Atypical Ductal Hyperplasia Lesions Research Articles

Determination of Factors Associated with Upstage in Atypical Ductal Hyperplasia to Identify Low-Risk Patients Where Active Surveillance May be an Alternative.

Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, "regional"; OR 19.28, 95% CI3.47-106.97, p < 0.001, "linear"). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery.

Contrast-enhanced ultrasound to predict malignant upgrading of atypical ductal hyperplasia

BackgroundA malignancy might be found at surgery in cases of atypical ductal hyperplasia (ADH) diagnosed via US-guided core needle biopsy (CNB). The objective of this study was to investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in predicting ADH diagnosed by US-guided CNB that was upgraded to malignancy after surgery.MethodsIn this retrospective study, 110 CNB-diagnosed ADH lesions in 109 consecutive women who underwent US, CEUS, and surgery between June 2018 and June 2023 were included. CEUS was incorporated into US BI-RADS and yielded a CEUS-adjusted BI-RADS. The diagnostic performance of US BI-RADS and CEUS-adjusted BI-RADS for ADH were analyzed and compared.ResultsThe mean age of the 109 women was 49.7 years ± 11.6 (SD). The upgrade rate of ADH at CNB was 48.2% (53 of 110). The sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for identification of malignant upgrading were 96.2%, 66.7%,72.9%, and 95.0%, respectively, based on BI-RADS category 4B threshold. The two false-negative cases were low-grade ductal carcinoma in situ. Compared with the US, CEUS-adjusted BI-RADS had better specificity for lesions smaller than 2 cm (76.7% vs. 96.7%, P = 0.031). After CEUS, 16 (10 malignant and 6 nonmalignant) of the 45 original US BI-RADS category 4A lesions were up-classified to BI-RADS 4B, and 3 (1 malignant and 2 nonmalignant) of the 41 original US BI-RADS category 4B lesions were down-classified to BI-RADS 4A.ConclusionsCEUS is helpful in predicting malignant upgrading of ADH, especially for lesions smaller than 2 cm and those classified as BI-RADS 4A and 4B on ultrasound.

Atypical ductal hyperplasia on vacuum-assisted breast biopsy: a scoring system to predict the risk of upgrade to malignancy.

Our multicentric study analysed clinical, radiologic and pathologic features in patients with atypical ductal hyperplasia (ADH) diagnosed with vacuum-assisted biopsy (VAB), to identify factors associated with the risk of upgrade, to develop a scoring system to support decision making. Patients with ADH on VAB under stereotactic/tomosynthesis guidance (2012-2022) were eligible. Inclusion criteria were availability of surgical histopathological examination of the entire lesion or radiologic follow-up (FUP) ≥ 24months. VAB results were compared with surgical pathological results or with imaging FUP evolution to assess upgrade. A backward stepwise linear regression was used to identify predictors of upgrade. The discriminatory power of the model was calculated through the area under the receiver operating curve (ROC-AUC); the Hosmer-Lemeshow test was used to assess model calibration. The points system was developed based on the selected risk factors, and the probability of upgrade associated with each point total was determined. 112 ADH lesions were included: 91 (91/112, 81.3%) underwent surgical excision with 20 diagnosis of malignancy, while 21 (21/112, 18.7%) underwent imaging FUP with one interval change (mean FUP time 48months). Overall upgrade rate was 18.7% (21/112). Age, menopausal status, concurrent breast cancer, BIRADS classification and number of foci of ADH were identified as risk factors for upgrade. Our model showed an AUC = 0.85 (95% CI 0.76-0.94). The points system showed that the risk of upgrade is < 2% when the total score is ≤ 1. Our scoring system seemed a promising easy-to-use decision support tool for management of ADH, decreasing unnecessary surgeries, reducing patients' overtreatment and healthcare costs.

Imaging Characteristics of and Multidisciplinary Management Considerations for Atypical Ductal Hyperplasia and Flat Epithelial Atypia: Review of Current Literature.

High-risk lesions of the breast are frequently encountered in percutaneous biopsy specimens. While benign, these lesions have historically undergone surgical excision due to their potential to be upgraded to malignancy. However, there is emerging evidence that a tailored management approach should be considered to reduce overtreatment of these lesions. Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are two of the most commonly encountered high-risk lesions. FEA has been shown to have a relatively low rate of progression to malignancy, and some guidelines are now recommending observation over routine excision in select cases. Selective observation may be reasonable in cases where the target lesion is small and completely removed at biopsy and when there are no underlying risk factors, such as a history of breast cancer or genetic mutation or concurrent ADH. ADH has the highest potential upgrade rate to malignancy of all the high-risk lesions. Most society guidelines continue to recommend surgical excision of this lesion. More recently, some literature suggests that ADH lesions that appear completely removed at biopsy, involve limited foci (less than two or three) with no necrosis or significant atypia, manifest as a small group of mammographic calcifications, or demonstrate no enhancement at MRI may be reasonable for observation. Ultimately, management of all high-risk lesions must be based on a multidisciplinary approach that considers all patient, radiologic, clinical, and histopathologic factors. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Development and Validation of a Simple-to-Use Nomogram for Predicting the Upgrade of Atypical Ductal Hyperplasia on Core Needle Biopsy in Ultrasound-Detected Breast Lesions.

BackgroundThe rate of carcinoma upgrade for atypical ductal hyperplasia (ADH) diagnosed on core needle biopsy (CNB) is variable on open excision. The purpose of the present study was to develop and validate a simple-to-use nomogram for predicting the upgrade of ADH diagnosed with ultrasound (US)-guided core needle biopsy in patients with US-detected breast lesions.MethodsTwo retrospective sets, the training set (n = 401) and the validation set (n = 186), from Fudan University Shanghai Cancer Center between January 2014 and December 2019 were retrospectively analyzed. Clinicopathological and US features were selected using univariate and multivariable logistic regression, and the significant features were incorporated to build a nomogram model. Model discrimination and calibration were assessed in the training set and validation set.ResultsOf the 587 ADH biopsies, 67.7% (training set: 267/401, 66.6%; validation set: 128/186, 68.8%) were upgraded to cancers. In the multivariable analysis, the risk factors were age [odds ratio (OR) 2.739, 95% confidence interval (CI): 1.525–5.672], mass palpation (OR 3.008, 95% CI: 1.624–5.672), calcifications on US (OR 4.752, 95% CI: 2.569–9.276), ADH extent (OR 3.150, 95% CI: 1.951–5.155), and suspected malignancy (OR 4.162, CI: 2.289–7.980). The model showed good discrimination, with an area under curve (AUC) of 0.783 (95% CI: 0.736–0.831), and good calibration (p = 0.543). The application of the nomogram in the validation set still had good discrimination (AUC = 0.753, 95% CI: 0.666–0.841) and calibration (p = 0.565). Instead of surgical excision of all ADHs, if those categorized with the model to be at low risk for upgrade were surveillanced and the remainder were excised, then 63.7% (37/58) of surgeries of benign lesions could have been avoided and 78.1% (100/128) malignant lesions could be treated in time.ConclusionsThis study developed a simple-to-use nomogram by incorporating clinicopathological and US features with the overarching goal of predicting the probability of upgrade in women with ADH. The nomogram could be expected to decrease unnecessary surgery by nearly two-third and to identify most of the malignant lesions, helping guide clinical decision making with regard to surveillance versus surgical excision of ADH lesions.

High-Risk Lesions Detected by MRI-Guided Core Biopsy: Upgrade Rates at Surgical Excision and Implications for Management.

OBJECTIVE. The purpose of our study was to evaluate the upgrade rates of high-risk lesions (HRLs) diagnosed by MRI-guided core biopsy and to assess which clinical and imaging characteristics are predictive of upgrade to malignancy. MATERIALS AND METHODS. A retrospective review was performed of all women who presented to an academic breast radiology center for MRI-guided biopsy between January 1, 2015, and November 30, 2018. Histopathologic results from each biopsy were extracted. HRLs-that is, atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH), radial scar, papilloma, flat epithelial atypia (FEA), benign vascular lesion (BVL), and mucocelelike lesion-were included for analysis. Clinical history, imaging characteristics, surgical outcome, and follow-up data were recorded. Radiologic-pathologic correlation was performed. RESULTS. Of 810 MRI-guided biopsies, 189 cases (23.3%) met the inclusion criteria for HRLs. Of the 189 HRLs, 30 cases were excluded for the following reasons: 15 cases were lost to follow-up, six cases were in patients who received neoadjuvant chemotherapy after biopsy, two lesions that were not excised had less than 2 years of imaging follow-up, and seven lesions had radiologic-pathologic discordance at retrospective review. Of the 159 HRLs in our study cohort, 13 (8.2%) were upgraded to carcinoma. Surgical upgrade rates were high for ADH (22.5%, 9/40) and FEA (33.3%, 1/3); moderate for LCIS (6.3%, 3/48); and low for ALH (0.0%, 0/11), radial scar (0.0%, 0/28), papilloma (0.0%, 0/26), and BVL (0.0%, 0/3). Of the upgraded lesions, 69.2% (9/13) were upgraded to ductal carcinoma in situ (DCIS) or well-differentiated carcinoma. ADH lesions were significantly more likely to be upgraded than non-ADH lesions (p = .005). CONCLUSION. ADH diagnosed by MRI-guided core biopsy warrants surgical excision. The other HRLs, however, may be candidates for imaging follow-up rather than excision, especially after meticulous radiologic-pathologic correlation.

Abstract 2498: miFISH single cell analysis as a potential tool to stratify the progression risk in patients with Atypical Ductal Hyperplasia (ADH)

Abstract We previously studied synchronous ductal carcinomas in situ (DCIS) and invasive ductal carcinomas (IDC) using our novel approach of multiplex interphase Fluorescence in situ Hybridization (miFISH) that allows simultaneous enumeration of copy numbers of up to 20 gene loci per single cell, providing new insights into tumor clonality and intratumor heterogeneity (ITH). A high degree of chromosomal instability was present in DCIS, and we frequently observed a direct clonal evolution from DCIS to IDC. We now ask whether this degree of instability is also present in even earlier potential precursor lesions like atypical ductal hyperplasias (ADH). We are therefore conducting a retrospective study analyzing ADH lesions from patients without synchronous DCIS or IDC (pure ADH) and from patients with ADH adjacent to higher-grade lesions. Using our miFISH assay, we simultaneously assess copy number changes of six oncogenes (COX2 (1q), PIK3CA (3q), MET (7q), MYC (8q), CCND1 (11q), HER2 (17q), ZNF217 (20q)) and six tumor suppressor genes (FHIT (3p), DBC2 (8p), RB1 (13q), CDH1 (16q), TP53 (17q), NF2 (22q), typical for breast tumorigenesis. So far, we have analyzed fifteen pure ADH and five ADH with synchronous DCIS or IDC. The miFISH analysis showed that the majority of all pure ADH displayed a stable diploid genome without any copy number changes observed for the genes tested while only 3/15 (20%) showed changes, namely (i) a COX2 and HER2 gain in a diploid genome, (ii) a CDH1and MET loss in a tetraploid genome and (iii) a COX2 gain in a diploid genome. In the group of ADH with adjacent higher-grade lesions (n=5), all DCIS and IDC lesions analyzed displayed breast cancer specific copy number changes corroborating our previous results. Of note, two of the ADH lesions adjacent to these aberrant DCIS or IDC lesions had normal diploid genomes. Of the remaining three synchronous ADH lesions, one showed a complex gain and loss pattern similar to its adjacent DCIS, the second one was characterized by a simple COX2 gain which was maintained in the adjacent DCIS in addition to a DBC2 loss and MYC gain. The third ADH displayed a tetraploid clone without any gains or losses, while the adjacent IDC revealed a complex gain and loss pattern in its tetraploid genome. Our preliminary data indicate that the majority of pure ADH does not harbor copy number changes. However, there is a small subset of pure ADH revealing gain and loss patterns typical for DCIS and IDC often involving COX2 gain indicating it as an early event. Of note, ADH lesions adjacent to DCIS or IDC tend to display similar changes as their adjacent higher-grade lesions suggesting them as direct precursor lesions. We are currently analyzing more ADH samples and plan to add material from an ADH patient cohort with long-term follow-up to explore whether miFISH can stratify ADH patients into different risk groups. Citation Format: Kiara Whitaker, Jausheng Tzeng, Daniela Hirsch, Irianna Torres, Steven Brower, Gert Auer, Miguel Sanchez, Thomas Ried, Kerstin Heselmeyer-Haddad. miFISH single cell analysis as a potential tool to stratify the progression risk in patients with Atypical Ductal Hyperplasia (ADH) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2498.

Atypical Ductal Hyperplasia on Ultrasonography-Guided Vacuum-Assisted Biopsy of the Breast: Considerations for Further Surgical Excision.

The purposes of this study are to evaluate the upgrade rate of atypical ductal hyperplasia (ADH) diagnosed with ultrasonography (US)-guided vacuum-assisted biopsy (VAB) to malignancy and to identify the factors behind the underestimation. We retrospectively reviewed the pathologic results of US-guided VAB of the breast. A total of 50 ADH lesions that were surgically excised or with more than 12 months of follow-up were included. The upgrade rate of ADH was determined by dividing the number of lesions that were proven malignant on surgical excision by the total number of ADH diagnosed on VAB. Clinical, radiologic, procedural, and pathologic variables were analyzed to identify the factors behind the underestimation. The upgrade rate of ADH was found to be 16.0% (8/50 lesions). In univariable and multivariable analyses, the upgrade rates of ADH did not significantly differ among variables. In a subgroup analysis, according to history of breast cancer, the upgrade rates of ADH were significantly lower for lesions of mass than for lesions of nonmass (0% [0/23 lesions] vs 28.6% [4/14 lesions], P = 0.015), and for lesions without calcifications than for lesions with calcifications (0% [0/22 lesions] vs 26.7% [4/15 lesions], P = 0.021) in the negative history subgroup. ADH lesions in masses or without calcifications in patients without a family or personal history of breast cancer were associated with low upgrade rates. Thus, we suggest that ADH with these features can be followed rather than surgically excised after US-guided VAB.

Breast cancer events in women with atypical ductal hyperplasia who do not undergo surgical excision.

1562 Background: Atypical ductal hyperplasia (ADH) found on core needle biopsy is associated with an upgrade to carcinoma in 10-30% of women, thus surgical excision remains the standard of care. We sought to review the incidence of breast cancer in women with ADH managed by either observation or surgical excision over a 15 year period. Methods: Our prospectively maintained registry was reviewed to identify patients with ADH diagnosed by core needle biopsy between 1/2004 and 10/2018. Observed patients were deemed low risk for upgrade after multidisciplinary review confirmed adequate sampling, limited atypia and concordance between imaging and histology. Surgical patients were excluded if upstaged to carcinoma following excision. Patients with &lt; 1 year follow-up were excluded. Subsequent breast cancer was classified as ipsilateral or contralateral to the previous ADH and was further classified as index site if the new cancer was identified in the same quadrant as prior ADH. Multivariate logistic regression models were used to assess potential predictors of subsequent breast cancer events. Results: Four hundred and seventy-eight women with 483 ADH lesions met criteria; 305 were observed and 173 underwent excision. Median follow-up was 5.2 years, range 1.1-15.3. At the time of ADH diagnosis, 91 women had a personal history of breast cancer. Age &lt; 50 was the only statistically significant difference between the groups (24.6% vs. 33.3%, p = 0.04). Race, receipt of chemoprevention, prior breast cancer history and median follow-up were not significant between the groups. Prior history of breast cancer was associated with subsequent breast cancer risk in multivariate analysis (OR 2.25, 95% CI 1.04-4.87, p = 0.04). After excluding patients with a history of breast cancer, multivariate analysis demonstrated no association of age, race, use of chemoprevention or surgical excision with future cancer risk. Among the 387 patients without a prior breast cancer history, 21 patients developed a subsequent cancer; 10 in the surgical group and 11 in the observed group (7.3% vs. 4.4% respectively, p = 0.2). Two cancers were identified at the index site in the surgery group (2/137, 1.5%) and three in those observed (3/250, 1.2%). Conclusions: Observation, rather than surgical excision, is safe in selected women that have a core biopsy diagnosis of ADH. Index site failures are rare and are superseded by cancer risk elsewhere in the breast. National screening and diagnosis recommendations should consider recommending observation for this select group of patients with ADH.

Impact of Non-Calcified Specimen Pathology on the Underestimation of Malignancy for the Incomplete Retrieval of Suspicious Calcifications Diagnosed as Flat Epithelial Atypia or Atypical Ductal Hyperplasia by Stereotactic Vacuum-Assisted Breast Biopsy.

ObjectiveStereotactic vacuum-assisted breast biopsy (VABB) is considered a reliable alternative to surgical biopsy for suspicious calcifications. In most cases, the management of flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) after VABB with residual calcifications requires surgical excision. This study aimed to evaluate the impact of pathology of non-calcified specimens on the underestimation of malignancy.Materials and MethodsWe retrospectively reviewed 1147 consecutive cases of stereotactic VABB of suspicious calcifications without mass from January 2010 to December 2016 and identified 46 (4.0%) FEA and 52 (4.5%) ADH cases that were surgically excised for the retrieval of residual calcifications. Mammographic features and pathology of the calcified and non-calcified specimens were reviewed.ResultsSeventeen specimens (17.3%) were upgraded to malignancy. Mammographic features associated with the underestimation of malignancy were calcification extent (> 34.5 mm: odds ratio = 6.059, p = 0.026). According to the pathology of calcified versus non-calcified specimens, four risk groups were identified: Group A (ADH vs. high-risk lesions), Group B (ADH vs. non-high-risk lesions), Group C (FEA vs. high-risk lesions), and Group D (FEA vs. non-high-risk lesions). The lowest underestimation rate was observed in Group D (Group A vs. Group B vs. Group C vs. Group D: 35.0% vs. 20.0% vs. 15.0% vs. 3.6%, p = 0.041, respectively).ConclusionConsidering that the calcification extent and pathology of non-calcified specimens may be beneficial in determining the likelihood of malignancy underestimation, excision after FEA or ADH diagnosis by VABB is required, except for the diagnoses of FEA coexisting without atypia lesions in non-calcified specimens.

Is core needle biopsy effective at diagnosing male breast lesions?

The objective of this study was to examine the diagnostic accuracy of sonographically guided core needle biopsy (CNB) of breast lesions in men. This was a retrospective study where we analyzed consecutive sonographically guided 14-gauge CNB results on 234 male breast lesions. The CNB accuracy is determined by the comparison between the CNB and its corresponding excisional biopsy or to long-term follow-up imaging. Sonographically guided CNB was effective to collect satisfactory samples from all 234 lesions. Out of those, 58.55% (137/234) were benign, 38.0% (89/234) were malignant, 1.71% (4/234) were papilloma with atypia and 1.71% (4/234) were atypical ductal hyperplasia lesions. Underestimation occurred in 3.4% (8/234) of the lesions. As for the detection of breast malignancy, the sensitivity of the CNB is 98.9%, specificity is 100%, negative predictive value is 99.3%, positive predictive value is 100%, false positive is 0% and false negative is 1.1%. The overall accuracy of sonographically guided CNB as a diagnostic tool is 99.6%. Sonographically guided 14-gauge CNB is an accurate, reliable and low invasive procedure for assessing breast lesions in men. Triple tests and follow-up checks of benign cases are essential for a successful breast biopsy program in men.

Atypical ductal hyperplasia and the risk of underestimation: tissue sampling method, multifocality, and associated calcification significantly influence the diagnostic upgrade rate based on subsequent surgical specimens

BackgroundRisk assessment and therapeutic options are challenges when counselling patients with an atypical ductal hyperplasia (ADH) to undergo either open surgery or follow-up only.MethodsWe retrospectively analyzed a series of ADH lesions and assessed whether the morphological parameters of the biopsy materials indicated whether the patient should undergo surgery. A total of 207 breast biopsies [56 core needle biopsies (CNBs) and 151 vacuum-assisted biopsies (VABs)] histologically diagnosed as ADH were analyzed retrospectively, together with subsequently obtained surgical specimens. All histological slides were re-analyzed with regard to the presence/absence of ADH-associated calcification, other B3 lesions (lesion of uncertain malignant potential), extent of the lesion, and the presence of multifocality.ResultsThe overall underestimation rate for the whole cohort was 39% (57% for CNB, 33% for VAB). In the univariate analysis, the method of biopsy (CNB vs VAB, p = 0.002) and presence of multifocality in VAB specimens (p = 0.0176) were significant risk factors for the underestimation of the disease (ductal carcinoma in situ or invasive cancer detected on subsequent open biopsy). In the multivariate logistic regression model, the absence of calcification (p = 0.0252) and the presence of multifocality (unifocal vs multifocal ADH, p = 0.0147) in VAB specimens were significant risk factors for underestimation.ConclusionsMultifocal ADH without associated calcification diagnosed by CNB tends to have a higher upgrade rate. Because the upgrade rate was 16.5% even in the group with the lowest risk (VAB-diagnosed unifocal ADH with calcification), we could not identify a subgroup that would not require an open biopsy.

Prediction of Atypical Ductal Hyperplasia Upgrades Through a Machine Learning Approach to Reduce Unnecessary Surgical Excisions.

PurposeSurgical excision is currently recommended for all occurrences of atypical ductal hyperplasia (ADH) found on core needle biopsies for malignancy diagnoses and treatment of lesions. The excision of all ADH lesions may lead to overtreatment, which results in invasive surgeries for benign lesions in many women. A machine learning method to predict ADH upgrade may help clinicians and patients decide whether combined active surveillance and hormonal therapy is a reasonable alternative to surgical excision.MethodsThe following six machine learning models were developed to predict ADH upgrade from core needle biopsy: gradient-boosting trees, random forest, radial support vector machine (SVM), weighted K-nearest neighbors (KNN), logistic elastic net, and logistic regression. The study cohort consisted of 128 lesions from 124 women at a tertiary academic care center in New Hampshire who had ADH on core needle biopsy and who underwent an associated surgical excision from 2011 to 2017.ResultsThe best-performing models were gradient-boosting trees (area under the curve [AUC], 68%; accuracy, 78%) and random forest (AUC, 67%; accuracy, 77%). The top five most important features that determined ADH upgrade were age at biopsy, lesion size, number of biopsies, needle gauge, and personal and family history of breast cancer. Using the random forest model, 98% of all malignancies would have been diagnosed through surgical biopsies, whereas 16% of unnecessary surgeries on benign lesions could have been avoided (ie, 87% sensitivity at 45% specificity).ConclusionThese results add to the growing body of support for machine learning models as useful aids for clinicians and patients in decisions about the clinical management of ADH.

High risk breast lesions identified on MRI-guided vacuum-assistedneedlebiopsy: outcome of surgical excision and imaging follow-up.

To determine whether breast MRI-guided vacuum-assisted biopsy (MRI-VAB) high-risk lesion histology influences surgical or long-term imaging follow-up outcomes. Patients with imaging-concordant high-risk findings on 9-gauge breast MRI-VAB between January 2007 and July 2012 who had surgical histopathology or 2 year imaging follow-up were retrospectively reviewed. 90 patients with 99 lesions were included. Lesions were atypical ductal hyperplasia (ADH) (n=21), lobular neoplasia [n = 36; atypicallobular hyperplasia (ALH) (n = 22), lobularcarcinoma in situ (LCIS) (n = 6), and ALH plus LCIS (n = 8)], and other high-risk lesion (n = 42; papillary lesions, radial scar, flat epithelial atypia, atypia unspecified). Of 53 excised lesions, 6 (11%) were upgraded to invasive cancer or ductal carcinoma in situ (DCIS). 4 of 21 (19%) ADH lesions were upgraded to DCIS. 2 of 36 (6%) lobular neoplasia lesions, both combined ALH and LCIS, were upgraded to DCIS, and invasive lobular carcinoma, respectively. The remaining 46 lesions were managed conservatively with imaging follow-up: 17 (37%) had mammography only, while 29 (63%) had mammography and MRI follow-up. There was no evidence of breast cancer development at the site of MRI-VAB in the cases with only imaging follow-up. We conclude that the upgrade rate for high-risk lesions at MRI-VAB at surgical excision is low. Surgical excision is warranted for ADH and combined ALH-LCIS lesions. For other lesions, a multidisciplinary approach to decide on personalized management may be appropriate. Surgical excision is warranted for ADH lesions and combined ALH-LCIS lesions identified at breast MRI-VAB. A multidisciplinary approach to patient management of other high-risk lesions may be appropriate.

Abstract P6-10-08: Atypical ductal hyperplasia and rate of upgrade to carcinoma on excision at a safety net hospital

Abstract Purpose: Atypical ductal hyperplasia (ADH) is a high-risk lesion associated with an increased risk of developing breast cancer. Surgical excision following diagnosis of ADH on core needle biopsy is generally recommended due to high rate (10-30%) of upgrade to malignancy. Studies have been done to identify factors which may allow for observation rather than excision for management of ADH, however these have not been done in patients who obtain care from safety net health systems. The objective of our study was to examine the rate of upgrade to malignancy in a safety net hospital and to describe factors that may be associated with upstage. Methods: A retrospective review identified women diagnosed with ADH on core needle biopsy from 2002-2015. Women with a concurrent diagnosis of ductal carcinoma in situ (DCIS) or invasive cancer were excluded. Only women who underwent excision were included in the comparative analysis. Upgrade (UG) was defined as histopathologic diagnosis of DCIS or invasive carcinoma on the excised specimen. Univariate analysis was used to compare baseline and clinical characteristics of the UG vs. non-upgraded (Non-UG) group. Logistic regression was performed to identify factors independently associated with increased odds of upgrade. Results: ADH was diagnosed in 157 women and 122 (78%) underwent excision. The mean age was 53.3 ± 9.3 years, 48% were Hispanic, and the most common BIRADS score was 4A (58%). On diagnostic imaging, 78% had calcifications, 30% had a mass, and 6% architectural distortion. Time to excision from biopsy varied (median 2.3 months), however most women (81%) underwent excision within 6 months. 35 (29%) patients were upstaged to cancer (22 DCIS, 13 invasive cancer). UG was associated with African-American race (54% vs. non-UG 23%, p&amp;lt;0.01), history of non-breast cancer (11% vs. non-UG 0, p=0.01), BIRADS 5 (9% vs. non-UG 0, p=0.02) and mass on physical exam (36% vs. non-UG 15%, p=0.03) or diagnostic imaging (45% vs. non-UG 25%, p=0.03). Median follow up for the entire cohort was 813 days (IQR 327-1492). In Non-UG, 2 women subsequently developed cancer in a different area from the ADH. On logistic regression, African-American women (compared to Hispanic women, odds ratio [OR] 5.5, 95% confidence interval [CI]: 1.5-20.0, p=0.01) and those with a higher BI-RADS score of 4C and 5 (OR 13.2, 95% CI: 1.6-110.6, p=0.02) had increased odds of upstaging to malignancy. Conclusion: The rate of upgrade from ADH to cancer was 29% in our cohort. Women diagnosed with ADH in safety net hospitals, particularly African-American women and those with high BIRADS score (4C and 5), should be strongly advised to undergo excision. Further study on the impact of race on the rate of ADH lesions upgrading to malignancy on surgical excision is warranted. Citation Format: Vo E, Arita NA, Ortiz-Perez T, Awad SS, Hsu C, Silberfein EJ. Atypical ductal hyperplasia and rate of upgrade to carcinoma on excision at a safety net hospital [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-10-08.

Aromatase expression in atypical ductal hyperplasia in women.

To determine the levels of aromatase in atypical ductal hyperplasia (ADH) lesions, tissue surrounding the ADH, and in dense and non-dense normal breast tissue. We postulated that excess aromatase in breast tissue might, through production of increased estrogen, drive the carcinogenic process. Estrogens and their metabolites are thought to contribute to the development of breast cancer through estrogen receptor-mediated mechanisms and genotoxic effects of estrogen metabolites. ADH is a benign lesion of the breast which is associated with substantially increased risk for subsequent development of breast cancer. After 25 years, approximately 30% of women with ADH develop breast cancer. In women with three or more separate ADH lesions at the same time, 47% will develop breast cancer over that time period. Another important risk factor for breast cancer is the presence of mammographically dense breast tissue. We utilized quantitative immunochemical analysis of aromatase in biopsy tissue to test this possibility. Previously published results comparing dense with non-dense breast tissue in normal women (Vachon et al. Breast Cancer Res Treat 125:243-252, 2011) were used for comparisons with ADH. A well-characterized histochemical H-score was employed for quantitative assessment of aromatase in the various tissue studied. The H-score of aromatase staining was statistically significantly higher (p = 0.003) in the ADH epithelium than surrounding epithelial tissue. In order of H-score from highest to lowest were ADH, issue surrounding ADH, dense normal and non-dense normal breast tissues. The levels of aromatase in a subset of women with ADH who went on to develop breast cancer were not higher than in women who did not. We suggest from these studies that overexpression of aromatase in breast tissue and its resultant increase in estradiol levels may contribute to the later development of breast cancer in women with ADH.

Diagnosis of Columnar Cell Lesions and Atypical Ductal Hyperplasia by Ultrasound-Guided Core Biopsy: Findings Associated with Underestimation of Breast Carcinoma

The aim of the study described here was to determine underestimation rates and identify radiologic predictors of underestimation for columnar cell lesions (CCLs) and atypical ductal hyperplasia (ADH) detected by ultrasound-guided core needle biopsy. A total of 103 CCLs and ADH lesions in 100 patients diagnosed by ultrasound-guided core needle biopsy were evaluated. Breast sonographic and mammographic findings were reviewed, and underestimation rates were determined by surgical excision, percutaneous vacuum-assisted excision or 2-y imaging follow-up. All underestimated lesions were ductal carcinoma in situ, and the underestimation rates of flat epithelial atypia (FEA), FEA + ADH and ADH were 5.9% (1/17), 44.4% (4/9) and 27.3% (12/44), respectively. There was no underestimation of CCLs without atypia. The presence of calcifications on ultrasound was significantly associated with underestimation (p = 0.010). Therefore, except for CCLs without atypia, all other lesions may require excision, especially when calcification is present on ultrasound or when FEA + ADH is found.

Abstract P2-05-10: Explore the differences and relationships between normal and ADH, DCIS and IDC tissues in breast based on Raman spectroscopy

Abstract Background: Atypical ductal hyperplasia (ADH) is a premalignant breast lesion associated with an increased risk of breast cancer which shares some but not all the features of ductal carcinoma in situ (DCIS). The mechanism that ADH changes to DCIS and even invasive ductal carcinoma (IDC) is still not clear now. There is a pressing need to develop screening techniques that are accurate, minimally invasive and, more sensitive to identify early neoplastic changes and hence improve early breast cancer diagnosis. Our aim was to explore the differences and relationships between normal, ADH, DCIS and IDC lesions of the breast based on biochemical characteristics determined by Raman spectroscopy Methods: Frozen sections were collected from 39 patients (all ladies) who underwent surgical resection or mammotome biopsy at the Department of Breast Surgery, the First Hospital of Jilin University. After operation the samples were immediately frozen at -20-25 ° and two contiguous sections (6 µm thickness) were cut from a sample by freezing microtome. One was stained with haematoxylin and eosin for routine histopathological analysis; the same position of the other section was detected by Microscopic confocal Raman spectrometer (HORIBA JY Lab800, 633nm) with its mirror image (the H&amp;E section). After Raman measurement, the sections were routinely processed, stained with H&amp;E and histologically examined. Support vector machine (SVM) was used to differentiate different breast lesions. Results: A total of 475 Raman spectra were obtained from 9 normal breast tissues, 7 ADH, 8 DCIS, and 15 IDC breast tissues. Pronounced mean Raman spectra differences were observed between normal tissues, ADH, DCIS and IDC tissues. The significant features of normal tissues are 1301, 1438, 1652, and 1743 cm-1, these peak positions are attributed to lipids, and the spectra profiles of normal tissues have no strong protein peaks. Most noticeable was the increased protein and reduced lipid levels of ADH tissues compared to normal tissues. The peak relative intensity of 1158 cm-1 which is attributed to the vibrational modes of C-C stretch of proteins has significantly increased from normal tissues to DCIS and IDC in breast. The major spectra differences in ADH, DCIS and IDC spectra were evidenced by a red shift with a broad peak of CH2, the intensity of the stretching vibration peak of carotenoids, a relatively strong band of amide-I, and the nuclear acid peak. ADH tissues had the largest constituent variations between subjects. During the disease progression, IDC tissues have smaller inter-subject constituent variations than DCIS and ADH tissues. The accuracies of SVM are 93% and 95% in discriminating normal and IDC, while only 50% and 51% in discriminating ADH and DCIS. Conclusion: Malignant transformations in tissue are associated with complex biochemical changes and may provide an effective way to evaluate the malignancy by Raman spectroscopy as it reveals differences between normal tissues, ADH, DCIS and IDC tissues in the breast. Further study to explain the biochemical relationships between these differences will shed more light into a better understanding of the mechanism by which ADH and DCIS convert to IDC. Citation Format: Bing Han, Haipeng Zhang, Chao Zheng, Ye Du, Lijia Liang, Weiqing Xu, Zhimin Fan. Explore the differences and relationships between normal and ADH, DCIS and IDC tissues in breast based on Raman spectroscopy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-10.

Changes of fibroblast immunophenotype and their clinical significance in stromal remodeling of breast tumors

To evaluate the immunophenotype conversion of fibroblasts and its clinical significance in the process of breast tumor stromal remodeling. CD34, FAP-α, p63 and a-SMA were detected by immunohistochemistry in 273 breast biopsies, including 60 normal breast tissues, 46 atypical ductal hyperplasia (ADH), 60 ductal carcinoma in situ (DCIS), 47 DCIS microinvasive carcinoma (DCIS-MI) and 60 invasive ductal carcinoma (IDC). The positive expression rates of CD34, FAP-α and α-SMA in the stromal fibroblasts of normal breast tissues were 93.3%, 6.7% and 18.3%, respectively. Those in the stromal fibroblasts of ADH tissues were 95.7%, 4.3% and 10.9%, respectively. Those in the stromal fibroblasts of DCIS tissues were 95.0%, 8.3% and 15.0%, respectively. Those in the IDC tissues were 35.0%, 85.0% and 93.3%, respectively. The expressions of CD34, α-SMA and FAP-α in the stromal fibroblasts of normal, ASH and DCIS breast tissues did not show significant differences (χ(2) = 1.142, P = 0.896). The main immunophenotype of stromal fibroblasts in the tumor-host interface at the invasive front of ADH and DCIS lesions was CD34(+)α-SMA(+)FAP-α(+). There were statistically significant differences in the expression of CD34, α-SMA and FAP-α between IDC and ADH, DCIS and normal breast tissues (χ(2) = 8.351, P < 0.001). The immunophenotype of stromal fibroblasts in the IDC and DCIS-MI breast tissues was CD34(-) α-SMA(+) FAP-α(+). Immunophenotype conversion from CD34(+) α-SMA(-) FAP-α(-) to CD34(-) α-SMA(+)FAP-α(+) may be a sensitive indicator to judge whether DCIS has microinvasion. Detection of the immunophenotype conversion of stromal fibroblasts may be helpful to determine the presence of microinvasion, and to improve the diagnostic accuracy rate of DCIS.

Atypical ductal hyperplasia diagnosed at sonographically guided core needle biopsy: frequency, final surgical outcome, and factors associated with underestimation.

The purposes of this article were to review the mammographic and sonographic features of breast masses yielding atypical ductal hyperplasia (ADH) at sonographically guided biopsy, evaluate the surgical pathology outcome of these lesions, and determine whether clinical or imaging features can be used to predict upgrade to malignancy. Among 6325 sonographically guided biopsies (2003- 2010) (14-gauge cores), 56 yielded the diagnosis of ADH (0.9%). Six patients were excluded (lost to follow-up). Fifty lesions were surgically excised in 45 patients. Mammographic and sonographic features were analyzed in consensus by two radiologists using the BI-RADS lexicon. Forty-five patients (mean age, 56 years; 12 < 50 years; six with synchronous breast carcinoma) had 50 ADH lesions (median size, 0.6 cm). Surgical excision yielded malignancy in 28 cases (56% underestimation rate). Among 42 mammograms (47 lesions), 30 lesions were identified (30/47, 64%) as masses (12/30, 40%), asymmetric densities (10/30, 33%), microcalcifications (4/30, 13%), and architectural distortions (4/30, 13%). Sonographically, most lesions appeared as hypoechoic masses (64%, 30/47) with irregular shape (51%, 24/47), microlobulated margins (49%, 23/47), no posterior acoustic feature (25/47, 53%), abrupt interface (70%, 33/47), and parallel orientation (57%, 27/47). No mammographic and sonographic features were associated with malignant outcome, whereas age less than 50 years (p = 0.03) and synchronous malignancy (p = 0.03) were associated with malignant outcome. ADH diagnosed at sonographically guided 14-gauge core needle biopsy shows a high underestimation rate. Synchronous carcinoma or age less than 50 years is associated with malignant outcome.