Non-surgical Breast-conservation Treatment (KORTUC-BCT) Using a New Image-guided, Enzyme-targeted, and Breast Cancer Stem Cell-targeted Radiosensitization Treatment (KORTUC II) for Patients With Stage I or II Breast Cancer

Tumor tissue can be re-oxygenated by inactivating peroxidase/catalase in the tumor tissue through the application of H2O2. This H2O2 is then degraded to produce oxygen. In this way, low-LET radioresistant tumors can be transformed into radiosensitive ones. The purpose of the present study was to establish a non-surgical BCT utilizing KORTUC II radiosensitization treatment. A new radiosensitizing agent containing 0.5% H2O2 and 0.83% sodium hyaluronate (a CD44 ligand) has been developed for intra-tumoral injection. This new method, named KORTUC II, was approved by our local ethics committee for the treatment of breast cancer. A total of 39 early-stage breast cancer patients (stage I, 12 patients; stage II, 27) were enrolled in the KORTUC II trial after providing fully informed consent. Mean age of the patients was 61.1 years. A maximum of 6 mL of the agent was injected into breast tumor tissue twice a week under US guidance, just prior to each administration of RT. The injection was started immediately prior to the 6th fraction of RT. Concerning RT, hypofractional RT was administered using a tangential fields approach and field-in-field method; the energy level was 4 MV and the total dose was 44 Gy administered as 2.75 Gy/fraction. An electron boost of 3 Gy was added three times just following the 14th, 15th, and 16th administrations of X-ray irradiation. From a needle biopsy specimen, hormonal status (estrogen and progesterone receptors), HER-2 antigen, and CD44 receptor status were examined by immunohistochemistry. Treatment was well tolerated with minimal adverse effects in all 39 patients. A total of 36 patients achieved cCR according to dynamic MRI, and the study has not yet been performed for the remaining 3 patients. No patients showed any significant complications (excluding mild dermatitis: Grade I, 24 patients; Grade II, 15 patients), and cosmetic results were excellent/good for 35 patients. Fifteen patients under 75 years old with stage II breast cancer underwent induction chemotherapy prior to KORTUC II treatment, and 36 patients with estrogen receptor-positive tumors also received hormonal therapy following KORTUC II. The mean duration of follow-up as of the end of September 2011 was 30.1 months, at which time all 39 patients were alive without any distant metastases. Only 1 patient had local recurrence, which was discovered after 34 months of follow-up. Non-surgical KORTUC-BCT can be performed using KORTUC II, which has three major characteristics: image-guidance by US; enzyme-targeting of peroxidase/catalase; and targeting of breast cancer stem cells via the CD44 receptor. KORTUC-BCT offers great potential as a viable noninvasive replacement for surgical BCT.