Is there an Upgrading to Malignancy at Surgery of Mucocele‐Like Lesions Diagnosed on Percutaneous Breast Biopsy?

Management of pure mucocele‐like lesion (MLL) diagnosed on percutaneous breast biopsy (PBB) is controversial. To assess surgical upgrade rate and clinical outcome of pure MLL obtained as sole diagnosis on PBB. Patients diagnosed with a MLL as the most advanced lesion on PBB from April 1997 to December 2010 were reviewed for radiologic presentation, biopsy technique, and pathologic and clinical outcomes. Of the 21,340 image‐guided PBB performed during the study period, 50 women with 51 MLL (0.24%) were identified. Mean age was 53.1 ± 7.7 years. Radiologic findings were mostly microcalcifications (n = 47, 92.2%). Stereotactic PBB was performed for 49 lesions (96.1%). Surgery was performed shortly after biopsy in 35 women, with benign final pathology in 33, and upgrade to ductal carcinoma in situ (DCIS) in two patients (2/35, 5.7%). Mean follow‐up was 4.2 ± 2.5 years (3.7 ± 2.1 years for surgical patients; 5.9 ± 2.9 years for follow‐up only patients); three women were lost to follow‐up (3/50). Three invasive cancers (3/47, 6.4%) were diagnosed 1.2, 1.2, and 2.8 years after biopsy: two in surgical patients, and one in a follow‐up only patient. No cancer occurred at the same site as the original MLL. Pure MLL lesion of the breast is a rare entity and is mostly associated with a benign outcome. We observed an upgrade to DCIS slightly superior to 5%, but no invasive cancer. It is therefore unclear if these lesions should be excised or clinically and radiologically followed up when such lesions are found at PBB.     

Are Percutaneous Biopsy Rates a Reasonable Quality Measure in Breast Cancer Management?

Background

Utilization of percutaneous needle biopsy (PNB) has been proposed as a quality measure of breast cancer care. We evaluated rates and reasons for failure of patients undergoing PNB as the initial diagnostic procedure for evaluation of breast pathology.

Methods

We performed a retrospective review of sequential patients undergoing image-guided PNB and open surgical excisional breast biopsies from January 2006 to July 2009 at our institution. Factors associated with failure to undergo a percutaneous approach were analyzed.

Results

During the study period, 1196 breast biopsies were performed; 87 (7.3%) were open surgical biopsies, and 1109 (92.7%) were PNB. Imaging used for percutaneous guidance or needle localization was ultrasound in 58.9%, mammogram in 40.0%, and magnetic resonance imaging (MRI) in 0.9%. Open surgical excisional biopsy was associated with mammographic guidance (P < .001), location in the central or lower inner quadrant of the breast (P = .002), BIRADS score of 1 or 6 (P < .001), or calcifications as target (P < .001). There were no differences in rates of PNB by age, size of lesion, or breast density. Reasons for failure of PNB were technical (calcifications not visualized, proximity to implant, etc.) in 86.2% of cases. No reason was documented in 10.3%, and 3.4% of patients refused a percutaneous approach.

Conclusions

The majority of patients in this series underwent PNB as an initial diagnostic approach. Most percutaneous failures are due to technical reasons. PNB rates are a reasonable quality measure in breast cancer care. Documentation of failure to meet this benchmark should be stringently monitored.

     

Management of Papillary Lesions of the Breast: Can Larger Core Needle Biopsy Samples Identify Patients Who May Avoid Surgical Excision?

Background

The ability to distinguish benign from atypical/malignant papillary lesions on core needle biopsy is limited by the representative nature of the biopsy method, thus follow-up excision is usually recommended. We aimed to determine if larger samples of tissue obtained by core needle biopsy can more reliably predict the true benign nature of a papilloma.

Methods

We reviewed the pathology slides and medical records of 51 patients who were diagnosed with benign papillomas on core needle biopsy from 2000 to 2010, who subsequently underwent surgical excision. The characteristics of the core needle biopsy that were associated with retention of benign histology on excision were determined and analyzed.

Results

Atypical ductal hyperplasia and carcinoma were identified in 5.8 % (3/51) and 5.8 % (3/51) of papillary lesions, respectively, when excised. Patients whose lesions were diagnosed as benign on excision were significantly distinguished by the area (mm²) of tissue sampled by core needle biopsy (mean ± standard deviation (SD): 101.5 ± 106.5) compared with those with atypia or carcinoma on excision (mean ± SD: 41.7 ± 24.0, P = 0.003). All biopsies performed with 12-gauge or larger needles retained benign features on excision. Core needle biopsy tissue samples consisting of ≥7 cores, or measuring >96 mm² in aggregate, had a negative predictive value for atypia/malignancy of 100 %.

Conclusions

Larger tissue samples significantly improved the predictive value of benign histology on core needle biopsy. A papilloma sampled by a 12-gauge or larger needle, ≥7 cores, or >96 mm² retained its benign features upon excision.     

Implementation of a Percutaneous Core Needle Biopsy Training Program: Results from the University of Michigan–Komfo Anokye Teaching Hospital Breast Cancer Research Partnership

Purpose

To describe a training program in percutaneous core needle biopsy implemented in conjunction with a breast cancer research collaboration between the University of Michigan (UM) and the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana.

Methods

In July 2007 a Ghana-based training program for performance of core needle biopsy was jointly coordinated by the UM and KATH principal investigators (L.N. and B.A.). This course required less than 1 week for implementation.

Results

Following the training course (July 2007 through August 2008), 82 core needle biopsies of breast masses were performed at KATH. Of these, 56 had tissue specimens available for review at UM for comparison with KATH primary pathology reports. Forty-six of the 56 UM-reviewed cases (82%) had a KATH diagnosis of breast cancer; UM pathology review was in agreement with the cancer diagnosis in all 46 cases (100%). Ten of the 56 UM-reviewed cases (18%) had a KATH diagnosis of benign fibroadenoma/fibrocystic breast tissue; UM review was concordant in all ten cases (100% concordance for benign lesions). For the remaining 26 procedures we were unable to retrieve either the KATH pathology report or tissue blocks for UM review.

Discussion

The design and implementation of appropriate diagnostic biopsy programs is important for delivery of high-quality, efficient breast cancer care in developing nations. This study demonstrates a successful 1-week training program in percutaneous core needle biopsy for a multidisciplinary group of physicians. Further work is needed for similar programs to accurately identify and classify breast cancer internationally.     

Can Sentinel Lymph Node Biopsy Be Omitted in Patients With Favorable Breast Cancer Histology?

Background The widespread use of sentinel lymph node biopsy (SLNB) to replace axillary dissection has broadened the indications for axillary staging in breast cancer. Recent studies have demonstrated a finite risk of lymphedema and sensory morbidity associated with SLNB. We undertook this study to determine whether SLNB could be omitted in clinically node-negative patients with favorable-histology breast cancer.Methods We conducted a retrospective review of a prospective database of SLNBs performed at Memorial Sloan-Kettering Cancer Center from 1996 to 2003 to determine the incidence of lymph node metastases by histological subtype. For the favorable subtypes, the patients age, tumor size, estrogen receptor status, lymphovascular invasion, nuclear grade, and histological grade were compared by nodal status to determine their predictive value.Results A total of 196 cases with favorable breast cancer subtypes were identified with a 4.1% (8 of 196) sentinel lymph node (SLN) positivity rate. Each of the histological subtypes included patients with positive SLNs, with the exception of adenoid cystic (n = 4) and secretory (n = 1) breast carcinoma, which were quite rare in our series. When compared by nodal status, the patients age, tumor size, estrogen receptor status, lymphovascular invasion, nuclear grade, and histological grade failed to predict those with positive SLNs.Conclusions Patients with favorable breast cancer histology have a small risk of axillary SLN metastases. The use of SLNB in these patients should be individualized, taking into consideration the small incidence of axillary metastases and the risks and benefits associated with the SLN procedure.     

Can Breast Magnetic Resonance Imaging Prevent Biopsy or Change the Management of BI-RADS® Category 4 Breast Lesions?

The BI-RADS® category 4 includes suspicious breast lesions which requires biopsy. The aim of this study is to investigate the contribution of breast magnetic resonance imaging to the management of BI-RADS® category 4 breast lesions detected by mammography and∕or ultrasonography. Thirty-four lesions classified as BI-RADS® category 4A, 4B, or 4C by conventional methods were evaluated with magnetic resonance imaging. All lesions were coded by using the American College of Radiology BI-RADS® lexicon. Each lesion was verified with the result of pathology. Lesions were evaluated as BI-RADS® category 1 in 1 patient (2.9%), category 3 (20.6%) in 7 patients, category 4 in 25 patients (73.6%), and category 5 in 1 patient (2.9%) with breast magnetic resonance imaging. Only the BI-RADS® 4A lesion categories were changed by breast magnetic resonance imaging, and these lesions were pathologically diagnosed as benign. The negative predictive value of breast MRI for BI-RADS® category 4A lesions was calculated as 100%. In all BI-RADS® category 4 lesions, pathologically 4 lesions found to be high risk and 3 lesions found to be malignant. The sensitivity, specificity, positive predictive, and negative predictive value of breast magnetic resonance imaging in BI-RADS® category 4 lesions were calculated as 100, 29.6, 26.9, and 100%, respectively. The area under the ROC curve was calculated 0.648. Breast magnetic resonance imaging is promising to be used as a problem-solving modality in BI-RADS® category 4A breast lesions.     

Whole-genome Sequencing of an Aggressive BRAF Wild-type Papillary Thyroid Cancer Identified EML4–ALK Translocation as a Therapeutic Target

Background

Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In radioiodine resistant aggressive papillary thyroid cancers, there remain few effective therapeutic options. A 62-year-old man who underwent multiple operations for papillary thyroid cancer and whose metastases progressed despite standard treatments provided tumor tissue.

Methods

We analyzed tumor and whole blood DNA by whole genome sequencing, achieving 80× or greater coverage over 94 % of the exome and 90 % of the genome. We determined somatic mutations and structural alterations.

Results

We found a total of 57 somatic mutations in 55 genes of the cancer genome. There was notably a lack of mutations in NRAS and BRAF, and no RET/PTC rearrangement. There was a mutation in the TRAPP oncogene and a loss of heterozygosity of the p16, p18, and RB1 tumor suppressor genes. The oncogenic driver for this tumor is a translocation involving the genes for anaplastic lymphoma receptor tyrosine kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4). The EML4–ALK translocation has been reported in approximately 5 % of lung cancers, as well as in pediatric neuroblastoma, and is a therapeutic target for crizotinib.

Conclusions

This is the first report of the whole genomic sequencing of a papillary thyroid cancer in which we identified an EML4–ALK translocation of a TRAPP oncogene mutation. These findings suggest that this tumor has a more distinct oncogenesis than BRAF mutant papillary thyroid cancer. Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers.     

Differential Association of BRCA1 and BRCA2 Genes with Some Breast Cancer–Associated Genes in Early and Late Onset Breast Tumors

Background: Accumulating evidence indicating more aggressive features of breast carcinoma (BC) in young women than their older counterparts have raised the question of whether these differences are present at the genetic level.Methods: For this purpose, we performed a comparative analysis of the frequency of deletions of BRCA1, BRCA2, BRCAX, TP53, ATM, and RB1 and amplification of Cyclin D1 and also studied the interrelation and prognostic significance of these genetic alterations in 30 early onset (40 years) and 33 late onset (>40 years) cases of BC. These gene alterations were also studied in 11 other types of breast lesions.Results: A differential pattern of alterations (deletion/amplification) was observed in the two age groups, with the sequence in younger women being BRCA1 (72%), TP53 (71%), ATM (64%), BRCA2 (62%), RB1 (60%), Cyclin D1 (43%), and BRCAX (24%) and that in the older group being TP53 (66%), RB1 (63%), BRCA1 (56%), ATM (53%), BRCA2 (45%), Cyclin D1 (24%), and BRCAX (23%). Similar, differential correlations were also seen with several clinicopathological parameters, prognosis, and combinations of alterations among these genes in the two age groups.Conclusions: Differential frequencies and interrelationships of genetic alterations and prognoses in these two age groups indicate that the molecular pathways for the development of tumors in both age groups may not be similar, though the ultimate effect is deregulation of cell cycle checkpoints and defects in the DNA repair pathway.     

Treatment of Metastatic Breast Cancer With Somatostatin Analogues—A Meta-Analysis

Background: Somatostatin analogues appear to have antiproliferative effects in breast cancer by inhibiting various hormones. Several small phase 1 and 2 clinical trails have evaluated the efficacy of somatostatin analogues, but the results are varied. The purpose of this study was to use the technique of meta-analysis to determine the effect of somatostatin analogues on tumor response, toxicity, and serum hormone levels in women with metastatic breast cancer.Methods: All published and unpublished trials were reviewed. Meta-analysis was preformed by best linear unbiased estimate regression with observations weighted inversely to their variance. Significance was considered at P < .05.Results: Fourteen studies (N = 210) were included. Positive tumor response was reported in 87 patients (41.4%). Mean duration of response was 3.9 months. Response was best when somatostatin analogues were given as first-line therapy (69.5% versus 28.5%, P < .006) and in patients with 2 metastases (45.0% versus 5.6%, P = .3). Mild side effects occurred in 47 of 185 patients (25.4%). Therapy was associated with a decrease in serum insulin-like growth factor (IGF-1) and an increase in growth hormone.Conclusions: In patients with metastatic breast cancer, treatment with somatostatin analogues was associated with a tumor response of over 40% with few side effects. Best results were achieved when somatostatin analogues were given as first-line therapy.     

Macroscopic Quality Control Improves the Reliability of Blue Dye–Only Sentinel Lymph Node Biopsy in Breast Cancer

Background: One of the problems of sentinel lymph node (SLN) biopsy is the risk of false negatives. At the Institut Curie, to reduce the false-negative rate, we have developed a histological quality control of the SLN performed by blue dye alone, which consists of verification of the SLN blue stain by the pathologist.Methods: A total of 324 patients underwent an SLN biopsy procedure with patent blue dye only followed by an immediate axillary dissection. Initially, SLNs were checked to ensure that they were blue by macroscopic examination. Finally, a search for immunohistochemistry micrometastasis was performed.Results: In 277 (85.5%) of 324 patients, an SLN was identified by the surgeon. After standard examination, the false-negative rate was 11.1% (10 of 90). After macroscopic checking of the 197 negative SLNs, 167 of the 197 were confirmed blue, and there were 5 false negatives, which brought the false-negative rate down to 5.6% (5 of 90). Sixty SLNs out of the 167 confirmed blue SLNs were then proved to be immunohistochemically micrometastatic, and there were 3 false negatives, giving a final false-negative rate of 2.2% (2 of 90; P = .002).Conclusions: In this series, the procedure of pathologic analysis of the SLN has resulted in a significant reduction of the false-negative rate.     

Is Blue Dye Indicated for Sentinel Lymph Node Biopsy in Breast Cancer Patients With a Positive Lymphoscintigram?

Background The use of isosulfan blue dye in sentinel node biopsy for breast cancer has been questioned because of its risk of allergic reaction. We hypothesized that blue dye could be safely omitted in the subgroup of patients who have evidence of successful sentinel node localization by lymphoscintigraphy.Methods A retrospective review of patients with breast cancer and sentinel node biopsy was conducted. Information was collected on lymphoscintigraphy results, use of blue dye, and intraoperative and pathologic findings of sentinel nodes.Results We identified 475 patients with breast cancer who underwent 478 sentinel node biopsies. Both dye and isotope were given in 418 cases, of which 380 had a positive lymphoscintigram. In 5 of the 380 cases with a positive lymphoscintigram, the sentinel nodes obtained were blue but not hot, for a 1.3% marginal benefit of dye in the technical success of the procedure. Sentinel nodes positive for metastasis were found in 102 of 380 cases; in 3 cases, the only positive sentinel node was blue but not hot. Omission of the blue dye tracer would have increased the false-negative rate of the sentinel node procedure by approximately 2.5%.Conclusions Even in sentinel node biopsy cases with a positive lymphoscintigram, the use of blue dye is beneficial for both improving the technical success of the procedure and reducing the false-negative rate of the procedure. Because the marginal benefits of dye justify its routine use, strategies to minimize the toxicity of blue dye are warranted.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

The Safety and Accuracy of Sentinel-Node Biopsy in Early-Stage Invasive Breast Cancer—Turkish Experience

The purpose of this prospective study was to investigate the correlation of sentinel lymph node (SLN) and axillary lymph node (ALN) metastasis in early-stage invasive breast cancer in a single institution. One hundred and fifteen patients with early-stage invasive breast cancer first underwent SLND followed by an appropriate surgical procedure (modified radical mastectomy, lumpectomy + axillary dissection, simple mastectomy + mammoplasty). In this series, a radioactive agent (technetium) was used to investigate the sentinel lymph node/nodes. In 28 (24.3%) patients, metastases were found in both SLN and axillary dissections. There were no metastases in either of these procedures in 69 (60%) patients. SLN metastasis was found in 13 (11.3%) patients, but no axillary metastasis was found. No skip metastasis was detected. Five patients in whom the sentinel node was not found were also negative for axillary metastasis. As the studies progress in this direction, it might be possible to avoid axillary dissection in patients with early breast cancer in whom metastasis in SLN cannot be detected. We believe this will reduce morbidity from breast cancer surgeries.