Diagnosis Of Atypical Ductal Hyperplasia Research Articles

Is Surgical Excision of Focal Atypical Ductal Hyperplasia Warranted? Experience at a Tertiary Care Center.

The core-needle biopsy (CNB) diagnosis of atypical ductal hyperplasia (ADH) generally mandates follow-up excision, but controversy exists on whether small foci of ADH require surgical management. This study evaluated the upgrade rate at excision of focal ADH (fADH), defined as 1 focus spanning ≤2mm. We retrospectively identified in-house CNBs with ADH as the highest-risk lesion obtained between January 2013 and December 2017. A radiologist assessed radiologic-pathologic concordance. All CNB slides were reviewed by two breast pathologists, and ADH was classified as fADH and nonfocal ADH based on extent. Only cases with follow-up excision were included. The slides of excision specimens with upgrade were reviewed. The final study cohort consisted of 208 radiologic-pathologic concordant CNBs, including 98 fADH and 110 nonfocal ADH. The imaging targets were calcifications (n=157), a mass (n=15), nonmass enhancement (n=27), and mass enhancement (n=9). Excision of fADH yielded seven (7%) upgrades (5 ductal carcinoma in situ (DCIS), 2 invasive carcinoma) versus 24 (22%) upgrades (16 DCIS, 8 invasive carcinoma) at excision of nonfocal ADH (p=0.01). Both invasive carcinomas found at excision of fADH were subcentimeter tubular carcinomas away from the biopsy site and deemed incidental. Our data show a significantly lower upgrade rate at excision of focal ADH than nonfocal ADH. This information can be valuable if nonsurgical management of patients with radiologic-pathologic concordant CNB diagnosis of focal ADH is being considered.

Breast MRI assists in decision-making for surgical excision of atypical ductal hyperplasia

BackgroundAtypical ductal hyperplasia diagnosed on percutaneous breast biopsy typically undergoes surgical excision, upgrading to invasive breast cancer or ductal carcinoma in situ in 10% to 53%. In efforts to limit excision to those with highest upgrade risk, we sought to determine if breast magnetic resonance imaging has value in predicting upgrade. In this study, we will describe magnetic resonance imaging presentation of atypical ductal hyperplasia and assess magnetic resonance imaging accuracy in predicting upgrade. MethodsAll female patients ≥18 years with atypical ductal hyperplasia on percutaneous breast biopsy undergoing magnetic resonance imaging from 2008 to 2020 were included. Patient demographics, imaging presentation, magnetic resonance imaging enhancement kinetic curves, and pathology features were captured. Categorical variables were analyzed using Fisher exact to test for association between variables and upgrade. Continuous variables were analyzed using t tests. ResultsMagnetic resonance imaging was performed for 125 percutaneous breast biopsy with atypical ductal hyperplasia: 67 after and 58 before atypical ductal hyperplasia diagnosis. On magnetic resonance imaging, atypical ductal hyperplasia site had no enhancement in 45 (36%), nonmass enhancement in 50 (40%), and mass enhancement in 30 (24%). In total, 28% had atypical ductal hyperplasia diagnosed by magnetic resonance imaging–guided percutaneous breast biopsy. Surgical excision was performed for 96 (76.8%) and 15 (15.6%) upgraded (11 ductal carcinoma in situ, 4 invasive breast cancer). All 15 upgrades had enhancement. Any kinetic pattern enhancement was significantly associated with upgrade (P = .009) with upgrade most strongly associated with type III washout. The lowest risk for upgrade was pure atypical ductal hyperplasia and no magnetic resonance imaging enhancement (0%, n = 25). ConclusionsActive monitoring may be safely offered to women with pure atypical ductal hyperplasia on percutaneous breast biopsy when magnetic resonance imaging shows no enhancement. Any enhancement at atypical ductal hyperplasia site, particularly type III washout kinetics, should continue to undergo excision.

Atypical Ductal Hyperplasia of the Breast on Core Needle Biopsy: Risk of Malignant Upgrade on Surgical Excision.

PurposeThis study identified factors predicting malignant upgrade for atypical ductal hyperplasia (ADH) diagnosed on core-needle biopsy (CNB) and developed a nomogram to facilitate evidence-based decision making.MethodsThis retrospective analysis included women diagnosed with ADH at the National Cancer Centre Singapore (NCCS) in 2010–2015. Cox proportional hazards regression was used to identify clinical, radiological, and histological factors associated with malignant upgrade. A nomogram was constructed using variables with the strongest associations in multivariate analysis. Multivariable logistic regression coefficients were used to estimate the predicted probability of upgrade for each factor combination.ResultsBetween 2010 and 2015, 238,122 women underwent mammographic screening under the National Breast Cancer Screening Program. Among 29,564 women recalled, 5,971 CNBs were performed. Of these, 2,876 underwent CNBs at NCCS, with 88 patients (90 lesions) diagnosed with ADH and 26 lesions upgraded to breast malignancy on excision biopsy. In univariate analysis, factors associated with malignant upgrade were the presence of a mass on ultrasound (p = 0.018) or mammography (p = 0.026), microcalcifications (p = 0.047), diffuse microcalcification distribution (p = 0.034), mammographic parenchymal density (p = 0.008). and ≥ 3 separate ADH foci found on biopsy (p = 0.024). Mammographic parenchymal density (hazard ratio [HR], 0.04; 95% confidence interval [CI], 0.005–0.35; p = 0.014), presence of a mass on ultrasound (HR, 10.50; 95% CI, 9.21–25.2; p = 0.010), and number of ADH foci (HR, 1.877; 95% CI, 1.831–1.920; p = 0.002) remained significant in multivariate analysis and were included in the nomogram.ConclusionOur model provided good discrimination of breast cancer risk prediction (C-statistic of 0.81; 95% CI, 0.74–0.88) and selected for a subset of women at low risk (2.1%) of malignant upgrade, who may avoid surgical excision following a CNB diagnosis of ADH.

Atypical Ductal Hyperplasia after Vacuum-Assisted Breast Biopsy: Can We Reduce the Upgrade to Breast Cancer to an Acceptable Rate?

(1) Background: to evaluate which factors can reduce the upgrade rate of atypical ductal hyperplasia (ADH) to in situ or invasive carcinoma in patients who underwent vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. (2) Methods: 2955 VABBs were reviewed; 141 patients with a diagnosis of ADH were selected for subsequent surgical excision. The association between patients’ characteristics and the upgrade rate to breast cancer was evaluated in both univariate and multivariate analyses. (3) Results: the upgrade rates to ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) were, respectively, 29.1% and 7.8%. The pooled upgrade rate to DCIS or IC was statistically lower at univariate analysis, considering the following parameters: complete removal of the lesion (p-value < 0.001); BIRADS ≤ 4a (p-value < 0.001); size of the lesion ≤15 mm (p-value: 0.002); age of the patients <50 years (p-value: 0.035). (4) Conclusions: the overall upgrade rate of ADH to DCIS or IC is high and, as already known, surgery should be recommended. However, ADH cases should always be discussed in multidisciplinary meetings: some parameters appear to be related to a lower upgrade rate. Patients presenting these parameters could be strictly followed up to avoid overtreatment.

Type of Architecture, Presence of Punctate Necrosis, and Extent of Involvement in Atypical Ductal Hyperplasia Can Predict the Diagnosis of Breast Carcinoma on Excision: A Clinicopathologic Study of 143 Cases.

The literature shows a wide range in the frequencies of finding breast carcinoma in the excised specimens following a biopsy diagnosis of atypical ductal hyperplasia (ADH), likely due to a poor diagnostic reproducibility among different pathologists as well as an inherent heterogeneity in ADH. We evaluated whether histologic subtyping of ADH would help predict the risk of breast carcinoma. Our study consisted of 143 cases of ADH diagnosed by core needle biopsy and followed by excision. Of these, 54 cases (37.8%) showed carcinoma in the excised specimens (47 cases of ductal carcinoma in situ alone, 3 cases of invasive ductal carcinoma alone, and 4 cases of mixed invasive ductal carcinoma and ductal carcinoma in situ). We arbitrarily divided ADH into two subtypes: type A was considered when one or more ducts were completely replaced by low-grade ductal carcinoma in situ type cells but the lesion was <2 mm and type B was considered when one or more ducts were partially involved by low-grade ductal carcinoma in situ type cells regardless of lesion size. Type A was associated with a significantly higher frequency of breast carcinoma (63.6%) than type B (30.0%). ADH containing punctate necrosis showed a higher association of carcinoma (66.7%) compared to those without necrosis (35.1%). Within type B ADH, involvement of 3 or more foci had a higher frequency of carcinoma (50.0%) than involvement of fewer foci (26.6%). These histologic features of ADH may prove useful in predicting the likelihood of breast carcinoma and provide helpful information for patient's management.

Prospective Analysis Using a Novel CNN Algorithm to Distinguish Atypical Ductal Hyperplasia From Ductal Carcinoma in Situ in Breast

IntroductionWe previously developed a convolutional neural networks (CNN)-based algorithm to distinguish atypical ductal hyperplasia (ADH) from ductal carcinoma in situ (DCIS) using a mammographic dataset. The purpose of this study is to further validate our CNN algorithm by prospectively analyzing an unseen new dataset to evaluate the diagnostic performance of our algorithm. Materials and MethodsIn this institutional review board-approved study, a new dataset composed of 280 unique mammographic images from 140 patients was used to test our CNN algorithm. All patients underwent stereotactic-guided biopsy of calcifications and underwent surgical excision with available final pathology. The ADH group consisted of 122 images from 61 patients with the highest pathology diagnosis of ADH. The DCIS group consisted of 158 images from 79 patients with the highest pathology diagnosis of DCIS. Two standard mammographic magnification views (craniocaudal and mediolateral/lateromedial) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D slicer and resized to fit a 128 × 128 pixel bounding box. Our previously developed CNN algorithm was used. Briefly, a 15 hidden layer topology was used. The network architecture contained 5 residual layers and dropout of 0.25 after each convolution. Diagnostic performance metrics were analyzed including sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve. The “positive class” was defined as the pure ADH group in this study and thus specificity represents minimizing the amount of falsely labeled pure ADH cases. ResultsArea under the receiver operating characteristic curve was 0.90 (95% confidence interval, ± 0.04). Diagnostic accuracy, sensitivity, and specificity was 80.7%, 63.9%, and 93.7%, respectively. ConclusionProspectively tested on new unseen data, our CNN algorithm distinguished pure ADH from DCIS using mammographic images with high specificity.

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.

Factors Predicting Breast Cancer Development in Women During Surveillance After Surgery for Atypical Ductal Hyperplasia of the Breast: Analysis of Clinical, Radiologic, and Histopathologic Features.

This study aimed to evaluate the risk of breast cancer development for women under surveillance after surgery for atypical ductal hyperplasia (ADH), as well as the clinical and pathologic factors associated with breast cancer development. From November 2003 to December 2014, the study included 205 women (mean age, 47.1 ± 11.2years; range 18-73years) with a pathologic diagnosis of ADH at surgical excision who had preoperative mammography and ultrasonography (US) images and pathology slides available for review. The patients were classified into three groups according to the detection method as follows: negative group (with ADH occult on imaging), mammography group (with ADH detected on mammography), and US group (with ADH detected on US only). Clinical, radiologic, and histopathologic factors associated with breast cancer development after ADH surgery were evaluated. Breast cancer developed in 15 patients (7.3%) during surveillance after ADH surgery (follow-up period, 63.9 ± 40.8months). Palpable lesions had significantly higher rates of breast cancer development after ADH surgery (26.7% vs 6.8%; P = 0.045). Breast cancer development after ADH surgery did not differ according to the detection method (P = 0.654). Palpability was significantly associated with breast cancer development during surveillance after ADH surgery (hazard ratio, 3.579; 95% confidence interval 1.048-12.220; P = 0.042). The breast cancer development rate for women under surveillance after ADH surgery was 7.3%. Palpability at the time of ADH diagnosis was significantly associated with breast cancer development.

Atypical ductal hyperplasia: breast DCE-MRI can be used to reduce unnecessary open surgical excision.

To evaluate the diagnostic performance of dynamic contrast-enhanced (DCE)-MRI in predicting malignancy after percutaneous biopsy diagnosis of atypical ductal hyperplasia (ADH). In this retrospective study, 68 lesions (66 women) with percutaneous biopsy diagnosis of ADH and pre-operative breast DCE-MRI performed between January 2016 and December 2017 were included. Two radiologists reviewed in consensus mammography, ultrasound, and MR images. The final diagnosis after surgical excision was used as standard of reference. Clinical and imaging features were compared in patients with and without upgrade to malignancy after surgery. The diagnostic performance of DCE-MRI in predicting malignant upgrade was evaluated. A 9-gauge vacuum-assisted biopsy was performed in 40 (58.8%) cases and a 14-gauge core needle biopsy in 28 (41.2%) cases. Upgrade to malignancy was observed in 17/68 (25%) lesions, including 4/17 (23.5%) cases of invasive cancer and 13/17 (76.5%) cases of ductal carcinoma in situ (DCIS). In 16/17 (94.1%) malignant and 20/51 (39.2%) benign lesions, a suspicious enhancement could be recognized in DCE-MRI. The malignant lesion without suspicious enhancement was a low-grade DCIS (4mm size). Sensitivity, specificity, positive predictive value, and negative predictive value of DCE-MRI on predicting malignancy were respectively 94.1%, 60.7%, 44.4%, and 96.8%. No other clinical or imaging features were significantly different in patients with and without upgrade to malignancy. After a percutaneous biopsy diagnosis of ADH, malignancy can be ruled out in most of the cases, if no suspicious enhancement is present in the biopsy area at DCE-MRI. Breast DCE-MRI may be used to avoid surgery in more than half of the patients with final benign diagnosis. • Breast DCE-MRI can safely rule out malignancy if no suspicious enhancement is present in the biopsy area after a percutaneous biopsy diagnosis of ADH. • All cases of upgrade to high-grade DCIS and invasive cancers can be identified at breast DCE-MRI after a percutaneous biopsy diagnosis of ADH. • Breast DCE-MRI may be used to avoid surgery in more than half of the patients with final benign diagnosis.

Abstract P5-02-02: Artificial intelligence powered predictive analysis of atypical ductal hyperplasia from digitized pathology images

Abstract Background: Approximately 15-25% of patients with atypical ductal hyperplasia (ADH) diagnosed on breast core needle biopsy (CNB) are upgraded to ductal carcinoma in situ (DCIS) or invasive carcinoma (IC) on surgical excision. The reproducible identification of patients with ADH on CNB who are more likely to have upgrades at excision remains elusive. We hypothesized that a machine learning approach could be utilized to train models to recognize ADH on digitized pathology images and to identify cases of ADH more likely to be upgraded to DCIS or IC at excision. The purpose of this study was to determine the accuracy of the machine learning approach to identify ADH. Methods: 726 digitized images of CNB slides derived from 306 cases with a diagnosis of ADH between 11/2004-3/2018 were included in this study. Independent histologic review by two breast pathologists identified slides with and without ADH from each case. 39 board certified pathologists with experience in evaluation of breast biopsies were employed for tissue region annotation on the PathAI research platform (not intended for diagnostic purposes), yielding 14,118 tissue region annotations. Region annotations included ADH, ADH stroma, flat epithelial atypia (FEA), lobular neoplasia (LN), calcifications (Ca), columnar cell change/hyperplasia, sclerosing adenosis, papilloma, normal terminal duct lobular units and other non-atypical breast tissue regions. These annotations were used to train a convolutional neural network (CNN) with 35 layers and approximately 9 million parameters to identify ADH. The data were split into training and testing sets, representing 61.1% and 38.9% of the data respectively. The distribution of cases, images with ADH and cases with upgrade were balanced between the training and testing sets. Results: CNB specimens were assigned labels of “ADH” or “No ADH” based on histologic assessment. AI models were able to predict the diagnosis of ADH with 85% sensitivity (144 of 168 images within the test set) and 69% specificity (78 of 113 images within the test set). The slide-level area under the receiver operator curve (ROC) for this model was 0.84. Conclusions: A deep learning-based classifier showed strong performance for the identification of ADH from whole slide images of H&amp;E stained breast CNBs. With further development, this approach may improve the reproducibility and standardization of the diagnosis of ADH. Future analyses will focus on determining if morphologic features of ADH extracted by the deep learning system can be used to predict upgrade to DCIS and IC. This approach may help stratify patients with ADH on CNB into those who require surgical excision and those who can be followed with active surveillance. Citation Format: Jennifer K. Kerner, Allison Cleary, Suyog Jain, Harsha Pokkalla, Benjamin Glass, Sam Grossmith, Maya Harary, Elizabeth Mittendorf, Andrew H. Beck, Aditya Khosla, Stuart J. Schnitt, Ilan Wapinski, Tari King. Artificial intelligence powered predictive analysis of atypical ductal hyperplasia from digitized pathology images [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-02.

Complex sclerosing lesion of the breast displaying progression to invasive cancer: A case report

A 70 year old lady presented with two lumps in the right breast since around fifteen years which were increasing in size since the past one year. Mammography showed a solid-cystic and a lobulated lesion in the right breast which were categorized as BIRADS (Breast Imaging- Reporting and Data System) category 4/5. On FNAC, a diagnosis of Atypical Ductal Hyperplasia, NHSBSP (National Health Service Breast Screening Programme) Category C4 was made and histopathologic examination advised. Subsequently right sided simple mastectomy was received the larger mass in which showed extensive areas of sclerosing adenosis with superimposed ductal carcinoma in situ. The subareolar mass showed a papillary lesion displaying epithelial overgrowth with features compatible with ductal carcinoma in situ. A thorough search revealed invasive nests in the vicinity of the papillary lesion. A diagnosis of Infiltrating Ductal Carcinoma arising in a multifocal complex sclerosing lesion with extensive intraductal carcinoma and intracystic papillary carcinoma was made. This case offers to display a pathologic continuum of sclerosing breast lesions evolving into atypical hyperplasias, intraductal carcinoma and invasive carcinoma. This falls in line with the current thoughts on premalignant nature of sclerosing lesions of the breast.

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.

Atypical Ductal Hyperplasia and Lobular Neoplasia: Update and Easing of Guidelines.

OBJECTIVE. Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) are among high-risk lesions that have been previously recommended for surgical excision when diagnosed on core needle biopsy. Recent studies have examined whether imaging surveillance is a reasonable alternative to surgical management for these lesions. This article synthesizes the evidence regarding management of atypical hyperplasia and LCIS diagnosed on core needle biopsy and clinical implications of these diagnoses on future breast cancer risk as well as highlights areas of further research needed to improve practice guidelines for these high-risk lesions. CONCLUSION. Although surgical excision is still recommended after diagnosis of ADH on core needle biopsy, in specific circumstances ALH and LCIS can safely be managed by imaging surveillance.

Atypical Ductal Hyperplasia and Those Bordering on Ductal Carcinoma In Situ Should Be Included in the Active Surveillance Clinical Trials.

Women with atypical ductal hyperplasia (ADH), unlike those with ductal carcinoma in situ (DCIS), are denied eligibility for active surveillance clinical trials. We applied the inclusion criteria of the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) trial to the cases of women (n = 165) at the Roswell Park Cancer Institute who had a diagnosis of ADH, ADH bordering on DCIS, or low- to intermediate-grade DCIS on core biopsy taken during screening mammography. Upgrade of lesions to high risk was based on invasive carcinoma, high-grade DCIS, or DCIS with comedo necrosis. In total, nine (5.5%) lesions were upgraded: two (1.7%) reported ADH, one (5.9%) reported ADH bordering on DCIS, and six (19.4%) reported DCIS (P = .002); and two (1.6%) reclassified ADH vs seven (17.1%) reclassified DCIS (P < .001). In multivariate analysis, only increased number of foci had the potential to predict high risk (odds ratio: 1.39; P = .06). We conclude that ADH and ADH bordering on DCIS have lower upgrade rates than DCIS. We recommend opening an active surveillance clinical trial for women with these diagnoses.

Atypical ductal hyperplasia in men with gynecomastia: what is their breast cancer risk?

Atypical ductal hyperplasia (ADH) significantly increases the risk of breast cancer in women. However, little is known about the implications of ADH in men. Review of 932 males with breast pathology was performed to identify cases of ADH. Patients were excluded if ADH was upgraded to cancer on excision, or if they had contralateral breast cancer. Cases were reviewed to determine whether any male with ADH developed breast cancer. Nineteen males were diagnosed with ADH from June 2003 to September 2018. All had gynecomastia. Surgical procedure was mastectomy in 8 patients and excision/reduction in 11. One patient had their nipple areola complex removed, and 1 required a free nipple graft. Median patient age at ADH diagnosis was 25years (range 18-72years). Of the 14 patients with bilateral gynecomastia, 10 had bilateral ADH and 4 had unilateral. Five cases of ADH were described as severe, bordering on ductal carcinoma in situ. No patient reported a family history of breast cancer. No patient took tamoxifen. At a mean follow-up of 75months (range 4-185months), no patient developed breast cancer. Our study is the first to provide follow-up information for males with ADH. With 6years of mean follow-up, no male in our series has developed breast cancer. This suggests that either ADH in men does not pose the same risk as ADH in women or that surgical excision of symptomatic gynecomastia in men effectively reduces the risk of breast cancer.

Atypical ductal hyperplasia: Clinicopathologic factors are not predictive of upgrade after excisional biopsy

IntroductionNational Comprehensive Cancer Network (NCCN) guidelines currently recommend excisional biopsy for atypical ductal hyperplasia (ADH) diagnosed on core needle biopsy (CNB) due to the possibility of pathologic upgrade to breast cancer upon excisional biopsy. We aimed to quantify the current rate of upgrade and identify risk factors. MethodsA retrospective review of women in the Legacy Health Care System with a diagnosis of ADH was performed for 2014 through 2015. Initial pathology and patient factors were reviewed for potential predictors of upgrade. Results91 women with ADH were identified. 84 (92%) underwent excisional biopsy; 16 (19%) were upgraded to breast cancer. Those upgraded were significantly older than non-upgraded patients (64.6 versus 56.7 years, p < 0.01), and 15 (94%) had greater than one duct involved by ADH. ConclusionThe principal clinicopathologic factor associated with upgrade is increasing patient age, however this is not sufficiently predictive. Excisional biopsy in patients diagnosed with ADH on CNB should continue. Further study may provide an avenue for selective excisional biopsy in patients with ADH.

Active surveillance of women diagnosed with atypical ductal hyperplasia on core needle biopsy may spare many women potentially unnecessary surgery, but at the risk of undertreatment for a minority: 10-year surgical outcomes of 114 consecutive cases from a single center

A needle core biopsy diagnosis of atypical ductal hyperplasia is an indication for open biopsy. The launch of randomized clinical trials of active surveillance for low-risk ductal carcinoma in situ leads to the paradoxical situation of women with low-grade ductal carcinoma in situ being observed, whereas those with atypical ductal hyperplasia have surgery. If the malignancies diagnosed after surgery for atypical ductal hyperplasia are dominated by low-risk ductal carcinoma in situ, women with atypical ductal hyperplasia may also be considered for surveillance. This 10-year prospective observational study includes women diagnosed with atypical ductal hyperplasia on core biopsy after screening mammography. We retrieved their clinical, imaging and histologic data and carried out a blind review of core biopsy histology, sub-classifying the atypical ductal hyperplasia along a spectrum from hyperplasia to ductal carcinoma in situ. Using the final surgical pathology data, we calculated: (1) The proportion and grades of ductal carcinoma in situ and invasive cancers diagnosed at open biopsy. (2) The histologic extent of the malignancy at surgery. (3) The biomarker profile and nodal status of any invasive cancers. (4) Ascertained any independent predictors of (i) any malignancy, (ii) high-risk malignancy, defined in this study as invasive cancer, or high-grade ductal carcinoma in situ, or intermediate grade ductal carcinoma in situ with any necrosis. (5) Extrapolated the above to simulate active surveillance for women with screen-detected atypical ductal hyperplasia. Between January 2005 and December 2014, 114 women, mean age 59 years (range 40–79 years) were included. Surgical pathology, available in 110 (97%), confirmed malignancy in 46 (40%). All 46 malignant cases had ductal carcinoma in situ, accompanied by invasive carcinoma in 9 (8%) women. Together, 21 (19%) women had either invasive cancer (9%), high-grade ductal carcinoma in situ (6%), or necrotizing, intermediate grade ductal carcinoma in situ (6%). Only one of nine invasive breast cancers was grade 1, 3 were multifocal, all were ≤8 mm, node negative, and ER positive but two were HER2 amplified. The mean extent of the ductal carcinoma in situ in any one specimen was 19.8 mm, median 13 mm, range 2–110 mm. Overall 32 women, 29% of the whole cohort and 70% of those 46 with malignancy, required further surgery, including mastectomy in 12 (11%). A multivariable model for predicting the likelihood of any malignancy showed a statistically significant association only with the post review subtype of atypical ductal hyperplasia, adjusting for lesion size. Independent predictors of high-risk malignancy (invasive cancer or non-low-grade ductal carcinoma in situ) were not identified. If active surveillance is adopted for screen-detected atypical ductal hyperplasia diagnosed on core biopsy, 60% of women will avoid unnecessary surgery and a further 24% would meet eligibility criteria for ductal carcinoma in situ surveillance trials. However, 18% of women will have undiagnosed invasive breast cancer or non-low-risk ductal carcinoma in situ. These women with high-risk lesions are not reliably identified pre-operatively.

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.

Abstract P5-13-02: Chemoprevention utilization in patients with a history of atypical hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in-situ: A retrospective chart review of patients diagnosed at an urban hospital with a large minority patient population

Abstract Background: The Breast Cancer Prevention Trial (BCPT) and the Study of Tamoxifen and Raloxifene (STAR) trial showed that chemoprevention can reduce the risk of invasive breast cancer by nearly 50%. Despite these results, studies have shown that while an estimated 2 million women in the United States are eligible for chemoprevention, actual acceptance of these medications is low. Improving chemoprevention utilization rates hinges on better understanding current rates of utilization and factors affecting patient acceptance. Reported rates and barriers to chemoprevention use may not accurately reflect true utilization patterns in lower socioeconomic, minority patient populations. The aim of this IRB approved retrospective study was to characterize the rate and factors associated with chemoprevention use in patients with a diagnosis of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in-situ (LCIS) at an urban hospital with a high minority population. Methods – A retrospective chart review was performed for all diagnoses of ADH, ALH, and LCIS made at the University of Maryland Medical Center between the years 2005-2015. Concurrent DCIS or invasive cancer were excluded. Demographic and clinical information including age, race, education, GAIL score, BMI, and use of chemoprevention was recorded. Univariable and multivariable logistic regression were performed to identify factors associated with chemoprevention discussion and use. Results – 301 diagnoses of ADH/ALH/or LCIS were obtained and 127 women were eligible for analysis. The median age was 53 years old with 47% of patients being premenopausal. The majority were African-American (65%) and 51% had a high school degree or less. The median 5 year risk for developing breast cancer based on the GAIL model was 2.4%. The chemoprevention utilization rate for our patient population was 28% (n=34). Race, menopausal status, and breast density were not associated with chemoprevention discussion or use. We found that patients were more likely to have a chemoprevention discussion with their provider if they were older (p=0.03) or if they were referred to medical oncology (p&amp;lt;0.001, Fisher's exact test). Conclusions - Our study evaluated chemoprevention use in an understudied predominantly African-American patient population. We found a higher rate of chemoprevention utilization (28%) compared to previously reported rates. Age and medical oncology referral had a significant impact on provider-patient chemoprevention discussion. Though limited due to small sample size, our study nonetheless provided thought provoking results. Older patients may be at higher risk for developing breast cancer, however, it is important to consider that younger patients with risk factors may have a more favorable endocrine therapy benefit-risk ratio. In addition, our results highlight the importance of encouraging all physicians who are involved in women's' breast health to have a chemoprevention discussion with eligible patients, or for these physicians to refer patients to a medical oncologist for further discussion. Citation Format: DeRidder A, Mainor C, Goloubeva O, Ioffe O, Bellavance E, Tkaczuk K, Rosenblatt P. Chemoprevention utilization in patients with a history of atypical hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in-situ: A retrospective chart review of patients diagnosed at an urban hospital with a large minority patient population [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 P5-13-02.

Multivariate model to identify women at low risk of cancer upgrade after a core needle biopsy diagnosis of atypical ductal hyperplasia.

Atypical ductal hyperplasia (ADH) identified on percutaneous breast biopsy represents a high-risk lesion, upgrading to cancer with surgical excision in~7-45.8% of cases. Routine excision is questioned due to potential overtreatment and cost. This study evaluates clinical, imaging, and histologic features to predict the risk of upgrade. With IRB approval, a single-institution retrospective review was performed of patients who underwent surgical excision of ADH diagnosed by core biopsy from June 2005 to June 2013. We reviewed electronic medical records, breast imaging, and biopsy slides. Multiple imputation was used for missing data. Association of various features with cancer upgrade was assessed using logistic regression. Among 399 cases, the upgrade rate to cancer was 16.0%, (95% CI: 12.8-20.0%), with nine invasive cancers and 55 ductal carcinoma in situ (DCIS) only. Via a logistic regression approach, we defined a subgroup with low risk for upgrade: women whose biopsies showed no individual cell necrosis, and either a) 1 focus of ADH with ≥50% removal, or b) 2-3 foci with ≥90% removal. Cases meeting these criteria had an upgrade rate of 4.9% (95% CI: 1.0-8.9%), compared to 21.4% (16.4-26.3%) in cases that did not meet this low-risk definition. ADH on core biopsy with low risk of upgrade to cancer is defined by lack of individual cell necrosis, number of foci of ADH, and percent of imaging lesion removed. If these findings are validated, women whose biopsies meet low-risk criteria might be considered for prevention therapy and surveillance without surgical excision.