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The Association of Surgical Margins and Local Recurrence in Women with Ductal Carcinoma In Situ Treated with Breast-Conserving Therapy: A Meta-Analysis.

ABSTRACT: There is no consensus on adequate negative margins in breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We systematically reviewed the evidence on margins in BCS for DCIS.A study-level meta-analysis of local recurrence (LR), microscopic margin status and threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression (frequentist) and network meta-analysis (Bayesian) that allows for multiple margin distances per study, adjusting for follow-up time.Based on 20 studies (LR: 865 of 7883), odds of LR were associated with margin status [logistic: odds ratio (OR) 0.53 for negative vs. positive/close (p < 0.001); network: OR 0.45 for negative vs. positive]. In logistic meta-regression, relative to >0 or 1 mm, ORs for 2 mm (0.51), 3 or 5 mm (0.42) and 10 mm (0.60) showed comparable significant reductions in the odds of LR. In the network analysis, ORs relative to positive margins for 2 (0.32), 3 (0.30) and 10 mm (0.32) showed similar reductions in the odds of LR that were greater than for >0 or 1 mm (0.45). There was weak evidence of lower odds at 2 mm compared with >0 or 1 mm [relative OR (ROR) 0.72, 95 % credible interval (CrI) 0.47-1.08], and no evidence of a difference between 2 and 10 mm (ROR 0.99, 95 % CrI 0.61-1.64). Adjustment for covariates, and analyses based only on studies using whole-breast radiotherapy, did not change the findings.Negative margins in BCS for DCIS reduce the odds of LR; however, minimum margin distances above 2 mm are not significantly associated with further reduced odds of LR in women receiving radiation.

SUBMITTER: Marinovich ML

PROVIDER: S-EPMC5160992 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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The Association of Surgical Margins and Local Recurrence in Women with Ductal Carcinoma In Situ Treated with Breast-Conserving Therapy: A Meta-Analysis.

Marinovich M Luke ML Azizi Lamiae L Macaskill Petra P Irwig Les L Morrow Monica M Solin Lawrence J LJ Houssami Nehmat N

Annals of surgical oncology 20160815 12

<h4>Purpose</h4>There is no consensus on adequate negative margins in breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We systematically reviewed the evidence on margins in BCS for DCIS.<h4>Methods</h4>A study-level meta-analysis of local recurrence (LR), microscopic margin status and threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression (frequentist) and network meta-analysis (Bayesian) that allows for multiple margi ...[more]

PMID: 27527715

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Project description:BackgroundAge is a known risk factor for recurrence in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS). We explored the relationship between age, other risk factors, and recurrence.MethodsUsing a prospectively maintained database of DCIS patients undergoing BCS from 1978 to 2010, the association of age and recurrence risk was analyzed using Kaplan-Meier estimates, multivariable analysis, and competing risk multivariable analysis.ResultsOverall, 2996 cases were identified. Median follow-up for those without recurrence was 75 months; 732 were followed for ≥10 years, and 363 (12 %) had recurrence [192 (53 %) DCIS, 160 (44 %) invasive, 11 (3 %) unknown]. Risk of recurrence decreased with age, even after adjustment for eight clinicopathologic variables on multivariable analysis [hazard ratios (HR), with <40 years of age as the reference: 40-49 years, 0.82 (p = 0.36), 50-59 years, 0.46 (p = 0.0005), 60-69 years, 0.50 (p = 0.003), 70-79 years, 0.56 (p = 0.02), ≥80 years, 0.21 (p = 0.0015)]. This association persisted for cohorts with and without radiation therapy. Using competing risk multivariable analysis, the effect of age on invasive recurrence was empirically stronger than for DCIS recurrence. Ten-year invasive recurrence was 16 and 6.5 % in women <40 years of age and women ≥40 years of age, respectively. Only 0.6 % of the population ultimately developed distant disease; those <40 years of age constituted 4.7 % (141/2996) of the population, but 21 % (4/19) of those developed distant disease.ConclusionsThe risk of recurrence of DCIS decreases with age. This effect is particularly strong at the extremes of age and is independent of other clinicopathologic factors. The oldest women are at low risk of recurrence, while the youngest women have a higher overall, and especially invasive, recurrence rate, although mortality remains low. These findings should be incorporated into risk/benefit discussions of treatment options.

Project description:Purpose: We sought to explore the role of nomogram-combined biomarkers, mammographic microcalcification and inflammatory hematologic markers in guiding local therapy decisions in ductal carcinoma in situ (DCIS) subgroups with different ipsilateral breast tumour recurrence (IBTR) risk. Methods: Between January 2009 and December 2018, consecutive patients with DCIS and breast conserving surgery (BCS) were enrolled and randomly assigned to a training cohort (n = 181) and internally validation cohort (n = 78). Multivariate analyses were performed to identify predictors of IBTR. Model performance was evaluated by the concordance index (C-index) and calibration plot. The time-to-event curves were calculated by the Kaplan−Meier methods and compared by the log-rank test. Results: In total, 259 patients were enrolled and 182 of them received whole breast irradiation (WBI). After a median follow-up of 51.02 months, 23 IBTR events occurred in the whole cohort. By multivariate analyses of training cohort, presence of microinvasion, Ki67 index >14%, mammographic-clustered fine linear microcalcifications and neutrophil/lymphocyte ratio before BCS (preop-NLR), >1.1 remained independent risk factors of IBTR to develop a nomogram. The C-indexes of the nomogram were 0.87 and 0.86 in the training and internal validation set, respectively. Calibration plots illustrated good agreement between the predictions and actual observations for 5-year IBTR. Cut-off values of nomogram point were identified as 53 and 115 points, which divided all patients into low-, intermediate- and high-risk groups. Significant differences in IBTR existed between low-, intermediate- and high-risk subgroups (p < 0.01). For the whole cohort and ER-positive tumours, the benefit of WBI was found only in the intermediate-risk subgroup, but not in those with low or high risk. Fourteen out of 23 IBTRs occurred outside the original quadrant and all occurred in the high-risk group. Conclusions: The novel nomogram demonstrated potential to separate the risk of IBTR and locations of IBTR. For the whole cohort and ER-positive tumours, the benefit of WBI was restricted to an intermediate-risk subgroup.

Dataset Information

The Association of Surgical Margins and Local Recurrence in Women with Ductal Carcinoma In Situ Treated with Breast-Conserving Therapy: A Meta-Analysis.

Publications

The Association of Surgical Margins and Local Recurrence in Women with Ductal Carcinoma In Situ Treated with Breast-Conserving Therapy: A Meta-Analysis.

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