Ductal carcinoma in situ has been a recent topic of debate in the news because of a recent article by Narod et al1 and an accompanying editorial2 about the study in JAMA Oncology. This study, summarized in this issue of The ASCO Post, chronicled the long-term outcomes for women diagnosed with ductal carcinoma in situ.
The article reinforces what we have come to understand about ductal carcinoma in situ—that by itself, it is not lethal but rather a risk factor for developing breast cancer. Ductal carcinoma in situ, like invasive breast cancer, comes in many forms, so treatment on a one-size-fits-all basis does not work. A very small fraction of ductal carcinoma in situ cases carry more risk than we thought, including the chance of metastatic disease without a recurrence in the breast. Those cases are rare, however, and relatively easy to identify. The vast majority of cases appear to have less risk than we thought, which is good news for women with this type of breast cancer and opens the door to new approaches.
What We Have Learned
We learned from this study that over a long period, ductal carcinoma in situ confers a risk for bilateral cancer. This means ductal carcinoma in situ is much like other risk factors that we do not consider cancer—such as lobular carcinoma in situ or atypia. This bilateral risk finding is what reinforces the concept that ductal carcinoma in situ should be considered more of a risk factor than an indicator for targeted intervention.
One of the reasons it is so challenging to differentiate low-grade ductal carcinoma in situ from atypia is that they likely reflect the same or similar biology. This should propel us to think about ductal carcinoma in situ as an opportunity to institute a preventive strategy, to test these cases, and to find additional biomarkers that might indicate responsiveness to interventions.
How We Should Proceed
Several suggestions for how to proceed were presented in the JAMA Oncology editorial2 and appear here:
- Much of ductal carcinoma in situ should be considered a “risk factor” for invasive breast cancer and an opportunity for targeted prevention.
- Radiation therapy should not be routinely offered after lumpectomy for ductal carcinoma in situ lesions that are not high risk, since it does not impact mortality.
- Low- and intermediate-grade ductal carcinoma in situ do not need to be a target for screening and early detection.
- We should continue to improve our understanding of the biology of the highest-risk ductal carcinoma in situ (large, high-grade, hormone receptor-negative, HER2-positive disease, especially in very young and African American women) and test targeted approaches to reduce death from breast cancer.
Where the Challenges Lie
We think the most challenging areas will be the following two specific recommendations: (1) to abandon the use of radiation therapy as a standard practice and (2) to avoid screening patients with low-grade ductal carcinoma in situ.
First, we know that radiation decreases the “local” recurrence risk of both ductal carcinoma in situ and invasive cancer. However, the goal should be to avoid invasive cancer. The impact of radiation in reducing the chance of invasive cancer for a low-grade lesion is < 10%, and there is no impact on mortality. Additionally, if a person develops cancer, previous radiation therapy may preclude lumpectomy as a choice and may reduce the chance of a successful or straightforward reconstruction strategy. There is now an increasing amount of evidence that radiation therapy should not be offered as standard treatment for ductal carcinoma in situ and should only be considered for use in high-risk cases.
Second, we should not be recommending biopsies for amorphous calcifications that are unlikely to be cancer and, if anything, are likely to be low- or intermediate-grade ductal carcinoma in situ. There does not appear to be any good reason to know this early on. This approach would help us to avoid the many false-positive biopsies and take away the angst associated with a diagnosis of low-grade ductal carcinoma in situ and the difficult choices that follow for these women.
A recent article suggested that we spend $4 billion in the evaluation of mammographic findings that turn out to be benign.3 These data should provide comfort to the imaging community; there is no urgency to know about low-grade ductal carcinoma in situ. Over time, if tiny amorphous calcifications continue to evolve and become more suspicious, a biopsy can be recommended. This is reminiscent of how we used to worry that tiny lung nodules represented metastatic cancer. Now we ignore the ones we see on chest computed tomography scans.
So giving radiologists permission to avoid ordering or recommending a biopsy for these very low-risk lesions would improve the experience and outcome of screening. Together, as a community, we should establish better targets for screening.
Let’s Not Call It Cancer
The majority of ductal carcinoma in situ is not likely to be associated with a future cancer. Over the past 20 years, we have surgically treated approximately 1 million patients with ductal carcinoma in situ, so-called stage 0. However, we have not seen a big drop in the rate of invasive cancers, as we should have if most ductal carcinoma in situ is a precursor to cancer. Instead, the incidence of breast cancer has continued to increase, in contrast to what we have seen with the removal of colon polyps and cervical intralesional neoplasia and the lowering of the rates of colon cancer and cervical cancer, respectively.
The numbers for “stage 0 cancer” do not add up. The word carcinoma is not warranted for these conditions (with the exception of the highest-risk lesions). Clearly, the majority of these lesions are IDLE (indolent lesions of epithelial origin). We should push to change the terminology for the vast majority of the ductal carcinoma in situ lesions we diagnose. Ductal carcinoma in situ should not be called cancer. We need to acknowledge the uncertainty in the benefit of intervention when we discuss all the options of treatment with our patients.
The Right Ingredients for Shared Decision-Making
Surgical excision of ductal carcinoma in situ is not necessarily overtreatment, but it is an option, just as less treatment is an option. We have to help women navigate the options while understanding what makes the most difference to them: avoiding screening, avoiding a diagnosis of cancer in the future, or avoiding death from cancer.
Each treatment option has a different impact on these goals. We need to help each woman understand the impact of these treatments based on the type of ductal carcinoma in situ she has in the context of her underlying breast cancer risk and other health conditions. Those are the right ingredients for shared decision-making.
We have to support physicians who take the time to work with women this way and to provide the necessary shared decision-making tools. Understanding our patients’ goals provides an opportunity to start to do less for low-risk cases in controlled settings and learn more about the natural history of these lesions.
Clinical Trials and Registries
The optimal way to move the field forward is to set up and encourage participation in clinical trials and registries. Through the upcoming WISDOM study (Women Informed to Screen Depending on Measures of Risk), the Athena Breast Health Network4 is comparing personalized screening to annual screening.
In the personalized arm, we will use: (1) comprehensive risk assessment (all of the known genes that increase risk for breast cancer, including the recently described single nucleotide polymorphisms or small changes from one person to the other); (2) breast density; and (3) exposures (based on a health questionnaire) to assign women when to start screening, when to stop, how often to screen, and what modality to use.
We will learn whether this approach is safe, preferred, less morbid (associated with fewer false-positive results), and associated with greater uptake of prevention. Perhaps most important, we will learn who is at risk for what type of cancer and how better to triage women with ductal carcinoma in situ.
Background risk may be important and may influence outcome. To try to better understand that background risk, we are initiating a ductal carcinoma in situ registry across the Athena Breast Health Network under the leadership of Michael Alvarado, MD, at the University of California San Francisco and Rick Bold, MD, at the University of California Davis.
We will be analyzing the pathology (how it looks under the microscope), integrating new multigene assays (Oncotype DX® Breast Cancer Assay for Ductal Carcinoma in Situ), and giving women options based on their total picture. We will change the terminology for those with the lowest-risk lesions and offer active surveillance and prevention interventions as appropriate (such as tamoxifen for premenopausal women and raloxifene or exemestane for postmenopausal women).
We believe it is safe to offer those women who wish to wait to intervene an opportunity to be screened and followed. This concept is not unlike that for women who have a BRCA1 or BRCA2 mutation, who are offered high-risk screening even though they likely have a fourfold higher risk than a woman with low-grade ductal carcinoma in situ.
Time for a Change
We should not be afraid to step up and use these data. The Narod et al article showed that women with ductal carcinoma in situ have a 3% risk of dying of breast cancer, which is the quoted figure for the average person’s risk of dying of breast cancer on the American Cancer Society website.5 These data should give us courage to offer options that are less aggressive and likely just as safe. If we do not do something different, we cannot hope to create a better future for women with ductal carcinoma in situ.
The facts have been accumulating for many years now. It is time for a change. Women with ductal carcinoma in situ certainly are confronted with uncertainty. However, we have the tools now to practice medicine with precision and personalization, and that is precisely what we should do. We should acknowledge the uncertainty regarding the value of early intervention (and that the risk in watching is quite low), offer options, and discuss the associated outcomes. We especially need to let women know that there is plenty of time to consider their options and make a decision consonant with their values. ■
Disclosure: Drs. Esserman, Wong, Ewing, and Alvarado reported no potential conflicts of interest.
References
1. Narod SA, Iqbal J, Giannakeas V, et al: Breast cancer mortality after a diagnosis of ductal carcinoma in situ. JAMA Oncol. August 20, 2015 (early release online).
2. Esserman L, Yau C: Rethinking the standard for ductal carcinoma in situ treatment. JAMA Oncol. August 20, 2015 (early release online).
3. Ong MS, Mandl KD: National expenditure for false-positive mammograms and breast cancer overdiagnoses estimated at $4 billion a year. Health Aff (Millwood) 34:576-583, 2015.
4. Athena Breast Health Network: Available at http://athenacarenetwork.org/. Accessed September 14, 2015.
5. American Cancer Society: Lifetime risk of developing or dying from cancer. Available at www.cancer.org/cancer/cancerbasics/lifetime-probability-of-developing-or-dying-from-cancer. Accessed September 14, 2015.
Dr. Esserman is Director, Carol Franc Buck Breast Care Center, University of California San Francisco. Dr. Wong is Assistant Professor of Clinical Surgery, Division of General Surgery, University of California San Francisco. Dr. Ewing is Professor of Clinical Surgery, University of California San Francisco. Dr. Alvarado is Associate Professor, Department of Surgery, University of California San Francisco.
