Updates in Neoadjuvant Therapy for Triple Negative Breast Cancer

Neoadjuvant therapy in breast cancer refers to systemic therapy administered prior to definitive surgery. It was originally developed for patients with locally advanced breast cancer (stage III) with the intention of downstaging unresectable tumors, and decreasing the extent of surgical intervention, including axillary lymph node dissection. For patients with inflammatory breast cancer, neoadjuvant therapy is considered a standard of care. Increasingly, the neoadjuvant setting is being utilized to accelerate drug development and approval in triple negative breast cancer, a diverse and aggressive subgroup for which no approved targeted therapies are currently available. This review discusses the use of pathologic complete response as a clinical trial endpoint, the use of imaging and biomarkers to predict response to therapy, and standard of care treatment for triple negative breast cancer. Finally, we review novel targets and drug trials in the neoadjuvant setting.     

新辅助化疗在局部进展期乳腺癌保乳治疗中的临床价值*

目的:探讨局部进展期乳腺癌在新辅助化疗后保乳治疗的可行性。方法:选取1996年1 月~2006年12月经病理组织学检查确诊的局部进展期乳腺癌522 例,随机分为新辅助化疗组和对照组。新辅助化疗组给予FEC 或TEC 方案化疗4~6 个周期后进行影像学再评估,满足保乳条件者实施保乳手术,不满足保乳条件者实施全乳房切除术;对照组均实施全乳房切除术。分析新辅助化疗的有效率及其对局部进展期乳腺癌手术方式以及保乳手术后的局部复发率、远处转移率、总生存率、无瘤生存率及美容效果等的影响。结果:新辅助化疗组总有效率89.19%（231/259）,经影像学再评估82.20%（217/264）的患者达到保乳条件,实际实施保乳手术85例,保乳治疗者乳房外观满意率92.94% 。经67.4 个月（36～166 个月）的随访,其局部复发率、远处转移率、总生存率及无瘤生存率分别为7.06%（6/85）、10.59%（9/85）、85.88%（73/85）、78.82%（67/85）,与新辅助化疗后满足保乳条件行全乳房切除术的患者及对照组患者比较差异无统计学意义。结论:局部进展期乳腺癌在新辅助化疗后实施保乳治疗是可行的,影像学和病理学检查是选择恰当术式的必要依据。      

绝经后乳腺癌新辅助内分泌治疗近期疗效观察

目的：评价弗隆对绝经后、ER（＋）乳腺癌新辅助内分泌治疗（NET）的近期疗效及与临床病理因素的相关性。方法：32例绝经后Ⅱ、Ⅲ期乳腺癌,予弗隆NET,中位治疗时间4个月。结果：ER（＋）和（或）PgR（＋）的29例中,临床OR（CR＋PR）69.0%,超声评价OR55.2%,3例ER、PR（-）者疗效均为SD。病理评价（14例手术）为有效11例（78.6%）,显效2例（14.3%）,特效1例（7.1%）,无病理CR。组织学低分级的有效率高（P〈0.05）。ER和PR均为（＋）及ER强阳性（＋＋）的有效率高（分别为78.9%和78.6%）。疗效与HER-2表达情况无关。治疗中仅出现Ⅰ级不良反应（12.5%）。NET后行手术治疗14例,疗效均为PR,保乳手术4例（28.6%）,改良根治术10例。结论：绝经后、ER（＋）乳腺癌采用弗隆NET有效、安全、可靠,为缩小手术切除术式创造条件,尤对年迈、体弱、伴其他重要疾病患者是很好的治疗选择。     

T2期乳腺癌新辅助化疗后行保乳手术的临床观察

目的 探讨T2期乳腺癌新辅助化疗后保乳手术治疗的可行性及疗效.方法 对有保乳愿望的T2期乳腺癌患者术前行新辅助化疗,2个周期后评价疗效,达到保乳手术指征的行保乳术,共36例,并随机抽取同期36例T2期乳腺癌根治术患者进行疗效对比.结果 保乳组36例患者,术前均经过2个疗程的新辅助化疗,并达到保乳指征后行保乳手术治疗,术后常规放疗、化疗.对照组36 例均行根治术,随访3～5年,两组无复发生存率分别为88%、86%,两者比较无统计学意义,P＜0.05.结论 T2期乳腺癌新辅助化疗后可提高保乳率,改善患者生活质量,随访3～5年,与同期根治术相比,治疗效果相同,值得临床推广应用.     

来曲唑在老年乳腺癌新辅助内分泌治疗中的疗效观察

目的探讨来曲唑在老年绝经后乳腺癌新辅助内分泌治疗中的近期疗效,耐受性及与临床病理因素的相关性。方法对58例绝经后激素受体阳性的乳腺癌患者进行来曲唑新辅助内分泌治疗,以他莫昔芬新辅助内分泌治疗为对照组。结果来曲唑组临床疗效显著优于他莫昔芬组（P〈0.05）。来曲唑组临床分期晚,ER及PR均阳性的有效率高,与HER-2表达无关。他莫昔芬组HER-2阳性的有效率低。2组治疗前后Ki-67水平均显著下降,有统计学意义（P〈0.05）。2组未出现明显不良反应。结论绝经后、激素受体阳性的乳腺癌选择来曲唑新辅助内分泌治疗安全,有效,尤其适合有合并症的老年体弱者。     

绝经后ER阳性乳腺癌新辅助内分泌治疗疗效分析

[目的]评价弗隆对绝经后雌激素受体阳性(ER+)乳腺癌新辅助内分泌治疗疗效.[方法] 40例Ⅱ～Ⅲ期绝经后ER(+)乳腺癌行弗隆新辅助内分泌治疗4个月.所有患者治疗前均不适合行保乳手术.新辅助治疗后25例行手术治疗,其中保乳手术9例(36.0％),术后继续口服弗隆2～5年;另15例未手术者亦持续弗隆治疗,中位随访37个月.[结果]3年总生存率为100％,3年DFS为82.5％.未接受手术治疗的患者15例,1年、2年、3年临床受益率CBR (CR+PR+SD)分别为86.7％、66.7％和46.7％,中位TTP(至疾病进展时间)23个月.全组不良反应发生率为37.5％.[结论]绝经后ER(+)乳腺癌应用弗隆新辅助治疗后反应好,肿瘤分期降级后保乳手术安全,术后继续内分泌治疗可获得良好的DFS和生活质量.     

Neoadjuvant Therapy with Drug Arglabin for Breast Cancer with Expression of H-Ras Oncoproteins

Backgrounds: In breast cancer, blocking of Ras signaling and inhibition of H-Ras is quite promising. H-Ras may become a target for farnesyl transferase inhibitors, and in combination with other immunohistochemical factors it will contribute to the progression of a breast tumor. Purpose: The aim of this study was to evaluate the effectiveness of neoadjuvant therapy for breast cancer with the inclusion of farnesyl transferase inhibitor, arglabin interfering with the expression and concentration of H-Ras oncoproteins. Methods: Depending on the presence of H-Ras oncoproteins after Western-blot hybridization, the patients were divided a negative and positive expression of H-Ras groups. Results: Correlation analysis of methods used for determining the expression ability and concentration of H-Ras oncoproteins (immunohistochemistry and Western-blot analysis) demonstrated substantial statistical relationship Rs=0.71, p=0.03. The H-Ras oncoproteins were absent in patients receiving either “Arglabin” or standard AC regimen. However, in the AC + Arglabin group, there was a varying degrees of positive concentration of H-Ras oncoproteins (Kruskal-Wallis=6.92; p=0.03). Conclusion: These results indicate that Arglabin attenuates H-Ras oncoproteins expression which is a promising therapeutic target for breast cancer.     

体质指数对绝经后ER阳性乳腺癌新辅助内分泌治疗预后的影响

摘 要：［目的］ 探讨体质指数（BMI）对绝经后ER阳性乳腺癌患者的新辅助内分泌疗效及对预后的影响。［方法］ 对118例经新辅助内分泌治疗乳腺癌患者进行回顾性分析,评估BMI对无病生存率和总生存率的影响。肥胖定义为BMI≥28kg/m2。生存分析采用Kaplan-Meier法和Log-rank检验,单因素和多因素分析采用Cox风险比例模型。［结果］ 118例乳腺癌均为绝经后女性,其中BMI≥28kg/m2 46例（38．9％）,BMI＜28kg/m2 72例（61．1％）。BMI≥28kg/m2患者经新辅助内分泌治疗后有效率为56.5%（20/46）,BMI＜28kg/m2患者有效率为62.5%（45/72）,两组差异具有统计学意义（P=0.033）。中位随访时间39个月,BMI＜28kg/m2和BMI≥28kg/m2组乳腺癌患者的39个月无病生存率分别为91.7%和73.9%(P=0.008);BMI＜28kg/m2和BMI≥28kg/m2乳腺癌患者的39个月总生存率分别为93.1%和80.4%,差异有统计学意义(P=0.013)。多因素分析显示,BMI≥28kg/m2是影响乳腺癌患者新辅助内分泌疗效和预后的不良因素。［结论］ 超重和肥胖是影响乳腺癌患者内分泌治疗效果和预后的不良因素。     

Neoadjuvant Therapy for Breast Cancer: State of the Science and Future Directions

Systemic neoadjuvant chemotherapy has long been known to confer clinical benefits for breast cancer patients by downstaging inoperable disease or providing those with operable disease the opportunity for breast conservation, without compromising risk of recurrence. In recent years, its benefits have broadened as it has become a pivotal platform for clinical research, providing new prognostic and predictive insights into in vivo response to therapy and long-term outcomes. The use of neoadjuvant chemotherapy in the research setting has expanded our knowledge of heterogeneity in tumor biology and chemosensitivity and provided insights into the relationships between molecular signatures of tumors, pathologic complete response (pCR), and long-term outcomes. This has provided opportunities to specifically select patients who might benefit from novel therapies and test these in a more efficient manner. Despite these major advancements, however, the majority of patients do not attain a pathologic complete response with systemic neoadjuvant chemotherapy. This review describes the standard of care for systemic neoadjuvant therapy for breast cancer and discusses current management controversies and ongoing clinical trials designed to increase the proportion of patients who currently achieve a pCR.     

Influence of Biologic Subtype of Inflammatory Breast Cancer on Response to Neoadjuvant Therapy and Cancer Outcomes

Background

Few data exist on the influence of tumor biologic subtype on treatment response and outcomes for inflammatory breast cancer (IBC). We examined a contemporary cohort of IBC patients treated with current targeted systemic therapies, selected on the basis of tumor biologic subtype, to evaluate pathologic treatment response and cancer outcomes across biologic subtypes.

HER2阳性妊娠相关性乳腺癌新辅助治疗有效1例报道

<正>妊娠相关性乳腺癌(pregnancy-associated breast cancer,PABC)又称妊娠期与哺乳期乳腺癌,是指妊娠期间及分娩后1年内确诊的乳腺癌。近年来,由于二、三胎政策的放开及平均生育年龄的增长,PABC发病率逐年升高。在临床上,PABC患者行新辅助治疗的时机与方案选择存在较多顾虑和争议。本文报道1例新辅助治疗妊娠期确诊的HER2阳性乳腺癌患者,从药物治疗时机、治疗方案选择以及后续治疗等方面进行分析讨论,期待为PABC患者的临床治疗决策提供一定的参考。