MRI-Based Radiomics Approach Predicts Tumor Recurrence in ER+/HER2- Early Breast Cancer Patients

Oncotype Dx is a genetic assay providing a recurrence score (RS) correlated with the risk of cancer recurrence and adjuvant treatment response in breast carcinoma. We investigated the ability of an MRI-based radiomics approach to predict the risk of tumor recurrence in breast cancer. A total of 62 patients with biopsy-proved ER+/HER2- early breast cancer who underwent pre-treatment MRI and Oncotype Dx were included. An RS>25 was considered discriminant between low-intermediate and high risk of tumor recurrence. Two readers segmented each tumor. Radiomics features were extracted from the tumor and the peritumoral tissues. Partial least square (PLS) regression was used as the multivariate machine-learning algorithm. PLS β-weights of radiomics features included the 5% features with the largest β-weights in magnitude (top 5%). The diagnostic performance of the radiomics model was assessed through receiver operating characteristic (ROC) analysis. A null hypothesis probability threshold of 5% was chosen (p < 0.05). The predictive model delivered an AUC of 0.76. Of the 47 features included in the top 5%, 33 were texture-related and derived from the tumor and the peritumoral tissues. After a prospective evaluation in more extensive clinical trials, this approach may identify non-invasively patients who are more likely to benefit from adjuvant therapy.

Predicting oncotype DX recurrence scores using locally available immunohistochemical markers: experience in a district general hospital

AimsOncotype DX testing is a reliable widely used gene assay to determine whether chemotherapy is of additional value in oestrogen receptor (ER) positive Human Epidermal Growth Factor receptor 2 (HER2) negative, node negative breast cancer, but the high cost of the test can be a barrier for optimal therapy guidance for a substantial proportion of eligible patients around the world. We aimed to determine whether the commonly available immunohistochemical markers Ki67 and progesterone receptor (PR) can predict Oncotype DX Recurrence Score (RS) scores in a district general hospital setting.MethodsThe Oncotype DX RS scores from 58 tumours were regressed against corrected Ki67 values in a simple regression model, and against ER-derived and PR-derived indices and corrected Ki67 values in a multiple model. Model portability was assessed using leave-one-out cross-validation (LOOCV).ResultsAll terms in both regression models were significantly associated with RS scores at the 5% significance level (p<0.001 for all parameters). The multiple model was a better fit to the data (adjusted R2=0.784), and performed better under LOOCV (root mean square error=7.26), suggesting good predictive capability and model portability.ConclusionsLocally available, cheaper alternatives to multigene assays to determine therapy in ER positive HER2 negative patients is of benefit both from patient management and financial perspectives. A model has been derived with high capability to predict RS scores accurately from linear combinations of predictive biomarkers in a district general hospital setting, which should show good properties when applied to other samples.

Comparison of the Modified IHC4 Score and 21-Gene Recurrence Score Assay in Patients with Estrogen Receptor-Positive Breast Cancer

Introduction: Not only the 21-gene recurrence score (RS) assay but also online prognostic tools and immunohistochemical prognostic models predict chemotherapy benefits for women with early breast cancer. Multi-gene assays, including Oncotype DX, are expensive and not covered by insurance in some countries. Methods: In this study, we retrospectively analyzed a series of 155 patients with estrogen receptor-positive primary breast cancer for whom an Oncotype DX assay was performed between January 2016 and August 2021. The patients’ modified immunohistochemical marker (mIHC4) scores were calculated on the basis of their pathological reports. The correlations of the RS with the online tool PREDICT and mIHC4 scores were evaluated. Results: Of the patients, 43.9% were premenopausal, 147 (94.8%) had T1 or T2 tumor, and 55.5% had no positive lymph nodes. Low (0–10), intermediate (11–25), and high RSs (26–100) were obtained in 16.1%, 61.9%, and 21.9% of the patients, respectively. The RS showed no correlation with the PREDICT score (r = 0.2720) but correlated with the mIHC4 score (r = 0.6356). In addition, a stronger correlation was observed in the patients with no node involvement and in the postmenopausal patients (r = 0.6609 and r = 0.7277, respectively). Conclusions: A relatively strong correlation was observed between the RS and the mIHC4 score. The mIHC4 score is a potentially easy and useful tool to guide adjuvant chemotherapy decision making especially for postmenopausal patients with no node involvement if a genomic test could not be performed for some reason.

Is Oncotype DX Testing Necessary For Patients With Node Negative, Low-Grade Invasive Ductal Breast Carcinoma?

Introduction/Objective Oncotype DX (Genomic Health/Exact Sciences, Redwood City, CA) is a 21-gene expression test that is used to predict the risk of recurrence following hormonal therapy and adjuvant chemotherapy (CT) benefit for patients with early-stage, ER-positive and HER2-negative invasive breast carcinoma (IBC). Testing is performed on formalin-fixed, paraffin-embedded tumor tissue from patients that are either lymph node (LN) negative, have micro- metastases, or 1-3 positive LNs. For years pathologists have studied traditional prognostic features of IBC (tumor grade, size, and LN status), as well as biomarker testing results (ER, PR, HER2, and Ki-67), in an effort to identify surrogate equations that could help identify patients that would benefit from CT. The “TAILORx” clinical trial, performed to study CT benefit in patients with midrange recurrence scores (11-25), has shown that the majority of these patients do not derive benefit from CT. Post-TAILORx, we have observed that only a small subset of our node- negative patients who were tested showed a benefit for CT. Following the examination of Oncotype DX results from testing performed on our patients, we hypothesized that overall tumor grade (Nottingham) might predict which patients with invasive ductal breast carcinoma (IDBC) do not require Oncotype DX testing; therefore, eliminating the need for Oncotype DX testing. Methods/Case Report We reviewed the surgical pathology reports and Oncotype DX reports for 251 patients with node-negative disease who underwent surgery at our institution from September 2019 through June 2021. All excisional tumors sent for Oncotype DX testing were ER-positive (Allred score ≥6/8) and HER2-negative by IHC and/or FISH. Results (if a Case Study enter NA) Oncotype DX recurrence scores ranged from 0-65. A benefit for CT was seen in 10.4% (26/251) of the patients with node-negative IDBC. A benefit for CT was seen in 6.1% (7/114) of patients with an overall tumor grade of II and 44.2% (19/43) of patients with an overall grade of III. No patients (0/94) with IDBC and an overall tumor grade of I showed a benefit for CT. Conclusion In the post-TAILORx era, patients with ER-positive (Allred ≥6/8), HER2-negative IDBC, who are node- negative and show an overall tumor grade of I, apparently do not require Oncotype DX testing. Additional studies from other institutions are needed to confirm our observation.