Breast-conserving surgery with or without radiotherapy vs mastectomy for ductal carcinoma in situ: French Survey experience

From March 2003 to April 2004, 77 physicians throughout France prospectively recruited 1289 ductal carcinoma in situ (DCIS) patients and collected data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30–84). Ductal carcinoma in situ was diagnosed by mammography in 87.6% of patients. Mastectomy, conservative surgery alone (CS) and CS with radiotherapy (CS+RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Thus, 89% of patients treated by CS received adjuvant RT. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients (80% tamoxifen). Median tumour size was 14.5 mm (6, 11 and 35 mm for CS, CS+RT and mastectomy, respectively, P<0.0001). Nuclear grade was high in 21% of patients, intermediate in 38.5% and low in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS+RT) of patients. Oestrogen receptors were positive in 69.8% of assessed cases (31%). Treatment modalities varied widely according to region: mastectomy rate, 20–37%; adjuvant RT, 84–96%; hormone treatment, 6–34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin and grade) and treatment options, with several similar variations to those observed in recent UK and US studies.     

Comprehensive multiplexed immune profiling of the ductal carcinoma in situ immune microenvironment regarding subsequent ipsilateral invasive breast cancer risk

Background Ductal carcinoma in situ (DCIS) is treated to prevent subsequent ipsilateral invasive breast cancer (iIBC). However, many DCIS lesions will never become invasive. To prevent overtreatment, we need to distinguish harmless from potentially hazardous DCIS. We investigated whether the immune microenvironment (IME) in DCIS correlates with transition to iIBC.Methods Patients were derived from a Dutch population-based cohort of 10,090 women with pure DCIS with a median follow-up time of 12 years. Density, composition and proximity to the closest DCIS cell of CD20⁺ B-cells, CD3⁺CD8⁺ T-cells, CD3⁺CD8⁻ T-cells, CD3⁺FOXP3⁺ regulatory T-cells, CD68⁺ cells, and CD8⁺Ki67⁺ T-cells was assessed with multiplex immunofluorescence (mIF) with digital whole-slide analysis and compared between primary DCIS lesions of 77 women with subsequent iIBC (cases) and 64 without (controls).Results Higher stromal density of analysed immune cell subsets was significantly associated with higher grade, ER negativity, HER-2 positivity, Ki67 ≥ 14%, periductal fibrosis and comedonecrosis (P < 0.05). Density, composition and proximity to the closest DCIS cell of all analysed immune cell subsets did not differ between cases and controls.Conclusion IME features analysed by mIF in 141 patients from a well-annotated cohort of pure DCIS with long-term follow-up are no predictors of subsequent iIBC, but do correlate with other factors (grade, ER, HER2 status, Ki-67) known to be associated with invasive recurrences.Subject terms: Prognostic markers, Imaging the immune system, Breast cancer, Cancer microenvironment, Translational research

     

Ultrasonography- and/or mammography-guided breast conserving surgery for ductal carcinoma in situ of the breast: experience with 87 lesions

Background

It is very important to excise ductal carcinoma in situ (DCIS) with sufficient margins to prevent local recurrence. We describe the experience of ultrasonography (US)-guided and/or mammography (MMG)-guided breast conserving surgery (BCS) for DCIS.

Methods

In this retrospective study, we considered 87 consecutive lesions of 86 patients treated with US- and/or MMG-guided BCS between January and December 2006.

Results

The mean age of the 86 patients was 50.0 years (range 28–80 years). Preoperative mapping was performed using US alone for 49 lesions without microcalcifications and using US and MMG for 38 lesions with microcalcifications. Eighty-one (93.1%) of the 87 lesions were diagnosed as non-comedo type or mixed type, and 6 lesions (6.9%) were diagnosed as comedo type of DCIS. Sixty-five lesions (74.8%) were diagnosed as negative margins, 15 lesions (17.2%) as close margins, and 7 lesions (8.0%) as positive margins. Three lesions (3.4%) without microcalcifications that were mapped using US alone underwent additional resection in a second operation. The maximum tumor size was correlated with margin status (p = 0.043).

Conclusion

Thus US- and/or MMG-guided BCS is a reliable method for treating patients with DCIS regardless of histopathological type and offers the advantage of being noninvasive and nonstressful for patients.

     

乳腺导管原位癌术后辅助放疗

保乳术已成为导管原位癌(DCIS)最常见的治疗手段,术后放疗可降低其复发风险.然而,对于DCIS放疗的照射范围、可不行术后放疗低危人群的选择、部分乳腺加速放疗(APBI)在DCIS中的作用等还存在争议.然而,多数研究均显示DCIS保乳术患者均能从术后放疗中获益.进一步的前瞻性研究主要证实低危组的DCIS患者是否可以安全地省去术后放疗.对单纯保乳术后患者的长期随访结果显示,除有禁忌证的患者外,放疗成为保乳术后所有患者的常规治疗方式.     

Breast-conserving surgery with or without radiotherapy in women with ductal carcinoma in situ: a meta-analysis of randomized trials

Background

To investigate whether Radiation therapy (RT) should follow breast conserving surgery in women with ductal carcinoma in situ from breast cancer (DCIS) with objective of decreased mortality, invasive or non invasive recurrence, distant metastases and contralateral breast cancer rates. We have done a meta-analysis of these results to give a more balanced view of the total evidence and to increase statistical precision.

Methods

A meta-analysis of randomized controlled trials (RCT) was performed comparing RT treatment for DCIS of breast cancer to observation. The MEDLINE, EMBASE, CANCERLIT, Cochrane Library databases, Trial registers, bibliographic databases, and recent issues of relevant journals were searched. Relevant reports were reviewed by two reviewers independently and the references from these reports were searched for additional trials, using guidelines set by QUOROM statement criteria.

Results

The reviewers identified four large RCTs, yielding 3665 patients. Pooled results from this four randomized trials of adjuvant radiotherapy showed a significant reduction of invasive and DCIS ipsilateral breast cancer with odds ratio (OR) of 0.40 (95% CI 0.33 – 0.60, p < 0.00001) and 0.40 (95% CI 0.31 – 0.53, p < 0.00001), respectively. There was not difference in distant metastases (OR = 1.04, 95% CI 0.57–1.91, p = 0.38) and death rates (OR = 1.08, 95%CI 0.65 – 1.78, p = 0.45) between the two arms. There was more contralateral breast cancer after adjuvant RT (66/1711 = 3.85%) versus observation (49/1954 = 2.5%). The likelihood of contralateral breast cancer was 1.53-fold higher (95% CI 1.05 – 2.24, p = 0.03) in radiotherapy arms.

Conclusion

The conclusion from our meta-analysis is that the addition of radiation therapy to lumpectomy results in an approximately 60% reduction in breast cancer recurrence, no benefit for survival or distant metastases compared to excision alone. Patients with high-grade DCIS lesions and positive margins benefited most from the addition of radiation therapy. It is not yet clear which patients can be successfully treated with lumpectomy alone; until further prospective studies answer this question, radiation should be recommended after lumpectomy for all patients without contraindications.     

Subclinical ductal carcinoma in situ of the breast: treatment with conservative surgery and radiotherapy

AIMS AND BACKGROUND: In spite of the fact that ductal carcinoma in situ (DCIS) of the breast is a frequently encountered clinical problem, there is no consensus about the optimal treatment of clinically occult (i.e., mammographic presentation only) DCIS. Interest in breast conservation therapy has recently increased. Few data are available in Italy on the conservative treatment with surgery and adjuvant postoperative radiotherapy. METHODS: A retrospective multi-institutional study was performed in 15 Radiation Oncology Departments in northern Italy involving 112 women with subclinical DCIS of the breast treated between 1982 and 1993. Age of the patients ranged between 32 and 72 years (median, 50 years). All of them underwent conservative surgery: quadrantectomy in 89, tumorectomy in 11, and wide excision in 12 cases. The most common histologic subtype was comedocarcinoma (37%). The median pathologic size was 10 mm (range 1 to 55 mm). Axillary dissection was performed in 83 cases: all the patients were node negative. All the patients received adjunctive radiation therapy with 60Co units (77%) or 6 MV linear accelerators (23%) for a median total dose to the entire breast of 50 Gy (mean, 49.48 Gy; range, 45-60 Gy). Seventy-six cases (68%) received a boost to the tumor bed at a dose of 8-20 Gy (median 10 Gy) for a minimum tumor dose of 58 Gy. RESULTS: At a median follow-up of 66 months, 8 local recurrences were observed, 4 intraductal and 4 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease at this writing. The 10-year actuarial overall, cause-specific, and recurrence-free survival was of 98.8%, 100%, and 91%, respectively. CONCLUSIONS: The retrospective multicentric study, with a local control rate of more than 90% at 10 years with 100% cause-specific survival, showed that conservative surgery and adjuvant radiation therapy is a safe and efficacious treatment for patients with occult, non-palpable DCIS.     

Impact of concurrent proliferative high-risk lesions on the risk of ipsilateral breast carcinoma recurrence and contralateral breast carcinoma development in patients with ductal carcinoma in situ treated with breast-conserving therapy

BACKGROUND: The purpose of the study was to determine the risk of ipsilateral breast carcinoma recurrence (IBCR) and contralateral breast carcinoma (CBC) development in patients with a concurrent diagnosis of ductal carcinoma in situ (DCIS) with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). METHODS: Records of all 307 patients with DCIS treated with breast-conserving treatment (BCT) from 1968 to 1998 were analyzed. Initial pathology reports and all slides available were re-reviewed for evidence of ADH, ALH, or LCIS. Actuarial local recurrence rates were calculated. RESULTS: Fifty-five cases of DCIS were associated with ADH, 11 with ALH or LCIS, and 14 with both ADH and ALH or LCIS. Overall, IBCR occurred in 14% and no significant difference in the IBCR rate was identified for patients with proliferative lesions compared with patients without these lesions (P = 0.38). Development of CBC in patients with concurrent DCIS and ADH was 4.4 times (95% confidence interval [CI], 1.44-13.63) that in patients with DCIS alone (P < 0.01). The 15-year cumulative rate of CBC development was 22.7% in patients with ALH or LCIS compared with 6.5% in patients without these lesions (P = 0.30) and 19% in patients with ADH compared with 4.1% in patients with DCIS alone (P < 0.01). CONCLUSION: The risk of CBC development is higher with concurrent ADH than in patients with DCIS alone, and these patients may therefore be appropriate candidates for additional chemoprevention strategies. Concurrent ADH, ALH, or LCIS with DCIS is not a contraindication to BCT.     

Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component

Background Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.Methods Consecutive ER-positive, HER2-negative, N0–1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.Results A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.Conclusions IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.Subject terms: Genetics research, Surgical oncology, Breast cancer, Breast cancer     

Long-term outcome after breast-conservation treatment with radiation for mammographically detected ductal carcinoma in situ of the breast

BACKGROUND: Ductal carcinoma in situ (DCIS) is detected most commonly on routine screening mammography in the asymptomatic patient, and has a long natural history. The objective of the current study was to determine the long-term outcome after breast-conservation surgery followed by definitive breast irradiation for women with mammographically detected DCIS of the breast. METHODS: In total, 1003 women with unilateral, mammographically detected DCIS of the breast underwent breast-conserving surgery followed by definitive breast irradiation. These women were treated in 10 institutions in North America and Europe. The median follow-up was 8.5 years (mean, 9.0 years; range, 0.2-24.6 years). RESULTS: The 15-year overall survival rate was 89%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 97%. In total, there were 100 local failures (10%) in the treated breast. The 15-year rate of any local failure was 19%, and the 15-year rate of local only first failure was 16%. Patient age > or = 50 years at the time of treatment and negative final pathology margins from the primary tumor excision both were associated independently with a lower risk of local failure in univariate analysis (P = 0.00062 and P = 0.024, respectively) and in multivariate analysis (P = 0.00057 and P = 0.0026, respectively). For favorable subgroups of patients age > or = 50 years or with negative resection margins, the 10-year risk of local failure was < or = 8%. CONCLUSIONS: The current results support the use of breast-conserving surgery followed by definitive breast irradiation for the treatment of patients with mammographically detected DCIS of the breast. Patient age > or = 50 years at the time of treatment and negative resection margins both were associated independently with a decreased risk of local failure.     

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.     

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。     

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.

Racial disparities in risk of second breast tumors after ductal carcinoma in situ

The purpose of the study was to examine the impact of race/ethnicity on second breast tumors among women with ductal carcinoma in situ (DCIS). We identified 102,489 women diagnosed with primary DCIS between 1988 and 2009 from the 18 NCI-SEER Registries. Cox proportional hazard regression was used to estimate race/ethnicity-associated relative risks (RRs) and their 95 % confidence intervals (CI) of ipsilateral breast tumors (IBT; defined as DCIS or invasive carcinoma in the ipsilateral breast) and contralateral breast tumors (CBT; defined as DCIS or invasive carcinoma in the contralateral breast). Overall, 2,925 women had IBT and 3,723 had CBT. Compared with white women, black (RR 1.46; 95 % CI 1.29–1.65), and Hispanic (RR 1.18; 95 % CI 1.03–1.36) women had higher IBT risk, which was similar for invasive IBT and ipsilateral DCIS. A significant increase in IBT risk among black women persisted, regardless of age at diagnosis, treatment, tumor grade, tumor size, and histology. The CBT risk was significantly increased among black (RR 1.21; 95 % CI 1.08–1.36) and Asian/PI (RR 1.16; 95 % CI 1.02–1.31) women compared with white women. The association was stronger for invasive CBT among black women and for contralateral DCIS among Asian/PI women (P _{heterogeneity} < 0.0001). The black race-associated CBT risk was more pronounced among women ≥50 years at diagnosis and those with comedo DCIS; in contrast, a significant increase in risk among Asian/PI women was restricted to those <50 years and those with noncomedo DCIS. Racial/ethnic differences in risks of second breast tumors after DCIS could not be explained by pathologic features and treatment.