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Ductal carcinoma in situ (DCIS) has become a major driver of breast cancer overdiagnosis and overtreatment, in part because there are so many unanswered questions, noted the authors of a "Comments and Controversies" article in the

Treatment remains controversial, ranging widely from no surgery to total mastectomy, often with radiation and/or endocrine therapy, said Jean Wright, MD, of Johns Hopkins University in Baltimore, and co-authors, noting that a 2009 NIH recommended concerted efforts to decrease indolent DCIS diagnoses, unnecessary surgeries, and excessive adjuvant treatment.

"Yet, today, despite promising imaging and molecular assays to help optimize DCIS management, these patterns remain largely unchanged or perhaps more prevalent," Wright and colleagues wrote.

In the following interview, Wright, director of the Breast Cancer Program in the Department of Radiation Oncology and Molecular Radiation Sciences, discussed efforts to reduce unnecessary treatments and to answer outstanding questions about DCIS management.

To reduce unnecessary DCIS detection in lower-risk women, strategies to shift screening from population-based or age-based to risk-based approaches may be useful. Can you give us an example of one of these?

Wright: The idea behind risk-based screening is that not every patient needs the same intensity of screening. I think we all agree that women at the highest risk of breast cancer due to genetic mutations, such as BRCA 1 or 2 warrant aggressive screening, and detection of DCIS in those women is not overdiagnosis. But, what about those at much lower risk? Do we need to screen as often and find every early cancer? Probably not. If we can more precisely determine risk for all women, we might be able to tailor screening approaches so that overdiagnosis of DCIS does not occur in women at lower risk.

An example of a risk-based screening strategy is one that is being investigated in the trial. This is a very large study that will include over 65,000 women and compare the traditional age-based approach of annual screening mammograms starting at age 40, versus a tailored approach that will depend on a patient's specific risk for breast cancer.

The individual's risk is calculated based on breast density, genetic testing, and family history, among other factors. Depending on these factors, in the risk-based group screening recommendations will vary from mammogram every other year starting at age 50 for the lowest risk, to annual mammogram plus breast MRI for the highest-risk patients.

This study will determine if the risk-based approach is equally effective in detecting cancers compared with the age-based approach.

One outstanding question is about the need to immediately surgically excise DCIS. How is this question being investigated?

Wright: There are several ongoing studies that we describe in our commentary that investigate whether surgery can be safely avoided in some patients who are diagnosed with DCIS, an approach that is referred to as active surveillance. This approach is based on the observation that not all DCIS cases will progress to an invasive cancer, and the goal is to identify which kinds of DCIS have a low enough risk of progression that they do not need to be removed immediately.

While the studies differ in their details, they generally closely follow patients who have a biopsy showing DCIS, either with no therapy or with hormone therapy. If there is evidence that the DCIS progresses, then treatment can be started then, without reducing long-term cure rates. This approach might allow some women to avoid, or at a minimum delay, the need for treatment.

Perhaps the most prominent one that is still ongoing and has the most success in accruing patients is the trial -- likely due to having the least restrictive eligibility requirements. This study is nearing its target enrollment and will provide unique insight on the feasibility of avoiding surgery in some women, the natural history of DCIS that is not treated with surgery, and factors that predict risk of progression to invasive disease.

Investigators are also trying to determine which women with DCIS can safely avoid radiation therapy. What is the status of that research?

Wright: An overwhelming number of women who undergo lumpectomy after a DCIS diagnosis undergo radiation therapy to reduce the risk of recurrence. It should be noted that this approach has not been shown to reduce chances of death from breast cancer. As a result, several trials of omission of radiation therapy for DCIS that is considered low-risk based on clinical and pathology features have been performed. Unfortunately, these trials have not shown clear groups of patients who will have recurrence rates that are similar to those women who do receive radiation therapy.

Most recently, the 15-year results of a study called were published. This study compared the risk of an in-breast recurrence of either DCIS or invasive breast cancer for patients with low-risk DCIS features who underwent breast surgery, with or without radiation. Fifteen years after their diagnosis, women who did not have radiation had about a 15% risk of recurrence, while those who did have radiation had a risk of about 7%. At the same time as the risk of recurrence in the breast was improved with the radiation, the long-term cure rate for DCIS is not improved with radiation, because recurrences can generally be effectively treated.

The authors of that study recommend a shared decision-making process to determine if a specific patient should proceed with radiation treatment. This highlights the need to better understand patients' concerns and values; each patient will have a unique perspective on their desire to avoid recurrences, even treatable ones, versus their concerns about the side effects of radiation.

The studies also highlight the lack of quality markers to predict which DCIS lesions can forgo radiation therapy. Recent development of commercially available molecular tests, such as Oncotype DX DCIS Score and DCISionRT, have shown promise to improve this risk assessment, but no prospective randomized clinical trials have been conducted testing their benefit.

In addition, emerging fields of radiomics and pathomics may provide additional tools by which DCIS risk may be stratified. We believe that evaluation of how molecular and novel assays can be integrated into clinical decision-making should be a major focus of trials going forward.

How can quality-of-life metrics be used to tailor DCIS treatment decisions for patients?

Wright: There are multiple questionnaires that are available that assess patient-reported outcomes. These questionnaires shift the evaluation of the benefit of a treatment from a physician-oriented assessment to a patient-oriented assessment. As we learn more about patient experiences, ranging from living with a fear of recurrence, to living with the sometimes negative quality-of-life impact of treatments, we can learn how to account for a patient's priorities in the "shared decision" process.

When treatments are not life-saving, as is generally the case for DCIS, it becomes all the more important to understand patient preferences in defining the optimal treatment approach.

How can future studies be improved to better inform DCIS management?

Wright: Just from the questions you have asked above, it is clear that there is still so much to learn about DCIS. In our commentary, we laid out what we believe are the key research questions to better inform DCIS management. In addition to improving risk assessments to tailor screening so we can find less DCIS in low-risk women, identifying women with DCIS who can avoid surgery safely, and determining whether some women with DCIS can forgo radiation therapy, there are several other important areas that require additional research.

For example, one important imaging question is whether an MRI used to guide surgery for DCIS will improve surgical outcomes, such as reducing the need for a second surgery, or "re-excision," which is more common in DCIS than in invasive cancers. There is also a need to learn more about disparities in DCIS outcomes by racial, ethnic, and other groups, and to learn what we can do to reduce these disparities.

All of these questions can or already are being evaluated by researchers across the country and the world, and we expect to know a lot more about how to optimally manage DCIS in a tailored, patient-centric way over the upcoming decade. Along with my co-authors of this review, we are actively working on developing a trial within that will help answer these important questions to move the needle in how we diagnose and manage DCIS.

Read the study here.