Association of Peritumoral Radiomics With Tumor Biology and Pathologic Response to Preoperative Targeted Therapy for HER2 (ERBB2)-Positive Breast Cancer.

Authors:
Prateek Prasanna
Prateek Prasanna
Case Western Reserve University
Cleveland | United States
Jon Whitney
Jon Whitney
School of Biomedical Engineering and Sciences
United States
Salendra Singh
Salendra Singh
Lombardi Comprehensive Cancer Center
Niha Beig
Niha Beig
Case Western Reserve University
Cleveland | United States
Maryam Etesami
Maryam Etesami
Case Western Reserve University School of Medicine
Katherine Gallagher
Katherine Gallagher
University of Kansas Medical Center
United States

JAMA Netw Open 2019 Apr 5;2(4):e192561. Epub 2019 Apr 5.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.

Importance: There has been significant recent interest in understanding the utility of quantitative imaging to delineate breast cancer intrinsic biological factors and therapeutic response. No clinically accepted biomarkers are as yet available for estimation of response to human epidermal growth factor receptor 2 (currently known as ERBB2, but referred to as HER2 in this study)-targeted therapy in breast cancer.

Objective: To determine whether imaging signatures on clinical breast magnetic resonance imaging (MRI) could noninvasively characterize HER2-positive tumor biological factors and estimate response to HER2-targeted neoadjuvant therapy.

Design, Setting, And Participants: In a retrospective diagnostic study encompassing 209 patients with breast cancer, textural imaging features extracted within the tumor and annular peritumoral tissue regions on MRI were examined as a means to identify increasingly granular breast cancer subgroups relevant to therapeutic approach and response. First, among a cohort of 117 patients who received an MRI prior to neoadjuvant chemotherapy (NAC) at a single institution from April 27, 2012, through September 4, 2015, imaging features that distinguished HER2+ tumors from other receptor subtypes were identified. Next, among a cohort of 42 patients with HER2+ breast cancers with available MRI and RNaseq data accumulated from a multicenter, preoperative clinical trial (BrUOG 211B), a signature of the response-associated HER2-enriched (HER2-E) molecular subtype within HER2+ tumors (n = 42) was identified. The association of this signature with pathologic complete response was explored in 2 patient cohorts from different institutions, where all patients received HER2-targeted NAC (n = 28, n = 50). Finally, the association between significant peritumoral features and lymphocyte distribution was explored in patients within the BrUOG 211B trial who had corresponding biopsy hematoxylin-eosin-stained slide images. Data analysis was conducted from January 15, 2017, to February 14, 2019.

Main Outcomes And Measures: Evaluation of imaging signatures by the area under the receiver operating characteristic curve (AUC) in identifying HER2+ molecular subtypes and distinguishing pathologic complete response (ypT0/is) to NAC with HER2-targeting.

Results: In the 209 patients included (mean [SD] age, 51.1 [11.7] years), features from the peritumoral regions better discriminated HER2-E tumors (maximum AUC, 0.85; 95% CI, 0.79-0.90; 9-12 mm from the tumor) compared with intratumoral features (AUC, 0.76; 95% CI, 0.69-0.84). A classifier combining peritumoral and intratumoral features identified the HER2-E subtype (AUC, 0.89; 95% CI, 0.84-0.93) and was significantly associated with response to HER2-targeted therapy in both validation cohorts (AUC, 0.80; 95% CI, 0.61-0.98 and AUC, 0.69; 95% CI, 0.53-0.84). Features from the 0- to 3-mm peritumoral region were significantly associated with the density of tumor-infiltrating lymphocytes (R2 = 0.57; 95% CI, 0.39-0.75; P = .002).

Conclusions And Relevance: A combination of peritumoral and intratumoral characteristics appears to identify intrinsic molecular subtypes of HER2+ breast cancers from imaging, offering insights into immune response within the peritumoral environment and suggesting potential benefit for treatment guidance.

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2019.2561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481453PMC

Still can't find the full text of the article?

We can help you send a request to the authors directly.
April 2019
2 Reads

Publication Analysis

Top Keywords

breast cancer
16
response
9
pathologic complete
8
breast
8
patients received
8
imaging signatures
8
complete response
8
intratumoral features
8
imaging features
8
peritumoral intratumoral
8
molecular subtypes
8
209 patients
8
biological factors
8
breast cancers
8
bruog 211b
8
her2+ breast
8
her2+ tumors
8
association peritumoral
8
response her2-targeted
8
peritumoral
7

Similar Publications