Abstract

.Neoadjuvant chemotherapy (NACT) is routinely administered to subsets of breast cancer patients, including triple negative (TN) or human epidermal growth factor receptor 2-positive (HER2+) cancers. After NACT and subsequent surgical resection, 5% to 30% of patients have no residual invasive carcinoma, termed pathological complete response. Unfortunately, many patients experience little-to-no response after NACT and unnecessarily suffer its side effects. Methods are needed to predict an individual patient’s response to NACT. Core needle biopsies, taken before NACT, consist of tumor cells and the surrounding extracellular matrix. We performed second-harmonic generation (SHG) imaging of fibrillar collagen in core needle biopsy sections as a possible predictor of response to NACT. The ratio of forward-to-backward scattering (F/B) SHG was assessed in the “tumor bulk” and “tumor–host interface” in HER2+ and TN core needle biopsy sections. Patient response was classified post-treatment using the Residual Cancer Burden (RCB) score. In HER2+ biopsies, RCB class was associated with F/B derived from the tumor–stromal interface, but not tumor bulk. F/B was not associated with RCB class in TN biopsies. These findings suggest that F/B from needle biopsy sections may be a useful predictor of which patients will respond favorably to NACT, with the potential to help reduce overtreatment.

Highlights

  • Neoadjuvant chemotherapy (NACT) is a presurgical option for select breast cancer (BC) patients, including many triple-negative breast cancers (TNBCs) or human epidermal growth factor receptor 2-positive (HER2+) patients

  • We have previously shown that forward-to-backward scattering (F/B) from second-harmonic generation (SHG) images is prognostic of metastasis-free survival in a cohort of untreated ER+ lymph node-negative (LNN) invasive ductal carcinoma (IDC) patients

  • 3.3 TNBC Samples: Intensity Masks In TNBC needle biopsy samples, the average intensity maskbased F/B derived from the tumor bulk was significantly different from that of the tumor–host interface [F∕B 1⁄4 7.48 Æ 0.55

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Summary

Introduction

Neoadjuvant chemotherapy (NACT) is a presurgical option for select breast cancer (BC) patients, including many triple-negative breast cancers (TNBCs) or human epidermal growth factor receptor 2-positive (HER2+) patients. NACT is recommended based on pathological assessment of an initial core needle biopsy, which is routinely taken for diagnosis prior to any therapeutic or surgical intervention. Core needle biopsies utilize x-ray-guided stereotactic imaging, ultrasound guidance, or magnetic resonance imaging guidance to remove a sample of potentially diseased tissue that is sectioned, stained, and used for diagnosis and determination of treatment options, including NACT. Predicting who will and who will not benefit from NACT has proven to be challenging, exposing some patients to unnecessary toxicity and delaying administration of other life-saving treatments.[1] Methods to stratify patients based on expected response to NACT are greatly desired.

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