Magee Equation 3 predicts pathologic response to neoadjuvant systemic chemotherapy in estrogen receptor positive, HER2 negative/equivocal breast tumors

Abstract

Magee Equations were derived as an inexpensive, rapid alternative to Oncotype DX. The Magee Equation 3 utilizes immunohistochemical and FISH data for estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 for its calculation (24.30812+ERIHC × (−0.02177)+PRIHC × (−0.02884)+(0 for HER2 negative, 1.46495 for equivocal, 12.75525 for HER2 positive)+Ki-67 × 0.18649). We hypothesize that Magee Equation 3 scores from pretherapy core biopsy can predict response to neoadjuvant systemic chemotherapy. A prospectively-maintained database of patients who received neoadjuvant systemic therapy from 2010 to 2014 at a single institution was retrospectively reviewed. Pathologic complete response was defined as absence of invasive tumor in the breast and regional lymph nodes. Of the 614 cases, tumors with missing immunohistochemical results and those that were ER negative or HER2 positive were excluded. This resulted in 237 ER positive, HER2 negative/equivocal tumors that formed the basis of this study. Magee Equation 3 scores were divided into 3 categories similar to Oncotype DX, ie, 0 to o 18 (low), 18 to o 31 (intermediate), and 31 or higher (high) scores. The pathologic complete response rate for low, intermediate and high Magee Equation 3 scores was 0%, 4%, and 36%, respectively. Patients with high Magee Equation 3 scores were 13 times more likely to achieve pathologic complete response compared to those with Magee Equation 3 scores less than 31 (95% CI 5.09-32.87, Po 0.0001). For patients that did not achieve pathologic complete response, high Magee Equation 3 correlated with higher recurrence rate, with the majority occurring in patients with positive lymph nodes in the resection specimen. Magee Equation 3 score ≥ 31 predicts pathologic complete response in the neoadjuvant setting and for tumor recurrence, when pathologic complete response is not achieved. These results show the utility of Magee Equation 3 in predicting patients who will benefit from chemotherapy but warrant prospective multiinstitutional validation. Modern Pathology (2017Pathology ( ) 30, 1078Pathology ( -1085 doi:10.1038/modpathol.2017 published online 26 May 2017 The decision to recommend chemotherapy to patients with early stage breast cancer that is estrogen receptor positive (ER+) HER2 negative is challenging, as many of these tumors respond favorably to endocrine therapy alone. Clinical parameters, such as tumor size and lymph node status, are strong prognostic factors, 1,2 but appear to have limited predictive value in assessing responsiveness to chemotherapy. Although tumor grade predicts

The healthcare value of the Magee Decision Algorithm™: use of Magee Equations™ and mitosis score to safely forgo molecular testing in breast cancer

“…Our group has previously published multivariable models to estimate the oncotype score, first as proof of principle and later as a clinically useful tool to decide if a particular tumor needs oncotype testing [5,6]. The models, now commonly known as MEs have been shown to be strongly chemopredictive in the neoadjuvant setting and also appear to have prognostic value [7]. In light of the TAILORx results we recently described an algorithmic approach to safely forgo oncotype testing.…”

“…If the estimate is between 10 and 50, then 50-100 cells are counted in a representative area based on the pathologist's discretion to arrive at the labeling index. This approach seems to have worked as seen in this study and our prior neoadjuvant study, where the Ki-67 labeling index has been used in a multivariable model to predict chemotherapy benefit [7]. One potential weakness of the study is that all cases are from one institution where pathology reports are signed out by breast pathologists.…”

“…These models use routinely reported histopathology and breast cancer biomarker data to provide a score similar to oncotype. One of the equations (ME3) has been shown to predict for a pathologic complete response to neoadjuvant chemotherapy in ER+/HER2-negative tumors [7]. With the new oncotype recurrence score cut-off value of 25, we recently described a decision algorithm using MEs and tumor mitotic activity score to safely forgo oncotype testing [8].…”

<p>The Evaluation of Magee Equation 2 in Predicting Response and Outcome in Hormone Receptor-Positive and HER2-Negative Breast Cancer Patients Receiving Neoadjuvant Chemotherapy</p>

“…18 Magee Equation 3 score was previously reported to be accurately predict the response to NAC in HRpositive, HER2-negative breast cancer. 30 Due to Ki67 was not available in a significant proportion of the patients in our cohort, Magee Equation 2 that does not require Ki67 results was utilized in the current study. High Magee Equation 2 score was the independent predictor for pCR in HR-positive, HER2-negative breast cancer.…”

Practical Consequences Resulting from the Analysis of a 21-Multigene Array in the Interdisciplinary Conference of a Breast Cancer Center

“…This new Magee-equation (http://path.upmc.edu/onlineTools/mageeequations.html, accessed June 5th 2018) shows a high concordance with original Magee-equation and its use can diminish the need of multigene testing in breast cancer. Furthermore, Magee 3 equation could predict the response of ER-positive, Her2/neu negative breast cancers in neoadjuvant concepts [ 20 ]. Cuzick et al and Sheri et al described the use of IHC4 (values by immunohistochemistry of ER, PR, Her2/neu, and Ki67) with similar predictive intention in early breast cancer and neoadjuvant concepts [ 21 , 22 ].…”