A Prospective Study Evaluating the Accuracy of Indocyanine Green (ICG) Fluorescence Compared with Radioisotope for Sentinel Lymph Node (SLN) Detection in Early Breast Cancer.

BACKGROUND: Dual localization methods with blue dye and radioisotope represents the standard method for SLN identification. Side effects of blue dye and problems with access to radioisotope has prompted assessment of alternative tracers. This study has evaluated a combination of indocyanine green (ICG) fluorescence with radioisotope for SLN biopsy in early breast cancer. METHODS: In a prospective observational study 79 patients scheduled for SLN biopsy underwent dual localization with radioisotope nanocolloid and ICG (0.5%). The primary goal was to assess noninferiority of ICG compared with standard radioisotopic localization. Statistical analysis was performed using Stata (version 15.1). RESULTS: A total of 162 nodes were retrieved from 79 patients with an average nodal count of 2.04 (range 1-4) and an overall identification rate of 98.7% (78/79). Nodal detection rates for ICG alone or combined with radioisotope were 98.1% (151/154) and 73.4% (113/154) respectively. Metastasis were present in 13 nodes, all of which were both fluorescent and radioactive and distributed amongst 13 patients each with a single positive node containing macrometastases (n = 5), micrometastases (n = 6), or isolated tumor cells (n = 2). ICG was noninferior to radioisotope with the lower confidence interval not crossing within the predefined limit. No serious adverse reactions were recorded. CONCLUSIONS: These results confirm comparable performance parameters for ICG to the "gold standard" using radioisotope. ICG can reliably be employed as a sole tracer that avoids potential drawbacks of standard tracer agents, including availability and costs of radioisotope.

Axillary surgery in breast cancer: the beginning of the end.

Axillary surgery in breast cancer patients has shifted from more extensive to minimalist approaches with re-evaluation of the risks versus benefits of available treatment options which are increasingly tailored to individual patient characteristics. A radical axillary node dissection is rarely indicated nowadays due to several factors including screening with detection of small node negative cancers, introduction of targeted node sampling, less reliance on information from nodal staging for adjuvant therapy decision making and evidence that non-surgical treatments such as systemic therapies (chemotherapy, hormonal therapy, biological therapy) together with radiotherapy can safely treat low burden axillary disease. Sentinel lymph node biopsy (SLNB) alone with omission of further axillary surgery for nodal macrometastases (>2 mm) might be sufficiently extirpative to achieve local control when combined with adjuvant treatments. There remain unanswered questions on the safety of SLNB post chemotherapy in patients with biopsy-proven nodal disease at presentation and whether omission of axillary node dissection is feasible in selected cases. Emerging evidence suggests that a complete radiological response with removal of at least 3 nodes (including clipped nodes at time of biopsy) can yield false negative rates of <10% and be a safe option. New technologies involving percutaneous biopsy of sentinel nodes under radiological guidance are under investigation and could potentially replace surgical staging of the axilla in the future. Moreover, omission of any type of node biopsy might be a potential option in more favorable tumors and could herald the beginning of the end for histological axillary sampling in selected cases.

Management of ductal carcinoma in situ in the modern era.

Ductal carcinoma in situ (DCIS) has been the subject of much controversy since the advent of population based breast screening programs. An increasing number of asymptomatic women are being diagnosed with this condition and there is uncertainty over the best treatment algorithm for this condition if treatment is to be considered at all. Different subtypes of DCIS show innate differences in developmental pathways and biological behavior. This is not only determined by pathological subtypes but there is increasing understanding of molecular biomarkers related to DCIS progression. The ultimate management aim is to identify a subgroup of patients in whom DCIS will not progress to invasive disease such that they can avoid morbidity from surgical and adjuvant therapies. This has to be balanced by the potential risk of undertreatment of patients in whom DCIS is likely to progress to invasive cancer and hence a reduced life expectancy. Results of current ongoing prospective randomized trials assessing the safety of omitting surgery for what is considered to be low risk DCIS are eagerly awaited for by patients and clinicians. However the definition of what is considered to be "low risk" DCIS is still to be ascertained.

Novel techniques for intraoperative assessment of margin involvement.

Breast conserving surgery (BCS) is now the standard of care for the majority of women with early stage breast cancer. There is a finite rate of ipsilateral breast tumour recurrence (IBTR) for breast conserving therapy (BCT) with annual rates of less than 1% for specialist breast practices. There has been recent consensus on the definition of an adequate resection margin for both invasive and noninvasive breast cancer treated with BCS, although some variation in margin policy persists with definitions of 'no tumour at ink', 1 and 2 mm margin mandates. Despite the development of methods for intraoperative assessment of margins, up to 20% of patients require further surgery (cavity re-excision or completion mastectomy) to achieve clear surgical margins. In the past decade, several novel technologies for intraoperative margin assessment have been explored with the aim of reducing rates of re-operation and its attendant patient anxiety, inconvenience and additional cost. Ongoing studies are addressing the safety, feasibility and cost-effectiveness of these novel technologies relative to methods in routine clinical usage.

Idiopathic granulomatous mastitis: presentation, investigation and management.

Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory condition of the breast which although benign can mimic carcinoma. Establishing a diagnosis can be challenging and requires a high index of suspicion with exclusion of infective and autoimmune breast diseases. IGM is characterized histologically by noncaseating granulomas which are of a lobulo-centric pattern and often associated with microabscess formation. Management of confirmed cases remains controversial with proponents of initial surgical or medical therapies - each has its associated problems which can be worse than the original symptoms of IGM. However, many patients require more than one modality of treatment to completely resolve IGM lesions and careful judgment is necessary to ensure optimal type and sequencing of treatments.

Oncologic safety of conservative mastectomy in the therapeutic setting.

Conservative mastectomy is a form of nipple-sparing mastectomy which is emerging as a surgical option for selected breast cancer patients. This technique differs from subcutaneous mastectomy which is well established as a technique for risk reduction but leaves behind a finite remnant of retro-areolar breast tissue. Clinical trials have confirmed the efficacy and safety of breast conservation therapy for smaller localised breast tumors whereby a variable amount of surrounding normal tissue is excised with administration of breast radiotherapy post-operatively. Conservative mastectomy aims to remove all breast tissue with dissection continued into the core of the nipple. However, the indication for conservative mastectomy remains to be defined but generally includes tumors of modest size located at least 2 cm away from the nipple. Patients undergoing conservative mastectomy do not necessarily receive adjuvant radiotherapy and this may only be intra-operative irradiation of the nipple-areola complex (NAC). Preservation of the NAC as part of a skin-sparing mastectomy in patients who might otherwise require standard mastectomy is of unproven safety from an oncologic perspective but is associated with enhanced cosmetic outcomes and quality-of-life. The advent of conservative mastectomy has coincided with a trend for "maximal surgery" with bilateral extirpation of all breast tissue in conjunction with immediate breast reconstruction. It is essential there is no compromise of local recurrence and survival in terms of ipsilateral breast cancer treatment. Further studies are required to clarify the indications for conservative mastectomy and confirm oncologic equivalence to either wide local excision and breast irradiation or conventional/skin-sparing mastectomy with sacrifice of the nipple areola complex.