乳腺导管原位癌保留乳房手术后序贯放射治疗的研究进展

在过去的10年中,对于乳腺DCIS的局部治疗,保留乳房(简称保乳)手术得到了广泛的重视。目前,学者们认为保乳术后序贯放射治疗能够降低乳腺DCIS的局部复发风险,但是,一些研究者认为,对于本身低复发风险的患者而言,保乳术后序贯放射治疗可能存在过度治疗。笔者就乳腺DCIS保乳术后是否序贯放射治疗这一研究热点,总结了相关的回顾性研究、随机临床对照试验以及前瞻性队列研究,分析了乳腺DCIS保乳术后序贯放射治疗的获益与风险,最终发现乳腺DCIS保乳术后序贯放射治疗尚不能带来明确的生存获益,但是,对于局部复发风险较高的患者,放射治疗可以带来益处。而对于局部复发风险的判定目前常用的有以下3种方法：南加利福尼亚大学Van Nuys预后指数(USC/VNPI)、基于人口数据估测获益的评分表以及基于12基因的Oncotype DX DCIS评分系统。因此,笔者认为乳腺DCIS保乳术后是否序贯放射治疗应根据其复发风险决定。     

放射治疗对乳腺导管原位癌保乳术后复发率的影响一项基于随机对照试验的Meta分析

  目的  用Meta分析方法评价放射治疗能否降低乳腺导管原位癌(DCIS)保乳术后的复发率。  方法  计算机检索PubMed、EMBASE、CochraneLibrarlv、中国生物医学文献数据库、中文科技期刊全文数据库、中国期刊全文数据库、万方数据库, 手工检索搜集有关放疗辅助治疗DCIS的随机对照试验, 用RevMan5.0软件进行统计分析。  结果  纳入4篇随机对照试验共计2701例乳腺癌患者, Meta分析结果显示, 保乳术后联合放射治疗与单纯手术比较, 乳腺导管原位癌复发率较低, 两者相比差异有统计学意义(RR=0.45, 95%CI: 037~0.55)亚组分析均提示辅助放疗可以降低其复发率。  结论  DCIS患者保乳术后放射治疗可以降低其复发率, 高危患者可能受益更多。      

乳腺导管内原位癌治疗趋势和预后单中心分析

目的 分析乳腺导管内原位癌(DCIS)患者治疗模式变化、临床特征、治疗结果及预后因素。方法 回顾性分析2000-2013年收治的 617例女性患者资料。用Kaplan-Meier法计算局部控制率(LC)、无瘤生存率(DFS)及总生存率(OS),并用Logrank检验分析影响生存的预后因素分析。结果 随着DCIS收治病例数逐年增多,保乳手术比例逐渐增加,但全乳切除术仍然为主要手术方式。共 374例患者接受全乳切除术,160例患者接受保乳术及放疗,83例患者仅接受保乳术。术后激素受体阳性者中有 366例(83.6%)接受内分泌治疗。45例(7.3%)患者接受化疗。中位随访时间47个月,全组 5年LC、DFS、OS分别为98.4%、97.5%、98.9%。单因素分析显示 Her-2阳性是OS的不良预后因素(P=0.019)。尽管全乳切除术组较保乳术加或不加放疗组具有更多不良预后因素,三者总生存结果相似。全乳切除术比单纯保乳术有较高的LC及DFS。结论 DCIS具有极好的预后,保乳术组及全乳切术组总体生存结果相仿,但全乳切除术组可获得最佳LC。     

乳腺癌保乳术后放疗延迟对预后影响

早期乳腺癌标准手术治疗为改良根治术或保留乳房手术,术后常联合放疗、化疗和内分泌治疗等。改良根治术后部分患者需要行术后辅助放疗,如术后病理T₃—T₄期、腋窝淋巴结转移≥4个等;保乳治疗目前已成为早期乳腺癌首选治疗方式,术后多数患者需要辅助放疗和化疗^[1]。近年两项a分析结果显示,保乳术后放疗能显著改善LC率、特异生存率和OS率^[2-4]。保乳术后放疗显著提高了LC率和OS率,10年LR率从35%降至19.3%,15年乳腺癌相关死亡从25.2%降至21.4%^[3]。保乳手术后患者需要辅助放疗,大部分患者术后还需要辅助化疗等全身治疗,但放化疗顺序选择或其他因素均有可能导致放疗或化疗开始时间的延迟。目前为止,保乳手术后延迟放疗对预后影响的前瞻性研究较少,大部分为回顾性研究。本文通过文献回顾分析保乳术后单纯放疗、术后序贯治疗和术后同期放化疗等治疗时放疗延迟对预后的影响,探讨乳腺癌保乳术后最佳放疗时机。     

乳腺癌保乳术后大分割全乳照射研究现状

目前保乳治疗已成为早期乳腺癌的首选治疗方式,而放疗则是乳腺癌保乳治疗的重要组成部分。但常规分割全乳放疗疗程超过6周,过长的疗程成为部分患者放弃保乳治疗的原因,也使部分接受保乳手术患者放弃术后放疗,而且成为放化疗顺序安排纠结因素之一。     

乳腺导管原位癌个体化局部治疗的研究进展和前景

乳腺X线片的广泛应用,使乳腺导管原位癌(DCIS)的早期诊断率显著升高。DCIS的局部治疗模式也不断发展,从乳房切除术到乳房保留术续贯全乳放疗,再到大分割放疗及部分乳腺短程照射的应用。虽然全乳放疗疗效明确,但其在低危DCIS的应用价值仍存在争议。DCIS局部治疗的未来研究将集中于建立更精确的局部复发风险分层系统指导个体...     

保乳术后联合放疗和内分泌治疗的临床应用进展

乳腺癌保乳术后放疗联合三苯氧胺可降低复发率和对侧癌发生率。无论序贯还是合并使用放疗和三苯氧胺,预后均无差异。文章就乳腺癌患者保乳术后联合放疗和内分泌治疗的研究进展作一综述。     

乳腺癌保乳术后大分割放疗的不良反应研究进展

研究表明保乳术后大分割放疗与常规分割放疗相比,疗效相当且未增加不良反应,目前已成为全乳照射的优选方案。早期乳腺癌综合治疗后局部复发率低、生存时间长,放疗相关的不良反应是临床关注的焦点。而大分割放疗时代许多不良反应相关的危险因素尚不明确,有待进一步研究。本文就乳腺癌保乳术后大分割放疗的不良反应展开综述。     

乳腺导管内癌的腋窝淋巴结转移率与术式选择

目的：从腋窝淋巴结转移率的角度，探讨对乳腺导管内癌(DCIS)的合理治疗方法。方法：我院1994年1月～2003年12月间收治的16例女性DCIS患者，中位年龄43岁(30～84岁)，中位随访时间62(6～114)个月，2例作Halsted根治术，11例作改良根治术，2例作全乳切除术，1例作象限切除 腋窝淋巴结清扫，术后8例作辅助化疗，3例作放疗，10例作内分泌治疗。结果：16例DCIS中，2例腋窝淋巴结有微转移。术后随访无复发，无死亡，只有1例术后4年骨扫描发现有髋转移。结论：治疗DCIS宜行肿块扩大切除(保乳手术)加术后放疗。     

乳腺导管原位癌患者仅行局部切除而不加放射治疗的疗效观察：美国东部肿瘤协作组的临床试验结果

在美国,保乳手术已成为乳腺导管原位癌（ductalcarcinomainsitu,DCIS）患者的首选术式。随机临床试验结果显示,术后放射治疗可显著降低患者的局部复发率。但是,回顾分析研究结果提示：对于病灶较小尤其是组织学分级为中低级的患者而言,无论接受或不接受放射治疗,患者的局部复发率差异均无统计学意义。     

The Role of Radiotherapy in the Conservative Treatment of Ductal Carcinoma in Situ of the Breast

Breast-conserving surgery (BCS) followed by radiotherapy (RT) has become the standard of care for the treatment of early-stage (St. I-II) invasive breast carcinoma. However, controversy exists regarding the value of RT in the conservative treatment of ductal carcinoma in situ (DCIS). In this article we review the role of RT in the management of DCIS. Retrospective and prospective trials and meta-analyses published between 1975 and 2007 in the MEDLINE database, and recent issues of relevant journals/handbooks relating to DCIS, BCS and RT were searched for. In retrospective series (10,194 patients) the 10-year rate of local recurrence (LR) with and without RT was reported in the range of 9-28% and 22-54%, respectively. In four large randomised controlled trials (NSABP-B-17, EORTC-10853, UKCCCR, SweDCIS; 4,568 patients) 50 Gy whole-breast RT significantly decreased the 5-year LR rate from 16-22% (annual LR rate: 2.6-5.0%) to 7-10% (annual LR rate: 1.3-1.9%). In a recent meta-analysis of randomised trials the addition of RT to BCS resulted in a 60% risk reduction of both invasive and in situ recurrences. In a multicentre retrospective study, an additional dose of 10 Gy to the tumour bed yielded a further 55% risk reduction compared to RT without boost. To date, no subgroups have been reliably identified that do not benefit from RT after BCS. In the NSABP-B-24 trial, the addition of tamoxifen (TAM) to RT reduced ipsilateral (11.1% vs. 7.7%) and contralateral (4.9% vs. 2.3%) breast events significantly. In contrast, in the UKCCCR study, TAM produced no significant reduction in all breast events. Based on available evidence obtained from retrospective and prospective trials, all patients with DCIS have potential benefit from RT after BCS. Further prospective studies are warranted to identify subgroups of low-risk patients with DCIS for whom RT can be safely omitted. Until long-term results of ongoing studies on outcomes of patients treated with BCS alone (with or without TAM or aromatase inhibitors) are available, RT should be routinely recommended after BCS for all patients except those with contraindication.     

Local recurrences after different treatment strategies for ductal carcinoma in situ of the breast: a population-based study in the East Netherlands

PURPOSE: Outcomes after different treatment strategies for ductal carcinoma in situ (DCIS) of the breast were analyzed for a geographically defined population in the East Netherlands. METHODS AND MATERIALS: A total of 798 patients with a first diagnosis of DCIS between January 1989 and December 2003 were included and their medical records were reviewed. Survival rates for ipsilateral recurrences were calculated by the Kaplan-Meier method and a multivariate Cox proportional hazards regression model was used to evaluate the prognostic significance of different variables. RESULTS: The 5-year recurrence-free survival was 75% for breast conserving surgery (BCS) alone (237 patients) compared with 91% for BCS followed by radiation therapy (RT; 153 patients) and 99% for mastectomy (408 patients, p < 0.01). Independent risk factors for local recurrences were treatment strategy, symptomatically detected DCIS, and presence of comedo necrosis. Margin status reached statistical significance only for patients treated by BCS (hazard ratio, 2.0; 95% confidence interval, 1.1-4.0) whereas significance of other prognostic variables did not change. CONCLUSIONS: In a defined population outside a trial setting, RT after BCS for DCIS lowered recurrence rates. Besides the use of RT, a microscopically complete excision of DCIS is essential. This is especially true for patients with symptomatically detected DCIS and with tumors that contain comedo necrosis, as these groups are at particular high risk for recurrent disease.     

Radiotherapy following breast-conserving surgery for screen-detected ductal carcinoma in situ: indications and utilisation in the UK. Interim findings from the Sloane Project

Use of radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) varies according to country, precedent and prejudice. Results from a preliminary analysis of the data available within the UK Sloane Project can be appreciated in the context of the uncertainty concerning the selection of adjuvant RT following BCS for DCIS. There was a marked geographical variation in the use of RT within the United Kingdom. However, overall, patients with DCIS treated with BCS were significantly more likely to have RT planned (and given) if they had large (> or =15 mm), intermediate or high-grade tumours or if central comedo-type necrosis was present. Unexpectedly, margin width did not appear to have a significant effect on the decision-making process. However, the Van Nuys Prognostic Index did significantly affect the chances of getting planned RT in the univariate analysis, suggesting that clinicians may be starting to use this scoring system in routine practice to assist in decision making.     

Trends in Treatment Patterns and Clinical Outcomes in Young Women Diagnosed With Ductal Carcinoma In Situ

Background

Although it is known that the risk of a second breast cancer event among young women diagnosed with ductal carcinoma in situ (DCIS) is higher than in older women, the effect of current treatment options on long-term outcomes in this subgroup of women remains poorly defined. We aimed to evaluate national treatment trends and determine their effect on second breast cancer risk and overall survival among young women diagnosed with DCIS.

Towards optimal management of ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) represents a spectrum of heterogenous disease that accounts for approximately one fifth of all screen-detected breast cancers and is considered as a precursor of invasive breast cancer if left untreated (35-50% risk). DCIS can be treated by total mastectomy with or without immediate breast reconstruction, local excision (LE) plus adjuvant radiotherapy (RT) or LE alone. Total mastectomy is associated with low rates of local recurrence (1.4%) and breast cancer-specific mortality (0.59%). Three recent randomized controlled trials (RCTs) have demonstrated that adjuvant RT after LE of localized DCIS significantly reduces the incidence of local recurrence. However these trials did not identify any subgroups of patients where RT could be safely omitted. Retrospective studies suggest that RT can be safely omitted after adequate LE (margin width > or =1 cm) of small (< 15 mm), non-high grade DCIS not associated with necrosis. Further RCTs are required to validate these retrospective findings, with an emphasis on standardized and meticulous tissue processing and pathological evaluation.The role of adjuvant tamoxifen in the management of DCIS continues to evolve. Formal axillary dissection is not appropriate for DCIS, however, the potential role of the sentinel node biopsy (SNB) in selected high risk cases requires further evaluation. The International Breast Cancer Intervention Study (IBIS-II) trial aims to evaluate the potential role of third generation aromatase inhibitors in postmenopausal women with hormone-sensitive DCIS.Future research will focus on the relevance of gene expression profiling, proteomics, Laser therapy and mammary ductoscopy to the management of DCIS.     

A retrospective alternative for active surveillance trials for ductal carcinoma in situ of the breast

Ductal carcinoma in situ (DCIS) of the breast is a nonobligate precursor of invasive breast cancer, accounting for 20 % of screen-detected breast cancers. Little is known about the natural progression of DCIS because most patients undergo surgery upon diagnosis. Many DCIS patients are likely being overtreated, as it is believed that only around 50 % of DCIS will progress to invasive carcinoma. Robust prognostic markers for progression to invasive carcinoma are lacking. In the past, studies have investigated women who developed a recurrence after breast-conserving surgery (BCS) and compared them with those who did not. However, where there is no recurrence, the patient has probably been adequately treated. The present narrative review advocates a new research strategy, wherein only those patients with a recurrence are studied. Approximately half of the recurrences are invasive cancers, and half are DCIS. So-called “recurrences” are probably most often the result of residual disease. The new approach allows us to ask: why did some residual DCIS evolve to invasive cancers and others not? This novel strategy compares the group of patients that developed in situ recurrence with the group of patients that developed invasive recurrence after BCS. The differences between these groups could then be used to develop a robust risk stratification tool. This tool should estimate the risk of synchronous and metachronous invasive carcinoma when DCIS is diagnosed in a biopsy. Identification of DCIS patients at low risk for developing invasive carcinoma will individualize future therapy and prevent overtreatment.     

Influence of boost radiotherapy in patients with ductal carcinoma in situ breast cancer: a multicenter,retrospective study in Korea (KROG 11-04)

To estimate the effect of boost radiotherapy on local recurrence-free survival (LRFS) in patients with ductal carcinoma in situ (DCIS) breast cancer. We included patients from nine institutions who met the following criteria: having Tis, age 18 years or older, having breast conserving surgery (BCS) and radiotherapy within 12 weeks after surgery. From 1995 through 2006, 728 patients were analyzed retrospectively by the Korean Radiation Oncology Group. All patients received whole-breast radiation therapy (WBRT) after BCS. 232 patients (31.9 %) also received boost radiation therapy (RT) (median 10 Gy). After median follow-up of 82 months, 5-year LRFS was 98.4 % and 10-year LRFS was 95.8 % for all patients. There was no statistically significant difference of LRFS between the boost and no-boost groups. Nineteen (2.6 %) patients had ipsilateral breast recurrences, including 12 of invasive recurrence and 7 DCIS. The presence of the HER2 receptor was associated with more invasive recurrences. Nine (1.2 %) patients developed contralateral breast cancer, including six invasive breast cancer and three DCIS. In the multivariate analysis, only the margin status was a significant prognostic factor for LRFS. Boost RT was not associated with further improvement of local control in DCIS after BCS and WBRT. HER2 receptor-positive patients may need further treatment with the anti-HER2 agents.     

Incorporating margin status information in treatment decisions for women with ductal carcinoma in situ: a decision analysis

To integrate margin status information into the decision to undergo radiation therapy (RT) following breast-conserving surgery (BCS) for women with ductal carcinoma in situ (DCIS). We developed a decision-analytic Markov model to project quality-adjusted life years (QALYs) for a hypothetical cohort of 55-year-old women with DCIS over a lifetime horizon treated with or without RT following BCS. We estimated the transition probabilities of local DCIS and invasive recurrences based on the margin status (free, close, or positive) from a systematic literature review. Other probability estimates and utilities were collected from the published literature. Using the conditions defined in this model, expected QALYs after BCS alone were better than those after BCS with RT under the free-margin scenario (15.72 vs. 15.58) and worse in the close-margin (15.44 vs. 15.50) and positive-margin scenarios (15.20 vs. 15.33). The probability of receiving a salvage mastectomy varied from 10 to 28%, depending on margin status and treatment. One-way sensitivity analyses showed that the optimal treatment was sensitive to patients’ preferences and RT side effects. Probabilistic sensitivity analyses revealed that BCS alone would be the best strategy in 54% of the cases under the free-margin scenario, 48% under the close-margin scenario, and 44% under the positive-margin scenario. This study illustrates that margin status is able to provide supplementary information on the decision of DCIS treatment. Our analyses also highlight the importance of patients’ preferences in decision making. Our findings suggest that RT is not necessary for all patients with DCIS undergoing BCS.     

Age at diagnosis and outcome for women with ductal carcinoma-in-situ of the breast: a critical review of the literature.

PURPOSE: Patients younger than 35 to 45 years old at the time of diagnosis of invasive breast cancer have been found to have a worse prognosis than older patients in many studies. However, the impact of patient age at diagnosis on the outcome of treatment with either lumpectomy and radiation therapy (RT) or mastectomy for patients with ductal carcinoma-in-situ (DCIS) of the breast has not been extensively analyzed. MATERIALS AND METHODS: Articles addressing the effect of patient age at diagnosis on the outcome of treatment of DCIS with lumpectomy and RT or mastectomy were identified through the MEDLINE and CancerLit databases and reference lists of relevant articles. Studies were reviewed to determine the impact of patient age at diagnosis on clinical and pathologic features of DCIS, the influence of age on outcome after lumpectomy and RT, and the impact of age on outcome after mastectomy. RESULTS: DCIS in younger patients more frequently contains adverse prognostic pathologic factors and extends over a greater distance in the breast than in older patients. In series with adequate follow-up, younger patients treated with lumpectomy and RT had a significantly higher rate of local recurrence than older patients, especially for invasive local recurrences. Some studies have suggested that careful attention to margin status and excising larger volumes of tissue can reduce this difference substantially. No available data show that younger patients have better long-term cancer-free survival rates if treated by mastectomy rather than lumpectomy and RT. CONCLUSION: Successful treatment of younger patients with DCIS with lumpectomy and RT requires careful attention to patient evaluation, selection, and surgical technique. When this is done, age at diagnosis should not be a contraindication to breast-conserving therapy.     

Cost-effectiveness of radiation therapy following conservative surgery for ductal carcinoma in situ of the breast

PURPOSE: To assess the cost-effectiveness of radiation therapy (RT) in patients with ductal carcinoma in situ (DCIS) after breast-conserving surgery (BCS). METHODS AND MATERIALS: A Markov model was constructed for a theoretical cohort of 55-year-old women with DCIS over a life-time horizon. Probability estimates for local noninvasive (N-INV), local invasive (INV), and distant recurrences were obtained from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17. Utilities for eight nonmetastatic health states were collected from both healthy women and DCIS patients. Direct medical (2002 Medicare fee schedule) and nonmedical costs (time and transportation) of RT were ascertained. RESULTS: For BCS + RT vs. BCS alone, the estimated N-INV and INV rates at 12 years were 9% and 8% vs. 16% and 18%, respectively. The incremental cost of adding RT was 3300 US dollars despite an initial RT cost of 8700 US dollars due to higher local recurrence-related salvage costs incurred with the BCS alone strategy. An increase of 0.09 quality-adjusted life-years (QALYs) primarily reflected the lower risk of INV with RT, resulting in an incremental cost-effectiveness ratio (ICER) of 36,700 US dollars/QALY. Sensitivity analyses revealed the ICER to be affected by baseline probability of a local recurrence, relative efficacy of RT in preventing INV, negative impact of an INV on quality of life, and cost of initial RT. Cost of salvage BCS + RT and source of utilities (healthy women vs. DCIS patients) influenced the ICER albeit to a lesser degree. CONCLUSIONS: Addition of RT following BCS for patients with DCIS should not be withheld because of concerns regarding its cost-effectiveness.