Background: Oncotype Dx (ODx) is a 21-gene RT-PCR based assay that provides prognostic and predictive information in patients with hormone receptor (HR) positive breast cancer. The test predicts the likelihood of disease recurrence in the form of a recurrence score (RS), which is categorized into low, intermediate and high-risk types. We examined the relationship between ODx RS and histologic parameters, DNA ploidy, tumor markers (ER, PR, Her2, Ki67, p53) expression by immunohistochemistry (IHC).

Design: We identified 106 patients with HR-positive invasive breast cancer who were tested for ODx from the department files. Pathologic variables such as, tumor size, grade, histologic type, lymphovascular invasion (LVI) were reviewed. Tumor markers ER, PR, Her2, p53 expression, Ki67 index (KI) and ploidy were performed as part of the patient's diagnostic work-up using standard procedures. Scoring was done by automated image analysis. Results of biomarker expression were compared to the ODx RS. All Her2neu 3+ and 2+ results by IHC were confirmed by FISH. Ploidy was performed by the Autocyte system (Tripath) on Feulgen stained sections. Oncotype RS was reported as low (<18), intermediate (18-30) and high risk (>30).

Results: Mean tumor size was 1.96 cm. Of the 106 cases, 87 (82%), 14 (13.2%) and 2(1.8%) were ductal, lobular and mixed types respectively. Grade 1, 2 and 3 comprised 35 (33.0%), 62 (58.4%) and 9 (8.5%) respectively. Twenty-one (19.8%) had LVI. Oncotype RS was low in 56 (52.8%), intermediate in 45 (42.4%) and high in 5 (4.7%). Mean tumor size in low RS group was 2.2 cm versus 1.6 cm in the intermediate/high RS group (p <0.05). There was no significant association of grade and LVI with RS. ER Allred score was 7.2, 7.2 and 8.0 and percent positivity was 88.0%, 91.1% and 96.3% in low, intermediate and high RS respectively (p=0.6325). The PR Allred score was 6.0, 5.3 and 3.5 and percent positivity was 64.7%, 51.8% and 16.6% in low, intermediate and high RS respectively (p=0.0432). There was 100% concordance between ER by IHC and ODx. Concordance for PR was 71/75 (94.6%). The four discordant PR results by ODx had mean score of 20% by IHC. The mean KI was 14.4%, 21.8% and 25.6% in low, intermediate and high RS respectively (p=0.0248). Low KI (<14%) and high KI (>14%) showed significant correlation with RS (p=0.0055). Her2neu IHC was negative in 43/49 (87.7%) and borderline in 6/49 (12.2%) and all were negative by FISH. Her2 FISH showed 100% (44/44) concordance with Her2 results by ODx. There was no association between DNA ploidy and RS (p=0.7143). P53 expression showed no significant correlation with RS (p=0.2602). Patients in the intermediate/high RS group were more likely to be treated with a combination of chemo plus anti-hormonal therapy (P<0.0001) and radiation (P<0.05) compared to the low RS group.

Conclusions: This study shows a complete concordance between ER IHC and Her2 FISH with RT-PCR by ODx. Low PR scores and high KI predict

high RS by ODx. There is a significant association between KI and ODx RS. Ki67 index identifies low and high RS groups, which correspond to the luminal A, and B subtypes of breast cancer respectively.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-10.