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.     

Outcome after ipsilateral breast tumor recurrence in patients who receive accelerated partial breast irradiation

BACKGROUND:

The objective of this study was to examine clinical outcomes and patterns of failure in patients with early stage breast cancer who developed an ipsilateral breast tumor recurrence (IBTR) after breast‐conserving therapy (BCT) using accelerated partial breast irradiation (APBI).

METHODS:

In total, 1440 patients (1449 tumors) with early stage breast cancer who underwent BCT were treated with the MammoSite device to deliver APBI (34 Gray [Gy] in 3.4‐Gy fractions). One thousand two hundred fifty‐five patients (87%) had invasive breast cancer (IBC) (median tumor size, 10 mm), and 194 patients (13%) had ductal carcinoma in situ (DCIS) (median tumor size, 8 mm). The median follow‐up was 60 months.

RESULTS:

Fifty patients (3.5%) developed an IBTR for a 5‐year actuarial rate of 3.61% (3.65% for IBC and 3.36% for DCIS). It was determined that 36 recurrences (72%) represented new primary cancers, and 14 recurrences (28%) represented recurrences of the index lesion. Of the 32 recurrences with known histology, 78% were IBC, and 22% were DCIS. After IBTR, 28 of 38 patients (74%) underwent salvage mastectomy, and 9 of 38 patients (26%) had a second attempt at BCT. Adjuvant therapies included tamoxifen in 8 patients (16%) and systemic chemotherapy in 6 patients (12%). The 3‐year rates of disease‐free survival, cause‐specific survival, and overall survival after IBTR were 58.7%, 92.1%, and 80.5%, respectively.

CONCLUSIONS:

With 5 years of follow‐up, APBI produced clinical outcomes and patterns of failure comparable to those achieved with whole breast irradiation. Patients who developed an IBTR after APBI had excellent 3‐year survival outcomes after salvage treatments. Cancer 2012. © 2012 American Cancer Society.     

Three-year analysis of treatment efficacy, cosmesis, and toxicity by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation (APBI)

BACKGROUND: This report presents 3 years of data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite (Cytyc, Bedford, Mass) Breast Brachytherapy Registry Trial. METHODS: A total of 1440 patients (1449 cases) with early stage breast cancer who were undergoing breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial breast irradiation (APBI) (34 Gy in 3.4 Gy fractions). Of these, 1255 (87%) cases had invasive breast cancer (IBC; median size = 10 mm), and 194 (13%) cases had ductal carcinoma in situ (DCIS; median size = 8 mm). Median follow-up was 30.1 months. RESULTS: Twenty-three (1.6%) cases developed an ipsilateral breast tumor recurrence (IBTR) for a 2-year actuarial rate of 1.04% (1.11% for IBC and 0.59% for DCIS). No variables were associated with IBTR. Six (0.4%) patients developed an axillary failure. The percentages of breasts with good to excellent cosmetic results at 12 (n = 980), 24 (n = 752), 36 (n = 403), and 48 months (n = 67 cases) were 95%, 94%, 93%, and 93%, respectively. Breast seromas were reported in 23.9% of cases (30% in open-cavity implants and 19% in closed-cavity implants). Symptomatic seromas occurred in 10.6% of cases, and 1.5% of cases developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 37.5 months, the 3-year actuarial rate of IBTR was 1.79%. CONCLUSIONS: Treatment efficacy, cosmesis, and toxicity 3 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up.     

Ductal carcinoma in situ (DCIS) of the breast: perspectives on biology and controversies in current management

The incidence of ductal carcinoma in situ (DCIS) has increased because of increasing use of sensitive imaging modalities. MRI is commonly used for the detection of breast cancer but has not yet been validated in randomized trials. There have not been randomized trials addressing optimal margins of excision or axillary sampling. Whole breast radiation after lumpectomy decreases the risk of recurrence but may be omitted in selected patients. Adjuvant Tamoxifen reduces the risk of recurrence but has no impact on overall survival rates.     

Potential applicability of balloon catheter-based accelerated partial breast irradiation after conservative surgery for breast carcinoma

BACKGROUND: Balloon catheter-based accelerated partial breast irradiation (APBI) is an alternative to whole-breast external-beam irradiation during breast-conserving therapy (BCT) for breast carcinoma, but it is limited by the size of the segmental mastectomy cavity. There are scant data on the average or optimal volume of resection (VR) in BCT. The objective of the current study was to evaluate the percentage of patients who would be eligible for balloon catheter-based APBI based on the selection criteria of the American Society of Breast Surgeons and the surgical VR. METHODS: The authors reviewed the medical records of 443 patients with ductal carcinoma in situ (DCIS) or invasive carcinoma treated with BCT. Patient treatment and pathologic data were analyzed to assess VR and eligibility for APBI. RESULTS: BCT was performed for 178 patients with DCIS and 267 patients with invasive breast carcinoma. The majority of invasive carcinomas (63.3%) were infiltrating ductal carcinomas. The median overall lumpectomy volume was 67.61 cm3, with no significant difference between DCIS and invasive carcinoma (P>0.05). Although the majority (62.9-82.0%) of patients met the individual selection criteria for APBI, only 27.4% of the cohort was found to be eligible for any type of APBI when the selection criteria were considered together. Based on VR, only approximately one-half of the patients initially eligible for APBI would be candidates for immediate balloon catheter-based APBI using the 70 cm3 balloon device (13.3%). However, with the new, larger 125 cm3 balloon device, approximately three-fourths of patients initially eligible for APBI would be eligible for balloon catheter-based APBI at the time of the initial surgical procedure (20.7%). Although not evaluated in the current study, shrinkage of the lumpectomy cavity with time may increase the number of patients eligible based strictly on VR criteria. Patients with a very large VR (> or =125 cm3) were more likely to have invasive carcinoma (P=0.02; hazard ratio [HR], 7.4) and tumors > or =5 cm on final pathology (P<0.01; HR, 22.0). CONCLUSIONS: Approximately one-fifth to one-fourth of patients presenting for BCT may be eligible for balloon catheter-based APBI according to accepted national guidelines and VR. VR must be considered when selecting patients for balloon catheter-based APBI, because a minority of patients will have a lumpectomy cavity that exceeds the size limit of the current balloon device.     

Phase II trial of proton beam accelerated partial breast irradiation in breast cancer

Background and purpose

Here, we report the results of our phase II, prospective study of proton beam accelerated partial breast irradiation (PB-APBI) in patients with breast cancer after breast conserving surgery (BCS).

Materials and methods

Thirty patients diagnosed with breast cancer were treated with PB-APBI using a single-field proton beam or two fields after BCS. The treatment dose was 30 cobalt gray equivalent (CGE) in six CGE fractions delivered once daily over five consecutive working days.

Results

All patients completed PB-APBI. The median follow-up time was 59 months (range: 43–70 months). Of the 30 patients, none had ipsilateral breast recurrence or regional or distant metastasis, and all were alive at the last follow-up. Physician-evaluated toxicities were mild to moderate, except in one patient who had severe wet desquamation at 2 months that was not observed beyond 6 months. Qualitative physician cosmetic assessments of good or excellent were noted in 83% and 80% of the patients at the end of PB-APBI and at 2 months, respectively, and decreased to 69% at 3 years. A good or excellent cosmetic outcome was noted in all patients treated with a two-field proton beam at any follow-up time point except for one. For all patients, the mean percentage breast retraction assessment (pBRA) value increased significantly during the follow-up period (p = 0.02); however, it did not increase in patients treated with two-field PB-APBI (p = 0.3).

Conclusions

PB-APBI consisting of 30 CGE in six CGE fractions once daily for five consecutive days can be delivered with excellent disease control and tolerable skin toxicity to properly selected patients with early-stage breast cancer. Multiple-field PB-APBI may achieve a high rate of good-to-excellent cosmetic outcomes. Additional clinical trials with larger patient groups are needed.     

Margin width as a determinant of local control with and without radiation therapy for ductal carcinoma in situ (DCIS) of the breast

In order to assess the utility of margin width in relation to other histopathologic features as a determinant of local control in ductal carcinoma in situ (DCIS) of the breast, we retrospectively examined the treatment of 109 breasts treated with (n = 54) or without adjuvant radiotherapy (n = 55). Median follow‐up was 49 and 54 months for patients treated with excision alone (E) or excision plus adjuvant radiotherapy (E+XRT), respectively. Cases treated with E+XRT were significantly larger and had a trend towards closer surgical margins than those treated with E alone. For all cases, margin width ≤1 mm and lesion diameter >15 mm were significantly associated with increased local recurrence. Lesion size ≤15 mm was associated with no cases of local failure regardless of treatment arm. For lesions >15 mm in diameter, there was a significant decrease in 5‐year local failure with E+XRT compared to E alone (21% vs. 36%, P = 0.03). Tumor margin >1 mm was associated with a low rate of 5‐year local failure for either E alone or E+XRT (10.9% vs. 4.6%, P = NS). Tumor margin ≤1 mm had a high rate of local failure that was not significantly decreased by the addition of adjuvant radiotherapy. These results show that large diameter (>15mm) and close surgical margins (≤1 mm) are the dominant risk factors for local recurrence in DCIS. E+XRT significantly decreased local failure risk compared to E alone for large lesions but not for those with close margins. © 2002 Wiley‐Liss, Inc.     

Axillary lymph node failure in patients treated with accelerated partial breast irradiation

BACKGROUND:

Data on the risk of axillary failure (AF) after accelerated partial breast irradiation (APBI) are limited. In this study, the authors determined the rate of AF and regional lymph node failure (RNF) in patients who received various forms of APBI and identified factors that were associated with its occurrence.

METHODS:

In total, 534 patients with early stage breast cancer were treated at William Beaumont Hospital with APBI, including 466 patients (87%) with invasive breast cancer and 68 patients (13%) with ductal carcinoma in situ. Clinical variables (patient age, tumor location), pathologic variables (tumor size, grade, estrogen receptor status, margin status, lymph node status), and treatment‐related variables (receipt of hormone and systemic chemotherapy) were analyzed to determine which factors were associated with AF and RNF. The median length of follow‐up was 63 months (range, 1‐201 months).

RESULTS:

The 5‐year actuarial AF rate was 0.19%. Three patients (0.56%) developed RNF (all patients initially had invasive breast cancer) with a 5‐year actuarial rate of 0.37%. Two of the regional recurrences were in the supraclavicular fossa, and 1 was in the axilla. No variables were associated with AF. However, patient numbers were very small. The median survival after RNF was 0.8 years (range, 0.3‐1.7 years), and 2 of the 3 patients died of disease.

CONCLUSIONS:

The rate of AF and RNF after APBI was low and appeared to be similar to the rate observed with whole‐breast irradiation. No variables were associated with a higher rate of AF after APBI. Cancer 2012;. © 2011 American Cancer Society.     

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.     

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。     

Relationship between excision volume, margin status, and tumor size with the development of local recurrence in patients with ductal carcinoma-in-situ treated with breast-conserving therapy

BACKGROUND AND OBJECTIVES: We reviewed our institution's experience treating patients with ductal carcinoma-in-situ (DCIS) with breast-conserving therapy (BCT) to help define the interrelationship between excision volume, margin status, and tumor size with local recurrence. METHODS: From January 1980 to December 1993, 146 patients received BCT for DCIS. All patients underwent excisional biopsy and 95 cases (64%) underwent re-excision. Each patient received whole breast radiation to a median dose of 45 Gy. An additional 139 cases (94%) received a supplemental boost to the tumor bed (median total dose 60.4 Gy). The median follow-up is 7.2 years. RESULTS: Seventeen patients developed an ipsilateral breast failure for a 5- and 10-year actuarial rate of 10.2 and 12.4%, respectively. On multivariate analysis, patient age, margin status, the number of slides containing DCIS, the number of DCIS/cancerization of lobules (COL) foci near (< 5 mm) the margin, and a smaller volume of excision (< 60 cm(3)) were all independently associated with outcome. Although the local recurrence rate generally decreased as margin distance increased, these differences did not achieve statistical significance unless the volume of excision was taken into consideration. CONCLUSIONS: These findings suggest that the success of BCT is directly related to the degree of surgical removal of DCIS and that margin status alone may be suboptimal in defining excision adequacy.     

Five‐year outcome of patients classified using the American Society for Radiation Oncology consensus statement guidelines for the application of accelerated partial breast irradiation

BACKGROUND:

The American Society for Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) was applied to patients who were treated with this technique on the American Society of Breast Surgeons MammoSite Registry Trial to determine potential differences in clinical outcome based on classification group.

METHODS:

Patients were classified based on the CS groups of “suitable,” “cautionary,” and “unsuitable.” Rates of ipsilateral breast tumor recurrence (IBTR), regional lymph node failure, distant metastases, disease‐free survival, cause‐specific survival, and overall survival were assessed.

RESULTS:

Of the 1449 cases who were treated, 1025 patients (71%) could be classified according to the CS groupings, including 419 patients (41%) who fit the “suitable” criteria, 430 patients (42%) who fit the “cautionary” criteria, and 176 patients (17%) who fit the “unsuitable” criteria. At a median follow‐up of 53.5 months, the 5‐year actuarial rates of IBTR for the “suitable,” “cautionary,” and “unsuitable” groups were 2.59%, 5.43%, and 5.28%, respectively (P = .1884). Univariate analysis of factors potentially associated with IBTR indicated that negative estrogen receptor status was the only variable associated with IBTR among patients with invasive breast cancer (odds ratio [OR], 4.01; P = .0003). Larger tumor size was associated with a greater risk of distant metastasis (OR, 3.05; P = .0001). Among patients with ductal carcinoma in situ, only age <50 years and close‐positive margins were associated with IBTR (OR, 1.12 [P = .0079] and OR, 7.81 [P = .0131], respectively).

CONCLUSIONS:

The ASTRO CS groupings did not differentiate a subset of patients with a significantly worse rate of IBTR when they were treated with the MammoSite breast brachytherapy catheter to deliver APBI. Cancer 2010. © 2010 American Cancer Society.     

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。     

Controversies over the role of radiation therapy for ductal carcinoma in situ

Ductal carcinoma in situ is a premalignant disease of the breast with a rapidly rising incidence. For women with localized ductal carcinoma in situ, randomized trials have shown that radiation therapy following conservative surgery lowers the relative risk of progression to invasive disease by 60%. Therefore, following conservative surgery, radiation therapy to the breast is generally considered a reasonable standard of care. However, several clinical trials have investigated the safety of conservative surgery alone without radiation for select women with small tumors of low histologic grade excised with widely negative margins. At present, results of these trials are conflicting, and, therefore, radiation therapy is generally recommended following conservative surgery, even for patients with favorable pathologic characteristics.     

Trends in the use of implantable accelerated partial breast irradiation therapy for early stage breast cancer in the United States

BACKGROUND:

In 2002, the US Food and Drug Administration approved an implantable balloon catheter that delivers accelerated partial breast irradiation (APBI) after breast‐conserving surgery (BCS). The objective of the current study was to determine the use of implantable APBI (IAPBI) in the United States and factors associated with IAPBI use.

METHODS:

By using the Surveillance, Epidemiology, and End Results database, the authors conducted a retrospective analysis of patients who received whole‐breast radiotherapy (WBRT) or IAPBI after BCS for ductal carcinoma in situ, AJCC stage I, or stage II breast cancer from 2000 to 2007. WBRT and IAPBI rates were determined across time and demographic and tumor factors using chi‐square tests and Cochran‐Armitage tests for trend for the unadjusted analyses.

RESULTS:

A total of 127,257 patients who met inclusion criteria were identified. Over the study period, the proportion of patients receiving IAPBI increased by 1600% (from 0.4% in 2000 to 6.8% in 2007; P <.001). This trend remained significant when using logistic regression (odds ratio, 20.3; 95% confidence interval, 15.5‐26.6). The increase in IAPBI use was statistically significant across all stage and age categories >40 years (P <.001). The use of IAPBI was most notable in older women (ages 70‐79 years), with a >2100% increase in use noted during the study period (0.4% in 2000 vs 9.0% in 2007; P <.001). The authors also found significant variation in IAPBI use by region.

CONCLUSIONS:

IAPBI use has markedly increased since 2000, particularly in the elderly population. The rapid and widespread adoption of IAPBI is concerning, because large multicenter randomized controlled trials have not yet demonstrated the long‐term effectiveness of IAPBI compared with WBRT. Cancer 2011. © 2011 American Cancer Society.     

Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: Results of a matched-pair analysis

Background and Purpose

To compare 12-year outcomes of accelerated partial breast irradiation (APBI) versus whole-breast irradiation (WBI) in patients treated with breast conservation.

Materials and Methods

A matched-pair analysis was performed using 199 patients receiving WBI and 199 patients receiving interstitial APBI. Match criteria included tumor size, age, nodal status, ER status, and the use of adjuvant hormonal therapy. Patterns of failure and efficacy of salvage treatments were examined.

Results

No differences were seen in the 12-year rates of local recurrence (3.8% vs. 5.0%, p = 0.40), regional recurrence (0% vs. 1.1%, p = 0.15), disease free survival (DFS) (87% vs. 91%, p = 0.30), cause-specific survival (CSS) (93% vs. 95%, p = 0.28), or overall survival (OS) (78% vs. 71%, p = 0.06) between the WBI and APBI groups, respectively. The rate of distant metastases was lower in the APBI group (10.1% vs. 4.5%, p = .05). Following LR, no difference in outcome was seen between the two groups with 5 year post-LR rates of DFS (80% vs. 86%, p = 0.55), CSS (88% vs. 75%, p = 0.77), and OS (88% vs. 75%, p = 0.77), respectively.

Conclusions

With 12-year follow-up, APBI produced outcomes equivalent to WBI. Following LR, patients treated with APBI also had similar failure patterns to those managed with WBI.     

Pathologic characteristics of second breast cancers after breast conservation for ductal carcinoma in situ

BACKGROUND:

The number of women diagnosed with ductal carcinoma in situ (DCIS) is increasing. Although many eventually develop a second breast cancer (SBC), little is known about the characteristics of SBCs. The authors described the characteristics of SBC and examined associations between the pathologic features of SBC and index DCIS cases.

METHODS:

Women were identified in the National Comprehensive Cancer Network Outcomes Database who were diagnosed with DCIS from 1997 to 2008 and underwent lumpectomy and who subsequently developed SBC (including DCIS or invasive disease that occurred in the ipsilateral or contralateral breast). The Fisher exact test and the Spearman test were used to examine associations between the pathologic characteristics of SBC and index DCIS cases.

RESULTS:

Among 2636 women who underwent lumpectomy for DCIS, 150 (5.7%) experienced an SBC after a median of 55.5 months of follow‐up. Of these 150 women, 105 (70%) received adjuvant radiotherapy, and 50 (33.3%) received tamoxifen for their index DCIS. SBCs were ipsilateral in 54.7% of women and invasive in 50.7% of women. Among the index DCIS cases, 60.6% were estrogen receptor (ER)‐positive, and 54% were high grade, whereas 77.5% of SBCs were ER‐positive, and 48.2% were high grade. Tumor grade (P = .003) and ER status (P = .02) were associated significantly between index DCIS and SBC, whereas tumor size was not (P = .87).

CONCLUSIONS:

After breast conservation for DCIS, SBC in either breast exhibited pathologic characteristics similar to the index DCIS, suggesting that women with DCIS may be at risk for developing subsequent breast cancers of a similar phenotype. Cancer 2012. © 2012 American Cancer Society.