Background: Pathologic complete response (pCR) or a low Residual Cancer Burden (RCB) score following neoadjuvant chemotherapy (NACT) predicts a superior survival in breast cancer (BC) patients. An early predictive marker of tumor response during NACT would provide a way to optimize treatment for non-responders; however, no ideal technology currently exists. Diffuse optical tomography (DOT) is a novel, fast, safe, and low-cost technique that uses near infrared light to provide 3D data on tissue vascularity without the use of radiation, making it a promising technology for assessing early tumor response to NACT. We hypothesized that a 2-week change in DOT parameters would predict response to NACT as measured by the RCB score.
Methods: Women with stage II-IIIc invasive BC scheduled to undergo NACT with 12 cycles of a weekly taxane followed by 4 cycles of doxorubicin with cyclophosphamide (AC) were enrolled. Treatment with additional biologic therapies was allowed. DOT measurements were made before starting NACT, 2 weeks into treatment, and before surgery. Concentrations of oxyhemoglobin [HbO2], deoxyhemoglobin [Hb], total hemoglobin [HbT], and tissue scattering (SC) were measured by DOT. Final pathology specimens were scored for the RCB index (continuous measure), RCB class (0, 1, 2, 3), and a dichotomized RCB score (RCB class 0 or 1: responders to NACT; RCB class 2 or 3: non-responders). Correlation analysis, ANOVA testing, and two sample t-tests were used to evaluate the relationship between the two-week changes in DOT parameters and the RCB score.
Results: Since July 2011, we have recruited 11 pts, of whom 7 have undergone surgery. Complete data is available for 6 pts. Two of 7 pts had a pCR (RCB 0), 1 had RCB 1, 3 had RCB 2, and 1 had RCB 3. The Pearson correlation between the 2-week change in [Hb] and the continuous RCB index was 0.94 (p = 0.0047), and that between the 2-week change in SC and the RCB index was 0.93 (p = 0.0073). At 2 weeks, the [Hb] decreased by 6.7% for pts whose pathology demonstrated an RCB 0 (pCR), 1.8% for RCB 1, 0.6% for RCB 2, and increased 0.7% for RCB 3. ANOVA and Tukey testing demonstrated a significant difference in the [Hb] change for pts with RCB 0 compared to pts with RCB 1, 2, or 3 (p <0.05). At 2 weeks, SC decreased by 26.5% for pts with RCB 0, 19.3% for RCB 1, 3.7% for RCB 2, and increased by 25.1% for RCB 3. There was a significant difference in the SC change for pts with RCB 0 compared to pts with RCB 3 (p <0.05). Responders (RCB 0/1) had a 5% decrease in [Hb] at 2 weeks compared to non-responders (RCB 2/3) who had a decrease in 0.18% in [Hb] (p = 0.0045), and responders had a 24% decrease in SC compared to non-responders who had an increase in 6% (p = 0.044).
Conclusions: DOT change is an early predictor of response to NACT as measured by the RCB score. We found a significant linear association between the RCB index and the 2-week change in [Hb] and SC. Significantly different changes in DOT parameters were associated with the other RCB classifications. Additional recruitment is ongoing and differences by tumor subtype will be evaluated.
*These two authors contributed equally to this study
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-07.