Abstract P1-10-07: The presence of ductal carcinoma in situ in core needle biopsy and microcalcifications on mammography in TNBC is associated with a lower pCR and worse long term outcome
Authors: Ardui Jan , Vandamme Sophie , Van Ongeval Chantal , Floris Giuseppe , Izci Hava , Wildiers Hans , Punie Kevin , Geukens Tatjana , Vergote Ignace , Berteloot Patrick , Van Gorp Toon , Smeets Ann , Van Nieuwenhuysen Els , Han Sileny , Laenen Annouschka , Weltens Caroline , Janssens Hilde , Neven Patrick 
Published: March 2020

Abstract
Purpose Predictors for pathological Complete Response (pCR) in TNBC are very important given pCR is considered a surrogate marker for breast cancer-related survival. Associated DCIS in TNBC (accom-DCIS) as well as presence of microcalcifications on initial mammography (micro-MG) have been correlated with Androgen Receptor positive TNBC, known to achieve lower pCR rates. We aim to investigate the predictive impact of accom-DCIS and micro-MG on pCR. We also validated known clinico-pathological predictors for pCR. Long term outcome was analyzed for pCR and accom-DCIS. Methods A retrospective cohort study (diagnosed 1/1/2000 - 31/12/2017) of prospectively registered consecutively treated TNBC patients was performed. TNBC was defined as IHC-ER&lt;1%, IHC-PR&lt;1% and IHC-HER2 0-1+ and FISH negative if HER2 IHC 2/3+. All patients had standard of care neoadjuvant chemotherapy (NAC) in our hospital. Patients with at least 2 years of documented follow up and only TNBC of no special type on core needle biopsy (CNB) were included. We evaluated the predictive value of patient factors (age, BMI, symptomatic/screening-detected), imaging (micro-MG) and tumor related factors as reported in the pathology-report (grade, cT, focality, cN, lymphovascular invasion, accom-DCIS) for pCR (defined as pT0-TisN0). We used distant relapse rate and death to evaluate outcome. The Cox proportional hazards model was used to analyze the effect of pCR and accom-DCIS on distant relapse rate as well as overall survival (OS) in a multivariate model (corrected for size, nodal state, grading). Results are presented as hazard ratios (HR) with 95% confidence intervals (CI). Results The study contains 219 patients; accom-DCIS was reported in 53/219 (24.2%) CNB’s; pCR was achieved in 90/219 (41,1%). Patient related factors were comparable in patients who achieved pCR and those who had residual disease. Unifocal, smaller clinical size tumors and high tumor grade were significant predictors for pCR in our series. Analysis of 194 available mammographies showed micro-MG in 63/194 (32.5%). Micro-MG predicted for residual disease after NAC [HR = 3.350; 95% CI (1.708 - 6.569), p=0.005]. Accom-DCIS was a strong negative predictor of pCR [HR = 3.333; 95% CI (1.558 - 7.143), p=0.002)] and was associated with more distant relapse and worse survival [HR = 2.664; 95% CI (1.575 - 4.505), p=0.003]. pCR was strongly associated with a lower distant relapse rate and a better OS [HR = 2.210; 95% CI (1.282 - n3.811), p=0.004]. In the 129 cases without pCR, remaining tumor size [HR = 1.019; 95% CI (1.012 - 1.025), p=&lt; 0,001), ypN [HR = 1.917; 95% CI (1.539 - 2.388), p=&lt; 0,001) and presence of LVI [HR = 3.720; 95% CI (2.057 - 6.728), p=&lt; 0,001] significantly predicted for secondary metastasis. There was only a trend towards more distant relapses if accom-DCIS was found in the resection specimen in those who had residual disease [HR = 1.347; 95% CI (0.780 - 2.325), p=0.2855]. Conclusion Presence of accom-DCIS in CNB as well as micro-MG predicts for less pCR in TNBC. Accom-DCIS in CNB is associated with more distant relapse and worse OS. For accom-DCIS on resection specimen, there was only a tendency towards more distant relapses.
Citation Format: Jan Ardui, Sophie Vandamme, Chantal Van Ongeval, Giuseppe Floris, Hava Izci, Hans Wildiers, Kevin Punie, Tatjana Geukens, Ignace Vergote, Patrick Berteloot, Toon Van Gorp, Ann Smeets, Els Van Nieuwenhuysen, Sileny Han, Annouschka Laenen, Caroline Weltens, Hilde Janssens, Patrick Neven. The presence of ductal carcinoma in situ in core needle biopsy and microcalcifications on mammography in TNBC is associated with a lower pCR and worse long term outcome [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 P1-10-07.