Confusion Over Differences in Registration and Randomization Criteria for the LORIS (Low Risk DCIS) Trial: A Reply

See original letter here.

Letter to the Editor

By Melissa Pilewskie, MD, Kimberly J. Van Zee, MS, MD, and Monica Morrow, MD, Memorial Sloan Kettering Cancer Center, New York, NY

To the Editors:

We agree that the LORIS trial will provide insights regarding the safety of observation alone for a very select cohort of patients with DCIS. Although the two randomized clinical trials assessing the safety of observation alone, LORIS and LORD [1] [2] are ongoing and results are not yet available, there is increasing discussion among surgeons in the community, including at the 2016 Society of Surgical Oncology Annual Cancer Symposium, regarding the potential for observation of "low risk" DCIS outside of a clinical trial.

Our study[3] found a clinically significant upgrade rate of 20% among a select cohort of patients who met the published LORIS low-risk eligibility criteria,[2] which include age ≥ 46 years with low or intermediate grade DCIS diagnosed by VACB for screen-detected calcifications without additional high-risk features (any mass component, nipple discharge, strong family history of breast cancer, or personal history of invasive breast cancer or ipsilateral DCIS). The trial details published by Francis et al state that "only patients with low-grade, or intermediate grade with low-grade features" will be randomized into the trial.[2] In the letter to the editor by Rea et al,[4] the following pathologic requirements for determining eligibility at central pathology review are listed: 1) no comedo-type necrosis; 2) no more than occasional mitoses—no more than 1 per 3 duct cross section; and 3) nuclei with minimal pleomorphism no more than 2.5 red blood cells in diameter. While all of these features are used by pathologists to determine grade, these are not pathologic descriptors commonly reported for a DCIS lesion, thereby limiting the applicability of these criteria in clinical practice.

One noted limitation of our retrospective review is a lack central pathology review. Rea et al[4] emphasize that patients' materials for LORIS are reviewed by 2 or 3 pathologists prior to randomization. While this was not done in our study, such a review is extremely unlikely to be undertaken in clinical practice prior to determining if a patient is a candidate for observation alone. The pathology reports in our series were generated by a group of specialist breast pathologists who review approximately 3,000 breast surgical cases, including over 400 DCIS cases annually, using standard definitions for low and intermediate grade, a level of expertise substantially greater than the average general pathologist.

Based on the low-risk eligibility criteria published by Francis et al[2] and used in our review, only approximately 17% of patients with DCIS undergoing breast-conserving surgery at our facility were eligible for LORIS trial registration. If the proportion that is ineligible for randomization is similar to the experience of Rea et al[4] (two-thirds ineligible), then at most 6% of women undergoing breast-conserving surgery for DCIS at our facility would be eligible for randomization. Therefore, the LORIS results would be of very limited impact on the population of women with DCIS.

Our series highlights that even for the small subset of women with DCIS (i.e., the 17% that meet the published criteria for LORIS eligibility) that we believe are at low risk based on frequently used clinical, radiologic, and pathologic characteristics, there remains a 20% risk of harboring synchronous invasive carcinoma. Until data emerge establishing the safety of alternative management strategies for DCIS with criteria that are reproducible in the community, surgery remains the standard of care, which is the point we are making in our study.


1. 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;51(12):1497-510.

2. 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;51(16):2296-303.

3. Pilewskie M, Stempel M, Rosenfeld H, Eaton A, Van Zee KJ, Morrow M. Do LORIS Trial Eligibility Criteria Identify a Ductal Carcinoma In Situ Patient Population at Low Risk of Upgrade to Invasive Carcinoma? Ann Surg Oncol. 2016 (Epub ahead of print).

4. Rea D, Young J. Letter to the Editor: Confusion Over Differences in Registration and Randomisation Criteria for the LORIS (Low Risk DCIS) Trial. Ann Surg Oncol Letters to the Editor, 2016

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