PD07-05: Local Recurrence Risk in 6377 Patients with Early Breast Cancer Receiving Neoadjuvant Anthracycline-Taxane +/− Trastuzumab Containing Chemotherapy.
Authors: von Minckwitz G , Kaufmann M , Kümmel S , Fasching PA , Eiermann W , Blohmer JU , Costa SD , Hilfrich J , Jackisch C , Gerber B , Barinoff J , Huober J , Hanusch C , Konecny G , Fett W , Stickeler E , Harbeck N , Mehta K , Loibl S , Untch M 
Published: June 2012

Background: Locoregional recurrence (LRR; defined according to Hudis C, JCO 2007) risk after neoadjuvant systemic treatment is considered as a possible hazard of this treatment approach. However, few data exist on the incidence and risk factors for LRR after anthracycline-taxane+/−trastuzumab (AT+/−H) containing neoadjuvant treatment. We analyzed individual data of 7 prospective neoadjuvant trials conducted by the German Breast Group and the AGO Breast Group.

Patients (Pts) and methods: 6377 Pts with operable or locally advanced, non-metastatic breast cancer were analyzed (for details see von Minckwitz G et al, BCRT 2010). Postsurgical radiotherapy was indicated after breast conservation for all patients and after mastectomy for patients with cT3/4 or cN+ disease. Endocrine treatment was given to ER− and/or PgR-positive patients. 485 LRR were observed during a median follow up of 46.2 (0-127) months.

Results: LRR was similar for patients treated by tumorectomy (7.2% of N=1123), segmentectomy (6.8% of N=1121), quadrantectomy (7% of 557), or breast conservation (BCT) (not otherwise specified) (7.7% of N=819), but higher in patients treated by mastectomy (ME) (12.1% of N=1670) (p&lt;0.001). Rate of breast conservation decreased by increasing initial tumor size (cT1(N=198): 77.7%, cT2(N=3675): 78.1%, cT3(N=795): 49.4%, cT4a-c(N=348): 35.9%, cT4d(N=235):19.1%). LRR in patients treated by BCT or ME were 9.1% vs 9.1% for cT1 (p=0.9); 6.9% vs. 9.8% for cT2 (p=0.001); 9.7% vs 14.2% for cT3 (p=0.04); 3.2% vs. 11.7% for cT4a-c (p=0.004; and 22.2% vs 18.9% for cT4d (p=0.4). LRR increased with surgical yT-stage from 4.7% for ypT0 (N=990), 11.8% for ypTis (N=340), 9.1% for ypT1 (N=1555), 8.2% for ypT2 (N=926), 13.8% for ypT3 (N=232), 20% ypT4a-c (N=80), to 31.2% for ypT4d (N=16) (p&lt;0.001). Comparable results were obtained for cN and ypN stages. Patients with a pathological complete response (pCR = ypT0 ypN0) showed a lower LRR of 3.7% compared to patients not achieving a pCR (3.7% vs 9.9% (HR 0.36 p&lt;0.001). Patients with a pCR showed low LRR in all intrinsic subtypes except Luminal B/HER2+ -like tumors (Luminal A-like tumors (N=105; 3.8%), Luminal B/HER2− -like (N=40; 0%), Luminal B/Her2+ -like (N=124; 8.1%), HER2+(non-luminal)-like (N=158; 1.9%), triple-negative (N=276; 2.5%) (p=0.016). Patients without a pCR showed an excessive LRR for HER2+(non-luminal) and triple-negative tumors (Luminal A-like tumors (N=1498; 5.1%), Luminal B/HER2− -like (N=304; 11.9%), Luminal B/HER2+ -like (N=602; 8.5%), HER2+(non-luminal)-like (N=367; 18%) and triple-negative (N=276; 17.8%) (p&lt;0.001). cT, cN, ypN, intrinsic subtype, but not ypT stage and type of surgery were independent predictors of LRR for patients without pCR in a Cox regression model. None of these factors except Luminal B/HER2+ (p=0.012) were significant in patients with pCR.

Conclusions: LRR in this large pooled analysis after AT+/−H containing neoadjuvant treatment appears to be low, especially in all patients with a pCR except Luminal B/HER2+ disease. In patients without a pCR low cT, cN, ypN and Luminal tumor type predict a low LRR. Other stages and subtypes without pCR should be carefully followed up irrespective of type of surgery.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD07-05.