Abstract P5-21-01: pT1a, bpN0M0 breast cancer: clinicopathological characteristics and their impact on treatment decision. Central review of the prospective ODISSEE cohort
Authors: Lacroix-Triki M , Radosevic-Robin N , Louis B , Roche-Comet I , Soubeyrand M-S , Bourgeois H , Chauvet M-P , Fourrier-Réglat A , Gligorov J , Peyrat J-P , Dalenc F , Belkacemi Y , Penault-Llorca F 
Published: August 2014

Background: The incidence of infra-centimetric breast cancer (BC) is increasing due to mass screening. The management remains controversial opposing locoregional treatment only based on low stage and potentially aggressive tumor biology (especially for triple negative and HER2 positive tumors). The objectives of the prospective multicenter ODISSEE study were i) to describe daily practice management of pT1ab BC, ii) to identify potential new biomarkers and iii) to describe long term outcome (10-year follow up).

Methods: 616 patients with unifocal pT1a, b pN0M0 BC were included after surgery from May 2009 to March 2010 in 116 centers. Paraffin blocks were available for central pathology review in 350 patients. Due to the small tumor size, tissue microarray (TMA) construction was finally achieved for 287 cases. Collection of additional tumor blocks is ongoing. Review of the cases was performed independently by two pathologists and discordant cases were reviewed under a multihead microscope. Histological characteristics (histological type, tumor size and grade, presence of in situ component, presence of lymphovascular invasion) were assessed on whole tissue sections. Immunohistochemical detection of ER, PR, HER2, Ki67, EGFR, cytokeratin 5/6, Bcl-2 was performed on TMAs.

Results: Clinicopathological characteristics of the 287 centrally reviewed cases were similar to those of the 616 patients included in the cohort. Median age: 60.1 years (range [31–89] years). Median tumor size: 7.8 mm (range [1–10] mm) with 11% pT1a and 89% pT1b. Histological types: 72% ductal, 11% lobular and 17% other types (among which 53% of tubular). Minor in situ component was found in 36% of the cases, and invasive carcinoma with an extensive in situ component in 1.9%. Most of tumors were histological grade I and II (52% and 40% respectively), 8% were grade III. Proliferation was low as assessed by mitotic count (low 82%, intermediate 13% and high 5%) or by Ki67 index (&lt;5% in 61% of the cases). Almost all tumors were HR (hormone receptors) positive (95%) and 4% were HER2 positive (HER2+). According to the intrinsic subtypes described by Cheang et al., 84% of the cases were classified as luminal A, 11.6% as luminal B, 1.5% as HER2 (HR−/HER2+), 2.5% as basal-like and 0.4% as triple negative non basal. Ki67 index was higher in the HER2 and basal-like subgroups (p &lt; 0,05). In contrast, Bcl-2 expression was higher in the luminal subgroup (p &lt; 0,001). All the HER2, triple negative basal like and 87% of the luminal B were pT1b. 20 patients received chemotherapy, mainly based on HER2+ or triple negative status (72.7% and 36.4% respectively). Furthermore, 72.7% of HER2+ BC patients received trastuzumab.

Conclusions: The pT1a, bpN0M0 BC ODISSEE patients were mainly grade I or II, low proliferative HR+/HER2− tumors (i.e. the so-called luminal A subtype). Adjuvant treatment decision was mainly based on the presence of an aggressive phenotype such as HER2+ and triple negative tumors. A further exploration of ER/luminal pathway (FoxA1, GATA3, androgen receptor, Cox-2) and of PI3K/Akt/mTOR pathway (eIF4E, 4EBP, p70S6) is ongoing and will be presented.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-21-01.