Abstract P1-14-08: Prediction of pathological response (pCR) to neoadjuvant dose dense and intense cyclophosphamide and anthracycline in a prospective series of triple negative locally advanced breast cancers (TNLABC)
Authors: Giacchetti S , De Roquancourt A , Groheux D , Piron P , Lehmann-che J , Cuvier C , Resche-rigon M , Albiter M , Roche B , Frank S , Hamy A-S , Teixeira L , Marty M , Lalloum M , Espié M 
Published: May 2016

Background: Stage II-III TNBC retains a poor outcome despite high chemosensitivity. Patients (pts) with pCR after neoadjuvant chemotherapy have a good prognosis whereas non-responding pts have a 25-40% risk of distant relapse at 5 years. pCR is thus a major goal in TNBC. We previously reported that TNLABC benefit the most of dose dense dose intense cyclophosphamide (C)-epirubicin (E) (S.Giacchetti; BJC, 2014)

Aim: To confirm these results prospectively and analyze the predictive factors of response to high dose chemotherapy in TNBC.

Patients and methods: From january 2009 to april 2015 non inflammatory TNLABC received high dose C (1200 mg/m2 d1 qw 2) with E (75 mg/m2/ d1 qw2) for 6 cycles. The pts had a breast biopsy with frozen tissue. We performed molecular studies: qRT-PCR for AR, FOXA1, PI3K and FASAY technic for p53 mutation.The percentage of stromal Tumor-infiltrating lymphocytes (TILs) was also evaluated by two independent pathologists and assessed as a continuous variable. A18F-FDG PET/CT was performed initially and after 2 courses of chemotherapy and the metabolic answer assessed as a variation of the tumor uptake (ΔSUVmax). We report here the pathological complete response (pCR) (absence of infiltrative carcinomas in the breast and in the lymph nodes) and the factors associated with pCR.

Results: The characteristics of the 74 pts are listed in table 1. The median age is 48 years old, 48 pts (65.8%) are premenopausal and 79% did not have any family history of breast cancers. TIL was divided in 3 groups &lt; 10 % (26 pts, 40 %); 10-50 % (30 pts, 46 %) &gt; 50% (9 pts, 14 %). Pathological response was assessed in 66 pts, one pt progressed during chemotherapy and 6 pts did not undergo surgery yet. 28 pts were in pCR (42.4 %). With a median follow up of 25 months, 13 pts (17.8 %) progressed and 8 (11%) died.

Table 1: Patients characteristics and pCR according to tumor features and metabolic responseCharacteristicsNumber of pts (%)N of pts evaluated for pCRpCR (%)OR [IC 95%]p-valueTumor size T2363519 (54)10.04T337319 (29)0.34 [0.12 ; 0.96]Nodal status N0363315 (46)10.62N1/N2/N3 24/11/33313 (39)0.78 [0.29 ; 2.07]Histological grade: 2660 (0) 0.04*3676028 (47)TILs &lt;10 %26 (40)2510 (40)10.02610-50 %30 (46)267 (27)0.55 [0.17 ; 1.80]≥ 509 (14)9 7 (78)5.25 [0.90 ; 30.62]P53 Mutated54 (89)5121 (41)10.43WT7 (12)53 (60)2.14 [0.33; 13.96]AR Negative43 (83)4318 (42)10.46Positive 9 (17)95 (56)1.74 [0.41 ; 7.38]FOXA1 Negative40 (77)4015 (38)10.08Positive 12 (23)128 (60) 3.33 [0.86 ; 12.99]Molecular Apocrine8 (17)85 (63)10.19TN38 (83)3814 (37)0.35 [0.07 ; 1.69]PI3K Non mutated44 (88)4419 (43)10.75Mutated6 (12)63 (50)1.31 [0.24 ; 7.26]SUVmax at 2 courses0.0001&lt; 70 %27 (53)221 (5)1≥ 70 %24 (47)2318 (78)79.2 [8.48 ; 739.82]* Measured with a Fisher Test

Tumor size, tumor grade, percentage of TILs, the change in 18F-fluorodeoxyglucose tumor uptake (ΔSUVmax) were significantly associated with pCR at univariate analysis. Only one factor remained significant at multivariate analysis, the ΔSUVmax, OR: 0.04 [0.007- 0.27], p = 0.0008.

Conclusion: In this prospective phase III trial we confirm the efficacy of a dose dense EC in TNBC. The metabolic response evaluated with 18 F-FDG PET/CT is a strong and reliable predictor of pCR and could allow an early change of treatment for the non responders. A clinical trial is planned to test this strategy.

Citation Format: Giacchetti S, De Roquancourt A, Groheux D, Piron P, Lehmann-che J, Cuvier C, Resche-rigon M, Albiter M, Roche B, Frank S, Hamy A-S, Teixeira L, Marty M, Lalloum M, Espié M. Prediction of pathological response (pCR) to neoadjuvant dose dense and intense cyclophosphamide and anthracycline in a prospective series of triple negative locally advanced breast cancers (TNLABC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-08.