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      Trends in Treatment Patterns and Outcomes for Ductal Carcinoma in Situ

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          Abstract

          Background:

          Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS).

          Methods:

          The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)–adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided.

          Results:

          One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%).

          Conclusions:

          We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.

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          Most cited references27

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          Adjusted survival curves with inverse probability weights.

          Kaplan-Meier survival curves and the associated nonparametric log rank test statistic are methods of choice for unadjusted survival analyses, while the semiparametric Cox proportional hazards regression model is used ubiquitously as a method for covariate adjustment. The Cox model extends naturally to include covariates, but there is no generally accepted method to graphically depict adjusted survival curves. The authors describe a method and provide a simple worked example using inverse probability weights (IPW) to create adjusted survival curves. When the weights are non-parametrically estimated, this method is equivalent to direct standardization of the survival curves to the combined study population.
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            Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update.

            To provide evidence-based recommendations to practicing oncologists, surgeons, and radiation therapy clinicians to update the 2005 clinical practice guideline on the use of sentinel node biopsy (SNB) for patients with early-stage breast cancer.
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              Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS.

              Ipsilateral breast tumor recurrence (IBTR) is the most common failure event after lumpectomy for ductal carcinoma in situ (DCIS). We evaluated invasive IBTR (I-IBTR) and its influence on survival among participants in two National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized trials for DCIS. In the NSABP B-17 trial (accrual period: October 1, 1985, to December 31, 1990), patients with localized DCIS were randomly assigned to the lumpectomy only (LO, n = 403) group or to the lumpectomy followed by radiotherapy (LRT, n = 410) group. In the NSABP B-24 double-blinded, placebo-controlled trial (accrual period: May 9, 1991, to April 13, 1994), all accrued patients were randomly assigned to LRT+ placebo, (n=900) or LRT + tamoxifen (LRT + TAM, n = 899). Endpoints included I-IBTR, DCIS-IBTR, contralateral breast cancers (CBC), overall and breast cancer-specific survival, and survival after I-IBTR. Median follow-up was 207 months for the B-17 trial (N = 813 patients) and 163 months for the B-24 trial (N = 1799 patients). Of 490 IBTR events, 263 (53.7%) were invasive. Radiation reduced I-IBTR by 52% in the LRT group compared with LO (B-17, hazard ratio [HR] of risk of I-IBTR = 0.48, 95% confidence interval [CI] = 0.33 to 0.69, P < .001). LRT + TAM reduced I-IBTR by 32% compared with LRT + placebo (B-24, HR of risk of I-IBTR = 0.68, 95% CI = 0.49 to 0.95, P = .025). The 15-year cumulative incidence of I-IBTR was 19.4% for LO, 8.9% for LRT (B-17), 10.0% for LRT + placebo (B-24), and 8.5% for LRT + TAM. The 15-year cumulative incidence of all contralateral breast cancers was 10.3% for LO, 10.2% for LRT (B-17), 10.8% for LRT + placebo (B-24), and 7.3% for LRT + TAM. I-IBTR was associated with increased mortality risk (HR of death = 1.75, 95% CI = 1.45 to 2.96, P < .001), whereas recurrence of DCIS was not. Twenty-two of 39 deaths after I-IBTR were attributed to breast cancer. Among all patients (with or without I-IBTR), the 15-year cumulative incidence of breast cancer death was 3.1% for LO, 4.7% for LRT (B-17), 2.7% for LRT + placebo (B-24), and 2.3% for LRT + TAM. Although I-IBTR increased the risk for breast cancer-related death, radiation therapy and tamoxifen reduced I-IBTR, and long-term prognosis remained excellent after breast-conserving surgery for DCIS.
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                Author and article information

                Journal
                J Natl Cancer Inst
                J. Natl. Cancer Inst
                jnci
                jnci
                JNCI Journal of the National Cancer Institute
                Oxford University Press (US )
                0027-8874
                1460-2105
                December 2015
                30 September 2015
                : 107
                : 12
                : djv263
                Affiliations
                Affiliations of authors: Division of Advanced Oncologic and GI Surgery, Department of Surgery , (MW, RG, DS, ESH), Center for Population Health and Aging (IA), Department of Obstetrics and Gynecology (ERM), and Department of Mathematics (MDR), Duke University Medical Center , Durham NC;
                Department of Visceral Surgery and Medicine, Inselspital, Berne University Hospital and University of Berne , Berne, Switzerland (MW).
                Author notes
                Correspondence to: E. Shelley Hwang, MD, MPH, Chief of Breast Surgery, Duke University Medical Center, Department of Surgery, Division of Surgical Oncology, Durham, NC (e-mail: shelley.hwang@ 123456duke.edu ).
                Article
                PMC4707192 PMC4707192 4707192
                10.1093/jnci/djv263
                4707192
                26424776
                df8b41dc-d57b-48f5-9c23-d66dcbdefcaa
                © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
                History
                : 30 September 2014
                : 12 February 2015
                : 25 August 2015
                Page count
                Pages: 10
                Categories
                Article

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