Abstract
Abstract Objectives: To determine the predictive value for ipsilateral breast tumour recurrence (IBTR), molecular subtyping using six immunohistochemical (IHC) biomarkers were evaluated on the breast cancer specimens from patients age 50 and older with T1 and T2 node negative breast cancer, who were participants in a randomized trial of tamoxifen (Tam) +/− whole breast radiation (WBRT). Methods: Between December 1992 and June 2000, 769 women were randomized to WBRT and Tamoxifen (Tam/WBRT; n=386) 20 mg daily for 5 years, or Tam alone (Tam; n=383). Median age was 68 years; 639 (83%) had pT1 tumors. Intrinsic molecular subtyping was determined using semi-quantitative analysis of ER, PR, Ki-67, HER2, EGFR and cytokeratin (CK) 5/6 on tissue microarrays (TMAs) constructed from the tumor blocks of 304 of the 345 available tumors. Patients were classified into the following categories: luminal A, luminal B, luminal-HER2, HER2 enriched, basal-like, or triple-negative phenotype-nonbasal. The median follow-up for this cohort was 10 years. Results: For the overall group, IBTR at 10 years was 13.8% with Tam compared to 5.0% with Tam/WBRT (p<0.0001). Tumour size (HR 1.54, p=0.001), ER positive status (HR 0.35, p=0.006), age (HR 0.96, p=0.014), and treatment with Tam/WBRT (HR 0.28, p<0.0001) were significant factors for IBTR. For the 304 TMAs, 145 patients were treated with Tam alone, 159 with both. Luminal A tumors (ER or PR positive, HER2 negative, Ki-67<14%, n=133) had the lowest rate of IBTR: 8% with Tam alone vs. 4.6% with Tam/WBRT (p=0.3). In women aged > 60, IBTR was 4.3% with Tam alone vs. 6% with Tam/WBRT (n=103, p=0.9). Grade I/II Luminal A tumors (n=114) had a similar rate of IBRT regardless of treatment: 4.9% with Tam alone vs. 5.5% with Tam/WBRT (p=0.9). In contrast, luminal B tumours (Ki-67>14%, n=82) demonstrated an IBTR rate of 16.1% with Tam alone vs. 3.9% with Tam/WBRT (p=0.05). Lum HER2 (n=11), HER2-enriched (n=11) and basal-like (n=16) demonstrated even higher risks of IBTR, although the number is small in each group. Conclusions: These preliminary data demonstrate that the 6-marker IHC subtype appears to prognosticate for IBTR for women with early stage breast cancer. In particular, older (age >60) luminal A patients with grade I/II tumors demonstrated the lowest risk of breast relapse, for which RT had minimal impact, suggesting that such patients could be managed with Tam alone. It is of note that this subgroup represents a significant proportion of women in this trial (133/304 or 43%). In contrast, breast RT remains beneficial for women with higher risk subtypes (Luminal B, HER2 enriched, and basal). Further corroborations are required using the remaining tumour blocks, and validated in a prospective study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1032. doi:1538-7445.AM2012-1032
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