Is Low Risk DCIS Really Low Risk?

By Melissa L. Pilewskie, MD, FACS,

Thursday, June 23, 2016

The DCIS Treatment Controversy

The appropriate management of women with ductal carcinoma in situ (DCIS) remains an area of ongoing controversy. DCIS is a noninvasive breast lesion diagnosed in more than 60,000 patients annually in the United States, currently accounting for 20 to 25 percent of all breast cancer diagnoses. The standard treatment of DCIS is associated with excellent survival and includes surgical excision by lumpectomy or mastectomy, with or without adjuvant radiation or endocrine therapy. While little data exist on the natural history of untreated DCIS, some small studies suggest that 40 to 50 percent of low-to-intermediate-grade DCIS will progress to invasive carcinoma. (1), (2), (3) Given that more than half of patients with DCIS may not progress to a potentially life-threatening disease, there has been growing interest in studying observation and alternative strategies for this patient cohort.

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DCIS Observation Trials

Two current European trials are comparing the safety of observation to standard surgical excision, with or without adjuvant therapy, for women with low-risk DCIS. (4), (5) The LORIS trial is currently enrolling patients who meet the definition of low-risk DCIS: women 46 years of age or older, with no significant family history or personal history of breast cancer, who are diagnosed with screen-detected calcifications alone, asymptomatic, non-high−grade DCIS by core needle biopsy. Patients are randomized to surgery versus observation alone, consisting of an annual mammogram and exam, and the primary endpoint is ipsilateral invasive disease-free survival at five years. The LORD study is often discussed in addition to the LORIS study, but it has not yet started recruiting patients

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Is “Low-Risk” DCIS Truly Low-Risk?

We recently examined our DCIS patient population at Memorial Sloan Kettering Cancer Center (MSK) and identified patients who met the LORIS trial eligibility criteria. Only 16 percent of our patients with DCIS met these inclusion and exclusion criteria, emphasizing that the observation study results will apply to a minority of our patients. However, even among this highly select cohort of our patients who underwent surgical excision, 20 percent were found to have invasive breast cancer on final pathology. This upgrade rate is very similar to that reported in a meta-analysis of all patients with DCIS at the time of surgical excision, regardless of tumor grade or presentation. (6)Interestingly, the invasive cancers identified in this highly select, “low-risk” population were not all small, estrogen receptor positive, node-negative tumors, but rather were heterogeneous in regards to tumor grade, size, receptor status, and nodal involvement.

While adjuvant therapy is often considered optional for women with DCIS alone, it is the standard of care for women with invasive cancer. Our study found that 93 percent of women with invasive cancer received additional adjuvant radiation and/or endocrine therapy, and 18 percent required chemotherapy. Thus, the finding of invasive cancer at excision significantly changed management.

These results emphasize that outside of a clinical trial, surgical excision is warranted for patients with DCIS diagnosed by core needle biopsy given the clinically significant upgrade rate to invasive carcinoma.

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The Road Ahead: Novel Therapeutic Targets

The results of the LORIS and LORD randomized clinical trials will provide important data on the risk of invasive cancer development over time among a select DCIS patient population, as well as patient preference and comfort with the omission of therapy for stage 0 breast cancer. Patient preference should be a strong driver to inform future DCIS study development, as it is unknown whether women would prefer five years of endocrine therapy versus a one-time surgical excision or potentially alternative novel therapies.

We are currently in the early stages of studying the use of both exercise and topical endocrine agents that may provide therapeutic benefits without significant systemic side effects. While these emerging endeavors are exciting, the available research highlights the need for improved risk stratification to improve identification of DCIS patients with a lower risk of harboring invasive carcinoma who may safely avoid standard therapy. 

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  1. Rosen PP, Braun DW, Jr., Kinne DE. The clinical significance of pre-invasive breast carcinoma. Cancer 1980; 46(4 Suppl):919-25.

  2. Sanders ME, Schuyler PA, Dupont WD, Page DL. The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. Cancer 2005; 103(12):2481-4.

  3. Collins LC, Tamimi RM, Baer HJ, Connolly JL, Colditz GA, Schnitt SJ. Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy: results from the Nurses’ Health Study. Cancer 2005; 103(9):1778-84.

  4. Elshof LE, Tryfonidis K, Slaets L, van Leeuwen-Stok AE, Skinner VP, Dif N, et al. Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study. Eur J Cancer 2015.

  5. Francis A, Thomas J, Fallowfield L, Wallis M, Bartlett JM, Brookes C, et al. Addressing overtreatment of screen detected DCIS; the LORIS trial. Eur J Cancer 2015.

  6. Brennan ME, Turner RM, Ciatto S, Marinovich ML, French JR, Macaskill P, et al. Ductal carcinoma in situ at core-needle biopsy: meta-analysis of underestimation and predictors of invasive breast cancer. Radiology 2011; 260(1):119-28.