Austin D. Williams

Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer

Transiently expressed chimeric antigen receptor T cells specific for c-Met, expressed in breast cancer, were injected into breast cancer tumors of six patients in a phase 0 clinical trial. Injections resulted in tumor necrosis and were well tolerated. Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule c-Met was expressed in ∼50% of breast tumors, prompting the construction of a CAR T cell specific for c-Met, which halted tumor growth in immune-incompetent mice with tumor xenografts. We then evaluated the safety and feasibility of treating metastatic breast cancer with intratumoral administration of mRNA-transfected c-Met-CAR T cells in a phase 0 clinical trial (NCT01837602). Introducing the CAR construct via mRNA ensured safety by limiting the nontumor cell effects (on-target/off-tumor) of targeting c-Met. Patients with metastatic breast cancer with accessible cutaneous or lymph node metastases received a single intratumoral injection of 3 × 107 or 3 × 108 cells. CAR T mRNA was detectable in peripheral blood and in the injected tumor tissues after intratumoral injection in 2 and 4 patients, respectively. mRNA c-Met-CAR T cell injections were well tolerated, as none of the patients had study drug–related adverse effects greater than grade 1. Tumors treated with intratumoral injected mRNA c-Met-CAR T cells were excised and analyzed by immunohistochemistry, revealing extensive tumor necrosis at the injection site, cellular debris, loss of c-Met immunoreactivity, all surrounded by macrophages at the leading edges and within necrotic zones. We conclude that intratumoral injections of mRNA c-Met-CAR T cells are well tolerated and evoke an inflammatory response within tumors. Cancer Immunol Res; 5(12); 1152–61. ©2017 AACR.

Overall survival is similar between women who seek care at one or more institutions after diagnosis of operable breast cancer in the community

BACKGROUND As breast cancer diagnoses increase, so does the number of patients who are critically evaluating hospital attributes to determine where to receive their treatment. Evidence suggests that complex surgeries have better outcomes in high volume academic centers. Whether clinical outcomes of women diagnosed with operable breast cancer, who are treated by multiple disciplines including non-complex surgical approaches, differ for those received all or part of their treatment at their community cancer center is unclear. We hypothesize that the clinical outcomes do not differ for those who received all or part of their care at their community cancer center. Our aim is to analyze data from the National Cancer Database (NCDB) to assess the clinical characteristics and outcomes of patients who received all their treatment at community cancer center when compared with those who had part or all of their care elsewhere. METHODS A cohort of 162,803 women diagnosed at a community cancer center with an operable breast cancer (clinical stage I - III) between 2005 and 2014 from the NCDB was evaluated. Demographics, cancer-specific characteristics and overall survival differences between patients who stay at or leave their home institution for breast cancer treatment were compared. RESULTS Within this cohort, patients treated at multiple institutions were younger, traveled further from home for their care, and were more likely to have no comorbidities (p < 0.001). Overall survival adjusted for demographics and cancer stage and subtype did not differ based on treatment at one or multiple institutions. CONCLUSIONS The decision for patients to undergo breast cancer treatment in a different institution after being diagnosed in a community center does not appear to impact overall survival.

The impact of preoperative magnetic resonance imaging and lumpectomy cavity shavings on re-excision rate in pure ductal carcinoma in situ-A single institution's experience

The impact of preoperative magnetic resonance imaging (pMRI) and cavity shave margins (CSM) on re‐excision rate (RR) in DCIS is unclear. We investigated whether either modality was associated with RR in DCIS.

Immunotherapy for Breast Cancer: Current and Future Strategies

Purpose of ReviewThe breast tumor microenvironment is immunosuppressive and is increasingly recognized to play a significant role in tumorigenesis. A deeper understanding of normal and aberrant interactions between malignant and immune cells has allowed researchers to harness the immune system with novel immunotherapy strategies, many of which have shown promise in breast cancer. This review discusses the application of immunotherapy to the treatment of breast cancer.Recent FindingsBoth basic science and clinical trial data are rapidly developing in the use of immunotherapy for breast cancer. The current clinical trial landscape includes therapeutic vaccines, immune checkpoint blockade, antibodies, cytokines, and adoptive cell therapy.SummaryDespite early failures, the application of immunotherapeutic strategies to the treatment of breast cancer holds promise.