This randomized multicenter Phase III clinical trial is intended to provide histopathological and clinical information on an innovative, minimally-invasive approach (focused microwave thermotherapy) to the preoperative treatment of breast cancer, using a minimally invasive focused microwave phased array device, the Medifocus, Inc. APA 1000 Breast Thermotherapy Treatment System (heat treatment). Subjects with large primary operable breast cancer, in the intact breast, with clinical tumor size greater than or equal to 3.5 cm (including tumor classification T2 or T3), clinically node negative N0 or node positive (N1 or N2) with distant metastasis (M1) or without distant metastasis (M0) will be randomized (ratio 1:1) to receive (1) preoperative thermotherapy combined with preoperative anthracycline-based combination chemotherapy and standard of care versus (2) preoperative anthracycline-based combination chemotherapy and standard of care alone. The anthracycline-based regimen will be limited to those of the current National Comprehensive Cancer Network (NCCN) guidelines for dose/drug/schedule at the time of patient enrollment. In both arms of the study, standard of care including breast imaging, drugs, and radiation therapy will be provided to all eligible subjects during and following the preoperative regimen. At the clinical discretion of the treating physician, subjects that are estrogen-receptor positive may receive Tamoxifen therapy the day following the completion of chemotherapy. Radiation therapy to the breast tissues and lymph nodes will be given as part of the standard of care for eligible subjects. Treatment Arm I (new arm) regimen includes three preoperative thermotherapy treatments at intervals corresponding to the first three cycles of anthracycline-based combination chemotherapy plus standard of care. The addition of preoperative thermotherapy to preoperative anthracycline-based combination chemotherapy may improve the tumor response rate in terms of shrinkage (the primary endpoint) and may increase the option to perform breast conservation (a secondary endpoint) compared to that achieved with preoperative anthracycline-based combination chemotherapy and standard of care alone. Note: Since there is no consensus combination drug regimen for neoadjuvant treatment of large breast cancer tumors, each study site will use its own standard of care which will include other chemotherapy/drug agents commonly used in combination with an anthracycline (Doxorubicin (trade name Adriamycin) or Epirubicin (trade name Ellence)), which is the study base drug type.