乳腺导管内癌保留乳房术后全乳腺大分割放疗研究进展

目的 大分割放疗在早期浸润乳腺癌保留乳房手术(breast conserving surgery,BCS)后放疗已逐渐得到认可.本研究对大分割放疗方案在乳腺导管内癌(ductal carcinoma in situ,DCIS) BCS后的研究现状进行综述.方法 应用PubMed、中国知网和中国生物医学文献数据库检索系统,以“乳腺导管内癌或导管原位癌(carcinoma,ductal,breast;carcinoma,intraductal,noninfiltrating;ductal carcinoma in situ)、保留乳房术(breast-conserving surgery;mastectomy,segmental)、放射治疗(radiotherapy)、剂量分割(dose fractionation)、大分割或低分割(hypofraetionation)”为主题词或关键词,检索1979-01-01 2016-3-11发表的文章,共检索到中文文献0篇,英文40篇.纳入标准:乳腺导管内癌保留乳房术后全乳腺大分割放疗的临床研究,根据纳入标准,纳入12篇.剔除标准:(1)部分乳腺放疗;(2)单纯剂量学研究.根据剔除标准,剔除3篇.最终纳入分析文献19篇.结果 乳腺导管内癌保留乳房术后全乳腺大分割放疗局部控制、晚期放疗副反应与常规放疗相当,但最佳剂量分割方式仍不是很清楚.结论 对DCIS BCS后患者而言,大分割放疗治疗周期短,且花费低,可望成为DCIS BCS后的标准治疗方案,但仍需要进一步研究.     

Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

PURPOSE: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. MATERIALS AND METHODS: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). RESULTS: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy < or = 9 MeV (p = 0.03, HR 1.41), final margins < or = 2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. CONCLUSIONS: After treatment for DCIS, 10-year rates of local control, CSS, and overall survival were similar after mastectomy and BCT. Young age (<45 years), close/positive margins (< or = 2 mm), no breast radiation, and lower electron boost energies (< or = 9 MeV) were associated with IBTR. Local failure and predominant nuclear Grade 3 were found to have a small (4%-12%) but statistically significantly negative impact on the rates of distant metastasis and CSS. These results suggest that optimizing local therapy (surgery and radiation) is crucial to improve local control and CSS in patients treated with DCIS.     

The treatment outcome of patients undergoing breast-conserving therapy: the clinical role of postoperative radiotherapy

Background  Treatment outcome was evaluated in patients who underwent breast-conserving therapy and tangential irradiation. After verifying background factors including systemic therapy, the clinical efficacy of postoperative irradiation was investigated. Method  There were 708 study subjects, all of whom had early breast cancer treated between 1992 and 2002. The median follow-up period was 83 months. After breast-conserving surgery, in patients with negative surgical margins, only tangential irradiation at 48 Gy/24 fr was performed. In contrast, in those with positive surgical margins, 10 Gy of radiation boost to the tumor bed with electrons was administered after tangential irradiation with 50 Gy/25 fr. Treatment outcome was analyzed using the Kaplan–Meier method and Cox’s proportional hazards regression model. Results  The disease-free survival and no-recurrence rates within the ipsilateral breast after 5 years were 93.4 and 97.2%, respectively. Risk factors for recurrence within the ipsilateral breast included younger age of patient, the number of positive lymph nodes, and no endocrine therapy. However, the surgical margin was not a risk factor. Risk factors for relapse outwith the ipsilateral breast included younger age, the number of positive lymph nodes, and recurrence within the ipsilateral breast. Conclusions  From our analysis of 708 Japanese women who received breast-conserving therapy, which can be regarded as a standard method in Japan, the treatment outcome was compatible with previous reports from other countries. Presented in part at the 19th meeting of the Japanese Society for Therapeutic Radiation Oncology (JASTRO), 23–25 November 2006, Sendai, Japan.     

Ductal carcinoma in situ treated with breast-conserving surgery and radiotherapy: a comparison with ECOG study 5194

BACKGROUND:

Recent data from Eastern Cooperative Oncology Group (ECOG) Study 5194 (E5194) prospectively defined a low‐risk subset of ductal carcinoma in situ (DCIS) patients where radiation therapy was omitted after lumpectomy alone. The purpose of the study was to determine the ipsilateral breast tumor recurrence (IBTR) in DCIS patients who met the criteria of E5194 treated with lumpectomy and adjuvant whole breast radiation therapy (RT).

METHODS:

A total of 263 patients with DCIS were treated between 1980 and 2009 who met the enrollment criteria for E5194: 1) low to intermediate grade (LIG) with size >0.3 cm but <2.5 cm and margins >3 mm (n = 196), or 2) high grade (HG), size <1 cm and margins >3 mm (n = 67). All patients were treated with lumpectomy and whole breast RT with a boost to a median total tumor bed dose of 6400 cGy. Standard statistical analyses were performed with SAS (v. 9.2).

RESULTS:

The average follow‐up time was 6.9 years. The 5‐year and 7‐year IBTR for the LIG cohort in this study was 1.5% and 4.4% compared with 6.1% and 10.5% in E5194, respectively. The 5‐year and 7‐year IBTR for the HG cohort was 2.0% and 2.0% in this study compared with 15.3% and 18% in E5194, respectively.

CONCLUSIONS:

Adjuvant whole breast radiation therapy reduced the rate of local recurrence by more than 70% in patients with DCIS who met the criteria of E5194 (6.1% to 1.5% in the LIG cohort and 15.3% to 2% in the HG cohort). Additional follow‐up is necessary given that 70% of IBTRs occurred after 5 years. Cancer 2011. © 2010 American Cancer Society.     

Correlation between clinical features and prognosis of local recurrence after breast-conserving therapy

Background. In patients with early stage breast cancer who have breast-conserving therapy (BCT), the impact of local recurrence on the risk of distant metastasis is still controversial. Local recurrence after BCT is an uncommon event, so it is impossible to determine a standard treatment method by a clinical trial because not enough patients can be enrolled. Methods. Between February 1988 and December 1997, 399 patients with clinical stage I and II breast cancer underwent BCT in our department. Of these 399 patients, 22 developed local recurrence during this period. To assess the relationship between their clinical characteristics and prognosis, we performed a retrospective review of these 22 patients. Results. The 5-year overall survival rate after local recurrence was 66.7%. All four patients who had cutaneous or inflammatory type recurrence developed distant metasta-sis after salvage treatment. Of three patients with multiple recurrence, two developed disseminated disease after salvage treatment. Two of four patients treated by repeat lumpectomy developed further local recurrence after salvage lumpectomy. Conclusion. To improve prognosis in patients with multiple, cutaneous, or inflammatory recurrence, aggressive adjuvant systemic therapy may be required after salvage surgery. Received: May 13, 1999 / Accepted: September 22, 1999     

早期乳腺癌保留乳房术后放射治疗临床研究

目的 观察早期乳腺癌保留乳房术后放射治疗的疗效、乳房美容效果及并发症.方法 随访2001年1月至2008年9月治疗的78例早期乳腺癌患者,其中Ⅰ期36例,Ⅱ期42例.术后全乳切线照射50 Gy,瘤床追加电子线照射10 Gy.淋巴结阳性者,患侧锁骨上X线和电子线混合照射50 Gy.结果 随访6～98个月,局部复发率4.9%,3年总体生存率96.6%,5年总体生存率92.7%,乳房美容满意率94.9%,治疗后并发症主要有皮肤急性反应及上肢水肿.结论 乳房保留手术加术后根治性放射治疗早期乳腺癌可获得满意的生存率及美容效果,提高了患者的存活质量.     

Ipsilateral breast recurrence after breast conserving surgery in patients with small (≤2 cm) breast cancer treated with modern adjuvant therapies

Background

Modern multimodality treatment greatly influences the rate and the predictive factors for ipsilateral cancer recurrence (IBR) after breast conserving surgery.

Material and nethods

The study is based on 1297 patients with pT1 breast cancer and treated with breast conserving surgery in February 2001-August 2005. The median duration of follow-up was 57 months.

Results

IBR occurred in 27 (2.1%) patients. It was located in the quadrant of prior breast resection in 17 (63%) cases. The median time to an IBR was 41 months (range, 6-78) regardless of whether the recurrence was located in the same or in another quadrant. Omission of radiotherapy was associated with a higher IBR incidence, HR 10,344 (95% CI 1904-56,184; p = 0.007). The IBRs occurred particularly often, in 27% of the 11 patients who refused radiotherapy. Patients diagnosed with ER+ cancer had a lower risk of IBR when compared with those with ER−/HER2+ cancer, HR 0.215 (95% CI 0.049-0.935; p = 0.040).

Conclusions

The risk of IBR was low during the first 5 years after breast resection among patients with pT1 breast cancer and treated with modern surgical and adjuvant therapies. The majority IBRs still occur at or close to the prior resection site underlining the importance of local therapies. Omission of radiotherapy was the most significant risk factor for IBR.     

Ductal carcinoma in situ treated with breast-conserving surgery and accelerated partial breast irradiation: comparison of the Mammosite registry trial with intergroup study E5194

BACKGROUND:

The purpose of this study was to determine the ipsilateral breast tumor recurrence (IBTR) in ductal carcinoma in situ (DCIS) patients treated in the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial who met the criteria for E5194 treated with local excision and adjuvant accelerated partial breast irradiation (APBI).

METHODS:

A total of 194 patients with DCIS were treated between 2002 and 2004 in the Mammosite registry trial; of these, 70 patients met the enrollment criteria for E5194: 1) low to intermediate grade (LIG)—pathological size >0.3 but <2.5 cm and margins ≥3 mm (n = 41) or 2) high grade (HG)—pathological size <1 cm and margins ≥3 mm (n = 29). All patients were treated with lumpectomy followed by adjuvant APBI using MammoSite. Median follow‐up was 52.7 months (range, 0‐88.4). SAS (version 8.2) was used for statistical analysis.

RESULTS:

In the LIG cohort, the 5‐year IBTR was 0%, compared with 6.1% at 5 years in E5194. In the HG cohort, the 5‐year IBTR was 5.3%, compared with 15.3% at 5 years in E5194. The overall 5‐year IBTR was 2%, and there were no cases of elsewhere or regional failures in the entire cohort. The 5‐year contralateral breast event rate was 0% and 5.6% in LIG and HG patients, respectively (compared with 3.5% and 4.2%, respectively, in E5194).

CONCLUSIONS:

This study found that patients who met the criteria of E5194 treated with APBI had extremely low rates of recurrence (0% vs 6.1% in the LIG cohort and 5.3% vs 15.3% in the HG cohort). Cancer 2011. © 2010 American Cancer Society.     

Margin width and local recurrence after breast conserving surgery for ductal carcinoma in situ

Introduction

Ductal Carcinoma in situ (DCIS) represents 5% of symptomatic and 20–30% of screen detected cancers. Breast conserving surgery (BCS) ± radiotherapy is performed in over 70% of women with DCIS. What constitutes an adequate margin for BCS remains unclear.

乳腺癌保乳术中近距离瘤床放疗的临床应用评估

目的:探讨早期乳腺癌保乳术中采用近距离瘤床放疗取代常规术后全乳放疗后瘤床加量外照射的安全性和可行性.方法:共入组30例患者,其中15例早期乳腺癌患者接受保乳术中近距离瘤床放疗,术后常规行全乳放疗;另选择15例早期乳腺癌患者作为配对,接受保乳手术及术后全乳和瘤床加量放疗.比较2组患者术后24～48 h残腔引流量、切口Ⅰ期愈合率、术后住院天数和乳房外形满意度.结果:研究组与对照组的术后24～48 h残腔引流量、切口Ⅰ期愈合率、平均住院天数及辅助化疗开始时间的差异均无统计学意义(P＞0.05).2组患者的短期随访结果显示,均能保持满意的乳房外形.结论:早期乳腺癌保乳术中近距离瘤床放疗具有较好的安全性和临床可操作性.     

Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation.

An analysis was performed of 39 consecutive women with microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation during the period 1977 to 1988. Microinvasive ductal carcinoma was defined as predominantly intraductal carcinoma with microscopic or early invasion. Surgical treatment of the primary tumor included excisional biopsy or wide resection. Axillary lymph node staging showed that 37 patients were pathologically node negative and two patients were pathologically node positive, each with only one positive lymph node. The median follow-up was 55 months (mean = 65 months; range = 25-135 months). The 5-year actuarial rate of overall and cause-specific survival were both 97%. The 5-year actuarial rate of freedom from distant metastases was 93%. Nine patients developed a recurrence in the breast; eight of the nine patients had isolated local only first failures, and one of the nine patients had a local recurrence simultaneously with distant metastases. The median time to local failure was 42 months (mean = 53 months; range = 20-116 months). Of the eight patients with local only first failure, seven patients have been salvaged with further treatment and remain free of disease at the time of last follow-up, and one patient has died of subsequent distant metastatic disease. Median follow-up after salvage treatment was 29 months (mean = 27 months; range = 0-54 months). Comparison of the patients with microinvasive ductal carcinoma with two control groups of intraductal carcinoma and invasive ductal carcinoma was performed. Although the rate of local failure was significantly higher for patients with microinvasive ductal carcinoma as compared to the two control groups, the rates of survival and freedom from distant metastases for patients with microinvasive ductal carcinoma were intermediate to the two control groups. Because of the high rates of survival and freedom from distant metastases and because of the ability to salvage patients with local recurrence, breast-conserving surgery and definitive irradiation should continue to be considered as an alternative to mastectomy for appropriately selected and staged patients with microinvasive ductal carcinoma of the breast.     

乳腺导管内癌与乳腺浸润性导管癌的超声特征及病理对照分析

目的探讨乳腺导管内癌与乳腺浸润性导管癌的超声特征及病理情况。方法选取2014年2月至2016年1月间广东省肇庆市第一人民医院收治的45例乳腺导管内癌患者与45例乳腺浸润性导管癌,分析两种乳腺癌患者的超声声像特点与病理情况的差异。结果两种乳腺癌患者的病灶大小、形状、血流信号、病灶周边毛刺与边界情况比较,差异均有统计学意义(均P<0.05)。结论乳腺导管内癌与乳腺浸润性导管癌的超声特征及病理情况上有差异明显,有助于临床疾病的鉴别诊断。     

老年人早期乳腺癌保乳手术的临床研究

目的探讨保乳手术在老年人早期乳腺癌治疗中的临床应用。方法回顾性分析2002年1月至2007年12月间在克拉玛依市中心医院和新疆医科大学第二附属医院接受保乳手术的46例老年早期乳腺癌患者的临床资料。手术方式为乳腺部分切除加腋窝淋巴清扫,术后辅助放射治疗、化疗和（或）内分泌治疗。结果46例患者手术成功,术后无严重并发症,标本石蜡病理切片显示各切缘均无癌细胞残留,随访9～68个月,2例局部复发,均无远处转移。结论保乳手术创伤小、术后并发症少,是老年人早期乳腺癌安全有效的治疗方法。掌握适应证及禁忌证,以及规范化和个体化治疗是保乳手术成功的关键。     

Use of postexcision preirradiation mammography in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy

PurposePostexcision preirradiation mammography (PPM) is frequently performed in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving therapy (BCT) to evaluate for residual suspicious calcifications; but no clear evidence supports this practice. The current study was undertaken to investigate the value of PPM in the management of patients with DCIS.Methods and MaterialsWe conducted a retrospective review of patients treated for DCIS with BCT at the University of Pennsylvania. The impact of PPM on surgical management and on local recurrence was evaluated. Factors associated with the use of PPM, the results of PPM, and the likelihood of finding residual malignancy at the time of re-excision in patients with PPM were also examined.ResultsOne hundred forty-four of 281 patients (51%) underwent PPM. Of the 144 patients who received PPM, 34 (24%; 95% confidence interval, 17%-31%) had residual suspicious calcifications (a “positive PPM”). Of the 34 patients with a positive PPM, all underwent a re-excision and 19 (56%; 95% confidence interval, 35%-70%) were found to have residual malignancy. Ten of 34 patients with a positive PPM had negative margins, of which 6 had a residual malignancy. Assuming all patients with close, positive, or indeterminate surgical margins would have undergone re-excision regardless of the findings of PPM, PPM resulted in a change in surgical management in 7% (10/144) of patients and removal of residual DCIS in 4% (6/144). With a median follow-up of 9.5 years, the use of PPM was not associated with an improvement in 10-year local recurrence-free survival (94.8% vs 91.5%, P = .368).ConclusionsIn this study, PPM affected surgical management in only a small percentage of patients and had no impact on local recurrence. The routine use of PPM in women undergoing BCT for DCIS may not be warranted.     

An analysis of relapsed breast cancer in patients previously treated with breast conserving surgery

BACKGROUND: Recent advances in breast surgery have focused on breast conserving surgery in combination with radiotherapy. In the present study, we examine by retrospective analysis 105 patients with breast cancer who received breast conserving surgery for factors influencing disease free survival. METHODS: The analysis was performed on 105 patients with breast cancer who received breast conserving surgery in our department, including 38 patients without radiotherapy and 67 patients treated with radiotherapy. The disease-free survival of the patients was analyzed using the Kaplan-Meier method. The relapsed patients were assessed by examining pathological features and gene expression by immunohistochemical staining. RESULTS: There was no significant difference in the disease free survival at 5 years between patients without radiotherapy (89.6%) and with radiotherapy (94.5%). Relapse after breast conserving surgery was found in 6 patients including 4 patients without radiotherapy and 2 patients with radiotherapy. Local relapse and bone metastasis were found in 4 (3.8%) and 2 patients, respectively. Among the 4 local relapses, 1 patient had received radiotherapy and 3 patients had not. There was no significant difference between the type of relapse in terms of lymph node metastasis, hormone receptor, nuclear grade and intraductal component, but more vessel invasion was observed in the 2 cases with bone metastasis. The overexpression of apoptosis and angiogenesis genes such as p53, Bax, Bcl-XL, Bcl-2 and VEGF was not common in the relapsed patients, whereas the overexpression of drug resistance genes, either P-gp or MRP1, was found in the all patients. CONCLUSIONS: Although radiotherapy may reduce the incidence of local relapse and increase disease free survival after breast conserving surgery, the development of an effective adjuvant chemotherapy based on drug resistance markers, is also required.     

Treatment outcome of breast-conserving therapy in patients with positive or close resection margins: Japanese multi institute survey for radiation dose effect

BACKGROUND: The relationship between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) is controversial. To evaluate the radiation dose and other factors influencing the ipsilateral breast tumor control (IBTC) in patients with positive or close resection margins after breast conserving surgery (BCS), the Japanese Radiation Oncology Study Group (JROSG) S-99-3 study group conducted a multi-institute survey of these patients. METHODS: The patients with less than 5 mm tumor-free margins after BCS were eligible for this study. A total of 971 patients from 18 institutes were enrolled in the analysis. The final pathological margin status was classified into 3 groups. Radiation doses to the tumor bed were less than 60 Gy in 252 patients, 60 Gy in 456 patients and more than 60 Gy in 233 patients. RESULTS: IBTR was observed in 55 patients (5.8%). The IBTC rates at 5 and 10 years by the Kaplan Meier method were 95.6% and 87.3%, respectively. There was no significant difference in 10-year IBTC rates according to marginal status; 85.9% in positive margin patients, 91.0% in equal or less than 2 mm margin patients and 87.0% in 2.1-5 mm margin patients. Radiation dose to the tumor bed was a marginally significantly associated with the 10-year IBTC rate (> or = 60 Gy 90.8% vs < 60 Gy 84.2%, p = 0.057). In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better (p = 0.039). The other factors influencing the IBTC were age (> or = 35 years vs < 35 years: p < 0.0001), menopausal status (p < 0.0001) and tumor size (p = 0.023). CONCLUSIONS: In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better than the others. We recommend that the tumor bed be irradiated with at least 60 Gy in the patients with positive margins. Further follow-up is necessary to draw final conclusions.