Kate Krause

Effect of adjuvant trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-positive breast cancer treated with post-mastectomy radiation therapy.

61 Background: HER2 overexpression is associated with an increased risk of LRR after mastectomy in the era prior to the use of adjuvant trastuzumab. The purpose of this study was to examine the effect of adjuvant trastuzumab on rates of LRR and whether this effect varied with the use of PMRT. METHODS From our institutional database, 474 women with Stage I-III HER2+ invasive breast cancer treated with mastectomy +/- adjuvant therapy from 1999-2007 were identified. Those patients lost to follow-up, treated with lapatinib, or diagnosed between 5/2004 to 5/2005 (when trastuzumab prescribing practices varied) were excluded; leaving 395 in the final study population. Two cohorts were compared: 139 women who received trastuzumab (5/2005-12/2007) and 256 women who did not (prior to 5/2005). Competing risks analyses were used to estimate cumulative incidence of LRR. Competing risks regression was used to evaluate the association between treatment factors and LRR. To minimize lead-time bias, patient data was censored at 5 years after mastectomy in both groups. RESULTS There were 18 LRRs in the entire cohort (16 no trastuzumab, 2 trastuzumab). Women in the no trastuzumab group were less likely to be node positive, receive chemotherapy or PMRT (all p<0.001). The hazard ratio for LRR was 0.218in the trastuzumab group (p= 0.04, 95% C.I. 0.05-0.94) with a 5-year risk of LRR of 1.5% in the trastuzumab versus 6.6% in the no trastuzumab group. After adjusting for PMRT and chemotherapy receipt, trastuzumab trended towards significance in decreasing LRR (p= 0.063). On subset analysis of 139 women who received PMRT, trastuzumab significantly reduced LRR (7.3% no trastuzumab, 0% trastuzumab, p=0.025). Among those who did not receive PMRT (256), trastuzumab did not significantly decrease LRR (6.3% no trastuzumab, 2.9 % trastuzumab, p=0.28). CONCLUSIONS Adjuvant trastuzumab significantly reduced LRR in women with HER2+ breast cancer who received PMRT. A trend toward decreased LRR was observed in the entire population, but did not reach statistical significance, suggesting that the benefit is greater in HER2+ patients receiving multimodality therapy.

Does biologic subtype and pathologic response after neoadjuvant chemotherapy predict locoregional recurrence

65 Background: The relative contribution of biological subtype and response to neoadjuvant chemotherapy (NAC) to locoregional recurrence (LRR) is uncertain. We aim to determine if these factors identify a high risk population for LRR. METHODS 233 patients received anthracycline/taxane-based NAC, mastectomy and postmastectomy radiation therapy (PMRT) in 2000-2009 for Stage II-III breast cancer. 53% (n=123) were HR+ (ER or PR+/HER2-), 23% (53) HER2+ (HER2+/HR+ or HR-), and 24% (57) TN (HR-/HER2-). 76% of HER2+ received trastuzumab. Median PMRT dose was 50 Gy to chest wall and regional nodes. Pathologic complete response (pCR) rates were compared using Fishers exact test. Rates of LRR and distant recurrence (DR) were estimated by Kaplan-Meier methods. Cox regression analysis was performed. RESULTS Median follow-up was 62 months (range 7-161) with 21 LRR, 84 DR and 58 deaths. pCR rate and 5-year LRR rates were 14% and 7% in the entire cohort, respectively. Significantly more TN and HER2+ patients achieved pCR than HR+ patients (Table 1, p=0.003). TN patients had higher 5-year LRR rate compared to HR+ and HER2+ patients (18% vs. 4% and 6%, p=0.02). The 5-year LRR rate was 0% in pCR patients versus 9% in non-pCR patients (p=0.06). In patients without pCR, TN subtype was associated with increased LRR (23% at 5-year vs. 4% HR+ and 7% HER2+; p=0.001). TN patients without pCR were also associated with increased DR (48% at 5-year vs. 29% HR+ and 30% HER2+, p=0.02). On univariate analysis, TN subtype (HR=2.0, p=0.008), pathologic stage (HR=2.2, p=0.02), and pN+ status (HR=9.3, p=0.03) were associated with increased LRR. CONCLUSIONS Although response to NAC strongly correlates with breast cancer subtype, patients with HR+ and HER2+ breast cancer had favorable rates of LRR regardless of response to NAC, perhaps because of additional postoperative targeted therapy. In contrast, while no LRR was seen in TN patients with pCR, those with poor response to NAC had significantly higher LRR risk, underscoring the need for potential new treatment strategies to improve local control in this population. [Table: see text].