Stereotactic vacuum-assisted breast biopsy in 268 nonpalpable lesions

The new imaging technology made available today allows for an early detection of small subclinical breast lesions which frequently call for guided presurgical micro-histology. To evaluate the relationship between vacuum-assisted breast biopsy (VABB) histopathological diagnoses and mammographic findings in non-palpable breast lesions. The breast lesions of 1393 women who had received consecutive screening mammograms between 2001 and 2007 were assessed by VABB. The mammographic breast lesions, classified according to the Breast Imaging Reporting and Data System (BI-RADS), were subjected to VABB only if rated as highly suspicious (2%), suspicious (64.5%) for malignancy, or probably benign (33.5%). VABB findings included 981 (70.5%) probably benign lesions, 407 (29.2%) suspicious/malignant lesions, and five (0.3%) cases which were considered as inappropriate for diagnostic purposes. At histology, 10.2% of the suspicious/malignant lesions were classified as proliferative lesions, 11.1% as ductal carcinoma in situ (DCIS), and 8% as invasive ductal carcinoma (IDC). The positive predictive value (PPV) of BI-RADS assessment categories 3, 4 and 5 was 4.1%, 25.3% and 75%, respectively. The occurrence of obscured or spiculated masses was found to exhibit the highest PPV for malignancy (12.5% in BI-RADS 3 and 63% in BI-RADS 4), followed by microcalcifications which showed a malignancy rate of 6.4% in BI-RADS 3, and 20% in BI-RADS 4. VABB turns out to be effective in the assessment of many malignant and benign preclinical tumour lesions thus allowing for a significant reduction of the number of surgical biopsies.

Stereotactic vacuum-assisted breast biopsies in 500 women with microcalcifications: radiological and pathological correlations

Stereotactic vacuum-assisted breast biopsies in 500 women with microcalcifications: radiological and pathological correlations

Objective To explore the expression and diagnostic significance of β-tubulin-Ⅲ proteins, E-cadherin and α-catenin in breast precancerous lesions, including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC). Methods The expressions of β-tubulin-Ⅲ, E-cadherin and α-catenin were investigated by immunhistochemical UltraSensitiveTM S-P method of precancerous Lesions including 20 cases of ADH, 60 cases of DCIS, and 90 cases of carcinoma of the breast. 30 cases of normal breast tissues were selected as a control group. Results (1)Significant differences of the β-tubulin-Ⅲ proteins expression were found among the four groups of normal breast tissues(20%), ADH(55.0%), DCIS(71.7%)and IDC(84.4%), (χ2=22.298, P<0.05), (P<0.05). (2)The expressions of E-cadherin and α-catenin in observed and controll groups: The expressions of E-cadherin in normal group, ADH, DCIS and IDC were 100%, 75.0%, 68.3% and 41.1%.The expressions of α-catenin in normal group, ADH, DCIS and IDC groups were 100%, 80.0%, 73.3% and 56.7%.There were significant differences of the expressions of E-cadherin and α-catenin between DCIS and IDC(χ2=18.650, 10.970, P<0.05). Conclusions Abnormal expression of β-tubulin-Ⅲ may be an early event in the development of breast tumor. The aberration of β-tubulin-Ⅲ may play a key role during oncogenesis and promote breast cellular transformation into malignancy. The abnormal expressions of E-cadherin and α-catenin with the degree of breast disease relates to the development, progression and metastasis of breast carcinoma, which may serve as one of the parameters for diagnosis of breast carcinoma and determine biological behavior and prognosis of breast carcinoma. Key words: Breast neoplasms; Precancerous Lesions; Microtubulin; Cadherin; Catenin

Previous studies have shown the chromosomal alterations in usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) in the breast with bilateral ductal hyperplasia or adjacent to invasive ductal carcinoma (IDC). However, the role of UDH as a putative precursor of breast IDC is not clear and has not been fully addressed. The aim of this study was to clarify the role of UDH in breast carcinoma pathogenesis. To investigate chromosomal imbalances and commonality, samples of pure unilateral UDH (n=20) were obtained by laser capture microdissection and analyzed by comparative genomic hybridization. Other ductal lesions, including ADH (n=2), high-grade DCIS (n=3), and grade III IDC (n=5), were assessed at the same time for comparison. The mean values of alteration were 1.95 (39/20) in UDH, 9.5 (19/2) in ADH, 11.0 (33/3) in DCIS and 18.2 (89/5) in IDC, respectively. Some common predisposition regions for the deletions were at chromosomes 1p36-pter, 13q11-14, and 16q11-23, while the high frequency amplification regions were 1q31-qter, 3p21-pter, 6p21-pter, 11q11-14, 12q11-qter, 13q21-qter, 16p12-pter, 17q12-22, and 20q. The genetic abnormalities in the spectrum of breast ductal hyperplasia revealed that the deletion of DNA copy in UDH was the lowest, and gradually increased in the lineages of ADH, DCIS and IDC. Results showed that a significant portion of UDH shares common genetic alterations with ADH, DCIS and IDC, indicating UDH as a precursor of invasive breast ductal carcinoma.

Breast cancer progression involves stepwise transition from atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Percutaneous core needle biopsy (CNB) is the standard procedure after an abnormal mammography finding. However, a CNB diagnosis with either ADH or DCIS is often non-conclusive. A definitive diagnosis relies on surgical excision for further pathological analysis to differentiate simple ADH (sADH) from ADH coexisted with advanced lesions such as DCIS and/or IDC (cADH). Therefore, development of reliable molecular biomarkers is essential to avoid unnecessary surgical excision. microRNAs (miRNAs) are single-stranded non-coding RNAs that play an important role in breast cancer progression. A series of miRNAs that are differentially expressed during stepwise transition of breast carcinogenesis were identified earlier, of which miR-638 and miR-671-5p were functionally characterized. The expression of these miRNAs was decreased gradually from ADH, DCIS, to IDC. We hypothesize that these miRNAs may serve as valuable biomarkers following abnormal mammogram and CNB procedure. Using an improved microdissection protocol, we isolated normal, hyperplasia, DCIS, and/or IDC lesions from FFPE tissue of CNB. We also collected patients’ blood samples before CNB procedure. In addition, we employed the Human 21T breast epithelial cell lines, which were originally derived from the same patient diagnosed with metastatic breast cancer, including H16N2 (normal mammary epithelial), 21PT (ADH), 21NT (DCIS) and 21MT-1 (IDC) for in vitro model study. Real-time qRT-PCR assay was performed for examination of miRNA expression. Cell proliferation and invasion capability were examined by MTT and Transwell assays, respectively after transfection of candidate miRNAs. EMT markers were evaluated by Western blot and Immunofluorescence assays. In clinical samples, we found a synergistic expression pattern between miR-671-5p and miR-638 in cADH but not in sADH lesions. Interestingly, decreased miR-671-5p expression was detected in cADHs, but not in sADHs in both FFPE and serum samples. To explore the potential function of the two miRNAs in the transition from sADH to cADH, we performed further analysis in the Human 21T breast epithelial cell lines. Forced expression of miR-671-5p significantly inhibited cell proliferation in H16N2, 21PT, 21NT and 21MT-1 series cell lines. Overexpression of miR-671-5p attenuated invasion in 21PT, 21NT, and 21MT-1 cell lines but not in H16N2 cell line. Further, miR-671-5p overexpression resulted in significant suppression of mesenchymal marker, vimentin, and promoted the expression of epithelial marker, E-cadherin, in 21PT, 21NT, and 21MT-1cell lines. Our data suggest that miR-671-5p and miR-638 expression in serum and/or CNB tissue may server as a novel companion screening tool following an abnormal mammogram and a subsequent ADH diagnosis by CNB. Citation Format: Xiaohui Tan, Woojin Lee, Xiaoling Wu, Weaam Alshenawy, Danielle Soberman, Katayoon Rezaei, Sana Tabbara, Christine Teal, Robert S. Siegel, Rachel F. Brem, Sidney W. Fu. miR-671-5p and miR-638 serve as novel biomarkers for early breast cancer detection. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1072.

The purposes of this study were to determine the frequency of diagnosis of atypical ductal hyperplasia (ADH) at MRI-guided 9-gauge vacuum-assisted breast biopsy and to assess the rate of underestimation of ADH at subsequent surgical excision. We conducted a retrospective review of medical records of 237 lesions consecutively detected with MRI and then subjected to MRI-guided 9-gauge vacuum-assisted breast biopsy during a 33-month period. Underestimated ADH was defined as a lesion yielding ADH at vacuum-assisted biopsy and cancer at surgery. Scientific tables were used to calculate 95% CI. Histologic analysis of MRI-guided vacuum-assisted breast biopsy specimens yielded ADH without cancer in 15 (6%) of 237 lesions. Among 15 patients in whom vacuum-assisted breast biopsy yielded ADH, the median age was 52 years (range, 46-68 years). The median number of specimens obtained was nine (range, 8-18 lesions). Median MRI lesion diameter was 1.3 cm (range, 0.7-7.0 cm). Among 15 MRI lesions, 10 (67%) were nonmasslike enhancement and five (33%) were masses. Surgical excision was performed on 13 lesions. Surgical histologic findings were malignancy in five (38%) of the cases, all ductal carcinoma in situ; high-risk lesion in six (46%) of the cases, including ADH without other high-risk lesions (n = 2), ADH and lobular carcinoma in situ (LCIS) (n = 1), ADH, LCIS, and papilloma (n =1), ADH and papilloma (n = 1), and LCIS (n = 1); and benign in two (15%) of the cases. These data indicated an ADH underestimation rate of 38% (95% CI, 14-68%). ADH without cancer was encountered in 6% of MRI-guided 9-gauge vacuum-assisted breast biopsies. ADH at MRI-guided vacuum-assisted breast biopsy is an indication for surgical excision because of the high (38%) frequency of underestimation of these lesions.

Purpose: we have previously described the "Milky Way Sign", which manifests as microcalcifications overlying noncalcified band-like density, best seen in digital breast tomosynthesis (DBT), in a patient with ductal carcinoma in situ (DCIS). Here, we describe a series of patients with DCIS, IDC, and rarely, Atypical Ductal Hyperplasia (ADH) with this sign. Materials and Methods: we performed a systemic search of all stereotactic core biopsies for suspicious calcifications performed at our institution from April 15, 2014, when we first implemented DBT with synthesized 2D mammogram, to October 2, 2014, and identified all cases that were diagnosed as DCIS, IDC, or high-risk lesions (such as ADH, atypical lobular hyperplasia (ALH), and intraductal papilloma) on pathology. From 89 biopsied performed in 87 patients, a total of 13 cases of DCIS, IDC, or IDC with DCIS were identified in 12 patients. 17 cases of high-risk lesions were identified in 16 patients, including 10 ADH in 9 patients, 4 ALH, two intraductal papillomas, and one atypical columnar cell change. Results: Among the 30 cases of suspicious calcifications with a diagnosis of DCIS, IDC, or high-risk lesions, 37% demonstrated the Milky Way Sign (11/30), including 71% of DCIS cases (5/7), 60% of cases of IDC (3/5), 100% of DCIS/IDC (1/1), and 12% of high-risk lesions (2/17). Both high-risk lesions with the Milky Way sign were ADH from the same patient. Among the 11 cases with the Milky Way sign, the breast density at the site of calcifications is either scattered (6/11) or heterogeneously dense (5/11), whereas the density at 1 cm surrounding the calcifications is either fatty (8/11) or scattered (3/11). The breast is less dense surrounding the calcifications in all but one case. The calcifications seen in the Milky Way cases are predominantly fine pleomorphic calcifications except one case of fine linear and linear branching calcifications. The calcifications are grouped (6/11), linear (3/11), or segmental (2/11) in distribution. Five patients also had contrast-enhanced breast MRIs. Among them, three (one each with the diagnosis of DCIS, IDC or DCIS/IDC) had non-mass enhancement on breast MRI that correlated to the Milky Way sign seen on mammogram. The other two patients (one with DCIS and one with IDC) had post biopsy change instead of Non-mass enhancement were seen in the corresponding areas. Conclusion: The Milky Way sign, in the context of DBT, is a novel diagnostic sign for both DCIS and IDC. It may occasionally be seen in ADH cases as well. Features that often associate with the Milky Way sign include less dense tissue surrounding the calcifications, calcifications that are fine pleomorphic in morphology and grouped or linear in distribution. Preliminary results also suggest that the Milky Way sign may correspond to non-mass enhancement seen on contrast-enhanced breast MRI. Clinical Relevance Statement: We hope that the Milky Way sign will facilitate detection of both DCIS and IDC in the context of DBT. Citation Format: Allison K, Xu Y, Liu YI, Miyake KK, Downey JR, Lipson JA, Ikeda DM. A case series of the Milky Way sign: A diagnostic finding of ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IDC) on digital breast tomosynthesis (DBT). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-01-01.

Stereotactic vacuum-assisted breast biopsy: Comparison between 11- and 8-gauge needles

IntroductionWomen with ductal hyperplasia including usual ductal hyperplasia (UDH) and atypical ductal hyperplasia (ADH) have an increased risk of developing invasive ductal carcinoma (IDC) of breast. The importance of several molecular markers in breast cancer has been of considerable interest during recent years such as p53 and estrogen receptor alpha (ERα). However, p53 nuclear accumulation and ERα expression have not been assessed in ductal hyperplasia co-existing with ductal carcinoma in situ (DCIS) or IDC versus pure ductal hyperplasia without DCIS or IDC.Materials and methodsWe investigated p53 nuclear accumulation and ERα expression in breast ductal hyperplasia in a cohort of 215 Chinese women by immunohistochemistry (IHC), which included 129 cases of pure ductal hyperplasia, 86 cases of ductal hyperplasia co-existing with DCIS (41 cases) or IDC (45 cases).ResultsNuclear p53 accumulation was identified in 22.8% of ADH (31/136), 41.5% of DCIS (17/41) and 42.2% of IDC (19/45), and no case of UDH (0/79). No difference in nuclear p53 accumulation was observed between pure ADH and ADH co-existing with DCIS (ADH/DCIS) or IDC (ADH/IDC) (P > 0.05). The positive rate of ERα expression was lower in ADH (118/136, 86.8%) than that in UDH (79/79, 100%) (P < 0.001), but higher than that in DCIS (28/41, 68.3%) or IDC (26/45, 57.8%) respectively (P < 0.001). The frequency of ERα expression was lower in ADH/DCIS (23/29, 79.31%) and ADH/IDC (23/30, 76.67%) than that in pure ADH (72/77, 93.51%) respectively (P < 0.05). There was a negative weak correlation between p53 nuclear accumulation and ERα expression as for ADH (coefficient correlation -0.51; P < 0.001).ConclusionsDifferent pathological types of ductal hyperplasia of breast are accompanied by diversity in patterns of nuclear p53 accumulation and ERα expression. At least some pure ADH is molecularly distinct from ADH/CIS or ADH/IDC which indicated the two types of ADH are molecularly distinct entities although they have the same morphological appearance.

PurposeStereotactic vacuum-assisted breast biopsy (VAB) has been established as a standard method for histological diagnosis of microcalcification or nonpalpable breast lesions on mammography. Generally, the procedure has been done under the prone position or upright sitting position. We herein attempt to evaluate clinical utility of Stereotactic VAB under lateral decubitus position.MethodsOne hundred six women (mean age, 51.2 years) with mammographically detected microcalcification underwent lateral decubitus positioning VAB using the 8G probe. In all cases, we obtained mammography specimens for identification of microcalcification and postprocedure mammography. We reviewed mean procedure time, pieces of specimen, pathology and follow-up mammography.ResultsThe procedure took approximately 20 minutes (range, 15-24 minutes). Average number of obtained specimens was 8.5 pieces (range, 6-12 pieces). Microcalcifications were confirmed in both specimen mammography and microscopic slides. Of 106 cases, 10 cases were diagnosed as ductal carcinoma in situ. Additional surgical management was performed. Atypical ductal hyperplasias were found in 8 cases, and fibrocystic changes in 88 cases.ConclusionStereotactic VAB using the 8G probe under lateral decubitus position does not need a dedicated table, and is easier to maintain the position. Also, this procedure is accurate and safe. Thus, stereotactic VAB using the 8G probe under lateral decubitus position will be a useful method for diagnosis of microcalcification or nonpalpable breast lesions on mammography.

Abstract #4025 Background: Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) has demonstrated superior sensitivity for detecting earlier cancers compared with x-ray mammography, and is being used increasingly for high-risk screening, diagnostic imaging and to evaluate extent of malignant disease. When assessing lesion malignancy both the morphology and contrast uptake and washout—or kinetics—of the lesion are important. At our institution DCEMRI breast examinations have been performed on three different MR systems. The purpose of this study was to compare the MR kinetic curve data of malignant lesions acquired by these systems.&amp;#x2028; Methods: 445 patients with 485 malignant lesions were selected for an IRB approved review. The lesions were classified as ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and 'other'. Dynamic MR protocol: 1 pre and 3-7 post-contrast images, acquired on a system using a non fat-suppressed dynamic sequence (NFS) and 2 newer systems by different manufacturers using fat suppressed dynamic sequences (FS1 and FS2). Kinetic curve data was processed and displayed on a CADstream workstation. Analysis of kinetic curve shape was made by an experienced radiologist according to the BI-RADS lexicon. Several quantitative kinetic parameters were calculated, both directly from the curve data and after fitting to an empirical mathematical model (EMM). The kinetic parameters of malignant lesions were compared between the three systems.&amp;#x2028; Results: 299 malignant lesions (185 IDC, 57 DCIS) were imaged on NFS, 104 lesions (69 IDC, 21 DCIS) on FS1, and 82 on FS2 (61 IDC, 17 DCIS). Compared to both systems NFS and FS1, IDC lesions acquired on FS2 demonstrated significantly lower initial enhancement, longer time to peak enhancement and slower washout rate (p &amp;lt; 0.0004). 80% of IDC lesions acquired on FS1 were classified as 'washout', compared with only 46% of IDC lesions on FS2. On both FS1 and FS2, we did not find a difference in the kinetic parameters of IDC vs. DCIS lesions. However, IDC lesions imaged on NFS exhibited significantly higher contrast uptake, shorter time to peak and stronger washout compared to DCIS lesions (p &amp;lt; 0.0001).&amp;#x2028; Discussion: The kinetic curve data of malignant lesions acquired by one system exhibited significantly lower initial contrast uptake and different curve shape compared with the other two. In addition, on both newer systems, the kinetic parameters of DCIS were comparable with IDC, which is contrary to what was found on the older system. Differences in k-space sampling, T1 weighting or magnetization transfer effects may be possible explanations. The results of this study underscore the importance of developing standardized acquisition and analysis methods, to ensure that across all available systems (i) malignant lesions are sufficiently conspicuous and thus reliably detected and (ii) interpretation of kinetic data is consistent. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4025.

Utility of Breast Magnetic Resonance Imaging in Determining Candidacy for Partial Breast Irradiation

14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression

International guidelines recommend open surgery for atypical ductal hyperplasia (ADH) in the breast due to risk of underestimating malignant disease. Considering the ongoing randomized trials of active surveillance of low-risk ductal carcinoma in situ (DCIS), it seems reasonable to define a low-risk group of women with ADH where a conservative approach is appropriate. The aim here was to evaluate the management and risk for upgrade of lesions diagnosed as ADH in percutaneous breast biopsies in two Swedish hospitals. All women with a screen-detected or symptomatic breast lesion breast imaging-reporting and data system (BI-RADS) 2-4 and a percutaneous biopsy showing ADH between 2013 and 2022 at Sundsvall Hospital and Umeå University Hospital were included. Information regarding imaging, histopathology, clinical features, and management was retrieved from medical records. Odds ratio (OR) and 95% confidence intervals (CI) for upgrade to malignant diagnosis after surgery were calculated by logistic regression analysis. Altogether, 101 women were included with a mean age 56.1 (range 36-93) years. Most women were selected from the national mammography screening program due to microcalcifications. Biopsies were performed with vacuum-assisted biopsy (60.4%) or core-needle biopsy (39.6%). Forty-eight women (47.5%) underwent surgery, of which 11 were upgraded to DCIS, and 7 to invasive breast cancer (upgrade rate 37.5%). Among the 53 women managed conservatively (median follow-up 74 months), one woman (1.9%) developed subsequent ipsilateral DCIS. The combined upgrade rate was 18.8%. No clinical variable statistically significantly correlating to risk of upgrade was identified. The upgrade rate of 37.5% in women undergoing surgery compared to an estimated 5-year risk of ipsilateral malignancy at 1.9% in women managed conservatively indicate that non-surgical management of select women with ADH is feasible. Research should focus on defining reproducible criteria differentiating high-risk from low-risk ADH.