Clinical Impact of a Novel Model Predictive of Oncotype DX Recurrence Score in Breast Cancer

Abstract

Background/Aim: Oncotype DX recurrence score (RS) for breast cancer is a useful tool for determining chemotherapy indication but it is expensive and time-consuming. We determined whether four immuno-histochemical markers, namely human epidermal growth factor 2 (HER2), estrogen receptor (ER), progesterone receptor (PgR), and Ki-67, are predictive of an RS ≥26 in Japanese patients. Patients and Methods: The study included 95 Japanese patients evaluated for RS. A predictive model was created using logistic regression analysis. Results: The discriminant function was calculated as follows: p=1/{1+exp [−(4.611+1.2342×HER2−0.0813×ER− 0.0489 ×PgR+0.0857×Ki67)]}. Using a probability of 0.5 as the cutoff, the accuracy, sensitivity, specificity, positive predictive and negative predictive values were 90. 5%, 72.2%, 94.8%, 76.4% and 93.5%, respectively. Conclusion: The model had a high negative predictive value in predicting RS ≥26 in Japanese patients, indicating that Oncotype DX testing may be omitted in patients with a negative result according to the predictive model.Oncotype DX recurrence score (RS) (Genomic Health, Redwood City, CA, USA), which is calculated based on the expression levels of 21 genes in paraffin-embedded specimens using reverse transcriptase-polymerase chain reaction assay, predicts the probability of distant recurrence in patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (1). Albeit a globally utilized tool, the RS results are not immediately available. Moreover, performing Oncotype DX testing for all patients with ER-positive/HER2-negative breast cancer is not medically economical.RS is based on the measurement of the expression levels of 16 cancer-related genes and five reference genes. The cancer-related genes evaluated for RS can be categorized into five classes: Proliferation-related, invasion-related, HER2, ER, and 'other'. The information obtained by Oncotype DX testing is more extensive than that obtained by routine immunohistochemical staining for the four markers, ER, progesterone receptor (PgR), HER2 and Ki-67, which are used in daily clinical practice to determine the intrinsic breast cancer subtype. Although it is not possible to predict RS using immunohistochemical staining for these four markers alone, the data obtained with the immunohistochemical approach might be sufficient to determine whether the RS is low or high. Several models for estimating RS have been reported to date (2); however, to the best of our knowledge no study has evaluated RS predictive models using data from Japanese patients with breast cancer.The results of the Trial Assigning Individualized Options for Treatment demonstrated that endocrine treatment alone was non-inferior to chemotherapy plus endocrine treatment for invasive disease-free survival in patients with an RS<26 (3). Therefore, we aimed to establish a model based on the four immunohistochemical markers and to evaluate its ability to predict an RS of ≥26 in Japanese patients with breas...

Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature

“…Two studies from 2022, 27 , 28 also used the older cutoffs, likely because their patient cohorts were taken from before 2018. Six 18 , 19 , 23 , 26 , 29 , 31 studies used the new cutoffs which categorize <15 as low risk, 16 to 25 as intermediate risk, and ⩾26 as high risk, while 3 studies 20 , 21 , 24 used both criteria for their analyses. One study treated the ODx RS as a continuous variable.…”

“…Therefore, clinicians may consider the use of ODx if the Ki-67 index and other markers indicate tumor aggressiveness, rather than using this score for every patient. 19 , 20 , 26 Furthermore, validated equations have been developed to estimate the ODx RS. The Magee equations incorporate various clinicopathologic and immunohistochemical parameters, including Ki-67, to provide a score that has been shown to correlate with the ODx RS.…”

Stratification of Prognosis by Biological Features Following Neoadjuvant Chemotherapy in Luminal Breast Cancer

“…We previously demonstrated that a model based on four markers (ER, PgR, HER2, Ki-67) could predict RS ≥26 (10). The discriminant function was as follows: YR-IHC4=1/{1+exp[−(4.611+1.2342×HER2− 0.0813×ER− 0.0489×PgR+0.0857×Ki-67)]}.…”

BCR-Net: A deep learning framework to predict breast cancer recurrence from histopathology images

“…Similarly, lack of benefit from adjuvant chemotherapy was noted in post-menopausal women and metastases to 1-3 axillary lymph nodes with ODX recurrence score of 25 or less [20]. Unfortunately, ODX and similar gene assays are expensive, time-consuming, and tissue destructive [21][22][23][24][25][26]. Therefore, many studies seek to predict ODX recurrence risk using more routine and less tissue invasive methods, including MR imaging [27], modified Magee equations [28], nomograms [29], and histopathology [30].…”