Cryoablation for breast cancer: No need to turn a cold shoulder

It was not that long ago that it was suggested that mastectomy might not be necessary to treat breast cancer and that lumpectomy and whole breast radiation could be a suitable alternative. When Dr. Fisher and the NSABP first proposed doing a randomized trial of lumpectomy, lumpectomy, and radiation or mastectomy [1], it was met with tremendous skepticism. Many surgeons were quite vocal in their concern regarding local recurrence and the impact it might have on survival. Nevertheless, the trial took place, and today the majority of breast cancer patients in the United States avoid mastectomy. This sort of skepticism is not unusual in surgery. The idea that the gallbladder could be removed via a small umbilical incision, using laparascopic technology, was considered outlandish, and would fade away once an inordinate number of common bile duct injuries were reported. The concept of not diverting the colon after penetrating trauma, of the nonoperative management of splenic injuries, of treating vascular disease with stents rather than surgery, or the suggestion of staging melanoma or breast cancer by removing just one or two lymph nodes rather than a complete lymph node dissection are all examples of changes in surgical paradigm that met tremendous resistance when first proposed but became standard surgical practice. Today, a similar surgical reluctance surrounds the idea of in situ ablation for the treatment of breast cancer, and specifically the use of cryoablation. Cryoablation involves the introduction of a cryoprobe into the center of a tumor under ultrasound guidance in order to freeze the tissue to temperatures between 160 and 1908C. Several small studies have now demonstrated the safety, feasibility, efficacy, and limitations of cryoablation in the treatment of breast cancer [2–5]. Data from these studies, most of which involve cryoablation followed by standard surgical resection, are being used to design larger studies pursuing the ultimate goal of cryoablation; an alternative to lumpectomy. However, the idea of ablating a tumor and leaving it in place, without the opportunity for histological evaluation of the margins, seems like surgical heresy to many surgical oncologists. As with the shift from mastectomy to breast conservation, there is significant concern regarding leaving untreated disease, particularly in situ disease, leading to an unacceptable local recurrence rate. These are highly legitimate concerns, and certainly no one is advocating the immediate introduction of cryoablation as an alternative to lumpectomy. However, there are many potential advantages to cryoablation over lumpectomy that warrant its further investigation. Cryoablation is technically simple and extremely safe, with minimal discomfort or side effects for the patient [6]. Successful cryoablation requires only moderate proficiency with ultrasound, which is rapidly becoming an essential component of any breast practice [7]. After percutaneous ultrasound guided placement of the probe within the center of the tumor, the procedure involves monitoring the formation of the iceball and occasionally injecting saline between the iceball and the skin to prevent thermal damage. After two freeze-thaw cycles, the probe is removed and a bandage placed over the incision. Because the freezing procedure itself anesthetizes the breast tissue, no local or regional anesthesia is required past the placement of the probe. Patients report minimal discomfort or use of narcotic pain medications afterwards [4]. Compared with lumpectomy, cryoablation would represent a tremendous reduction in the cost and morbidity of breast cancer treatment. More importantly to the patient, the cosmesis achieved with cryoablation is superior to that obtained with lumpectomy. Even for small tumors, lumpectomy and radiation can be associated with not only a scar, but volume loss and asymmetry, retraction and concavity. Cryoablation leaves a scar no bigger than that of a percutaneous core biopsy. By leaving the frozen tissue in situ for resorption by the body, the breast maintains its natural size and shape, with no resultant volume loss or deformity. The cosmetic appeal of cryoablation is well known both to dermatologists, who use it routinely for the ablation of skin cancers, and breast surgeons, who use cryoablation for the treatment of fibroadenomas. Several studies have now demonstrated the outstanding safety, efficacy, cosmetic outcome, and patient satisfaction with cryoablation as a treatment of benign breast disease [8–10]. Another unique feature of cryoablation that may be exploited is the immunologic response initiated by the absorption of the frozen tissue. The uptake of intact tumor antigens by antigen presenting cells and the release of proinflammatory cytokines, both of which are hallmarks of cryoablation, represent the perfect equation for initiating a tumorspecific immune response. The ‘‘cryoimmunologic’’ response has been well documented in both pre-clinical and clinical investigations [3,11,12]. The use of immunotherapy in the treatment of breast cancer is fraught with challenges, and cryoablation alone, or more likely in combination with immune adjuncts, may overcome these obstacles [13,14]. It is feasible that this aspect may elevate cryoablation beyond lumpectomy in terms of local or distant recurrence. This may also further support the role of cryoablation in other aspects of breast cancer therapy, such as the treatment of primary tumors in the face of stage IV disease, the eradication of chest wall recurrences, or the ablation of metastatic foci as an alternative to metastatectomy. Of course, none of this potential means anything if cryoablation of primary malignant disease is associated with an unacceptably high rate of local recurrence. The importance of local recurrence in the