Minimally invasive approach to neoplastic breast disease

Surgical excision is considered the primary treatment for breast cancer. Potentially less deforming approaches such as in situ ablative treatments aim to preserve the greatest amount of normal breast tissue. Previous studies on radiofrequency ablation (RFA) for the local control of small breast cancers reported complications of burns due to monopolar electrodes. By using a bipolar application device the electrical current can be applied locally. This novel application device was used in patients with invasive breast carcinoma, followed by immediate resection. Histopathology revealed complete cell death in 77 per cent of patients, without causing any burns. Based on this early evaluation, ultrasound-guided RFA with a bipolar needle-electrode appears to be a safe local treatment technique for invasive breast cancers up to 2 cm. As a consequence of these novel ablation techniques, the core needle biopsy (CNB) specimen will be the only tissue available for assessment of tumour characteristics and clinical risk assessment. Patient selection for adjuvant systemic treatment will need to be made based on the CNB. Although there is a substantial discordance in tumour grading between CNB and resection specimen, this thesis found the indication for adjuvant therapy affected in only a small minority of patients. Therefore, the indication for systemic treatment in patients undergoing in situ ablative therapies may safely be set using the CNB grade. Conventional diagnostic procedures are not sensitive in patients with pathologic nipple discharge (PND). Surgery is considered the diagnostic gold standard, but since malignancy is the underlying diagnosis in a minority, most women undergo the invasive procedure for a benign cause. Ductoscopy is a minimally invasive procedure performed under local anesthesia that visualizes the ductal epithelium of the breast via the nipple. In this thesis the diagnostic accuracy of ductoscopy in patients with PND was assessed by a systematic review and meta-analysis, including twenty studies with a total of 3189 cases. Ductoscopy had a pooled sensitivity of 94 per cent and specificity of 47 per cent. Malignancy was diagnosed in 7.6 per cent. These results imply that histological diagnosis remains inevitable to exclude malignancy in patients with PND. Due to the high sensitivity and the low incidence of malignancy in patients with PND, surgery can be waived in case of negative ductoscopy. The therapeutic efficacy of interventional ductoscopy was assessed in a prospective study where intraductal lesions were removed by ductoscopic extraction. In 79 per cent of the attempted ductoscopic extractions the lesion could be removed. In 68 per cent of patients surgery was avoided. This study showed the feasibility of interventional ductoscopy for acquiring diagnosis and effectuation of symptom resolvement and aiding in reduction of surgery for a benign cause. In order to increase therapeutic efficacy intraductal thulium laser ablation was assessed in a first-in-man study showing that laser ablation of intraductal papillomas is feasible and can effectuate symptom resolvement. Since most breast cancers are thought to arise from the ductal epithelium an appealing approach would be to target breast cancer precursors through ductoscopy. Ductoscopy was equipped with an autofluorescence image enhancement technique. This study is the first in showing in vivo feasibility of autofluorescence ductoscopy to detect intraductal abnormalities that are occult under white light.