Sentinel node biopsy using a magnetic tracer versus standard technique: the SentiMAG Multicentre Trial.

BACKGROUND: The SentiMAG Multicentre Trial evaluated a new magnetic technique for sentinel lymph node biopsy (SLNB) against the standard (radioisotope and blue dye or radioisotope alone). The magnetic technique does not use radiation and provides both a color change (brown dye) and a handheld probe for node localization. The primary end point of this trial was defined as the proportion of sentinel nodes detected with each technique (identification rate). METHODS: A total of 160 women with breast cancer scheduled for SLNB, who were clinically and radiologically node negative, were recruited from seven centers in the United Kingdom and The Netherlands. SLNB was undertaken after administration of both the magnetic and standard tracers (radioisotope with or without blue dye). RESULTS: A total of 170 SLNB procedures were undertaken on 161 patients, and 1 patient was excluded, leaving 160 patients for further analysis. The identification rate was 95.0 % (152 of 160) with the standard technique and 94.4 % (151 of 160) with the magnetic technique (0.6 % difference; 95 % upper confidence limit 4.4 %; 6.9 % discordance). Of the 22 % (35 of 160) of patients with lymph node involvement, 16 % (25 of 160) had at least 1 macrometastasis, and 6 % (10 of 160) had at least a micrometastasis. Another 2.5 % (4 of 160) had isolated tumor cells. Of 404 lymph nodes removed, 297 (74 %) were true sentinel nodes. The lymph node retrieval rate was 2.5 nodes per patient overall, 1.9 nodes per patient with the standard technique, and 2.0 nodes per patient with the magnetic technique. CONCLUSIONS: The magnetic technique is a feasible technique for SLNB, with an identification rate that is not inferior to the standard technique.

Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer.

Previous studies suggest that disease recurrence peaks at around 2 years in patients with early stage breast cancer (EBC), but provide no data regarding recurrence type. This retrospective analysis aimed to identify early recurrence types and risk factors in estrogen receptor-positive (ER+) EBC patients treated with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women diagnosed with ER+ EBC from 1995 to 2004 were evaluated. Annual hazard ratios (HR) for recurrence at different sites were calculated. Time-dependent Cox regression analysis was used to identify predictors of recurrence within 2.5 years of diagnosis, including factors that were more strongly predictive of early than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95% confidence interval) were: overall 6.3% (5.5-7.1), locoregional 1.1% (0.7-1.5), contralateral 0.5% (0.3-0.7), and distant 4.8% (4.0-5.6). The annual HR of overall recurrence peaked at 2 years (4.3% per annum). The majority of this peak represented distant recurrence (3.4% per annum). In Cox regression analysis, tumor size and grade, lymph node involvement, lymphovascular invasion, and symptomatic presentation were significant independent predictors of early recurrence. Age at diagnosis was independently predictive of recurrence within 2.5 years of diagnosis but not later recurrence. This study identified an early recurrence peak at 2 years, most of which were distant recurrences. Implementing an aromatase inhibitor after an initial 2-3 years of tamoxifen fails to address this early peak of distant recurrence and the potential breast cancer-associated mortality.

Detection of breast cancer metastasis in sentinel lymph nodes using intra-operative real time GeneSearch BLN Assay in the operating room: results of the Cardiff study.

BACKGROUND: Intra-operative assessment is not routinely performed in the UK due to poor sensitivity of available methods and overburdened pathology resources. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay (Veridex, LLC, Warren, NJ) to confirm its potential usefulness within the UK healthcare system. METHODS: In the assay 50% of the lymph node was processed to detect the presence of cytokeratin-19 and mammaglobin mRNA. The assay was calibrated to detect metastases >0.2 mm. Assay results were compared to H&E performed on each face of approximately 2 mm alternating node slabs and 3 additional sections cut at approximately 150 microm interval from each face of the node slab. RESULTS: 124 sentinel lymph nodes were removed from 82 breast cancer patients. The assay correctly identified all 6 patients with sentinel node macrometastases (>2.0 mm), and 2 of 3 patients with sentinel node micrometastases (0.2-2.0 mm). Sentinel lymph nodes in 4 patients were assay positive but histology negative. Two of these four patients had isolated tumor cells seen by histology. The overall concordance with histology was 93.9% (77/82), with sensitivity of 88.9% (8/9, 95% CI 56.5-98%), specificity of 94.6% (69/73, 95% CI 86.7-97.8%), positive predictive value of 66.7% (8/12, 95% CI 39.1-86.2%) and negative predictive value of 98.6% (69/70, 95% CI 92.3-99.7%). The assay was performed in a median time of 32 min (range 26-69 min). CONCLUSION: Intra-operative assessment of sentinel lymph node can be performed rapidly and accurately using the GeneSearch BLN Assay.

Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial.

BACKGROUND: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. METHODS: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. RESULTS: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval [CI] = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P < .001), and axillary operative time was reduced (P = .055). Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout (all P < or = .003). These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group (P > .05). CONCLUSION: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.

Is there a role of sentinel lymph node biopsy in ductal carcinoma in situ?: analysis of 587 cases.

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in patients with a core needle-biopsy diagnosis of ductal carcinoma in situ (DCIS) has been intensely debated. Core needle-biopsy has an inherent sampling error leading to histologic underestimation of invasive disease. If SLNB is not performed at the time of the definitive operative procedure, patients found to have an invasive cancer, will require a second operative procedure. The study was designed to determine when the risk of finding invasive disease on final pathology in patients with an initial diagnosis of DCIS was sufficiently high to justify the use of SLNB. METHODS: We identified 587 women with an initial core needle-biopsy diagnosis of DCIS in the prospective Breast Test Wales (BTW) database from 1995 through 2005. A variety of clinical, mammographic and histologic features were identified and correlated with the presence of invasion at excision using univariate and multivariate analyses. RESULTS: Median age of patients at the time of diagnosis was 58 years (range 41 to 83 years). 201 patients (36%) were treated by mastectomy and 354 (64%) by breast conservation surgery. 220 of 587 patients (38%) were found to have invasive disease on final pathology. On univariate analysis, the rate of upstaging was related to the presence of a clinically palpable mass and size of the mass (both p<0.0001, Mann-Whitney test); mammographic presence of a mass and size of the mass (both p<0.0001, Mann-Whitney test). Multivariate logistic regression analysis revealed 2 independent predictors of invasive cancer on final pathology: mass on clinical examination (odds ratio [OR], 5.09; p<0.0001) and mammographic mass (OR, 7.37; p<0.0001). Age, grade of DCIS, microinvasion and presence of comedonecrosis did not help in distinguishing between patients with DCIS and those upstaged to invasive carcinoma at definitive surgery. Axillary nodal staging (four node sampling or clearance) was done at the time of surgery in 269 patients. Axillary nodal metastases were found in 35 of 269 patients (13%). All 35 patients had invasive carcinoma on final pathology. CONCLUSION: The indiscriminate use of SLNB in patients with DCIS seems excessive. Our study suggests that patients with a mass on clinical examination or mammogram have an increased risk of invasive disease at the time of definitive operative procedure and should undergo SLNB at the initial procedure. In addition, SLNB should be performed in patients undergoing mastectomy because mastectomy precludes SLNB if invasive disease is subsequently discovered.

The role of tamoxifen in the management of gynaecomastia.

Gynaecomastia affects half of the male population at some stage in their life. Only a small proportion of them would require treatment for cosmetic appearance or to relieve pain and tenderness. Recently, tamoxifen has shown some promising results in the management of gynaecomastia. To assess the efficacy of tamoxifen, we carried out a retrospective study of all men treated for gynaecomastia with particular emphasis on those treated medically. Men with painful gynaecomastia were given 10 mg of tamoxifen for 3 months. Response to treatment was categorised as good, moderate and no response. Thirteen men (median age 36) were placed on tamoxifen. Ten patients responded well to tamoxifen. One patient developed calf tenderness and stopped the medication. No other adverse effects were reported. Two patients could not be followed up. Tamoxifen appears safe and effective in men with painful idiopathic or physiological gynaecomastia and should be considered as an initial option before contemplating surgery.