Effects of neoadjuvant chemotherapy on the contralateral non-tumor-bearing breast assessed by diffuse optical tomography.

BACKGROUND: The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR). METHODS: In this retrospective evaluation of 105 patients with stage II-III breast cancer, oxy-hemoglobin (ctO2Hb) from the contralateral non-tumor-bearing breast was collected and analyzed at different time points during NAC. The earliest monitoring imaging time point was after 2-3 weeks receiving taxane. Longitudinal data were analyzed using linear mixed-effects modeling to evaluate the contralateral breast ctO2Hb changes across chemotherapy when corrected for pCR status, age, and BMI. RESULTS: Patients who achieved pCR to NAC had an overall decrease of 3.88 µM for ctO2Hb (95% CI, 1.39 to 6.37 µM), p = .004, after 2-3 weeks. On the other hand, non-pCR subjects had a non-significant mean reduction of 0.14 µM (95% CI, - 1.30 to 1.58 µM), p > .05. Mixed-effect model results indicated a statistically significant negative relationship of ctO2Hb levels with BMI and age. CONCLUSIONS: This study demonstrates that the contralateral normal breast tissue assessed by DOTBIS is modifiable after NAC, with changes associated with pCR after only 2-3 weeks of chemotherapy.

Diffuse optical tomography breast imaging measurements are modifiable with pre-surgical targeted and endocrine therapies among women with early stage breast cancer.

PURPOSE: Diffuse optical tomography breast imaging system (DOTBIS) non-invasively measures tissue concentration of hemoglobin, which is a potential biomarker of short-term response to neoadjuvant chemotherapy. We evaluated whether DOTBIS-derived measurements are modifiable with targeted therapies, including AKT inhibition and endocrine therapy. METHODS: We conducted a proof of principle study in seven postmenopausal women with stage I-III breast cancer who were enrolled in pre-surgical studies of the AKT inhibitor MK-2206 (n = 4) or the aromatase inhibitors exemestane (n = 2) and letrozole (n = 1). We performed DOTBIS at baseline (before initiation of therapy) and post-therapy in the affected breast (tumor volume) and contralateral, unaffected breast, and measured tissue concentrations (in µM) of total hemoglobin (ctTHb), oxyhemoglobin (ctO2Hb), and deoxyhemoglobin (ctHHb), as well as water fraction (%). RESULTS: We found consistent decreases in DOTBIS-measured hemoglobin concentrations in tumor volume, with median percent changes for ctTHb, ctHHb, ctO2Hb, and water fraction for the entire cohort of - 27.1% (interquartile range [IQR] 37.5%), - 49.8% (IQR 29.3%), - 33.5% (IQR 47.4%), and - 3.6% (IQR 10.6%), respectively. In the contralateral breast, median percent changes for ctTHb, ctHHb, ctO2Hb, and water fraction were + 1.8% (IQR 26.7%), - 8.6% (IQR 29.3%), + 6.2% (IQR 29.5%), and + 1.9% (IQR 30.7%), respectively. CONCLUSION: We demonstrated that DOTBIS-derived measurements are modifiable with pre-surgical AKT inhibition and endocrine therapy, supporting further investigation of DOTBIS as a potential imaging assessment of response to neoadjuvant targeted therapies in early stage breast cancer.

Changes in Diffuse Optical Tomography Images During Early Stages of Neoadjuvant Chemotherapy Correlate with Tumor Response in Different Breast Cancer Subtypes.

PURPOSE: This study's primary objective was to evaluate the changes in optically derived parameters acquired with a diffuse optical tomography breast imaging system (DOTBIS) in the tumor volume of patients with breast carcinoma receiving neoadjuvant chemotherapy (NAC). EXPERIMENTAL DESIGN: In this analysis of 105 patients with stage II-III breast cancer, normalized mean values of total hemoglobin ([Formula: see text]), oxyhemoglobin ([Formula: see text]), deoxy-hemoglobin concentration ([Formula: see text]), water, and oxygen saturation ([Formula: see text]) percentages were collected at different timepoints during NAC and compared with baseline measurements. This report compared changes in these optical biomarkers measured in patients who did not achieve a pathologic complete response (non-pCR) and those with a pCR. Differences regarding molecular subtypes were included for hormone receptor-positive and HER2-negative, HER2-positive, and triple-negative breast cancer. RESULTS: At baseline, [Formula: see text] was higher for pCR tumors (3.97 ± 2.29) compared with non-pCR tumors (3.00 ± 1.72; P = 0.031). At the earliest imaging point after starting therapy, the mean change of [Formula: see text] compared with baseline ([Formula: see text]) was statistically significantly higher in non-pCR (1.23 ± 0.67) than in those with a pCR (0.87 ± 0.61; P < 0.0005), and significantly correlated to residual cancer burden classification (r = 0.448; P < 0.0005). [Formula: see text] combined with HER2 status was proposed as a two-predictor logistic model, with AUC = 0.891; P < 0.0005; and 95% confidence interval, 0.812-0.969. CONCLUSIONS: This study demonstrates that DOTBIS measured features change over time according to tumor pCR status and may predict early in the NAC treatment course whether a patient is responding to NAC.

Diffuse optical tomography of the breast: a potential modifiable biomarker of breast cancer risk with neoadjuvant chemotherapy.

The purpose of this study is to evaluate whether a diffuse optical tomography breast imaging system (DOTBIS) can provide a comparable optical-based image index of mammographic breast density, an established biomarker of breast cancer risk. Oxyhemoglobin concentration (ctO2Hb) measured by DOTBIS was collected from 40 patients with stage II-III breast cancer. The tumor-free contralateral breast was used for this evaluation. We observed a moderate positive correlation between the patient's mammogram density classification and ctO2Hb, rs = 0.486 (p = 0.001). In addition, significant reduction in ctO2Hb levels were noted during neoadjuvant chemotherapy treatment (p = 0.017). This observation indicates that ctO2Hb levels measured by DOTBIS could be a novel modifiable imaging biomarker of breast cancer risk and warrants further investigation.