A third key insight is that aggressive treatment (radiation therapy after lumpectomy) of almost all DCIS does not lead to a reduction in breast cancer mortality (eFigure 7 in the Supplement of Narod et al4), confirming the conclusions from the analysis of the NSABP trials.8 Worse, there may be a slight increase in mortality with radiation therapy, especially if the disease is on the left side.9 We can test alternatives, either no radiation therapy or intraoperative radiation therapy,10 and reserve external-beam radiation therapy largely for breast conservation if invasive cancer occurs.

Numerous studies have demonstrated that the type of DCIS is predictive of the type of invasive cancer that develops. Some DCIS detected may be the precursor of luminal and ultralow–risk invasive cancer in which there is only a small but very late mortality risk.11 Many of these invasive lesions do not require radiation therapy in postmenopausal patients with invasive cancer.12 It should not be a surprise that there is no mortality benefit of radiation therapy in patients with noninvasive cancer.

A fourth insight is bilateral risk over the long term. We have always assumed that DCIS meant a higher local risk—but the similarity of the ipsilateral and contralateral invasive breast cancer risk (5.9% and 6.2%) in this study suggests that we need to think about DCIS as if it were a risk factor like atypia. A unilateral recurrence of DCIS or contralateral DCIS event has no impact on mortality, but an invasive cancer does — 18-fold for unilateral and 13-fold for contralateral — suggesting that all risk depends on whether you get an invasive cancer.

Ductal carcinoma in situ may best represent an opportunity to alter the environment of the breast. For the lowest-risk lesions, observation and prevention interventions alone should be tested. Diet, exercise, moderate alcohol intake, and avoidance of postmenopausal hormone therapy with progesterone-containing regimens should be the starting point for prevention. We should think about ways to better characterize the biology of the DCIS lesions, using available tools such as Oncotype DCIS, which demonstrate that low-risk lesions simply excised appear to carry the risk equivalent to a Gail risk of 2.5.13 For premenopausal women, tamoxifen therapy is a good choice for hormone-positive DCIS. For postmenopausal women, aromatase inhibitor therapy has been shown to have a bigger impact on risk reduction.14 Raloxifene hydrochloride is a better-tolerated prevention alternative. Adverse effects of endocrine risk–reducing agents can be a problem. Different doses and schedules should be investigated to mitigate adverse effects, improve tolerability, and avoid serious complications.15

High-risk lesions (eg, HER2 positive, patient age <40 years, hormone receptor negative, large size) are lesions that should still be aggressively treated, but the analysis of Narod et al4 suggests that our current approach of surgical removal and radiation therapy may not suffice for the rare cases that lead to breast cancer mortality and thus new approaches are needed. In a study characterizing the immune microenvironment of high-risk lesions most likely to recur, we found that the tumor microenvironment associated with recurrence was replete with activated macrophages, and a paucity of activated T cells.11 On the basis of these data, we will be starting studies to determine whether we can activate the immune system and reverse these lesions, with a more targeted approach to address the specific mortality risk.

Narod and colleagues4 have assembled an impressive analysis on the basis of SEER data. There are limitations of SEER, but the large numbers and long-term follow-up provide a compelling case that it is time for change. The community of radiologists and surgeons needs to be part of the call for change. Given the low breast cancer mortality risk, we should stop telling women that DCIS is an emergency and that they should schedule definitive surgery within 2 weeks of diagnosis. The sum total of the data on DCIS to date now suggest that:

 Much of DCIS should be considered a "risk factor" for invasive breast cancer and an opportunity for targeted prevention.

1. Radiation therapy should not be routinely offered after lumpectomy for DCIS lesions that are not high risk because it does not affect mortality.

2. Low- and intermediate-grade DCIS does not need to be a target for screening or early detection.

3. We should continue to better understand the biological characteristics of the highest-risk DCIS (large, high grade, hormone receptor negative, HER2 positive, especially in very young and African American women) and test targeted approaches to reduce death from breast cancer.

• Questions remain — but there is room to innovate. If we want the future to be better for women with DCIS, we have to be committed to testing new approaches to care.

  Corresponding Author: Laura Esserman, MD, MBA, UCSF, Mt Zion Carol Franc Buck Breast Care Center, 1600 Divisadero St, Second Floor, San Francisco, CA 94115 (laura.esserman@ucsf.edu). Published Online: August 20, 2015. doi:10.1001/jamaoncol.2015.2607.