Colm Power

Ultrasound-Guided Core Biopsy: An Effective Method of Detecting Axillary Nodal Metastases

BACKGROUNDnAxillary nodal status is an important prognostic predictor in patients with breast cancer. This study evaluated the sensitivity and specificity of ultrasound-guided core biopsy (Ax US-CB) at detecting axillary nodal metastases in patients with primary breast cancer, thereby determining how often sentinel lymph node biopsy could be avoided in node positive patients.nnnSTUDY DESIGNnRecords of patients presenting to a breast unit between January 2007 and June 2010 were reviewed retrospectively. Patients who underwent axillary ultrasonography with or without preoperative core biopsy were identified. Sensitivity, specificity, positive predictive value, and negative predictive value for ultrasonography and percutaneous biopsy were evaluated.nnnRESULTSnRecords of 718 patients were reviewed, with 445 fulfilling inclusion criteria. Forty-seven percent (n = 210/445) had nodal metastases, with 110 detected by Ax US-CB (sensitivity 52.4%, specificity 100%, positive predictive value 100%, negative predictive value 70.1%). Axillary ultrasonography without biopsy had sensitivity and specificity of 54.3% and 97%, respectively. Lymphovascular invasion was an independent predictor of nodal metastases (sensitivity 60.8%, specificity 80%). Ultrasound-guided core biopsy detected more than half of all nodal metastases, sparing more than one-quarter of all breast cancer patients an unnecessary sentinel lymph node biopsy.nnnCONCLUSIONSnAxillary ultrasonography, when combined with core biopsy, is a valuable component of the management of patients with primary breast cancer. Its ability to definitively identify nodal metastases before surgical intervention can greatly facilitate a patients preoperative integrated treatment plan. In this regard, we believe our study adds considerably to the increasing data, which indicate the benefit of Ax US-CB in the preoperative detection of nodal metastases.

Analysis of margin index as a method for predicting residual disease after breast-conserving surgery in a European cancer center.

Breast-conserving surgery (BCS), followed by appropriate adjuvant therapies is established as a standard treatment option for women with early-stage invasive breast cancers. A number of factors have been shown to correlate with local and regional disease recurrence. Although margin status is a strong predictor of disease recurrence, consensus is yet to be established on the optimum margin necessary. Margenthaler et al. recently proposed the use of a “margin index,” combining tumor size and margin status as a predictor of residual disease after BCS. We applied this new predictive tool to a population of patients with primary breast cancer who presented to a symptomatic breast unit to determine its suitability in predicting those who require reexcision surgery. Retrospective analysis of our breast cancer database from January 1, 2000 to June 30, 2010 was performed, including all patients who underwent BCS. Of 531 patients who underwent BCS, 27.1% (144/531) required further reexcision procedures, and 55 were eligible for inclusion in the study. Margin index was calculated as: margin indexxa0=xa0closest margin (mm)/tumor size (mm)xa0×xa0100, with index >5 considered optimum. Of the 55 patients included, 31% (17/55) had residual disease. Fisher’s exact test showed margin index not to be a significant predictor of residual disease on reexcision specimen (Pxa0=xa00.57). Of note, a significantly higher proportion of our patients presented with T2/3 tumors (60% vs. 38%). Although an apparently elegant tool for predicting residual disease after BCS, we have shown that it is not applicable to a symptomatic breast unit in Ireland.IntroductionBreast-conserving surgery (BCS), followed by appropriate adjuvant therapies is established as a standard treatment option for women with early-stage invasive breast cancers. A number of factors have been shown to correlate with local and regional disease recurrence. Although margin status is a strong predictor of disease recurrence, consensus is yet to be established on the optimum margin necessary. Margenthaler et al. recently proposed the use of a “margin index,” combining tumor size and margin status as a predictor of residual disease after BCS. We applied this new predictive tool to a population of patients with primary breast cancer who presented to a symptomatic breast unit to determine its suitability in predicting those who require reexcision surgery.MethodsRetrospective analysis of our breast cancer database from January 1, 2000 to June 30, 2010 was performed, including all patients who underwent BCS. Of 531 patients who underwent BCS, 27.1% (144/531) required further reexcision procedures, and 55 were eligible for inclusion in the study. Margin index was calculated as: margin indexxa0=xa0closest margin (mm)/tumor size (mm)xa0×xa0100, with index >5 considered optimum.ResultsOf the 55 patients included, 31% (17/55) had residual disease. Fisher’s exact test showed margin index not to be a significant predictor of residual disease on reexcision specimen (Pxa0=xa00.57). Of note, a significantly higher proportion of our patients presented with T2/3 tumors (60% vs. 38%).ConclusionsAlthough an apparently elegant tool for predicting residual disease after BCS, we have shown that it is not applicable to a symptomatic breast unit in Ireland.

A comparison of intra-operative margin management techniques in breast-conserving surgery: a standardised approach reduces the likelihood of residual disease without increasing operative time

IntroductionBreast-conserving surgery (BCS) is established as a standard treatment option for women with early-stage invasive breast cancers. Margin status predicts local disease recurrence. Up to 59xa0% of patients may undergo re-excision of their tumour cavity to establish clear margins. Intra-operative margin assessment may decrease re-excision rates. It is unclear if this procedure increases operative time. We compared intra-operative macroscopic assessment of margins, routine cavity shave margins and no formal intra-operative margin assessment to assess their impact on re-excision rates, residual disease burden and operative time.MethodsOver a 42xa0month period, 188 patients from our retrospective breast cancer database were reviewed in our study. Of these, 68 had macroscopic margin assessment, 70 had cavity shave margins and 50 had no formal intra-operative assessment. Statistical analysis was performed as appropriate.ResultsFormal intra-operative margin assessment had a re-excision rate of 25xa0%, compared with 34xa0% for those without formal assessment. Formal assessment had a significantly reduced likelihood of having residual disease following the primary procedure (pxa0=xa00.02). Close margins (<2xa0mm) also predicted the presence of residual disease (pxa0=xa00.01). There was no difference in operative duration between the groups.ConclusionDirected intra-operative margin assessment reduces residual disease burden in BCS without increasing operative duration.

Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies.

BackgroundThe Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because ERBB family mutations can activate the PI3K/AKT pathway and likely have similar canonical signalling effects to PI3K pathway mutations, we investigated their combined impact on response to neoadjuvant HER2-targeted therapies.MethodsBaseline tumour biopsies were available from 74 patients with HER2-positive breast cancer who were enrolled in the phase II TCHL neoadjuvant study (ICORG 10-05) assessing TCH (docetaxel, carboplatin, trastuzumab) (nu2009=u200938) versus TCL (docetaxel, carboplatin, lapatinib) (nu2009=u200910) versus TCHL (docetaxel, carboplatin, trastuzumab, lapatinib) (nu2009=u200940), each for six cycles. Activating mutations in PIK3CA and ERBB family genes were identified using mass spectrometry-based genotyping. Phosphatase and tensin homolog (PTEN) expression was assessed by immunohistochemistry.ResultsPIK3CA and/or ERBB family mutations were detected in 23 (31.1%) tumour samples tested, whereas PTEN expression was low in 31.1% of cases tested. Mutation frequency was similar in each treatment arm (31.3% in TCH arm, 30% in TCL arm and 31.3% in TCHL arm) and was not influenced by oestrogen receptor (ER) status (27.6% in ER-negative patients, 33.3% in ER-positive patients) or progesterone receptor (PR) status (32.6% in PR-negative patients, 29% in PR-positive patients). There was no significant difference in pathological complete response (pCR) rates between 47 patients with wild-type (WT) tumours and 22 patients whose tumours carried mutations (in either PIK3CA or ERBB family genes) (42.5% vs. 54.5%; pu2009=u20090.439). Similarly, there was no significant difference in pCR rates between patients with PIK3CA/ERBB family mutated/PTEN-low (i.e., PI3K-activated) tumours and patients without PI3K activation (50% vs. 44%; pu2009=u20090.769). However, in the TCHL (but not the TCH) group, the pCR rate was higher for 9 patients with PIK3CA/ERBB family mutated tumours than for 20 patients with PIK3CA/ERBB family WT tumours (77.8% vs. 35%; pu2009=u20090.05).ConclusionsOur results indicate that patients who receive neoadjuvant TCHL and have PIK3CA/ERBB family mutated tumours may be more likely to have a pCR than patients with WT tumours.Trial registrationClinicalTrials.gov, NCT01485926. Registered on 2 December 2011.

The significance of receptor status discordance between breast cancer primary and brain metastasis

The cumulative incidence of brain metastases in breast cancer (BCBM) is 5%-10% and has increased in recent years. Metastasectomy rates for BCBM have accordingly increased with improvements in perioperative and long-term outcomes. Receptor status is a crucial determinant of management and prognosis in breast cancer. Triple-negative breast cancer has a worse prognosis than estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) positive disease after BCBM. HER2 positive disease more commonly metastasises to the brain and this may be related to the inability for trastuzumab to cross the blood-brain-barrier. However, few studies compare the receptor status of the primary tumor with that of the BCBM, because the most report on a range of organs with the brain being least accessible to tissue diagnosis. This is important because discordance in receptor status is common and informsmanagement. Discordance refers to disagreement in receptor status between the primary and metastasis. Increased metastasectomy rates over the past decade have provided an opportunity to study this phenomenon. A total of 49 women with previous breast cancer underwent resection of a BCBM between January 2011 and December 2015 in Beaumont Hospital. All tissue was reviewed by a consultant neuropathologist. Data were collected from the National Cancer Registry and patient records. Beaumont Research Ethics Committee granted ethical approval (ref-16/80). K-values represented concordance, where k = 1 was perfectly concordant. Kaplan-Meier, log-rank tests, and cox multiple regression analyses determined differences in survival. Statistical analysis was performed in SPSS version 22. 2 | BREAST CANCER

Reply Letter to the Editor: Letter to the Editor

Thank you for your interest in our article. You raised a good point and it is one we have considered; however, due to the word‐limit restrictions, there are some data that we were unable to present in this article. The presence of distant metastases outside the central nervous system tended to be associated with a poorer overall survival, which approached statistical significance (P = 0.063) in our univariate analysis (see table below). For this reason, it was included in our multiple regression analysis, where the presence of distant metastases (ie, extracranial distant metastases) was associated with a worse prognosis (HR 3.2, P = 0.029) as seen in figure 1 of our paper, but this did not affect the relationship between HER2 status and overall survival, which was maintained on univariate and multiple regression analyses (table 2 and figure 1). Note the locations of the extracranial metastases below as well, for your interest.

Knowledge of breast cancer risk factors, screening, and treatment methods in patients attending the breast clinic: A survey of 1,018 women

Breast cancer is the most common cancer in women, with 1.8 million new cases annually. Early diagnosis is essential, with 5‐year survival being 99% in stage I disease compared to 26% in stage IV. Breast cancer screening is crucial for earlier detection, having been directly linked with reduced mortality. Despite this, many screening programmes have reported reduced attendance, with evidence that patient knowledge of breast cancer directly influences attendance. Among the most important risk factors for breast cancer is family history, with the breast cancer susceptibility gene mutations (BRCA 1 and 2) playing a significant role. However, the importance of BRCA has not reached the public uniformly. One study demonstrated no difference in breast cancer knowledge between patients with and without a family history. Inadequate knowledge regarding breast cancer risk factors may be a significant barrier in earlier detection of malignancy. The aim of this study was to assess the knowledge of breast cancer risk factors, screening practises, detection methods, and treatment options in women attending the breast clinic. This knowledge could be used to inform breast cancer education resources aimed at improving attendance at screening, leading to earlier diagnosis and an improved prognosis. An anonymous paper‐based survey was offered to all women attending the breast clinic between February 2015 and March 2015 in two European cancer centers, Beaumont Hospital (BH) and University Hospital Waterford (UHW). Ethical approval was granted by the local research ethics committee in each respective hospital. The 18‐item survey collected data on knowledge of breast cancer risk factors, screening methods, and treatment options. Statistical analysis was performed using SPSS Statistics Version 24. One thousand and eighteen patients partook in the survey, giving a response rate of 95.3% Table 1. In relation to risk factors, most (91.4%) were aware of the role of family history, but only 41.8% believed that BRCA was a risk factor, with most having never heard of the term. More than a third of patients did not know at what age breast cancer screening commences, with one in four