Abstract P6-16-06: Improved early stratification of invasive cancer risk using MRI in a ductal carcinoma in-situ short-term active surveillance cohort treated with neoadjuvant endocrine therapy
Authors: Paul Kim, Heather I. Greenwood, Rita I. Freimanis, Gillian L Hirst, Megan Fischer-Colbrie, Jessica Gibbs, Nola M Hylton, Christina Yau, Eun-Sil Shelley Hwang, Laura J. Esserman, Rita A Mukhtar
Journal: Cancer Research (2020)

Abstract Purpose Standard treatment for ductal carcinoma in situ (DCIS) involves surgical excision and radiation treatment, and often adjuvant endocrine therapy (ET). However, this may constitute overtreatment for some women. The purpose of this neoadjuvant ET study in patients with biopsy-proven DCIS was to evaluate the relationship between the primary outcome of upstaging at surgery (invasive disease) and changes in the pre- and post-ET MRI appearances of both (1) lesion and (2) background parenchymal enhancement (BPE), with the goal to better inform de-escalated therapy. Methods Outcomes of patients with DCIS who were prospectively enrolled in a neoadjuvant ET trial between 2002 and 2009 were retrospectively analyzed with IRB approval. All patients had dynamic contrast-enhanced breast MRI prior to and following an average of 3.1 months of ET (range 1.9 – 5 months), followed by surgical excision within one year of the second MRI. Pathology reports were used to confirm initial biopsy results and to determine the nature and extent of disease postoperatively. Surgeon and radiologist’s reports were used to assess improvement of lesion after ET based on 1) less prominently enhancing pattern or 2) reduction in size of DCIS lesion after treatment. BPE response to ET on imaging was assessed by two radiologists specialized in breast imaging who compared pre- and post-ET MRI’s, blinded to all imaging reports. The change in BPE of the ipsilateral breast with treatment was scored subjectively as increased, decreased, or unchanged. Readers reached a consensus on discordant classifications of the change in BPE. The correlation between imaging change (of lesion and BPE) and incidence of invasive ductal carcinoma (IDC) at surgery was determined using Fisher’s exact test. Results: Of 34 patients evaluated, six (18%) had IDC at surgery. The prevalence of IDC in each group is shown in Table 2. Those with improvement of lesion on MRI had a lower likelihood of IDC at surgery compared to patients with no imaging improvement (Table 2, p= 0.048). Addition of change in BPE to the evaluation of lesion improvement significantly increased the chance of identifying specific patients who were much more likely to have an underlying invasive cancer at surgery (Table 2, p= 0.032). The risk of having IDC at surgery was considerably higher in the group whose lesion was assessed as not improved and who had decreased BPE scores on MRI (Table 2, p= 0.018). Conclusion: In our unique population of patients with mostly ER+ DCIS receiving pre-operative endocrine therapy, the combination of lack of lesion improvement and reduction in BPE score in blinded reads was significantly associated with the finding of invasive disease at surgical excision. This result may reflect the unmasking of a more aggressive lesion in those with underlying IDC and help identify patients with a higher likelihood of the presence of IDC at surgery. Although this study is small, it suggests that risk-stratifying patients with DCIS based on lesion and parenchymal imaging features associated with treatment response may aid in tailoring therapy for DCIS. We are testing this prospectively in an active surveillance cohort. Table 1. Incidence of IDC at surgery depending on image features (n= 34)Improvement of lesion in MRINo Improvement of lesion in MRIP-value (Fisher’s Exact Test)&amp; No Reduction in BPE&amp; Reduction in BPE&amp; No Reduction in BPE&amp; Reduction in BPEIncidence of IDC at surgery (n)0204Incidence of Not IDC at surgery (n)121024%IDC at surgery when assessing lesion only (%)9.1%40%0.048*%IDC at surgery when assessing lesion AND BPE (%)0%16.7%0%50%0.032*%IDC at surgery when assessing lesion AND BPE (%)8.3%50%0.018* Citation Format: Paul Kim, Heather I. Greenwood, Rita I. Freimanis, Gillian L Hirst, Megan Fischer-Colbrie, Jessica Gibbs, Nola M Hylton, Christina Yau, Eun-Sil Shelley Hwang, Laura J. Esserman, Rita A Mukhtar. Improved early stratification of invasive cancer risk using MRI in a ductal carcinoma in-situ short-term active surveillance cohort treated with neoadjuvant endocrine therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-16-06.