Local-Regional Control According to Surrogate Markers of Breast Cancer Subtypes and Response to Neoadjuvant Chemotherapy in Breast Cancer Patients Undergoing Breast Conserving Therapy.
Authors: Yu T. , Tereffe W. , Bedrosian I. , Eskambi S. , Strom E. , Litton J. , Gonzalez-Angulo A. , Buchholz T. , Hunt K. , Mittendorf E. 
Published: December 2010

Abstract
PURPOSE: Breast cancers of the 4 subtypes defined by gene profiling have been reported to have different rates of local-regional control (LRC). The goal of this study was to identify patients at high risk for LR recurrence (LRR) according to response to neoadjuvant chemotherapy (NCT) and surrogate markers of gene profile subtypes in patients undergoing breast conserving therapy (BCT).METHODS: Clinicopathologic data from 644 breast cancer patients (clinical stage: 43 I, 468 II, 133 III) who received NCT and BCT from 1997 to 2005 were reviewed. Estrogen receptor (ER), progesterone receptor (PR) and HER2/neu (Her2) expression were used as surrogates for subtypes: luminal A (52%) = ER+ or PR+ and Her2-; luminal B (9%) = ER+ or PR+ and Her2+; Her2+ (7%) = ER- and PR- and Her2+; basal (32%) = ER- and PR- and Her-2-. All patients received NCT and adjuvant radiation (RT). Anthracycline-based chemotherapy was used in 98% and taxane in 84% of patients. None of the patients received trastuzumab. Actuarial rates were calculated using the Kaplan-Meier method and compared using log-rank test. Cox proportional hazards models were used for multivariate analysis (MVA).RESULTS: With a median follow-up of 65 months, the 5-year LRC and overall survival for all patients were 94.2% and 87.9%, respectively. The 5-yr LRC of each subtype is listed in the Table 1. Compared to other subtypes, basal and Her2+ subtypes were associated with decreased LRC in patients whose tumors did not have pathologic complete response (No pCR) to NCT, especially those with disease in ≥ 4 LNs on pathologic examination (pLN+). However, a higher proportion of patients with basal and Her2+ disease had ≥ 4 pLN+ and a higher proportion of basal and Her2+ patients achieved pCR (p≤ .001 for all).Table 1 5-year LRC Lum ALum BHer2+BasalAll patients* (n=644)97%98%85%90%pCR^ (n=126)96%100%86%99%No pCR* (n=467)98%98%83%84%≥ 4 pLN+* (n=77)94%100%67%56%*p&lt;.001; ^p=.12 For the entire cohort, 5-yr LRC was significantly worse in patients with lymphovascular space invasion (LVSI- 95% vs LVSI+ 88%, p = .005), residual cancer in ≥ 4 pLN+ (0-3 pLN+ 95% vs ≥ 4 pLN+ 88%, p = .03) and clinical stage III disease (I/II 95% vs. III 89%, p=.01). On MVA with lum A as reference, basal [Hazard Ratio (HR) 6.7, 95% CI 2.7-16.4, p&lt;.001] and Her-2+ [HR 7.1, 95% CI 2.4-21.2, p&lt;.001] subtypes were associated with worse LRR. Disease in ≥ 4 pLN+ [HR 3.1, 95% CI 1.3-7.5, p=.011] and LVSI [HR 2.3, 95% CI 1.1-4.9, p=.037] were also independently associated with worse LRR.CONCLUSIONS: Patients with Lum A and B subtypes had good LRC regardless of the tumor response to NCT. However, patients with basal and Her-2+ subtypes who responded poorly to NCT had poor LRC after BCT. Additional study is needed to determine the potential benefit of trastuzumab treatment on LRC in HER2+ patients. We advocate for the use of NCT in basal subtype to better delineate patients at high risk of LRR. Furthermore, our data suggest that in patients with basal subtype, particularly those with ≥ 4 pLN+, strategies to improve LRC should be explored, including mastectomy or radiosensitizer use to enhance RT effect in BCT patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 957.