Abstract P6-09-13: The association between pCR status after neoadjuvant chemotherapy and sites of first distant relapse after surgery: A substudy of the EORTC 10094/BIG-1-00 trial
Authors: Touati N , Aalders K , Slaets L , Tryfonidis K , Cameron DA , Bonnefoi H 
Published: March 2017

Abstract
Background
Chemotherapy in eligible patients is increasingly applied in the neoadjuvant setting, as it offers the possibility for 'in vivo' monitoring of the activity to the administered treatment, prevention of early micrometastatic spread and often allows less invasive surgery in patients that would otherwise have needed a mastectomy. The achievement of a pathologic complete response (pCR) after neoadjuvant chemotherapy is a prognosticator for better outcome. However, less is known about the patterns of distant relapse between patients that did and did not achieve pCR. We assessed the differences in sites of first distant relapse after pCR versus non-pCR after neoadjuvant chemotherapy in patients enrolled in the EORTC 10094/BIG-1-00 “p53” trial.
Methods
The analyzed population consisted of patients enrolled in the “p53” trial that received ≥1 cycle of chemotherapy before surgery and who have been diagnosed with a distant relapse. pCR was defined as no evidence of residual invasive cancer (or very few scattered tumor cells) in the primary tumor and axillary lymph nodes with or without residual ductal carcinoma in situ (DCIS). Intrinsic subtype classification was performed using the 2011 St Gallen consensus. The first site of distant relapse was collected for all patients and was classified as soft tissue, visceral, skeletal or CNS. As primary analysis, the associations between achievement of pCR and sites of distant relapse were investigated in 4 multivariate logistic regression models, one for each site, adjusting for intrinsic subtype and preceding local recurrence (yes/no). Adjusted P-values are reported (Benjamini-Hochberg correction). Secondary analyses include: associations between site of first distant relapse and pCR by subtype, description of concomitant sites of relapse.
Results
The study included 383 (21%) eligible patients out of the 1856 randomized for the 'p53' trial, of whom 28 (7%) had achieved pCR and 355 (93%) did not. Median follow-up was 5.4 years. Achievement of pCR was associated with a trend towards a decreased presentation with skeletal metastases (21% (pCR) vs 50% (non-pCR), OR=0.32, adj-p=0.071, see Table) and we observed an increase in the proportion of patients with CNS tissue as first site of distant relapse (21% vs 9%, OR=2.39, adj-p=0.183). The trend for skeletal metastases was seen in all subtypes except for Luminal A. Patients with pCR were more likely to present with only one relapse location category when compared to non-pCR (86% vs 69%).
Association between site of first distant relapse and pCRSite of first distant relapseNon-pCR N=355pCR N=28Total N=383Median of time from surgery till first distant relapsepCR: Yes vs NoCategoryN(%)N(%)N(%)MonthsOR (95% CI)Adj. p-valueSoft tissue43 (12.1)4 (14.3)47 (12.3)250.94 (0.30, 2.95)0.909Visceral183 (51.5)14 (50.0)197 (51.4)220.80 (0.36, 1.74)0.756Skeletal179 (50.4)6 (21.4)185 (48.3)280.32 (0.12, 0.82)0.071CNS32 (9.0)6 (21.4)38 (9.9)162.39 (0.87, 6.58)0.183
Conclusion
In this group of patients treated with neoadjuvant chemotherapy, patients that achieved a pCR were less likely to present with skeletal metastases as first site of distant relapse, even after adjustment for intrinsic subtype.
Citation Format: Touati N, Aalders K, Slaets L, Tryfonidis K, Cameron DA, Bonnefoi H. The association between pCR status after neoadjuvant chemotherapy and sites of first distant relapse after surgery: A substudy of the EORTC 10094/BIG-1-00 trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-13.