. Modified radical mastectomy is now the most common type of procedure employed in the management of stage I breast cancer, with 89% of respondents in favor of this approach compared to 15% in 1971 and 60% in 1977. Fifty-nine percent of the respondents are not opposed to breast reconstruction following mastectomy versus 14% in 1971 and 49% in 1977. For patients with axillary nodes, chemotherapy with multiple agents was recommended by 76% of general surgeons in 1982, compared to 58% in 1977. These results indicate a continuing trend towards increasing use of needle aspiration and routine mammography for diagnosis and for employment of chemotherapy with multiple agents in the adjuvant treatment of patients with positive axillary nodes. Furthermore, modified radical mastectomy is the operation of choice for stage I cancer of the breast for increasing numbers of surgeons.     

保乳手术在乳腺癌治疗中的应用

目的 :研究保乳手术在Ⅰ、Ⅱ期乳腺癌中的治疗效果。方法 :从 1990年 3月到 2 0 0 4年 3月 ,对直径≤3cm ,肿瘤边缘距乳晕≥ 2cm的部分患者施行保乳手术 ,部分肿瘤直径 >3cm的患者先行术前化疗 ,肿瘤缩小后再做保乳手术。手术切除肿瘤周围约 2cm的正常组织 ,达到切缘阴性 ,腋窝清扫范围为Ⅰ、Ⅱ水平淋巴结。开始时应用 1切口设计 ,后来改为 2切口。术后先进行放疗 ,再进行化疗和 (或 )内分泌治疗。结果 :2 6 5例保乳手术腋窝淋巴结清扫数目为 5～ 2 9个 ,平均 16个。本组患者局部复发部位均为乳腺 ,无腋窝复发者 ,三年、五年、十年生存率分别为 99%、94 %、80 % ,局部复发率为 5 .4 %、7%、7.7% ,乳房保留率为 97.8%、93%、88% ,保留乳房的美容效果满意率为 83.2 %。结论 :保乳手术适用于Ⅰ、Ⅱ期乳腺癌患者 ,可以取得良好的生存率、局部控制率和美容效果 ,是乳腺癌治疗的首选术式。     

Decreased rates of advanced breast cancer due to mammography screening in The Netherlands

The effect of the implementation of the Dutch breast cancer screening programme during 1990-1997 on the incidence rates of breast cancer, particularly advanced breast cancer, was analysed according to stage at diagnosis in seven regions, where no screening took place before 1990. The Netherlands Cancer Registry provided detailed data on breast cancer incidence in 1989-1997 by tumour stage, age and region. Annual age-adjusted incidence rates of all breast cancers and advanced cancers, defined as large tumours T2+ with lymph node and/or distant metastases, were compared with rates in 1989. In general, breast cancer incidence rose strongly in the early 1990s, especially in the age category 50-69 years (estimated annual percentage change (EAPC) 4.25; 95% CI 1.70, 6.86). The increase was mainly due to the increase in small T1 cancers and ductal carcinoma in situ. However, in women aged 50-69, advanced cancer incidence rates showed a significant decline by 12.1% in 1997 compared with 1989 (EAPC -2.14, 95% CI -3.47, -0.80), followed by a breast cancer mortality reduction of similar size after approximately 2 years. We confirm that breast cancer screening initially leads to a temporary strong increase in the breast cancer incidence, which is followed by a significant decrease in advanced diseases in the women invited for screening. It is evident that breast cancer screening contributes to a reduction in advanced breast cancers and breast cancer mortality.     

Chemotherapy and pattern of metastases in breast cancer patients

A retrospective analysis of all breast cancer patients who died of their disease at Harper Grace Hospital during 1962 to 1976, was conducted to determine the pattern of metastases and its relation to chemotherapy. The autopsy incidence of distant metastases, to all organ sites, was noted to be higher among patients who previously received cytotoxic therapy, compared with those who did not. Such incidence was unrelated to differences in patients' age, menopausal status, and disease-free interval. It is postulated that chemotherapy contributes to the wider metastases, especially to the central nervous system and meninges, in a breast cancer patient. This is possibly due to a longer survival of patients treated.     

即刻乳房再造在乳腺癌治疗中的应用

随着乳腺癌治疗水平与整形外科技术的提高,即刻乳房再造越来越广泛地应用于乳腺癌的治疗中,成为乳腺癌综合治疗的一部分,因而即刻再造与乳腺癌辅助治疗的关系及其可能对乳腺癌预后带来的影响成为研究的热点.本文对近年来这一方面的研究进展做一综述.