Objective: While performing surgical excision for breast cancer (lumpectomy), it is important to ensure a clear margin of normal tissue around the cancer to achieve complete resection. The current standard is histopathology; however, it is time-consuming and labour-intensive requiring skilled personnel. Method: We describe a Hybrid Spectral-IRDx -a combination of the previously reported Spectral-IRDx tool with multimodal ultrasound and NIR spectroscopy techniques. We show how this portable, cost-effective, minimal-contact tool could provide rapid diagnosis of cancer using formalin-fixed (FF) and deparaffinized (DP) breast biopsy tissues. Results: Using this new tool, measurements were performed on cancerous/fibroadenoma and its adjacent normal tissues from the same patients (N=14). The acoustic attenuation coefficient (α) and reduced scattering coefficient (µ's) (at 850, 940, and 1060 nm) for the cancerous/fibroadenoma tissues were reported to be higher compared to adjacent normal tissues, a basis of delineation. Comparing FF cancerous and adjacent normal tissue, the difference in µ's at 850 nm and 940 nm were statistically significant (p=3.17e-2 and 7.94e-3 respectively). The difference in α between the cancerous and adjacent normal tissues for DP and FF tissues were also statistically significant (p=2.85e-2 and 7.94e-3 respectively). Combining multimodal parameters α and µ's (at 940 nm) show highest statistical significance (p=6.72e-4) between FF cancerous/fibroadenoma and adjacent normal tissues. Conclusion: We show that Hybrid Spectral-IRDx can accurately delineate between cancerous and adjacent normal breast biopsy tissue. Significance: The results obtained establish the proof-ofprinciple and large-scale testing of this multimodal breast cancer diagnostic platform for core biopsy diagnosis.

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