Navigated Breast Tumor Excision Using Electromagnetically Tracked Ultrasound and Surgical Instruments.

OBJECTIVE: Lumpectomy, breast conserving tumor excision, is the standard surgical treatment in early stage breast cancer. A common problem with lumpectomy is that the tumor may not be completely excised, and additional surgery becomes necessary. We investigated if a surgical navigation system using intraoperative ultrasound improves the outcomes of lumpectomy and if such a system can be implemented in the clinical environment. METHODS: Position sensors were applied on the tumor localization needle, the ultrasound probe, and the cautery, and 3-D navigation views were generated using real-time tracking information. The system was tested against standard wire-localization procedures on phantom breast models by eight surgical residents. Clinical safety and feasibility was tested in six palpable tumor patients undergoing lumpectomy by two experienced surgical oncologists. RESULTS: Navigation resulted in significantly less tissue excised compared to control procedures (10.3 ± 4.4 versus 18.6 ± 8.7 g, p = 0.01) and lower number of tumor-positive margins (1/8 versus 4/8) in the phantom experiments. Excision-tumor distance was also more consistently outside the tumor margins with navigation in phantoms. The navigation system has been successfully integrated in an operating room, and user experience was rated positively by surgical oncologists. CONCLUSION: Electromagnetic navigation may improve the outcomes of lumpectomy by making the tumor excision more accurate. SIGNIFICANCE: Breast cancer is the most common cancer in women, and lumpectomy is its first choice treatment. Therefore, the improvement of lumpectomy outcomes has a significant impact on a large patient population.

Role of the integrin-binding protein osteopontin in lymphatic metastasis of breast cancer.

Although a primary route of breast cancer metastasis is believed to be via lymphatics, the molecular factors involved are poorly understood. We hypothesized that one such factor may be the integrin-binding protein osteopontin (OPN), and we investigated this clinically and experimentally. In breast cancer patients undergoing sentinel lymph node biopsy, OPN levels were significantly higher in lymph node metastases than in the primary tumor (P < 0.001). To test the functional contribution of OPN to lymphatic metastasis and to determine whether the RGD (Arg-Gly-Asp) integrin-binding sequence of OPN is important for this process, we transfected wild-type OPN or mutant OPN (lacking the RGD sequence) into MDA-MB-468 human breast cancer cells. In vitro, cells overexpressing OPN demonstrated increased anchorage-independent growth in soft agar (P = 0.001) and increased RGD-dependent adhesion (P = 0.045). Following mammary fat pad injection of nude mice, cells overexpressing OPN showed increased lymphovascular invasion, lymph node metastases, and lung micrometastases at earlier time points (P = 0.024). Loss of the RGD region partially abrogated this effect in the lymphatics (P = 0.038). These novel findings indicate that OPN is a key molecular player involved in lymphatic metastasis of breast cancer, potentially by affecting RGD-mediated adhesive interactions and by enhancing the establishment/persistence of tumor cells in the lymphatics.