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.     

Prognostic Significance of Clinicopathologic Features in Patients With Breast Ductal Carcinoma-in-Situ Who Received Breast-Conserving Surgery

Purpose

To identify whether a certain group of breast ductal carcinoma-in-situ (DCIS) patients can be treated with breast-conserving surgery (BCS) alone; to analyze the clinicopathologic features of DCIS and tamoxifen administration in patients treated with BCS who developed ipsilateral breast tumor recurrence (IBTR).

Concurrent lobular neoplasia increases the risk of ipsilateral breast cancer recurrence in patients with ductal carcinoma in situ treated with breast‐conserving therapy

BACKGROUND:

Multiple clinicopathologic factors have been analyzed for their association with an increased risk of ipsilateral breast tumor recurrence (IBTR) after women receive breast‐conserving treatment (BCT) for ductal carcinoma in situ (DCIS). The reported incidence of proliferative lesions, such as atypical ductal hyperplasia (ADH), columnar cell changes (CCC), and lobular neoplasia associated with breast cancer, has been as high as 23%; however, the relevance of these lesions on the natural history of DCIS and the risk of IBTR remains unknown.

METHODS:

Two hundred ninety‐four patients with DCIS who received BCT between 1991 and 1995 were identified from the authors' institutional database. Slides were reviewed by a dedicated breast pathologist with particular attention to the presence of lobular neoplasia, ADH, and CCC. The actuarial 5‐, 10‐, and 15‐year IBTR rates were calculated using the Kaplan‐Meier method and were compared using the log‐rank test.

RESULTS:

Concurrent lobular neoplasia was present in 41 of 294 patients (14%), ADH was present in 37 of 294 patients (13%), and CCC was present in 71 of 294 patients (24%). The median follow‐up was 11 years. IBTR occurred in 40 of 227 patients without lobular neoplasia (18%) versus 15 of 41 patients with lobular neoplasia (37%; P=.005; hazard ratio [HR], 2.49). The 5‐, 10‐, and 15‐year cumulative incidence rates of IBTR were twice as high in women who had DCIS and lobular neoplasia compared with women who had DCIS alone (P=.002). Concomitant ADH (HR, 1.53) and CCC (HR, 1.24) were not associated significantly with IBTR (P=.20 and P=.44, respectively).

CONCLUSIONS:

Concurrent lobular neoplasia is associated with a significantly higher risk of IBTR in women with DCIS who received BCT. Women with coexisting DCIS and lobular neoplasia who receive BCT should consider using additional risk‐reducing strategies. Cancer 2009. © 2009 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.     

Ipsilateral breast tumor recurrence (IBTR) in patients with operable breast cancer who undergo breast-conserving treatment after receiving neoadjuvant chemotherapy: Risk factors of IBTR and validation of the MD Anderson Prognostic Index

BACKGROUND:

There is limited information about the risk factors for ipsilateral breast tumor recurrence (IBTR) after patients undergo breast‐conserving surgery plus radiotherapy (breast‐conserving treatment [BCT]) subsequent to neoadjuvant chemotherapy (NAC). The objective of the current study was to analyze these risk factors.

METHODS:

The authors collected data from 375 patients who underwent BCT and received NAC and analyzed the risk of IBTR associated with undergoing BCT after NAC. The usefulness of the MD Anderson Prognostic Index (MDAPI) for IBTR also was validated using the current data set.

RESULTS:

The median follow‐up was 47.8 months, and the 4‐year IBTR‐free survival rate was 95.6%. Multivariate analysis demonstrated that estrogen receptor (ER) status and multifocality of the residual tumor were associated significantly with IBTR‐free survival. In addition, patients who had ER‐positive and human epidermal growth factor 2 (HER2)‐negative tumors did not develop IBTR during the observation period. Although prognostic stratification according to MDAPI was relatively good for the prediction of IBTR in the study patients, the IBTR rate in the high‐risk group was not very high and was lower than that in the intermediate‐risk group. Multivariate analyses demonstrated that IBTR was an independent predictive factor for overall survival.

CONCLUSIONS:

ER status and multifocality of the residual tumor after NAC were independent predictors of IBTR after BCT. The MDAPI was barely adaptable to the study patients in terms of predicting IBTR. Patients with ER‐positive and HER2‐negative tumors had a favorable prognosis, whereas patients who developed IBTR after NAC had significantly worse overall survival. The authors propose a new IBTR prognostic index using the 2 factors that were identified as predictive of IBTR: ER status and multifocality of the residual tumor. Cancer 2012. © 2012 American Cancer Society.     

Defining an optimal role for breast magnetic resonance imaging when evaluating patients otherwise eligible for accelerated partial breast irradiation

Background and purpose

Pre-treatment breast magnetic resonance imaging (MRI) findings in a cohort of women prospectively evaluated for accelerated partial breast irradiation (APBI) are reviewed and characterized to determine the optimal use of MRI in these patients.

Materials and methods

Candidates initially deemed eligible for a prospective APBI trial based on physical examination, mammography, and ultrasound (US) were further evaluated with breast MRI before treatment. All abnormal MRI findings were biopsied.

Results

Between 2002 and 2011, 180 women who met inclusion criteria for APBI underwent breast MRI prior to treatment (median age = 59; range 38–86). 126 tumors (70%) were invasive carcinomas with or without associated DCIS, while 54 (30%) were pure DCIS. Breast MRI confirmed unifocal disease in 109 patients with 111 cancers (60.5% of MRI cohort). Multifocal disease was identified in 19 patients (10.5% of MRI cohort), while multicentric disease was present in 3 patients (1.6% of MRI cohort). Five patients (4%) had an MRI-detected contralateral cancer. False positive MRI findings were seen in 45 patients (25% of MRI cohort). Pre-menopausal patients and patients with tumors >2 cm were more likely to have MRI-detected multifocal/multicentric disease. While there was no statistically significant correlation between multifocal/multicentric disease and breast density, tumor histology, grade, ER status, or Her2/Neu expression, numbers in each category were small, suggesting a lack of statistical power to detect differences that may be clinically meaningful. One hundred and fifty-two of the 180 patients (84.4%) successfully completed lumpectomy and APBI, while 6.7% of the cohort underwent mastectomy.

Conclusions

Breast MRI identified additional disease in 12% of APBI candidates. Premenopausal women and patients with tumors >2 cm were more likely to have MRI-detected multifocal/multicentric disease.     

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.     

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.     

Clinicopathologic factors of the recurrent tumor predict outcome in patients with ipsilateral breast tumor recurrence

BACKGROUND:

The role of clinicopathologic characteristics of the recurrent tumor in determining survival in a cohort of patients with ipsilateral breast tumor recurrence (IBTR) was investigated.

METHODS:

Among 6020 women with pT1‐T2, pN0‐1, M0 treated with breast‐conserving surgery from 1989 to 1999, 269 developed isolated IBTR. Ten‐year Kaplan‐Meier breast cancer‐specific survival (BCSS) and overall survival (OS), calculated from date of IBTR, were analyzed according to clinicopathologic characteristics.

RESULTS:

Factors that were associated with diminished OS and BCSS on univariate analysis were: time to IBTR ≤48 months, lymphovascular invasion positive status, estrogen receptor (ER) negative status, high grade, clinical IBTR detection, biopsy alone, and close/positive margins (all P < .05). On multivariate analysis, time to IBTR ≤48 months (hazard ratio [HR], 1.87, P = .012), lymphovascular invasion positive status (HR, 2.46; P < .001), ER negative status (HR, 2.08; P = .013), high‐grade recurrent disease (HR, 1.88; P = .013), and close/positive margins after surgery for IBTR (HR, 1.94; P = .013) retained significance for prediction of diminished OS. When stratified according to number of adverse prognostic features, 10‐year OS was 70.4% in patients with 1 factor, 35.8% with 2 factors, and 19.9% with 3 or more factors (P < .001).

CONCLUSIONS:

Time to recurrence ≤48 months, lymphovascular invasion positive status, ER negative status, high‐grade histology, and close/positive margins in association with the recurrent tumor are independent prognostic factors for survival after IBTR. The presence of 2 or more of these features at recurrence is significantly associated with poor OS. These criteria can be used to prognosticate and guide clinical decisions after recurrence. Cancer 2011. © 2010 American Cancer Society.     

Breast conservation for ductal carcinoma in situ: Results at an Australian institution with evidence to recommend prospective assessment of the utility of a lumpectomy boost

Aim: We reviewed outcomes for ductal carcinoma in situ (DCIS) of the breast at our institution to assess risk factors for ipsilateral breast tumour recurrence (IBTR) after breast conservation (BCT). Methods: Records were reviewed of all patients who presented with biopsy‐confirmed DCIS of the breast prior to 1 January 2004. Variables analyzed included patient age, tumour size, grade, resection margins, comedonecrosis, surgery, tamoxifen, whole breast radiotherapy dose and addition of a boost. We also attempted to validate the University of Southern California/Van Nuys prognostic index (USC/VNPI). Results: One hundred and thirty patients had DCIS: four were excluded from analysis and another 10 had mastectomies. A total of 116 patients had BCT and this group comprised the study population. Median follow‐up was 7.7 years (1.6–12.4) and median age was 58 years. Five‐ and 10‐year overall survivals were 98% (93.5–99.6 95% CI) and 89% (74–95 95% CI). Five‐ and 10‐year breast failure‐free survivals were 96% (90–98 95% CI) and 93% (85–97 95% CI). Young age was the only significant factor associated with IBTR (P = 0.018). Patients with a high USC/VNPI score were also significant for increased IBTR (P = 0.04), but this effect disappeared when age was omitted from the index. There was a trend towards an increased risk of IBTR with a lower whole breast dose of less than 50 Gy (P = 0.18). A boost was not associated with reduced IBTR. The 10‐year IBTR for patients under 55 who received adjuvant radiotherapy to a whole breast dose of <50 Gy but no tamoxifen was 25%. Conclusion: Overall BCT local control and survival outcomes are excellent. There is a suggestion that younger patients should be treated with a whole breast dose equivalent to 50 Gy in 25 daily fractions regardless of a boost. However, this requires confirmation in a randomized phase III trial and therefore the currently active Trans‐Tasman Radiation Oncology Group randomized controlled trial 07.01 should be supported by the breast cancer treating community.     

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.

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.     

Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes

Purpose

Better tools are needed to estimate local recurrence (LR) risk after breast-conserving surgery (BCS) for DCIS. The DCIS score (DS) was validated as a predictor of LR in E5194 and Ontario DCIS cohort (ODC) after BCS. We combined data from E5194 and ODC adjusting for clinicopathological factors to provide refined estimates of the 10-year risk of LR after treatment by BCS alone.

Methods

Data from E5194 and ODC were combined. Patients with positive margins or multifocality were excluded. Identical Cox regression models were fit for each study. Patient-specific meta-analysis was used to calculate precision-weighted estimates of 10-year LR risk by DS, age, tumor size and year of diagnosis.

Results

The combined cohort includes 773 patients. The DS and age at diagnosis, tumor size and year of diagnosis provided independent prognostic information on the 10-year LR risk (p ≤ 0.009). Hazard ratios from E5194 and ODC cohorts were similar for the DS (2.48, 1.95 per 50 units), tumor size ≤ 1 versus  > 1–2.5 cm (1.45, 1.47), age ≥ 50 versus < 50 year (0.61, 0.84) and year ≥ 2000 (0.67, 0.49). Utilization of DS combined with tumor size and age at diagnosis predicted more women with very low (≤ 8%) or higher (> 15%) 10-year LR risk after BCS alone compared to utilization of DS alone or clinicopathological factors alone.

Conclusions

The combined analysis provides refined estimates of 10-year LR risk after BCS for DCIS. Adding information on tumor size and age at diagnosis to the DS adjusting for year of diagnosis provides improved LR risk estimates to guide treatment decision making.

     

Preoperative breast magnetic resonance imaging in early breast cancer

BACKGROUND:

Accelerated partial breast irradiation (APBI) of patients with early breast cancer is being investigated on a multi‐institutional protocol National Surgical Adjuvant Breast and Bowel Project (NSABP) B‐39/RTOG 0413. Breast magnetic resonance imaging (MRI) is more sensitive than mammography (MG) and may aid in selection of patients appropriate for PBI.

METHODS:

Patients with newly diagnosed breast cancer or ductal carcinoma in situ (DCIS) routinely undergo contrast‐enhanced, bilateral breast MRI at the Cleveland Clinic. We retrospectively reviewed the medical records of all early‐stage breast cancer patients who had a breast MRI, MG, and surgical pathology data at our institution between June of 2005 and December of 2006. Any suspicious lesions identified on MRI were further evaluated by targeted ultrasound ± biopsy.

RESULTS:

A total of 260 patients met eligibility criteria for NSABP B‐39/RTOG 0413 by MG, physical exam, and surgical pathology. The median age was 57 years. DCIS was present in 63 patients, and invasive breast cancer was found in 197 patients. MRI identified suspicious lesions in 35 ipsilateral breasts (13%) and in 16 contralateral breasts (6%). Mammographically occult, synchronous ipsilateral foci were found by MRI in 11 patients (4.2%), and in the contralateral breast in 4 patients (1.5%). By univariate analysis, lobular histology (infiltrating lobular carcinoma [ILC]), pathologic T2, and American Joint Committee on Cancer stage II were significantly associated with additional ipsilateral disease. Of patients with ILC histology, 18% had ipsilateral secondary cancers or DCIS, compared with 3% in the remainder of histologic subtypes (P = .004). No patient older than 70 years had synchronous cancers or DCIS detected by MRI.

CONCLUSIONS:

Breast MRI identified synchronous mammographically occult foci in 5.8% of early breast cancer patients who would otherwise be candidates for APBI. Cancer 2009. © 2009 American Cancer Society.     

Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery

Purpose

A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions.

Methods

Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC).

Results

Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5–12%), 23% (95% CI 13–32%), and 51% (95% CI 26–75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well.

Conclusions

This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.

     

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.     

Clinicopathological predictive factors for ipsilateral and contralateral events following initial surgery to treat ductal carcinoma in situ

Background

Ipsilateral breast tumor recurrence (IBTR) after partial breast resection and contralateral breast tumor recurrence (CBTR) have been shown to occur relatively frequently in patients with ductal carcinoma in situ (DCIS). However, there is only limited data from Japanese institutes to support this.

Methods

Of 301 consecutive DCIS patients, 179 patients underwent a mastectomy, and the other 122 underwent partial resection in the National Cancer Center Hospital, Tokyo, with a median follow-up period of 2,106 days. We reviewed clinicopathological parameters including age, menopausal status, body mass index, family history (FH) of breast cancer, tumor size, histological subtype, nuclear grade (NG), hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, treatment, and the surgical margin status of partially resected specimens. The risk associated with each of these parameters for IBTR in 122 patients who underwent partial resections, and for CBTR in a total of 301 patients were calculated using Cox proportional hazard general linear models.

Results

Of the 122 patients who underwent partial breast resection, IBTR occurred in 7 (5.7 %). The risk of IBTR was higher or tended to be higher in younger patients or those with lower NG tumors, but did not change significantly with respect to margin status or irradiation. Amongst the entire cohort of 301 patients, CBTR occurred in 18 cases (6.0 %). CBTR occurred significantly more frequently in patients with a FH of breast cancer and with HR+/HER2? subtype tumors by univariate analyses, and tumor subtype was an independent risk factor for CBTR by multivariate analysis.

Conclusions

The local recurrence rate was low following partial resection of DCIS. Younger age was a risk factor for IBTR, whereas the HR+/HER2? tumor subtype and a FH of breast cancer were risk factors for CBTR.

     

Repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery: the impact of radiotherapy on second IBTR

Objectives

There are limited data on the outcomes of patients treated with repeat lumpectomy at the time of ipsilateral breast tumor recurrence (IBTR). Especially, the impact of radiotherapy (RT) on a second IBTR is unknown.

Methods

We retrospectively analyzed 143 patients from 8 institutions in Japan who underwent repeat lumpectomy after IBTR. The risk factors of a second IBTR were assessed.

Results

The median follow-up period was 4.8 years. The 5-year second IBTR-free survival rate was 80.7 %. There was a significant difference in the second IBTR-free survival rate according to RT (p = 0.0003, log-rank test). The 5-year second IBTR-free survival rates for patients who received RT after initial surgery, RT after salvage surgery, and no RT were 78.0, 93.5, and 52.7 %, respectively. Multivariate analysis revealed that RT was a significantly independent predictive factor of second IBTR-free survival.

Conclusion

Repeat lumpectomy plus RT is a reasonable option in patients who did not undergo RT at the initial surgery. In contrast, caution is needed when RT is omitted in patients who have undergone repeat lumpectomy.     

Long-term Survival Comparison of Repeated Breast-conserving Surgery Versus Mastectomy for Patients with DCIS with Ipsilateral Breast Tumor Recurrence: A Real-world Longitudinal Study

BackgroundAlthough patients diagnosed with ductal carcinoma in situ (DCIS) harbor excellent overall survival (OS) after breast-conserving therapy, the evidence regarding to surgical management for ipsilateral breast tumor recurrence (IBTR) is scarce. This study aimed to assess the prognosis of repeated breast-conserving surgery (BCS) versus mastectomy for IBTR in DCIS survivors.Materials and MethodsHerein, 5344 DCIS cases with IBTR were identified during 702,748 person-years of follow-up, 3532 (66.09%) received mastectomy, and 1812 (33.91%) received repeated BCS. Cox regression and competing risk regression were employed to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and breast cancer–specific survival (BCSS), which was respectively calculated within spontaneous and matched cohorts.ResultsAfter adjustment for confounders, no statistically significant survival difference was observed between the repeated BCS and mastectomy for patients with DCIS with IBTR. The stratified analyses further revealed that patients with DCIS with IBTR receiving repeated BCS combined with radiation therapy were associated with both superior OS (HR, 0.79; CI, 0.64-0.98; P = .04) and BCSS (HR, 0.54; CI, 0.33-0.90; P = .02) compared with counterparts undergoing mastectomy. Furthermore, patients with DCIS who were age older than 60 years at IBTR diagnosis benefit from repeated BCS with radiotherapy (HR, 0.44; CI, 0.24-0.84; P = .01) than mastectomy.ConclusionWe suggest that repeated BCS with radiation therapy deserves consideration when DCIS survivors suffered IBTR. The choice of surgical management should be tailored based on patients’ age at IBTR diagnosis and size of recurrent disease.