Citations

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8–4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.

Abstract Background: Intra-operative identification of positive margins and lymph nodes continues to be a challenge for breast cancer surgeons. Current techniques such as frozen section or touch prep cytology are time consuming and vary in accuracy across institutions. Our study is the first part of a phase 2 trial of a systemically administered, ratiometric, activatable, cell-penetrating fluorescent peptide dye conjugate that visualizes breast cancer tumor tissue in vivo and ex vivo. We hypothesized that this method would be able to identify breast cancer close to the margin of lumpectomy specimens. Methods: AVB-620 is a cell penetrating peptide-fluorescent imaging agent which undergoes proteolytic cleavage by proteases in the matrix metalloproteinase family that have higher activity in cancerous tissue. After cleavage, the predominant fluorescent emission wavelength changes and fluorescent intensity increases, generating a ratiometric readout. AVB-620 was administered 3- 24 hours prior to operation via intravenous infusion to stage 0-III breast cancer patients. Patients were monitored for safety followed by primary breast surgery and either sentinel lymph node biopsy (SLNB) with radiotracer only or axillary lymph node dissection (ALND). Using a near-infrared camera system, fluorescent intensity of two wavelengths was measured intraoperatively both in vivo and ex vivo, including primary tumors, shave margins, and lymph nodes. The ratio of the intensity of these two wavelengths was utilized to distinguish between malignant and non-malignant tissues and visualized on a video monitor. Pathology reports were correlated to a computer-assisted human review of the fluorescent images. Results: Thirty-two patients were dosed without adverse events attributable to the agent; 31 were evaluable for fluorescent imaging. The average age of patients was 60 years (range 32-79). All patients underwent lumpectomy and axillary surgery. Two patients received neoadjuvant chemotherapy; 10% of patients had pure DCIS tumors. Among invasive tumors: 94% were ER+; 13% were high grade. All primary tumor images demonstrated fluorescent intensity and ratiometric changes that differentiated malignant and non-malignant tissue. 35% of patients had at least one positive margin (invasive tumor on ink or DCIS ≤2mm from ink). 61% of cases had at least one margin that was considered either close (≤2mm from ink for invasive tumor) or positive on H&E staining. 84% of patients with positive/close margins were identified utilizing fluorescent imaging. Four of the 5 patients with positive nodes had a positive fluorescent image. Discussion: These results demonstrate the ability of AVB-620 to identify and visualize malignant tumor and lymph nodes intraoperatively, illustrating the potential of such a tool to decrease reoperation rates. The second part of this phase II study is underway where intraoperative fluorescent imaging will be utilized to guide removal of additional shave margins. Citation Format: Chen SL, Baron PL, Lee MC, Feldman SM, McLaughlin SA, Terando AM, Harootunian A, Poonka P, Gonzalez JE. Use of an activatable cell penetrating peptide-fluorescent imaging agent (AVB-620) to identify positive and close margins intraoperatively [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-07.