Cancer Outcomes in DCIS Patients Without Locoregional Treatment

Marc D. Ryser; Donald L. Weaver; Fengmin Zhao; Mathias Worni; Lars J. Grimm; Roman Gulati; Ruth Etzioni; Terry Hyslop; Sandra J. Lee; E. Shelley Hwang

Disclosures

J Natl Cancer Inst. 2019;111(9):952-960. 

In This Article

Abstract and Introduction

Abstract

Background: The vast majority of women diagnosed with ductal carcinoma in situ (DCIS) undergo treatment. Therefore, the risks of invasive progression and competing death in the absence of locoregional therapy are uncertain.

Methods: We performed survival analyses of patient-level data from DCIS patients who did not receive definitive surgery or radiation therapy as recorded in the US National Cancer Institute's Surveillance, Epidemiology, and End Results program (1992–2014). Kaplan-Meier curves were used to estimate the net risk of subsequent ipsilateral invasive cancer. The cumulative incidences of ipsilateral invasive cancer, contralateral breast cancer, and death were estimated using competing risk methods.

Results: A total of 1286 DCIS patients who did not undergo locoregional therapy were identified. Median age at diagnosis was 60 years (inter-quartile range = 51–74 years), with median follow-up of 5.5 years (inter-quartile range = 2.3–10.6 years). Among patients with tumor grade I/II (n = 547), the 10-year net risk of ipsilateral invasive breast cancer was 12.2% (95% confidence interval [CI] = 8.6% to 17.1%) compared with 17.6% (95% CI = 12.1% to 25.2%) among patients with tumor grade III (n = 244) and 10.1% (95% CI = 7.4% to 13.8%) among patients with unknown grade (n = 495). Among all patients, the 10-year cumulative incidences of ipsilateral invasive cancer, contralateral breast cancer, and all-cause mortality were 10.5% (95% CI = 8.5% to 12.4%), 3.9% (95% CI = 2.6% to 5.2%), and 24.1% (95% CI = 21.2% to 26.9%), respectively.

Conclusion: Despite limited data, our findings suggest that DCIS patients without locoregional treatment have a limited risk of invasive progression. Although the cohort is not representative of the general population of patients diagnosed with DCIS, the findings suggest that there may be overtreatment, especially among older patients and patients with elevated comorbidities.

Introduction

The detection and clinical management of ductal carcinoma in situ (DCIS) poses a critical public health challenge. Each year, more than 50 000 women in the United States are diagnosed with DCIS,[1] and 98% of them undergo surgery in the form of a lumpectomy (with or without radiation therapy), mastectomy, or bilateral mastectomy.[2] There is concern that a clinically significant fraction of these women may be overtreated for indolent or slowly growing disease that would, in the absence of treatment, not develop into symptomatic or clinically significant breast cancer during their remaining lifetime.[3,4] Importantly, overtreated patients are at risk of experiencing treatment-associated harms—including pain and sensory disturbances, psychological distress, and radiation-induced malignancies—without any cancer-related benefits.[5,6]

To prevent potentially harmful overtreatment of DCIS, it is essential to identify well-defined subgroups of patients who are at minimal risk for progression to invasive breast cancer. The risk of breast cancer-specific mortality in the absence of locoregional treatment has been previously reported.[7] However, there are few available data on the risk of invasive progression of DCIS in the absence of definitive surgery and radiation with which to inform risk stratification.[8] To address this clinical question, three randomized clinical trials are currently enrolling low-risk patients to surgery or active surveillance, some of whom will undergo treatment with endocrine therapy.[9–11] The trials have slightly different definitions of "low-risk" DCIS,[12] yet all include criteria based on age at diagnosis and tumor pathology.

Because the progression dynamics of low-risk DCIS are expected to be slow, clinically actionable follow-up data from these trials will be available in 10 years at the earliest. In the meantime, it is important to summarize available evidence that could provide insights into the risk of progression to invasive disease. Despite the fact that observational data are subject to selection biases, they can inform plausible ranges of absolute risks, and they provide opportunity to estimate relative risks with respect to patient and tumor features.

In this study we extracted data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program[13] to characterize outcomes of DCIS patients in the absence of definitive surgery and radiation therapy. The aims of this study were to quantify the risks of ipsilateral invasive breast cancer, contralateral cancer, and competing death and to identify patient and tumor characteristics associated with these risks.

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