Early Assessment Window for Predicting Breast Cancer Neoadjuvant Therapy using Biomarkers, Ultrasound, and Diffuse Optical Tomography

Abstract

Background:Neoadjuvant Therapy (NAT) permits less aggressive breast and axillary surgery and better assessment of systemic response. Establishing accurate and early predictors of NAT response would help limit morbidity of ineffective regimens through modi cation of treatment regimens and thereby optimize clinical outcomes. The purpose of the study was to assess the utility of tumor biomarkers, ultrasound (US) and US-guided diffuse optical tomography (DOT) in early prediction of breast cancer response to NAT. MethodsThis prospective HIPAA compliant study was approved by the institutional review board. Forty one patients were imaged with US and US-guided DOT prior to NAT, at completion of the rst three treatment cycles, and prior to de nitive surgery from February 2017 to January 2020. Miller-Payne grading was used to assess pathologic response. Receiver operating characteristic curves (ROCs) were derived from logistic regression using independent variables, including: tumor biomarkers, US maximum diameter, percentage reduction of the diameter (%US), pretreatment maximum total hemoglobin concentration (HbT) and percentage reduction in HbT (%HbT) at different treatment time points. Resulting ROCs were compared using area under the curve (AUC). Statistical signi cance was tested using two-sided two-sample student t-test with P<0.05 considered statistically signi cant. ResultsThirty-eight patients (mean age =47, range 24-71 years) successfully completed the study, including 15 HER2+ of which 11 were ER+; 12 ER+ or PR+/HER2-, and 11 triple negative. The combination of HER2 and ER biomarkers, %HbT at the end of cycle 1 (EOC1) and %US (EOC1) provided the best early prediction, AUC = 0.941 (95% CI: 0.869-1.0). Similarly an AUC of 0.910 (95% CI: 0.810-1.0) with %US (EOC1) and %HbT (EOC1) can be achieved independent of HER2 and ER status. The most accurate prediction, AUC = 0.974 (95% CI: 0.933-1.0), was achieved with %US at EOC1 and %HbT (EOC3) independent of biomarker status. ConclusionThe combined use of tumor HER2 and ER status, US, and US-guided DOT may provide accurate prediction of NAT response as early as the completion of the rst treatment cycle.

Changes in the tumor oxygenation but not in the tumor volume and tumor vascularization reflect early response of breast cancer to neoadjuvant chemotherapy

“…Multiple studies have demonstrated DOSI data to be a prospective marker that reflects pathological tumor response at various times from the NACT starts [ 21 , 24 , 29 – 33 ] . The combined use of DOSI and assessment of the dynamics of tumor volume by the US, as well as taking into account tumor immunophenotype, made it possible to increase the predictive capabilities of the method [ 34 ] .…”

Hypoxia-Inducible Factor-1 Alpha Expression Is Predictive of Pathological Complete Response in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy

“…The total score is obtained by adding the staining score and intensity score. Any score between 0 and 2 is considered ER or PR negative; any score above 2 is considered ER or PR positive [ 19 ]. A case was considered positive when staining for ER and PR was found in 10% or more of tumor cells [ 20 ].…”

Predicting dynamic response to neoadjuvant chemotherapy in breast cancer: a novel metabolomics approach

“…Following these criteria, MP5 is considered as pCR with no malignant cells; MP4 is a very good response with <10% of malignant cells remaining, near the pCR; in MP3 the significant loss of tumor cells is too variable between 30 and 90%; MP2 shows a reduction of tumor cells < 30%, and MP1 has no reduction in malignant cells. Herein, we defined a response group (MP grades 4-5) and a nonresponse group (MP grades 1-3) according to the prognostic potential of the MP grading system [37][38][39][40].…”