乳腺癌保乳术后加速部分乳腺照射的研究进展

传统的乳腺癌保乳术后放疗是对全乳腺进行5周-6周的放疗。随着放射治疗技术的发展,加速部分乳腺照射可能会成为另一选择。该文就加速部分乳腺照射在乳腺癌治疗中的研究进展作一综述。     

乳腺癌保乳术后加速部分乳腺照射的靶区确定

目前,保乳治疗已经成为Ⅰ、Ⅱ期乳腺癌的主要治疗方式.保乳术后放疗的目的主要是提高局部肿瘤控制率和乳房保全率.一直以来,全乳房照射加瘤床补量的放疗模式是乳腺癌保乳术后放疗的常规选择,因为这种放疗模式明显降低了局部肿瘤复发率.大量研究证明,保乳术后复发绝大多数发生在瘤床及其附近区域,因此单纯针对瘤床的部分乳腺照射（partial breast irradiation,PBI）成为近期乳腺癌放疗研究的热点.PBI的剂量分割方式通常为加速分割,因此亦可称其为加速部分乳腺照射（accelerated partial breast irradiation,APBI）.以下重点综述APBI的靶区确定.     

乳腺癌保乳术后部分乳腺照射

保乳治疗作为早期乳腺癌的标准治疗选择目前已经成为国内外学者的共识，而且局部肿瘤扩大切除术作为原发肿瘤的主导手术模式也基本得到公认。多年来，全乳腺照射（whole breast irradiation，WBI）一直作为保乳术后相对固定的放疗模式，但随着对保留乳房术后复发模式认识的深入及放疗技术的进展，自20世纪90年代末期开始，加速部分乳腺照射（accelerated parial breast irradiation，APBI）作为WBI的替代模式用于部分保乳治疗的患者，目前APBI已经成为乳腺癌放疗研究的热点之一。     

放射治疗在早期乳腺癌中的应用

目前保乳治疗已经成为早期乳腺癌的标准治疗方案,而放射治疗在保乳治疗中的作用也日益得到体现.由于传统的全乳放射治疗存在着诸多的劣势,所以近些年来,部分乳腺放疗逐渐为人们所重视.相对于传统全乳腺照射,部分乳腺放疗可使患者的保乳治疗更快捷,且降低了远期并发症的风险.但是部分乳腺放疗研究的长期结果尚缺乏,而且病例选择及放疗实施也存在很多不确定性.部分乳腺放疗是有前途的方法,但在病例选择治疗技术以及处方剂量上仍有很多工作要完成.本文对放射治疗在早期乳腺癌保乳治疗中的应用情况做一综述.     

乳腺癌保乳术后大分割放疗的临床研究进展

乳腺癌保乳术后行全乳腺放疗在降低局部肿瘤复发同时也可改善患者生存情况。虽然全乳腺标准放疗可以实现良好的肿瘤控制及美容效果,且具有不良反应轻的特点,但5~7周的治疗时间对患者相对较长,甚至可能造成医疗资源浪费,因此临床上越来越倾向大分割放疗和加速部分乳腺照射的短疗程放疗。短疗程放疗与常规分割放疗均为安全有效的治疗模式,具有与常规放疗相似的生存和局部肿瘤控制效果,不良反应可以耐受。相较于常规分割放疗,短疗程放疗具有缩短治疗总时间,减少治疗费用,节约医疗资源,改善患者生存质量的显著优势。      

乳腺癌保留乳房术后的调强放疗

调强放疗在乳腺癌保留乳房术后的治疗中有重要地位，可有效降低保乳术后常规放疗的并发症，而且同步加速调强放疗可缩短治疗时间。就乳腺癌保乳术后调强放疗开始时机、调强放疗方式、照射野的范围以及实施调强放疗时患者固定、CT-SIM影像资料的获取和传输、放疗计划的制定、优化、验证以及实施过程进行综述.     

乳腺癌瘤床插植(保乳)放射治疗59例

目的　探讨乳腺癌保乳手术加根治性放疗和瘤床间质放疗的治疗原则及近期疗效。　方法　59例各期乳腺癌患者施保乳手术(单纯肿瘤切除 腋淋巴结清扫术)、术中或术后瘤床插植HDR192Ir针管放疗±化疗。靶区一次性放疗8Gy。手术后2～4周再接受全乳腺外照射,乳腺用切线野在5周被照射50Gy。随访时间平均为37个月。　结果　59例患者全部存活,无一例出现局部复发。无明显放射反应。双乳对称,外形美观。　结论　早期乳腺癌患者接受保乳手术加根治性放疗可以取得满意的临床效果,可成为早期乳腺癌的常规治疗方法     

早期乳腺癌保乳术后加速部分乳腺照射的研究进展

早期乳腺癌保乳术后行全乳腺照射（whole breast irradiation,WBI）已成为乳腺癌的标准治疗模式之一，具有与根治术相似的效果。对于早期乳腺癌患者，加速部分乳腺照射（accelerated partial breast irradiation,APBI）作为全乳腺照射的替代治疗是临床研究热点，其特点是短时间内单纯对瘤床进行局部照射。本文将APBI的照射技术、剂量分割模式和人群选择作一综述。     

左侧乳腺癌保乳术后调强放疗的剂量学研究

目的分析左侧乳腺癌保乳术后调强放疗(IMRT)靶区以及心脏、同侧肺的照射剂量分布情况。方法对保乳术后接受调强放疗的37例左侧乳腺癌患者采取CT定位并行调强放射治疗,采用IMRT及3D-CRT 2种照射计划,总剂量均为50 Gy,1次/d,5 d/周,共照射25次。观察比较两种计划的剂量学差异。结果 IMRT计划D95剂量高于3D-CRT计划,而IMRT的V105%、V110%、HI明显低于3D-CRT,具有统计学差异(P<0.05)。IMRT的肺V20、V30、V40以及心脏V5、V30、V40均显著低于3D-CRT的,具有统计学差异(P<0.05)。15例患者左侧乳腺体积超过500 cm3,22例小于500 cm3,经比较发现,两组患者IMRT计划的D95、V105、V110、HI比较无显著差异。结论 IMRT靶区剂量更接近于处方剂量,靶区剂量分布较3D-CRT更均匀,有更好的适形性,能更好地保护肺脏、心脏等周围组织,而且IMRT放射治疗受CTV影响较小,靶区内剂量均匀性较好。     

早期乳腺癌保乳术后放化疗的最佳顺序

目的 探讨早期乳腺癌保乳治疗后放化疗最佳顺序，使保乳治疗的局部控制、远处转移和保乳效果达到最佳。方法 2000年1月～2002年11月，对38例符合保乳治疗条件的早期乳腺癌实施了保乳治疗。手术方式为局部广泛切除术和腋窝淋巴结清扫，术后2周开始化疗，化疗2周期后再开始放疗，全乳剂量50Gy，瘤床补充照射10～18Gy。放疗结束后根据使用化疗方案选择立即化疗或休息1周后再开始化疗，化疗共6周期。治疗结束后每3个月复查1次，放疗后6个月行乳房钼靶摄影。此后1年1次乳房照片检查。结果 38例保乳治疗的患者均定期复查，中位随访24个月(5～35个月)。未发现局部复发和远处转移。放疗后1年或以上的28例患者乳房外观良好。结论 早期乳腺癌保乳治疗中“三明治”式放化疗能满足保乳治疗的目的。     

Preoperative breast MRI in early-stage breast cancer

Rapid uptake of new imaging technology is a major contributor to rising healthcare costs. Preoperative breast magnetic resonance imaging (MRI) for patients with early-stage breast cancer has dramatically increased in use without the evidence of improved outcomes compared to standard assessment and is associated with higher rates of mastectomy. A decision analytic model was developed to evaluate the impact of adding breast MRI to the preoperative evaluation of women with early-stage breast cancer who were candidates for breast-conserving therapy on patient outcomes measured in quality-adjusted life years (QALYs). Model inputs, including survival, recurrence rates, and health utilities, were obtained from a comprehensive literature review. One-way sensitivity analyses were performed to estimate threshold values for key parameters at which adding MRI would become the optimal imaging strategy over standard assessment. Preoperative MRI resulted in 17.77 QALYs compared to 17.86 QALYs with standard assessment, a decrease of 0.09 QALYs or 34?days. In sensitivity analyses, standard assessment was associated with better patient outcomes than preoperative breast MRI across all plausible probabilities for mastectomy, local recurrence, and health utilities. For routine preoperative breast MRI to become the optimal strategy, the conversion rate to mastectomy after preoperative MRI would need to be <1?% (versus the range of 3.6-33?% reported in the literature). Routine preoperative breast MRI appears to confer no advantage over the standard diagnostic evaluations for early-stage breast cancer and may lead to worse patient outcomes.     

Glycolytic enzymes in breast cancer, benign breast disease and normal breast tissue

The activities of hexokinase, phosphofructokinase, aldolase, enolase and pyruvate kinase were studied in breast cancer tissues, in comparison to benign breast disease and normal breast tissues. The enzyme activities in breast cancer were significantly increased compared to normal and benign breast tissues (p less than 0.001). Also the increase in activity in benign disease compared to normal was statistically significant (p less than 0.001). Within the group of benign diseases, fibroadenomas could be distinguished from fibrocystic disease, the former generally showing higher activities compared to the latter (p less than or equal to 0.05). Carcinoma subgroups, classified according to their histology, could not be recognized enzymologically. In addition, isozyme composition of pyruvate kinase and enolase was studied. We did not find a significant shift towards K type pyruvate kinase expression in benign disease compared to normal breast tissues. Also fibroadenomas did not differ from fibrocystic disease. However, the amount of K type pyruvate kinase in carcinomas proved to be significantly higher in comparison to benign disease and normal breast tissues (p less than 0.001). Expression of alpha gamma-enolase in normal breast tissue was virtually absent. In benign disease only a minority of specimens did show the hybrid alpha gamma-enolase. Nearly all carcinomas had alpha gamma-enolase expression and in 20% of the carcinomas gamma gamma-enolase could be detected (so-called neuron-specific enolase). By discriminant analysis, the function giving the best discrimination compared to the histological data was based on natural logarithm aldolase and the total of gamma-enolase subunits. Contrary to expectation, the regulator enzymes of glycolysis; i.e., hexokinase, phosphofructokinase and pyruvate kinase were not included in this discriminant function. The best fit produced a 90% correct classification in both benign and malignant disease. If these findings are confirmed to a larger series, the discrimination is sufficiently strong to form the basis of a clinically useful tool.     

倒T形切口缩乳术在乳房肥大或合并乳腺癌患者中的应用

目的探讨倒T形切口缩乳术在乳房肥大患者，特别是合并乳腺癌的患者手术中的应用及其临床意义。 方法本回顾性研究共纳入2007年10月到2017年10月分别在同济大学附属东方医院及附属同济医院乳腺外科行缩乳术的39例乳房肥大女性患者，均采用倒T形切口(内侧蒂25例，垂直蒂5例，外侧蒂9例)。其中，包括18例符合保留乳房手术指征的乳腺癌患者(内侧蒂10例，垂直蒂4例，外侧蒂4例)。术后6、12个月评价美容效果(乳腺癌患者待放射治疗结束后进行评价)。评估患者的术后并发症、满意度以及复发转移情况。 结果39例患者术后乳房外形自然、对称，明显缩小上提，乳头、乳晕血供和感觉良好，瘢痕不明显，患者满意度高。1例术后2周出现一侧乳房的乳头乳晕区坏死，经过清创换药后愈合。5例术后双侧乳头乳晕感觉减退，其中4例在术后6个月左右恢复正常感觉，1例在术后12个月恢复。5例出现术后局部乳房组织硬结，其中3例为接受过放射治疗的乳腺癌患者，二次手术切除硬结后无再次发生。3例出现瘢痕处猫耳畸形，再次局部麻醉手术修整后效果良好，3例瘢痕增粗，其余患者瘢痕正常。乳腺癌患者中有3例出现放射治疗后患侧乳房皮肤水肿，术后12个月消退。术后6个月进行了美容效果评价，极好25例，良好10例，中等4例，差0例(18例乳腺癌患者中，极好9例，良好6例，中等3例，差0例)。术后12个月的美容效果评价显示：极好25例，良好13例，中等1例，差0例(18例乳腺癌患者中，极好9例，良好8例，中等1例，差0例)。随访时间最长的1例患者(双侧乳房单纯性重度肥大)术后观察了10年，乳房外形无明显变化。全部患者术后随访15～120个月，中位随访61个月，18例乳腺癌患者均无局部复发转移。 结论对于乳房肥大，特别是合并乳腺癌的患者，采用倒T形切口缩乳术，既可切除病变，又可缩小并悬吊乳房。     

保乳术和延迟即刻再造术对乳腺癌患者生活质量的影响

目的探讨保乳术和延迟即刻再造术对乳腺癌患者手术后生活质量(QOL)的影响。方法选取2010年1月至2015年6月北京协和医院行保乳术和延迟即刻再造术后于2016年3月至2016年4月在医院乳腺外科门诊随访的64例患者,其中保乳手术30例(保乳组),延迟即刻再造术34例(乳房再造组)。应用肿瘤治疗功能评价系统(FACT-B)量表对两组患者进行生活质量测评比较。结果两组患者生理状况、社会/家庭状况、情感状况、功能状况、总体生活质量评价FACT-G和FACT-B条目状况比较,差异无统计学意义(P>0.05);乳房再造组患者附加关注(乳腺癌特异模块)方面QOL优于保乳术组,差异有统计学意义(29.37±2.72vs 24.05±7.01,P<0.05)。结论乳腺癌保乳术和延迟即刻再造术后患者生活质量无明显差异。     

早期乳腺癌保乳手术后加速部分乳腺照射与全乳照射剂量学的比较

目的比较早期乳腺癌患者保乳手术后加速部分乳腺照射(APBI)与全乳照射(WBI)剂量学的差异。方法选取2013年1月至2013年12月间收治的26例保乳术后采用APBI治疗的乳腺癌患者作为观察组,另选取同期保乳术后采用WBI治疗的28例乳腺癌患者作为对照组。采用剂量体积直方图(DVH)比较两组患者剂量学差异,总结两组患者的短期疗效;比较观察组患者在有无图像指导下的位移差异。结果观察组患者的平均剂量(Dmean)、照射体积百分比(V103、V105、V110)和靶区剂量不均匀指数(IHI)均显著低于对照组,各项危及器官(OARS)照射剂量均显著低于对照组,且心脏和肺的照射体积也显著低于对照组,差异均有统计学意义(均P<0.05)。观察组患者美容满意率为96.2%(25/26),对照组患者为67.9%(19/28),两组间差异有统计学意义(P<0.05)。观察组患者在有无图像引导下的位移差异均有统计学意义(均P<0.05)。结论早期乳腺癌患者保乳手术后APBI照射剂量低于WBI,改善靶区剂量分布,降低心肺等组织高剂量受照体积,结合图像引导,可以增加准确性。     

Controversies in breast conservation treatment for breast cancer

Breast conservation treatment has become the standard treatment for early breast cancer patients, after the equivalence of mastectomy and breast conservation treatment was demonstrated in prospective, randomized trials and large retrospective studies. New questions, such as the feasibility of neoadjuvant chemotherapy in improving breast conserving rate, the appropriateness of breast conservation treatment in ductal carcinoma in situ, the effectiveness of radiation therapy in patients treated by breast conservation, and patient selection for breast conservation without radiation, are now being raised. Future work that needs to be done to answer these questions is discussed in this review.     

保留乳房天然结构的乳腺癌改良根治术后即刻乳房成形术的临床应用

目的探讨保留乳房天然结构的乳腺癌改良根治术后即刻自体组织乳房成形术在临床中的运用价值。方法乳腺癌患者12例,其中DCIS 6例,浸润性导管癌3例,小管癌1例,髓样癌1例,黏液癌1例;保留乳房皮肤的乳腺癌改良根治术9例,保留乳头乳晕复合体的乳腺癌改良根治术3例。全组均保留或重建乳房下皱襞,切除乳腺组织和腋窝淋巴结,应用下腹部横行腹直肌肌皮瓣或背阔肌肌皮瓣即刻乳房成形。结果横行腹直肌肌皮瓣乳房成形术3例,背阔肌肌皮瓣乳房成形术9例,术后皮瓣均存活,皮瓣血管通畅,成形乳房外观良好。结论对早期乳腺癌患者行保留乳房天然结构的乳腺癌改良根治术后即刻自体组织乳房成形,切口隐蔽,成形乳房形态效果良好,可以获得较好的美容效果。     

Prostate specific antigen in breast cancer,benign breast disease and normal breast tissue

Prostate specific antigen (PSA) is a tumor marker used widely for the diagnosis and monitoring of prostatic adenocarcinoma. Recently, we provided evidence that PSA may also be produced by breast tumors. In this report we examined quantitatively the PSA levels in 199 breast tumors, 48 tissues with benign breast disease (BBD, 34 fibroadenomas), and 36 normal breast tissues. Significant amounts of PSA (≥ 0.030 ng of PSA per mg of total protein) were found in 28% of breast tumors, 65% of BBD tissues, and 33% of normal breast tissues. PSA positivity in breast tumors was highest in stage I disease (34%) and decreased with disease stage (24% in stage II and 18% in stage III–IV). Using polymerase chain reaction amplification we have shown PSA mRNA presence in patients with PSA protein-positive tissues (benign and malignant) but not in patients with PSA protein-negative tissues. Our data suggest that PSA is expressed frequently by normal breast tissue, by tissue of benign breast diseases, and by breast cancer tissue. Highest expression is seen in benign breast disease and lowest expression in advanced stage cancerous tissue. As PSA production is mediated by steroid hormones and their receptors, we propose that PSA may be a new marker of steroid hormone action in the normal or diseased female breast. The role of this enzyme in the development of breast diseases including breast cancer is currently unknown.     

早期乳腺癌部分乳腺加速放疗

随着乳腺癌术后复发模式的研究进展,部分乳腺照射方法 成为乳腺癌放疗的热点.组织间插植、球囊近距离治疗、术中放疗及三维适形放疗和调强放疗等部分乳腺加速放疗已进入临床研究.其局部控制率和安全性与全乳腺照射比较相当,同时具有治疗周期短、方便患者等优势.部分乳腺加速放疗在部分患者有望代替全乳腺放疗,成为早期乳腺癌保乳术后放疗的标准治疗之一.

Abstract：

With a view to patterns of local recurrence after breast conserving surgery, whole breast irradiation(WBI) after surgery is controversial and partial-breast irradiation(PBI) came up. Many clinical trials related with accelerated partial-breast irradiation using a variety of radiotherapeutic techniques such as interstitial brachytherapy (IBT), MammoSite Radiation Therapy System, intraoperative radiotherapy(IORT), threedimensional conformal radiotherapy(3-DCRT)and intensity modulated radiation therapy(IMRT) in selected patients have been carried out. Accelerated partial-breast irradiation that provides faster, more convenient treat-ment demonstrates local control rate and safety comparable to that of whole breast irradiation. Partial breast irradiation may be an alternative way to whole breast radiotherapy and will be one of the standard treatments in women with early breast cancer seeking breast conservation.