No abstract

e12604 Background: The safety of the sentinel lymph node biopsy procedure (SLNB) in the surgical management of breast cancer relies upon a false negative rate (FNR) being less than 10%. The accuracy of SLNB in invasive lobular carcinoma (ILC), the second most common type of breast cancer, has not been evaluated. Because of high rates of false negative imaging and the diffuse growth pattern in ILC, less accurate pre-operative staging and a potentially unreliable lymphatic drainage pattern may impact the accuracy of SLNB in this tumor type. We therefore sought to characterize the accuracy of SLNB in a cohort of patients with ILC. Methods: We queried an institutional database of 707 patients with ILC and identified 196 patients who underwent SLN mapping with excision of both sentinel and non-sentinel nodes. A false negative was defined as having negative sentinel lymph nodes and a positive non-sentinel node. We calculated the FNR and sensitivity of SLNB and evaluated clinicopathologic variables. Results: Of 196 cases, 183 were clinically node-negative, 9 were clinically node-positive, and 4 had unknown clinical node status. Of the 183 clinically node-negative patients, 69 (37.7%) patients had node-positive disease at surgery. Overall, 7 of 196 cases had false negative SLNB, yielding an FNR of 8.97%. The sensitivity of SLNB was 91%. Patients with a false negative SLNB were significantly older than patients without (mean age 63 versus 54.7 years, p = 0.041). Significantly fewer sentinel and non-sentinel nodes were removed in women aged 50 years or older compared to those under 50 (1.9 vs. 2.5 sentinel nodes, p = 0.0158; 4.7 vs. 7.9 non-sentinel nodes, p = 0.0077). There were no differences in tumor receptor subtype, grade, stage, presence of lymphovascular invasion, or receipt of neoadjuvant therapy in those with a false negative SLNB compared to those without. Conclusions: The high rate of nodal positivity in clinically node negative patients highlights the challenges of clinical nodal assessment in ILC. Despite this, the SLNB procedure had a FNR that fell within the acceptable range, supporting its use in ILC. The relationship between number of sentinel nodes removed and FNR deserves further study, particularly in older women where extent of nodal surgery continues to decline.

508 Background: I-SPY 2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint (MP) risk to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. SD-101 is an investigational Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide that stimulates the production of IFN-α and interleukin (IL)-12, functional maturation of plasmacytoid dendritic cells, and production of cytotoxic antibodies. IT SD-101 was combined with systemic anti-PD-1 antibody Pb to investigate the antitumor and immunologic activity of this novel immunotherapeutic strategy. Methods: Women with tumors ≥ 2.5cm were eligible for screening. Only pts (pts) with HER2- disease were eligible for this treatment. Treatment included weekly P x 12 in combination with IT SD-101 2 mg/ml (1 ml for T2 tumors, 2 ml for >T3 tumors) weekly x 4, then q3 weeks x 2, and IV Pb q3 weeks x 4, followed by doxorubicin/cyclophosphamide (AC) q2-3 weeks x 4 (SD-101+Pembro 4). Pts in the control arm received weekly P x 12 followed by AC q2-3 weeks x 4. The I-SPY 2 methods have been previously published. This investigational arm was eligible for graduation (>85% chance of success in a 300-person phase 3 neoadjuvant trial) in 3 of 10 pre-defined signatures: HER2-, hormone receptor (HR)+/HER2- and HR-/HER2-. Results: 75 pts were randomized and evaluable in SD-101+Pembro 4 treatment arm. The control arm included 329 historical controls enrolled since April 2010. The study arm was stopped due to maximal patient accrual. Pt characteristics were balanced; 56% HR+, 44% HR-. The probability that SD-101+Pembro4 was superior to control exceeded 97% for all eligible tumor signatures, but did not reach the threshold for graduation in any of the signatures. However, it is notable that the rate of pCR/Residual Cancer Burden 1 (RCB1) in the HR+/HER2- signature was 51%. Preliminary safety events for SD-101+Pembro 4 include increased rates of fever, neutropenia, febrile neutropenia, transaminitis, and immune-related events, including adrenal insufficiency. Conclusions: The SD-101+Pembro 4 regimen was active but did not meet the pre-specified threshold for graduation in I-SPY 2. pCR/RCB 1 analysis suggests improved response in the HR+/HER-negative signature compared to control. The clinical significance of these findings needs to be weighed against the potential risk of immune-related toxicities. Clinical trial information: NCT01042379. [Table: see text]

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.

No abstract