Breast cancer patients with a negative axillary ultrasound may have clinically significant nodal metastasis.

INTRODUCTION: The non-invasive nature of the preoperative axillary ultrasound (AUS) fits the current trend of increasingly conservative axillary management. Recent publications suggest that early disease patients with clinically and radiologically negative axillae do not require sentinel lymph node biopsy (SLNB). This study aims to determine the true extent of axillary node disease in negative preoperative AUS patients. METHODS: A 10-year breast cancer registry was reviewed to identify women with pathologically confirmed T1-2 invasive breast cancer and a negative preoperative AUS. Patients who received neoadjuvant chemotherapy were excluded. Combined positive lymph node count of SLNB ± ALND was used to determine total nodal burden (TNB). Axillae were classified into low nodal burden (LNB) defined as 1-2 positive nodes and high nodal burden (HNB) defined as ≥ 3 positive nodes. RESULTS: 762 patients with negative AUS were included. There were 46.9% and 53.0% T1 and T2 tumours, respectively. 76.9% were node negative (0 LN +), 18.9% had LNB (1-2 LN +) and 4.2% had HNB (≥ 3LN +). Specifically, HNB disease was seen in 2% of T1 tumours and 6.2 % of T2 tumours with a negative AUS. In multivariate analysis, T2 strongly associated with ≥ 3 positive ALNs (OR 2.66 CI 1.09-6.51 p = 0.03) as did lymphovascular invasion (OR 3.56 CI 1.52-8.30 p = < 0.01). CONCLUSION: This study shows that AUS in its current form cannot exclude HNB axillary metastasis to the extent of eliminating the need for surgical staging of the axilla. This may impact axillary local-regional recurrence and disease-free survival. We caution that a negative AUS has a rate of 4.2% of HNB. Therefore, in cases of negative AUS with a T2 tumour, we advocate continued use of SLNB.

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.

BACKGROUND: The 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. METHODS: Baseline 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) (n = 38) versus TCL (docetaxel, carboplatin, lapatinib) (n = 10) versus TCHL (docetaxel, carboplatin, trastuzumab, lapatinib) (n = 40), 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. RESULTS: PIK3CA 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%; p = 0.439). 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%; p = 0.769). 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%; p = 0.05). CONCLUSIONS: Our 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 REGISTRATION: ClinicalTrials.gov, NCT01485926 . Registered on 2 December 2011.

Clinically guided core biopsy and cutaneous punch biopsy in the evaluation of breast lesions: a necessary test or an obsolete skill?

OBJECTIVE: The vast majority of breast cancers are diagnosed via image-guided procedures yet despite significant advances, imaging does not identify all breast malignancies. Clinically suspicious breast lesions with normal breast imaging remain a cause for concern. The aim of this study is to determine the diagnostic value of clinical core and cutaneous punch biopsies in the diagnosis of breast malignancy in clinically suspicious lesions with normal breast imaging. METHODS: All patients with suspicious clinical breast findings and normal imaging who underwent a clinical core and/or cutaneous punch biopsy from 2012 to 2019 were reviewed retrospectively. Patients with subsequent breast malignant diagnosis were analysed. RESULTS: A total of 283 biopsies (166 clinical core, 117 cutaneous punch) performed over the 7-year period were included in the analysis. A total of 263/283 (93%) yielded a benign outcome. A total of 2/283 (0.7%) yielded B3 lesions (probably benign). These lesions were benign on final surgical excision. A total of 18/283 (6.3%) yielded a malignant histopathology. Sixteen out of 18 were cutaneous punch biopsies, and 2/18 were clinical core biopsies. A total of 14/18 patients presented with nipple changes, while 4/18 had a palpable area of concern. Histopathological analysis demonstrated Paget's disease of the nipple in 8/18, invasive carcinoma in 9/18 out of which two represented a recurrence of breast malignancy. Cutaneous squamous cell carcinoma was diagnosed in 1/18. CONCLUSION: Clinical core and cutaneous punch biopsies remain a valuable tool in the diagnosis of breast cancer particularly in the management of clinically suspicious radiographically occult malignancies.

Value of Long-term Follow-up in Surgically Excised Lesions of Uncertain Malignant Potential in the Breast - Is 5 Years Necessary?

INTRODUCTION: B3 lesions are a heterogeneous group of breast lesions of uncertain malignant potential which usually require excision. The aim was to assess the efficacy of 5 years routine radiological or clinical follow-up of patients who had "high-risk" B3 lesions surgically excised, by analyzing recurrence and subsequent development of invasive/in-situ cancer. PATIENTS AND METHODS: A 10-year retrospective review from 2010 to 2019 was performed of B3 lesions diagnosed on core needle biopsy, including patients who proceeded to surgical excision with a high-risk lesion on final histology. The database recorded 6 specific B3 lesion categories: 1. Atypical ductal hyperplasia (ADH), 2. Radial scars/complex sclerosing lesions (CSLs) with epithelial atypia 3. Classical Lobular neoplasia (ALH/LCIS), 4. Papillary lesions with epithelial atypia, 5. Mixed, 6. Flat epithelial atypia (FEA), including radiological and clinical follow-up data. RESULTS: Six hundred sixteen patients had a B3 lesion after core biopsy. 110 patients had "high risk" lesions. This included 17 (15.5%) Atypical Ductal Hyperplasia (ADH), 22 (20%) radial scars/CSLs with epithelial atypia, 47 (42.7%) classical lobular neoplasia (LCIS/ALH), 7 (6.4%) papillary lesions with epithelial atypia, 13 (11.8%) mixed lesions & 4 (3.6%) Flat Epithelial Atypia (FEA) lesions. 4 of 110 (3.6%) developed invasive/in-situ disease and 4 of 110 (3.6%) developed recurrence during follow-up. 33 of 616 (5.4%) upgraded to invasive/preinvasive disease after surgical excision. CONCLUSION: Five years of routine radiological surveillance may not be necessary in patients who undergo surgical excision of "high-risk" B3 lesions. Clinical surveillance appears to be of little benefit, especially in patients with radial scars, papillary lesions, and FEA. Subsequent development of invasive/in-situ disease in patients who undergo surgical excision of atypical B3 lesions remains low.

Background parenchymal enhancement on baseline screening breast MRI: impact on biopsy rate and short-interval follow-up.

OBJECTIVE: Background parenchymal enhancement on breast MRI refers to normal enhancement of the patient's fibroglandular tissue. The aim of this study was to determine the effect of background parenchymal enhancement on short-interval follow-up, biopsy, and cancer detection rate on baseline screening MRI in a high-risk group. MATERIALS AND METHODS: Two hundred fifty baseline high-risk screening MRI examinations were reviewed. For each, the background parenchymal enhancement pattern was recorded (minimal, ≤ 25%; mild, 26-50%; moderate, 51-75%; and marked, > 75%), as were BI-RADS category, biopsy rate, and final pathology result. Results were compared for each enhancement category. RESULTS: Of the 250 MRI examinations, 24.8% showed minimal enhancement; 34%, mild; 24%, moderate; and 17.2%, marked enhancement. Women with minimal enhancement had a significantly higher number of BI-RADS categories 1 and 2 examinations (64.5%) than women with mild (38.8%), moderate (40%), or marked (25.6%) enhancement. The BI-RADS category 3 rate was 43.6% overall and was significantly lower for women with minimal enhancement (27.4% vs 47.1% for women with mild, 45.0% for women with moderate, and 58.1% for women with marked enhancement). At follow-up, 86.2% of the BI-RADS 3 lesions were converted to BI-RADS category 1 or 2 and 13.8% were converted to BI-RADS 4, with a malignancy rate of 0.9% for lesions undergoing short-interval follow-up. There was no significant difference in biopsy rate or cancer detection rate among enhancement categories. CONCLUSION: Mild, moderate, and marked background parenchymal enhancement is associated with a significantly lower rate of BI-RADS categories 1 and 2 assessments and a significantly higher rate of BI-RADS category 3 assessments than minimal enhancement. There was no significant difference in biopsy rate or cancer detection rate among the enhancement categories.

Implementation of evidence-based guidelines for thyroid nodule biopsy: a model for establishment of practice standards.

OBJECTIVE: Multiple studies have defined criteria for the selection of thyroid nodules for biopsy. No set of criteria is sufficiently sensitive and specific. The aim of this study is to develop a method for assessing consistency of practice in an ultrasound group and to determine whether a 5-point malignancy rating scale can be used to select patients for biopsy. MATERIALS AND METHODS: One hundred one nodules (50 benign and 51 malignant) were selected from a thyroid biopsy database. Seven radiologists were educated on evidence-based criteria used to select nodules for biopsy. Using this information, readers graded the likelihood of malignancy using a 5-point malignancy rating scale, where 1 equals the lowest probability of malignancy and 5 equals the highest probability of malignancy, on the basis of overall impression of sonographic findings. Interobserver agreement on biopsy recommendation, reader sensitivity, specificity, and accuracy were determined. RESULTS: The sensitivity and specificity of biopsy recommendation were 96.1% and 52%, respectively. The misclassification rate was 25.7%, and accuracy was 74.3%. Interobserver agreement on biopsy recommendation was fair to substantial (κ, 0.38-0.69). The proportion of agreement was excellent for malignant nodules (0.88-1.0). The risk of malignancy increased with increasing malignancy rating: 4.3% of nodules with a malignancy rating of 1 were malignant versus 93.4% of those assigned a rating of 5. CONCLUSION: Our study illustrates a method to evaluate the standard of practice for thyroid nodule assessment among radiologists within an ultrasound group. Application of a 5-point malignancy rating scale to select nodules for biopsy is feasible and shows good diagnostic accuracy.

Comparison of digital mammography and screen-film mammography in breast cancer screening: a review in the Irish breast screening program.

OBJECTIVE: Clinical trials to date into the use of full-field digital mammography (FFDM) for breast cancer screening have shown variable results. The aim of this study was to review the use of FFDM in a population-based breast cancer screening program and to compare the results with screen-film mammography. MATERIALS AND METHODS: The study included 188,823 screening examinations of women between 50 and 64 years old; 35,204 (18.6%) mammograms were obtained using FFDM. All films were double read using a 5-point rating scale to indicate the probability of cancer. Patients with positive scores were recalled for further workup. The recall rate, cancer detection rate, and positive predictive value (PPV) of FFDM were compared with screen-film mammography. RESULTS: The cancer detection rate was significantly higher for FFDM than screen-film mammography (6.3 vs 5.2 per 1,000, respectively; p = 0.01). The cancer detection rate for FFDM was higher than screen-film mammography for initial screening and subsequent screening, for invasive cancer and ductal carcinoma in situ, and across all age groups. The cancer detection rate for cancers presenting as microcalcifications was significantly higher for FFDM than for screen-film mammography (1.9 vs 1.3 per 1,000, p = 0.01). The recall rate was significantly higher for FFDM than screen-film mammography (4.0% vs 3.1%, p < 0.001). There was no significant difference in the PPVs of recall to assessment for FFDM and screen-film mammography (15.7% and 16.7%, p = 0.383). CONCLUSION: FFDM resulted in significantly higher cancer detection and recall rates than screen-film mammography in women 50-64 years old. The PPVs of FFDM and screen-film mammography were comparable. The results of this study suggest that FFDM can be safely implemented in breast cancer screening programs.

Rotator cuff impingement: correlation between findings on MRI and outcome after fluoroscopically guided subacromial bursography and steroid injection.

OBJECTIVE: The purpose of this study was to describe the use of fluoroscopically guided subacromial bursography in the management of rotator cuff impingement and to correlate clinical outcome with preprocedural MRI findings. MATERIALS AND METHODS: Sixty-nine patients with clinically and MRI proven subacromial impingement referred for fluoroscopic subacromial bursography and steroid injection between January 2004 and January 2006 were included in the study. After contrast-enhanced bursography, each patient received an injection of 80 mg of methylprednisolone and 1-2 mL of 0.25% bupivacaine into the bursa. Outcome was determined retrospectively and classified as complete resolution of symptoms, partial resolution of symptoms, or no change. MRI findings of impingement were graded according to severity. Outcome was evaluated as complete resolution and as complete or partial resolution in relation to MRI findings, duration of symptoms, age, and sex. RESULTS: Complete resolution of symptoms was recorded in 40 (58%) of the patients. Fifty-seven (83%) of the patients reported some relief of symptoms after a mean follow-up period of 6 months. Shorter duration of symptoms and minor-grade MRI findings were associated with complete resolution. Younger age and minor-grade MRI findings were associated with complete or partial resolution. CONCLUSION: Imaging-guided subacromial steroid injection may be of benefit in the short-term management of clinically and MRI-proven subacromial impingement, with 83% of 69 patients reporting symptom relief at 6-month follow-up evaluation. Patients with shorter duration of symptoms and minor-grade MRI findings have improved outcome.

Restenosis following percutaneous renal artery revascularization.

BACKGROUND/AIMS: Restenosis following percutaneous transluminal renal angioplasty (PTRA) remains a concern even in the era of adjuvant stenting. The optimal form of therapy, and particularly the role of repeat PTRA in the treatment of recurrent hypertension associated with renal artery restenosis, is largely unknown. The aims of this study were to determine the risk factors for restenosis and to evaluate the blood pressure outcomes of patients who underwent repeat PTRA. METHODS: Clinical and procedural characteristics of 32 patients who developed recurrent hypertension and renal artery restenosis were compared to a control group of patients who maintained renal artery patency and adequate blood pressure control after the first procedure. The groups were matched for sex and initial procedure date. RESULTS: The restenosis group had a mean age of 71 +/- 12 years, a female/male ratio of 24/8, an average blood pressure of 179/87 mm Hg, despite three antihypertensive medications, and a serum creatinine level of 1.5 +/- 0.4 mg/dl. Repeat PTRA performed for clinically significant restenosis was 10.7 +/- 8 months after the first procedure, and 17 of the 32 patients had a measurable blood pressure benefit at last follow-up (177 +/- 119 weeks). The development of restenosis was positively associated with body weight (p = 0.003) and body mass index (p = 0.008), but independent of diabetes mellitus, hyperlipidemia, or statin therapy. Of the 15 patients who failed the second procedure, 4 went on to have third PTRA, none of whom had sustained benefit. CONCLUSIONS: An increased body mass index is associated with restenosis following initial PTRA. Patients with restenosis can be treated successfully with repeat PTRA which provides sustained improvement in blood pressure control in approximately half of these patients.