In our cohort of patients with breast cancer and CNS metastases, patients with HER2-positive disease treated with trastuzumab had longer times to development of and better survival from CNS metastases compared with patients with HER2-positive disease who had never received trastuzumab and patients with HER2-negative breast cancer.

Purpose-To compare inter-observer variations in delineating the whole breast for treatment planning using two contouring methods.Methods and Materials-Auto-segmented contours were generated by a deformable image registration-based breast segmentation method (DEF-SEG) by mapping the whole breast clinical target volume (CTVwb) from a template case to a new patient case. Eight breast radiation oncologists modified the auto-segmented contours as necessary to achieve a clinically appropriate CTVwb and then recontoured the same case from scratch for comparison. Times to complete each approach as well as inter-observer variations were analyzed. The template case was also mapped to 10 breast cancer patients with body mass indexes ranging from 19.1 to 35.9. Three-dimensional surface-tosurface distances and volume overlapping analyses were computed to quantify contour variations.Results-The median time to edit the DEF-SEG-generated CTVwb was 12.9 min (range, 3.4-35.9), compared to 18.6 min (range, 8.9-45.2) to contour the CTVwb from scratch (30% faster; p = 0.028). The mean surface-to-surface distance was noticeably reduced from 1.6 mm among contours generated from scratch to 1.0 mm using the DEF-SEG method (p = 0.047). Deformed contours in 10 patients can achieve 94% volume overlap prior to correction and required editing of 5% of the contoured volume (range, 1%-10%).Conclusions-Significant inter-observer variations suggest that there was a lack of consensus regarding the CTVwb, even among breast cancer specialists. Using the DEF-SEG method produced

Trastuzumab is a FDA-approved drug that has shown clinical efficacy against HER2+ breast cancers and is commonly used in combination with other chemotherapeutics. However, many patients are innately resistant to trastuzumab, or will develop resistance during treatment. Alternative treatments are needed for trastuzumab-resistant patients. Here, we investigate gold nanoparticle-mediated photothermal therapies as a potential alternative treatment for chemotherapy-resistant cancers. Gold nanoshell photothermal therapy destroys the tumor cells using heat, a physical mechanism, which is able to overcome the cellular adaptations that bestow trastuzumab resistance. By adding anti-HER2 to the gold surface of the nanoshells as a targeting modality, we increase the specificity of the nanoshells for HER2+ breast cancer. Silica-gold nanoshells conjugated with anti-HER2 were incubated with both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells. Nanoshell binding was confirmed using two-photon laser scanning microscopy, and the cells were then ablated using a near-infrared laser. We demonstrate the successful targeting and ablation of trastuzumab-resistant cells using anti-HER2-conjugated silica-gold nanoshells and a near-infrared laser. This study suggests potential for applying gold nanoshell-mediated therapy to trastuzumab-resistant breast cancers in vivo.

In this single-institutional study, patients with nonmetastatic triple receptor-negative breast tumors have a high early incidence of brain metastases associated with poor survival and maybe an ideal cohort to target brain metastases preventive strategies.