Preoperative Delays in the Treatment of DCIS and the Associated Incidence of Invasive Breast Cancer

Abstract

Background. Although treatment delays have been associated with survival impairment for invasive breast cancer, this has not been thoroughly investigated for ductal carcinoma in situ (DCIS). With trials underway to assess whether DCIS can remain unresected, this study was performed to determine whether longer times to surgery are associated with survival impairment or increased invasion. Methods. A population-based study of prospectively collected national data derived from women with a clinical diagnosis of DCIS between 2004 and 2014 was conducted using the National Cancer Database. Overall survival (OS) and presence of invasion were assessed as functions of time by evaluating five intervals (B 30, 31-60, 61-90, 91-120, 121-365 days) between diagnosis and surgery. Subset analyses assessed those having pathologic DCIS versus invasive cancer on final pathology. Results. Among 140,615 clinical DCIS patients, 123,947 had pathologic diagnosis of DCIS and 16,668 had invasive ductal carcinoma. For all patients, 5-year OS was 95.8% and unadjusted median delay from diagnosis to surgery was 38 days. With each delay interval increase, added relative risk of death was 7.4% (HR 1.07; 95% CI 1.05-1.10; P \ 0.001). On final pathology, 5-year OS for noninvasive patients was 96.0% (95% CI 95.9-96.1%) versus 94.9% (95% CI 94.6-95.3%) for invasive patients. Increasing delay to surgery was an independent predictor of invasion (OR 1.13; 95% CI 1.11-1.15; P \ 0.001). Conclusions. Despite excellent OS for invasive and noninvasive cohorts, invasion was seen more frequently as delay increased. This suggests that DCIS trials evaluating nonoperative management, which represents infinite delay, require long term follow up to ensure outcomes are not compromised. Ductal carcinoma in situ (DCIS) is a premalignant lesion composed of malignant mammary ductal epithelial cells that have not yet invaded the basement membrane, whose standard interventions have included lumpectomy and radiotherapy or total mastectomy alone, followed by endocrine therapy. 1-5 Defined as American Joint Commission of Cancer (AJCC) Stage 0, patient outcomes following standard treatment are excellent, with 5-year survival typically [ 95%. 2,6-8 Recently, therapies for DCIS have been scrutinized, as current data suggest that \ 50% of afflicted patients will develop invasive cancer without treatment. 1,2,8 Additionally, although DCIS detection has increased over recent decades secondary to mammographic improvements, advanced stage distributions have not correspondingly declined, suggesting that screening may detect some DCIS that would remain subclinical. 2,4,9-13 Many have Dr. Ward is a military service member. This work was prepared as part of his official duties. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.

Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. the COVID-19 pandemic breast cancer consortium

“…The need to minimize use of operating room resources requires selectively deferring surgery and triaging patients for use of an initial alternative therapy whenever possible. However, level II evidence demonstrates that preoperative delays may impact BC outcomes [5,6].…”

Association Between Time to Operation and Pathologic Stage in Ductal Carcinoma in Situ and Early-Stage Hormone Receptor-Positive Breast Cancer

“…The anxiety of nonoperative management of DCIS stems from known sampling error on core biopsy with pathologic upstaging rates ranging from 10% to 30% at the time of operation. 2,12 Although nonoperative treatment of non-high-grade DCIS is being explored in randomized clinical trials in Europe and the US (eg LORD [Low Risk DCIS], 13 LORIS [Low Risk DCIS], 14 and COMET [Comparison of Operative to Monitoring and Endocrine Therapy for Low-Risk DCIS] trials), 15 these trials are enrolling highly selected patients and have yet to report their results. In addition, retrospective data have shown that in patients meeting LORIS criteria, upstage rates at the time of operation might be 7% to 20%.…”

“…Time to operation has been shown to be associated with increase in upstaging from DCIS to invasive disease on the order of 1% per month, but with excellent survival rates even in upstaged patients. 2 In invasive cancer patients, studies using nodal positivity as a surrogate outcomes measure have demonstrated mixed results. 3,4 In addition, survival analyses have similarly reported varied findings, leaving surgeons without a clear sense of the repercussions that can result from treatment delays.…”

Breast cancer care during a pandemic: an opportune time for cryoablation?

“…The management of ductal carcinoma in situ (DCIS) with cryoablation is in keeping with the overall trend to managing DCIS non-operatively, such as with endocrine therapy or surveillance alone in selected patients [10]. However, a recent analysis of the impact on pre-operative delays in patients with DCIS revealed a statistically significant (7.4%) increased relative risk of death for every 30-day interval increase, which shows the potential hazard of simply postponing the management of DCIS until after the pandemic (Priority C) [11]. Indirect evidence supporting the efficacy of cryoablation in the management of DCIS may be derived from studies revealing no residual invasive cancer or DCIS in tissue samples obtained from needle biopsies of cryoablated tumors.…”