Active surveillance as a treatment modality in ductal carcinoma in situ

Ductal carcinoma in situ (DCIS) is considered a nonobligate precursor of invasive breast cancer and is commonly identified in routine screening mammography for asymptomatic women. Many of these cases would never cause clinical symptoms or become life-threatening; however, it is challenging to reliably distinguish between lesions that will progress to invasive disease and those that will not advance.

Because of limitations in the ability to identify nonprogressive disease, DCIS is usually managed similarly to localized invasive breast cancer. Conventional treatment consists of surgery, with or without adjuvant radiation, and endocrine therapy. Earlier research revealed extensive variation in DCIS management, including some treatment beyond current recommendations.¹ Interestingly, the data also demonstrate increasing use of mastectomy and contralateral risk-reducing mastectomy.² DCIS is generally associated with an excellent prognosis, regardless of the treatment pathway.³ Consequently, a significant proportion of women with DCIS may receive more extensive treatment than is medically necessary.⁴ The treatment of DCIS should involve a process of shared decision making with the patient to ensure that he or she fully comprehends the nature and clinical course of the disease, as well as all treatment options, incorporating individual priorities, and preferences.^2-4

Overtreatment of DCIS is a growing concern in the breast cancer community and has significant implications for patients. Recognizing that many cases of DCIS may remain stable without excision, clinical trials are exploring the role of active surveillance (AS) in DCIS.⁵ Specifically, in the U.S., the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) Trial for low-risk DCIS is a prospective randomized trial investigating the risks and benefits of AS in comparison with guideline-concordant care for low-risk DCIS. The hypothesis is that monitoring low-risk DCIS with endocrine therapy alone does not yield inferior outcomes compared with traditional management with surgery. The results of this trial and others like it may bring about a paradigm shift in the management of breast disease.

National trends in active surveillance

To further understand the role of active surveillance and its application in the treatment of DCIS, the authors turned to the National Cancer Database (NCDB) to explore practice trends in the management of DCIS outside of a U.S. clinical trial. In this case, AS treatment is defined as treatment for care given to any patient not undergoing surgery, chemotherapy, or radiation therapy. Of 84,281 patients in the NCDB diagnosed with DCIS between 2004 and 2015, only 342 (0.4 percent) underwent AS. Using multivariable logistic regression, we found that increasing age (OR 1.16), Hispanic or non-Hispanic Black ethnicity (OR 1.90; 1.54), and nonprivate insurance (OR 1.29) were associated with higher rates of AS. Patients treated at academic facilities also were more likely to undergo AS (OR 1.76).

One counterintuitive finding was that patients with a Charlson/Deyo score of one or more were less likely to undergo AS in comparison with patients who had a Charlson/Deyo score of 0 (OR .70). Most interestingly, our analysis revealed that of all patients undergoing AS, only 10.5 percent received hormonal therapy (HT). The use of HT for DCIS, especially estrogen receptor-positive lesions, has shown benefit in reducing the risk of recurrent disease and is a criterion for inclusion in the study arm of the only U.S. clinical trial of AS for DCIS.^5,6

Implications for clinical practice

Despite growing interest in nonsurgical management of DCIS, few patients nationally undergo monitoring alone for DCIS. Of note, our data represent a time period prior to the U.S. COMET Trial. Until the results of prospective randomized trials are available, the limited use of AS likely reflects appropriate clinical judgment.

The more frequent use of AS outside of a clinical trial and without HT observed in Black/Hispanic patients with nonprivate insurance may reflect persistent disparities in guideline-concordant care in these patient populations. These findings may also provide early insight into diversity considerations and practice trends relevant to enrollment in clinical trials of AS and subsequent adoption into clinical practice.

Conclusion

DCIS is a heterogeneous disease with variable biologic potential. A remaining challenge is the reliable identification of a truly low-risk DCIS population that can safely be managed nonoperatively. The results of ongoing clinical trials may ultimately inform alternative treatment options for DCIS.

In addition, the advent of genomic profiling holds the potential to differentiate indolent from progressive forms of DCIS, and help drive treatment decisions for patients. Until such time, patients undergoing AS for DCIS may be at increased risk of disease progression, including progression to invasive disease. In some cases, progression of disease might have an adverse psychological effect on the patient and even require more aggressive clinical treatment.⁷ However, such progression is unlikely to affect survival. Therefore, concerns regarding the AS approach should be balanced with the clear need to reduce overtreatment for a disease with little associated mortality.

References

1. Pontia A, Lynge E, James T, et al. International variation in management of screen-detected ductal carcinoma in situ of the breast. Eur J Cancer. 2014;50(15):2695-2704.
2. Shiyanbola OO, Sprague BL, Hampton JM, et al. Emerging trends in surgical and adjuvant radiation therapies among women diagnosed with ductal carcinoma in situ. Cancer. 2017;122(18):2810-2818.
3. Narod SA, Iqbal J, Giannakeas V, Sopik V, Sun P. Breast cancer mortality after a diagnosis of ductal carcinoma in situ. JAMA Oncol. 2015;1(7):888-896.
4. Vatovec C, Erten MZ, Kolodinsky J, et al. Ductal carcinoma in situ: A brief review of treatment variation and impacts on patients and society. Crit Rev Eukaryot Gene Exp. 2015;24(4):281-286.
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6. Youngwirth LM, Boughey JC, Hwang ES. Surgery versus monitoring and endocrine therapy for low-risk DCIS: The COMET Trial. Bull Am Coll Surg. 2017;102(1):62-63. Available at: facs.org/2017/01/surgery-versus-monitoring-and-endocrine-therapy-for-low-risk-dcis-the-comet-trial/. Accessed August 18, 2018.
7. James TA, Wade JE, Sprague BL. The impact of mammographic screening on the surgical management of breast cancer. J Surg Oncol. 2016;113(5):496-500.