OncotypeDX (ODX®) can enhance prediction of breast cancer recurrence, guiding adjuvant treatment options. However, the opportunity to access this test is not always possible. The aim of this study is to investigate the correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC) and recurrent score (RS) resulting from ODX®.
All breast cancer patients who underwent ODX® between 2014 and 2018 were retrospectively included in the study. The data selected for analysis were age, menopausal status, pathological and IHC features. IHC was performed with standardized quantitative methods. Dataset was split into two subsets (70% for training and 30% for internal validation). Logistic models were built with statistically significant features for predicting RS ≤ 25 or ≤ 20. An external validation set, provided by another center, was used to test reliability of prediction models.
The internal dataset included 407 patients (Table) who underwent ODX®. Mean age was 53.7 (31-80) and 222 patients (54.55%) were > 50 years old. ODX® results showed: 67 patients (16.6%) between 0-10, 272 patients between 11-25 (66.8%) and 68 pts > 26 (16.6%). At the logistic regression analysis, RS score was significantly associated with ER (p = 0.004), PgR (p < 0.001), and Ki67% (p < 0.001) with the threshold equal to 25. Above patients with RS ≤ 25, the generalized linear regression resulted in a well calibrated model with an AUC of 92.2% (sensitivity 84.2%; specificity 80.1%). External validation set included 180 patients and confirmed the model performance with an AUC of 82.3% and good calibration. A nomogram predicting RS score ≤25 was generated. 261P Tumor characteristics training set + internal test setTraining + internal test set – Tumor characteristics Histological subtype classification Invasive Ductal Carcinoma 318 pts (78,1%) Invasive Lobular Carcinoma 47 pts (11,5%) Other 42 pts (10,3%) Grading 1 28 pts (6.8%) 2 268 pts (65,8%) 3 111 pts (27,3%) pT 1a 3 pts (0,7%) 1b 38 pts (9,3%) 1c 216 pts (53,1%) 2 143 pts (35,1%) 3 6 pts (1,5%) 4 1 pt (0,3%) pN 0 233 pts (57,2%) 0i+ 12 pts (3%) 1mic 43 pts (10,6%) 1 108 pts (26,5%) NA 11 pts (2,7%) Mean T diameter [cm] 1.9 (Range 0,2-8,5) Mean Sentinel Lymph Node (SLN) diameter [mm] 1.7 (Range 0-40) Mean Axillary Lymph Node (ALN) diameter [mm] 0.8 (Range 0-25) Mean N Ratio 0.14 (0.00 – 1.00) SLN involvement [n° of nodes] 0 261 pts (64,1%) 1 112 pts (27,5%) 2 24 pts (5,8%) 3 1 pt (0,2%) NA 9 pts (2,2%) ALN involvement [n° of nodes] 0 338 pts (83%) 0i+ 4 pts (1%) 1mic 3 pts (0,7%) 1 31 pts (7,6%) 2 8 pts (2%) 3 5 pts (1,2%) 5 1 pt (0,2%) NA 17 pts (4,1%) Multifocality Yes 97 pts (23,8%) No 300 pts (73,7%) NA 10 pts (2.5%) Multicentricity Yes 20 pts (4,9%) No 376 pts (92,4%) NA 11 pts (2,7%) PVI Absent 242 pts (59,4%) Focal 51 pts (12,5%) Moderate 32 pts (7,8%) Massive 59 pts (14,5%) NA 23 pts (5,6%) Mean ER expression 87,9% (Range 1-100) Mean PgR expression 62.2% (Range 0-100) Mean AR expression 7.7% (Range 0-90) Mean Ki67% expression 29.8% (Range 0-90) Her2 Expression 0 187 pts (46%) 1 112 pts (27,5%) 2 104 pts (25,5%) NA 4 pts (0,9%) Fluorescence in situ hybridization (FISH) for HER-2 Not determined 300 pts (73,7%) Not amplificated 100 pts (23,7%) Undetermined 1 pt (0,2%) Equivocal 1 pt (0,2%)
Quantitative IHC presents a good correlation with RS score in patients with RS ≤ 25, also in external validation set. A nomogram for physician that enhances a cost/effectiveness clinical approach practice has been developed. Prospective clinical application will be tested in further studies.
Fabio Marazzi.
Has not received any funding.
All authors have declared no conflicts of interest.