Increased local adverse effect (breast inflamation and infection)

Background/Main objective: Radiofrequency ablation (RFA) is a minimally invasive procedure widespread accepted in the treatment of different tumors, especially in the liver but its benefit is not yet well-known in breast cancer.

Our main objective is to evaluate the usefulness of RFA in < 2cm malignant breast tumors to reduce the proportion of positive margins.

Methodology: The investigator propose a single-center, single-blind, phase I and II randomized controlled trial. Phase I:Security of the cool-tip cluster electrode assessing the potential adverse effects in three stages: initial,intermediate and final. Phase II: Randomized clinical trial, 2 parallel groups with 37 patients in each one.

Experimental group: percutaneous RFA previous to conventional lumpectomy. Control group: conventional surgery with lumpectomy. The number of positive margins in both groups, and the need of extending margin resection will be assessed intraoperatively. Inclusion criteria: women >40 years, infiltrating ductal breast carcinoma by biopsy. The tumor must be unique, visible by ultrasound, smaller than 2cm and located > 1 cm from the chest wall and the skin. Patients will be followed up for a period of two years to assess cosmetic result, short -term and long -term complications and recurrences.

Expected results: The "cool-tip" (cluster) ablation method reduces by at least 30% the risk of intraoperative extensions for positive margins during lumpectomy compared to conventional surgery in breast tumors with a diameter < 2 cm.

Therefore this procedure may reduce the risk of second surgeries and the removed volume of tissue.Consequently the final cosmetic result should be improved.

Main objectives of the project:

• To evaluate the usefulness of radiofrequency ablation (RFA) to achieve a lower percentage of positive margins.
• To validate clinically the efficacy and safety of the method in breast tumors smaller than < 2 cm.

Specific objectives of the project:

1. To demonstrate that , after RFA, clear margins are increased in the intraoperative pathological analysis compared to conventional surgery.

   1. To quantify the number of positive margins requiring intraoperative extension in each patient, comparing the ratio in both groups.
   2. To quantify the percentage of patients requiring intraoperative extension compared in both groups.

2. To demonstrate a reduction in the volume of breast tissue removed after RFA compared to conventional surgery.

   1. Comparing in both groups the anteroposterior, transverse and craniocaudal diameters of the excised specimen, measured in cm, and to calculate the volume.
   2. Tumor weight in grams (including extensions) will be measured to compare the weights in both groups.

3. To evaluate the differences in cosmetic outcome after RFA versus conventional surgery.

   a. An international scale will be used and the scores will be compared. There will be two independent assessments, one for the physician and another for the patient.

4. To demonstrate the effectiveness of the RFA by cluster "cool-tip" electrode in the experimental group.

   1. RFA is considered as complete when no viable tumor tissue is evidenced by oxidation-reduction reaction mediated by NADH-diaphorase after surgical resection. Mitochondrial dysfunction will be also evaluated by semiquantitative and quantitative method using the enzyme cytochrome c oxidase or Complex IV (COX) and tunel. Any residual viable tumor tissue will be considered as incomplete RFA.
   2. Risk factors for incomplete ablations will be analyzed, especially tumor vascularization.

5. To demonstrate the safety of RFA by cluster "cool-tip" electrode in breast cancer tumors a. To quantify all side effects that may occur after the RFA and / or surgery and to correlate the complication rate in each group with severity.

Inclusion Criteria:

• Breast single tumor,
• Clearly visible by ultrasound,
• Diameter < 2 cm
• Located >1 cm from the chest wall and skin;
• Ductal carcinoma according to previous biopsy,
• < 20% of intraductal carcinoma

Exclusion Criteria:

• Breast cancer in men;
• Personal history of ipsilateral breast cancer;
• Age <40 years;
• Pregnancy or breastfeeding;
• Suspicion of intraductal extension or multifocality by mammography or MRI;
• Tumour not visible by ultrasound;
• Diameter > 2 cm;
• Distance to muscle or skin <1 cm;
• Lobular carcinoma;
• Intraductal carcinoma in > 20% of the biopsy sample
• Patients undergoing neoadjuvant chemotherapy or hormonotherapy.