Abstract P3-08-09: The 21-gene recurrence score and chemotherapy use in triple negative breast cancer (TNBC) and HER2 positive breast cancer: A National Cancer Database study
Authors: Boughey JC , Hoskin TL , Cocco D , Day CN , Leon-Ferre R , Habermann EB , Goetz MP 
Published: May 2019

Background

The 21-gene (Oncotype DX) Recurrence Score (RS) is a multi-gene expression assay that is both prognostic and predictive of adjuvant chemotherapy (AdjCT) benefit in estrogen receptor (ER) positive/HER2 negative breast cancer (BC). Use of the RS in TNBC and HER2+ BC is not recommended by national guidelines. Using the National Cancer Database (NCDB), we sought to evaluate whether oncologists use the RS in these subtypes. Additionally, we assessed the prognostic effects of the RS in node negative patients (pts) who did or did not receive adjuvant chemotherapy.

Methods

Pts with TN and HER2+ BC diagnosed from 2010-2015 in the NCDB were analyzed. Pts with neoadjuvant therapy or stage IV were excluded. Cases with RS testing were classified as low (RS 0-17), intermediate (RS 18-30) or high (RS 31+). Analysis was performed using multivariable logistic regression; overall survival (OS) was analyzed using the Kaplan-Meier method with log-rank tests.

Results

142,330 pts were evaluable: 64,830 TNBC and 77,500 HER2+ (21,768 ER-/HER2+ and 55,732 ER+/HER2+). In these subtypes, RS was performed in 5,369 (3.8%) pts as follows: 1,479 (2.3%) TNBC, 185 (0.8%) ER-/HER2+, and 3,705 (6.6%) ER+/HER2+. Given the small ER-/HER2+ cohort, we focused on TNBC and ER+/HER2+. Within these subtypes, factors associated with RS testing included lower grade, smaller pathologic tumor size, pathologic N0 status, white race, age 60-69, and ILC or IMC histology (each p&lt;0.005).

Of the TNBC pts tested, the RS distribution was: low 16.3%, intermediate 13.1% and high 70.6%, while for ER+/HER2+ it was low 30.5%, intermediate 30.7% and high 38.8% (p&lt;0.001).

AdjCT was less frequently recommended in pts with low RS; however, this varied by tumor subtype with AdjCT recommended for 66.8% of TNBC with low RS and 37.9% of ER+/HER2+ with low RS. For intermediate RS, rates of AdjCT recommendation were 74.3% and 73.7%, and for high RS were 94.0% and 93.2% for TNBC and ER+/HER2+ respectively.

In a multivariable analysis among pts with low RS, factors associated with AdjCT recommendation included younger age, larger pathologic tumor size, node positive disease, and higher grade.

In AdjCT untreated TNBC, 5 yr OS did not differ for low RS (96.5%) vs intermediate RS (95.2%, p=0.82). In contrast OS was significantly worse for high RS (76.7%) than the other two groups, each p≤0.04.

In AdjCT untreated ER+/HER2+, 5 yr OS was significantly better for low RS (96.7%) vs intermediate RS (92.5%, p=0.03) and vs high RS (92.1%, p=0.003), with no difference between intermediate RS vs high RS (p=0.32).

Evaluating pts who did receive AdjCT, there was no significant difference in 5 yr OS for either subtype according to RS (p=0.46 and p=0.83).

Interestingly, in patients with low RS, 5 yr OS was similar with or without AdjCT in both TNBC (89.5% vs 96.5%, p=0.25) and ER+/HER2+ (97.6% vs 96.7%, p=0.47).

Conclusions

RS testing is being conducted in a small fraction of pts with TN and HER2+ BC with lower clinical risk features. The observation that RS is prognostic for survival in AdjCT untreated patients is hypothesis generating, and suggests that further evaluation of the RS and other multigene assays in ER negative and HER2+ BC is warranted.

Citation Format: Boughey JC, Hoskin TL, Cocco D, Day CN, Leon-Ferre R, Habermann EB, Goetz MP. The 21-gene recurrence score and chemotherapy use in triple negative breast cancer (TNBC) and HER2 positive breast cancer: A National Cancer Database study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-09.