Management of high-risk breast lesions diagnosed on core biopsies and experiences from prospective high-risk breast lesion conferences at an academic institution.

BACKGROUND: The management of high-risk breast lesions diagnosed on image-guided core biopsy remains controversial. We implemented a high-risk breast conference attended by breast pathologists, imagers, and surgeons to prospectively review all contemporary cases in order to provide a consensus recommendation to either surgically excise or follow on imaging at 6-month intervals for a minimum of 2 years. METHODS: Between May, 2015 and June, 2019, 127 high-risk lesions were discussed. Of these 127 cases, 116 had concordant radiology-pathology (rad-path) findings. The remaining 11 patients had discordant rad-path findings. Of the 116 concordant cases, 6 were excluded due to lack of the first imaging follow-up until analysis. Of the remaining 110 patients, 43 had atypical ductal hyperplasia (ADH), 12 had lobular carcinoma in situ (LCIS), 19 had atypical lobular hyperplasia (ALH), 33 had radial scar (RS), 2 had flat epithelial atypia (FEA), and 1 had mucocele-like lesion (ML). We recommended excision for ADH if there were > 2 ADH foci or < 90% of the associated calcifications were removed. For patients with LCIS or ALH, we recommended excision if the LCIS or ALH was associated with microcalcifications or the LCIS was extensive. We recommended excision of RS when < 1/2 of the lesion was biopsied. We recommended all patients with FEA and ML for 6-month follow-up. RESULTS: Following conference-derived consensus for excision, of the 27 ADH excised, 9 were upgraded to invasive carcinoma or ductal carcinoma in situ. Of the six LCIS cases recommended for excision, none were upgraded. Nine excised radial scars revealed no upgrades. Additionally, 3 patients with ADH, 2 with ALH, 1 with LCIS, and 2 with RS underwent voluntary excision, and none were upgraded. All other patients (13 with ADH, 5 LCIS, 17 ALH, 22 RS, 2 FEA and 1 ML) were followed with imaging, and none revealed evidence of disease progression during follow-up (187-1389 days). All 11 rad-path discordant cases were excised with 2 upgraded to carcinoma. CONCLUSIONS: The results of this prospective study indicate that high-risk breast lesions can be successfully triaged to surgery versus observation following establishment of predefined firm guidelines and performance of rigorous rad-path correlation.

Flat epithelial atypia: are we being too aggressive?

PURPOSE: The malignant upgrade rate of flat epithelial atypia (FEA) diagnosed on core needle biopsy varies between 0 and 30%. Excision versus observation with radiological follow-up for these lesions remains controversial. We hypothesize that the local rate of FEA is low and that close radiological surveillance is a reasonable treatment option for patients diagnosed with pure FEA on breast needle core needle biopsy. METHODS: This study was a retrospective review of a prospectively collated provincial pathology database. Patients diagnosed with FEA alone on needle core biopsy between 2006 and 2016 were included in our analysis. Patients who had FEA present together with either in situ or invasive carcinoma within the same biopsy cores were excluded. Along with patient demographics, the size of the lesion on preoperative imaging, the method of extraction, and the presence of co-existing benign and malignant pathology on final excision biopsy were analyzed. An independent pathological review was performed to confirm our results and help reduce inter-observer bias. RESULTS: The local rate of malignant upgrade when pure FEA is diagnosed on a breast needle core biopsy is 12%. Age at time of diagnosis, size of original lesion on mammogram, presence of atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia on core needle biopsy, the use of vacuum-assisted biopsy (VAB), or concordant imaging did not significantly correlate with malignant upgrade risk. None of the patients who were managed with radiological follow-up had malignant upgrade during follow-up. Patients undergoing radiological follow-up alone were more likely to have a VAB, concordant imaging, and no concurrent ADH. CONCLUSION: Our local malignant upgrade rate is consistent with published literature. We suggest radiological follow-up is a safe alternative in patients with pure flat epithelial atypia and concordant imaging, particularly those patients with small lesions in which microcalcifications can be removed completely with vacuum-assisted biopsy.

Flat epithelial atypia on core needle biopsy does not always mandate excisional biopsy.

Flat Epithelia Atypia (FEA) is a proliferative lesion of the breast where cells demonstrate columnar change and cytologic atypia. This lesion has been identified as distinct from the classic atypical hyperplasias (AH). While many patients undergo excisional biopsy, management of FEA identified on core needle biopsy (CNB) is controversial, and the rate of associated ductal carcinoma in situ (DCIS) or invasive cancer is not well defined. The aim of this study was to determine the upstage rate of FEA diagnosed by CNB. We identified patients from a prospectively maintained data base who had FEA diagnosed by CNB from 01/2010 to 07/2015. Patient variables collected included age at presentation, imaging findings, pathologic findings following surgical excision, and subsequent development of breast cancer. Of 132 patients, 62 (n = 62/132, 47.0%) patients had FEA associated with DCIS and invasive ductal carcinoma (IDC) on CNB and were excluded from analysis. Of the remaining 70 patients, median age was 52 (range 31-84) years. Thirty-two (45.7%) patients had FEA plus AH, 4 (5.7%) patients had FEA plus lobular carcinoma in situ (LCIS), and 34 (48.6%) patients had FEA alone or with another non-pathologic finding (pure FEA). Two (6.3%) patients with FEA plus AH had DCIS or IDC on subsequent excisional biopsy. Of the 34 patients with pure FEA who underwent excisional biopsy, only one (2.9%) was found to have IDC. Twenty-two (64.7%) patients with pure FEA who underwent excisional biopsy presented with calcifications on mammography. None of these patients had cancer on excisional biopsy, and 10 (45.5%) patients had AH (3 ADH, 3 ALH, and 4 both ALH and ADH). Twelve (n = 12/34, 35.3%) patients with pure FEA underwent CNB for a mass or asymmetry noted on imaging. Of these 12 patients, 9 (75.0%) had benign findings on excisional biopsy, two (16.7%) patients had AH, and one (8.3%) patient had IDC. Median follow-up was 4.6 years (IQR 3.1-6.5 years). Three (4.3%) patients subsequently developed IDC, two of which were in the contralateral breast. FEA is often found in combination with ADH and ALH as well as carcinoma on CNB. In our study, pure FEA was upstaged to cancer in only 2.9% of patients. Mammographic findings unlikely predict upstaging to malignancy. These findings suggest that excisional biopsy may not be warranted in patients with pure FEA and could be managed with close imaging surveillance.

How Do We Approach Benign Proliferative Lesions?

PURPOSE OF REVIEW: The aim of this review is to summarize recently published literature addressing atypical ductal hyperplasia (ADH), lobular neoplasia (atypical lobular hyperplasia [ALH] and classic lobular carcinoma in situ [C-LCIS]), non-classic lobular carcinoma in situ (NC-LCIS), papillary lesions, and flat epithelial atypia (FEA). RECENT FINDINGS: While ADH, ALN, and C-LCIS are well-established markers of an increased risk of future breast cancers, the risk implications are less clear for papillary lesions and FEA. NC-LCIS is the least well-characterized lesion, with scant published literature on its natural history and surgical management when encountered on needle biopsy. Recent data suggest that lobular neoplasia on core biopsy of a BI-RADS ≤ 4 concordant lesion does not require an excision, while ADH, atypical papillomas, and NC-LCIS should be excised. Evidence on FEA and papillomas without atypia suggests a low risk of upgrade on excision, and prospective studies on the upgrade of these lesions are ongoing.

Aberrant Level of Skp2 and p27KIP1 in Intraductal Proliferative Lesions is Associated with Tumorigenesis.

Breast cancer is one of the leading causes of cancer-related death in women worldwide. Here we aimed to examine the expression status of S-phase kinase-associated protein 2 (Skp2) and p27KIP1, and assess the significance of Skp2 plus p27KIP1 expression in patients with intraductal proliferative lesions, including ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH). Skp2 and p27KIP1 mRNA levels in DCIS, ADH, flat epithelial atypia, and usual ductal hyperplasia (UDH) were evaluated by quantitative real-time reverse transcription polymerase chain reaction and protein expression was evaluated immunohistochemically in 60 fresh tissues and 120 paraffin-embedded tissues from patients with the four subtypes above. We found that the protein and mRNA level of Skp2 were significantly increased in DCIS and ADH as compared with that in UDH. In contrast, p27KIP1 protein and mRNA levels were reduced. Based on the above findings, abnormal levels of Skp2 and p27KIP1 have probably been involved in the pathogenesis of ADH and DCIS. Thus, Skp2 and p27KIP1 may serve as important diagnosis markers.

Flat epithelial atypia and risk of breast cancer: A Mayo cohort study.

BACKGROUND: Based on its cytologic features, and its co-occurrence with atypical hyperplasia and breast cancer, flat epithelial atypia (FEA) has been proposed as a precursor lesion on the pathway to the development of breast cancer. It is often referred to as an "atypical" or high-risk lesion. However, to the authors' knowledge, the long-term risk of breast cancer in women with FEA is undefined. METHODS: Specimens with FEA were identified among excisional breast biopsies in the Mayo Clinic Benign Breast Disease Cohort, which includes 11,591 women who had benign biopsy findings at the Mayo Clinic in Rochester, Minnesota between 1967 and 2001. Breast cancer risk among subsets of patients with FEA and nonproliferative, proliferative, and atypical hyperplasia (AH) was assessed using standardized incidence ratios (SIRs) compared with the Iowa Surveillance, Epidemiology, and End Results registry. RESULTS: FEA was identified in 282 women (2.4%); 130 had associated AH (46%) and 152 (54%) were classified as having proliferative disease without atypia (PDWA). With median follow-up of 16.8 years, the SIR for breast cancer in patients with AH plus FEA was 4.74 (95% confidence interval [95% CI], 3.17-6.81) versus 4.23 (95% CI, 3.44-5.13) for those with AH without FEA (P = .59). The SIR for patients with PDWA plus FEA was 2.04 (95% CI, 1.23-3.19) versus 1.90 (95% CI, 1.72-2.09) for patients with PDWA without FEA (P = .76). CONCLUSIONS: FEA is an uncommon finding in women with benign breast disease. FEA does not appear to convey an independent risk of breast cancer beyond that of the associated PDWA or AH.

Predictors of underestimation of malignancy after image-guided core needle biopsy diagnosis of flat epithelial atypia or atypical ductal hyperplasia.

Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are precursors of breast malignancy. Management of FEA or ADH after image-guided core needle biopsy (CNB) remains controversial. The aim of this study was to evaluate malignancy underestimation rates after FEA or ADH diagnosis using image-guided CNB and to identify clinical characteristics and imaging features associated with malignancy as well as identify cases with low underestimation rates that may be treatable by observation only. We retrospectively reviewed 2,875 consecutive image-guided CNBs recorded in an electronic data base from January 2010 to December 2011 and identified 128 (4.5%) FEA and 83 (2.9%) ADH diagnoses (211 total cases). Of these, 64 (30.3%) were echo-guided CNB procedures and 147 (69.7%) mammography-guided CNBs. Twenty patients (9.5%) were upgraded to malignancy. Multivariate analysis indicated that age (OR = 1.123, p = 0.002, increase of 1 year), mass-type lesion with calcifications (OR = 8.213, p = 0.006), and ADH in CNB specimens (OR = 8.071, p = 0.003) were independent predictors of underestimation. In univariate analysis of echo-guided CNB (n = 64), mass with calcifications had the highest underestimation rate (p < 0.001). Multivariate analysis of 147 mammography-guided CNBs revealed that age (OR = 1.122, p = 0.040, increase of 1 year) and calcification distribution were significant independent predictors of underestimation. No FEA case in which, complete calcification retrieval was recorded after CNB was upgraded to malignancy. Older age at diagnosis on image-guided CNB was a predictor of malignancy underestimation. Mass with calcifications was more likely to be associated with malignancy, and in cases presenting as calcifications only, segmental distribution or linear shapes were significantly associated with upgrading. Excision after FEA or ADH diagnosis by image-guided CNB is warranted except for FEA diagnosed using mammography-guided CNB with complete calcification retrieval.

Do columnar cell lesions exist in the male breast?

AIMS: In females, columnar cell lesions (CCLs) have been recognized as putative precursor lesions of low-grade breast cancer, but their role in male breast carcinogenesis is as yet unclear. METHODS AND RESULTS: We reviewed surgical resections from males with breast cancer (n = 89), gynaecomastia (n = 20) and normal breast specimens from autopsies (n = 5) for the presence of CCL. In addition, we performed immunohistochemistry for cytokeratin 5/6 (CK5/6), CK14 and oestrogen receptor alpha (ER). In 19 of 89 resections (two DCIS cases and 17 invasive carcinoma), some individual ducts were found to contain cells with snouts on the luminal border but lacking further typical columnar cell lesion features. We mainly found three-layered ductal epithelium, characteristic for gynaecomastia and confirmed by immunohistochemistry. Moreover, we found a few ducts in male breast cancer sections that were clonally negative for basal cytokeratins. CONCLUSION: We found no lesions with convincing CCL morphology at the periphery of invasive male breast cancers, in gynaecomastia or in normal male breast specimens. Although we cannot completely exclude the existence of CCLs in the male breast, these lesions seem to be very uncommon and are therefore unlikely to play a major role in male breast carcinogenesis.

Does isolated flat epithelial atypia on vacuum-assisted breast core biopsy require surgical excision?

To determine whether flat epithelial atypia (FEA) found in isolation on large core vacuum-assisted biopsy (CNB) requires surgical excision. After Institutional Review Board approval, pathology reports of all patients who underwent CNB from January 1, 2005 to December 31, 2010 were reviewed. All patients with reports of isolated FEA without other atypia or in situ or invasive carcinoma were identified. Patient age, history, target on imaging, biopsy modality, and residual target post CNB noted. Histology of CNB's (blinded to surgical outcome) and subsequent surgical excisions were reviewed by a dedicated breast pathologist. Only cases with confirmed isolated FEA on review were used for data analysis. Of 2,556 CNB's performed over 6 years, 37 (1.4%) had isolated FEA confirmed on review, comprising our study population. Thirty (81%) had biopsy for calcifications on mammography and 7 (19%) for mass or non-mass like enhancement on magnetic resonance imaging. There were no US guided CNBs that met our inclusion criteria. 29 (78.4%) underwent surgical excision, 6 (16.2%) had imaging follow-up, and 2 (5.4%) were lost to follow-up. Of the 29 with surgery, 2 (6.9%) had "upgrade" to low-grade in situ carcinoma (1 ductal and 1 pleomorphic lobular), 5 (17.2%) had "change in diagnosis" to other atypia (ADH/ALH), 15 (51.7%) had additional FEA and 7 (24.2%) had benign tissue without atypia. Both "upgraded" cases had residual microcalcifications on imaging following CNB. There were no upgrades to invasive cancers. In our study, none of 29 with isolated FEA on CNB had invasive cancer on surgical excision. If there are residual microcalcifications or residual lesion after a CNB that shows isolated FEA, excision is warranted, due to the possibility of other atypia (ADH/ALH [17.2%] or DCIS [5.4%]). If there are no residual microcalcifications following CNB, imaging follow-up as an alternative to surgery may be a reasonable option.

Updates in the Surgical Management of Benign and High-Risk Breast Lesions.

Benign breast disease (BBD) is a heterogenous group of lesions often classified as nonproliferative or proliferative, with the latter group further categorized based on the presence of atypia. Although nonproliferative lesions are more common, the risk of breast cancer is elevated in women with proliferative lesions. Historically, the majority of proliferative lesions were excised due to concern for future and/or concomitant breast cancer at the site of the index lesion. However, contemporary data suggest that the risk of cancer associated with various proliferative lesions may be lower than previously thought, and management of BBD has become more nuanced. In this review, we will focus on recent updates in the management of a select group of benign and high-risk lesions.

Distance of Biopsy-Confirmed High-Risk Breast Lesion from Concurrently Identified Breast Malignancy Associated with Risk of Carcinoma at the High-Risk Lesion Site.

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series.

Isolated Flat Epithelial Atypia: Upgrade Outcomes After Multidisciplinary Review-Based Management Using Excision or Imaging Surveillance.

Objective: To compare flat epithelial atypia (FEA) upgrade rates after excision versus surveillance and to identify variables associated with upgrade. Methods: This single-institution retrospective study identified isolated FEA cases determined by percutaneous biopsy from April 2005 through July 2022 with excision or ≥2 years surveillance. All cases were recommended for excision or surveillance based on multidisciplinary discussion of clinical, imaging, and pathologic variables with emphasis on sampling adequacy and significant atypia. Truth was determined by pathology at excision or the absence of cancer on surveillance. Upgrade was defined as cancer occurring ≤2 cm from the biopsy site. Demographic, imaging, and biopsy variables were compared between those that did and did not upgrade. Results: Among 112 cases of isolated FEA, imaging findings included calcifications in 81.3% (91/112), MRI lesions in 11.6% (13/112), and distortions or masses in 7.1% (8/112). Excision was recommended in 12.5% (14/112) and surveillance in 87.5% (98/112) of cases. Among those recommended for excision, 28.6% (4/14) of cases were upgraded, all to ductal carcinoma in situ. In those recommended for surveillance, 1.0% (1/98) were upgraded to invasive cancer. Overall, FEA had a 4.5% (5/112) upgrade rate, and 2.7% (3/112) also developed cancer >2 cm from the FEA. There were no significant differences in demographic, imaging, and biopsy variables between those that did and did not upgrade to cancer. Conclusion: Multidisciplinary management of isolated FEA distinguishes those at higher risk of upgrade to cancer (28.6%) in whom surgery is warranted from those at low risk of upgrade (1.0%) who can be managed non-operatively.

Breast Lesions of Uncertain Malignant Potential (B3) and the Risk of Breast Cancer Development: A Long-Term Follow-Up Study.

Breast lesions of uncertain malignant potential (B3) are frequently diagnosed in the era of breast cancer (BC) screening and their management is controversial. They are generally removed surgically, but some international organizations and guidelines for breast research suggest follow-up care alone or, more recently, propose vacuum-assisted excision (VAE). The risk of upgrade to BC is known, but very little data exist on its role as risk factor for future BC development. We analyzed 966 B3 lesions diagnosed at our institution, 731 of which had long-term follow-up available. Surgical removal was performed in 91%, VAE in 3.8%, and follow-up in 5.2% of cases. The B3 lesions included flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), lobular intraepithelial neoplasia (LIN), atypical papillary lesions (PLs), radial scars (RSs), and others. Overall, immediate upgrade to BC (invasive or in situ) was 22.7%. After long-term follow-up, 9.2% of the patients were diagnosed with BC in the same or contralateral breast. The highest risk was associated with ADH diagnosis, with 39.8% of patients upgraded and 13.6% with a future BC diagnosis (p < 0.0001). These data support the idea that B3 lesions should be removed and provide evidence to suggest annual screening mammography for women after a B3 diagnosis because their BC risk is considerably increased.

Flat epithelial atypia diagnosed on core needle biopsy-Clinical challenge.

AIM: This paper describes our experience of 20 cases identified in the FEA vacuum core biopsy. BACKGROUND: Screening mammography has contributed to the increased recognition of early cancer, premalignant and preinvasive breast lesions. A premalignant lesion called FEA (flat epithelial atypia), although rarely recognized as the only lesion in the core biopsy, is a major challenge in clinical proceedings. Increasing recognition is associated with an increasing use of the vacuum core biopsy as a tool for verifying nonpalpable lesions identified by mammography, and suspected of being breast cancer. MATERIALS AND METHODS: Of 4326 mammotome biopsies performed at our institution in 2000-2006, FEA was diagnosed in 20 patients (0.46%). These patients underwent surgery for reexcsion. Data were collected for clinical, radiological and pathological findings to assess factors associated with the underestimation of invasive lesions. RESULTS: Among 20 patients with FEA diagnosis, the mean age was 59.6, range 52-71. When compared to the ADH group (mean age 55.45), the FEA patients were found to be statistically significantly older (p = 0.0002). Two patients 2/20 (10%) showed underestimation, with invasive cancer on the final pathology were G1 tubular cancer T1b, and G2 lobular cancer T1a. CONCLUSION: Although FEA is rarely diagnosed as the only lesion in a core biopsy, the ever more common use of this diagnostic technique forces us to establish a clear clinical practice. The problem is the underestimation of invasive lesions in the case of primary diagnosis of FEA. It seems that some percent of these cases can be identified by certain radiological or pathological features, thus helping implement appropriate clinical management.

Proliferative epithelial changes in tumour adjacent tissue in Sri Lankan women with breast carcinoma: do morphological changes support molecular models of breast carcinogenesis?

BACKGROUND: The multistep molecular model of breast carcinogenesis is based on the oestrogen receptor(ER) status of the tumour. Its two main arms comprise ER-positive and ER-negative breast carcinomas(BCa), which are associated with Nottingham grade(NG) of the tumour and different proliferative epithelial changes. According to the model, columnar cell lesions(CCL), lobular carcinoma in-situ(LCIS) and atypical ductal hyperplasia(ADH), low-grade ductal carcinoma in-situ (LG-DCIS) are associated with low grade ER-positive tumours and microglandular adenosis (MGA), pleomorphic LCIS(PLCIS), high-grade DCIS(HG-DCIS) are associated with ER-negative high grade tumours. This study aims to describe the association between proliferative epithelial changes in breast tissue adjacent to tumour, in relation to the ER status and NG of the tumour. METHODS: This descriptive cross-sectional study included 420, wide local excision and mastectomy specimens of BCa from National Hospital of Sri Lanka, between 2017-2019. The histopathological features of the tumour and proliferative epithelial changes in tumour adjacent tissue within 10 mm distance from the tumour-host interface were evaluated independently by two pathologists. The ER, PR(Progesterone receptor) and HER2 status assessed by immunohistochemistry(IHC) was reviewed. The associations between above epithelial lesions and ER status and NG{categorised as low grade (NG1 and NG2) and high grade (NG3)} of the tumour were analyzed. RESULTS: ER positive BCa showed significant associations with CCH (p = 0.04), FEA (p = 0.035) and LGDCIS (p < 0.001). Although PLCIS was more frequent in ER positive tumours, the association did not attain statistical significance. ER negative BCa showed a significant association with HGDCIS (p = 0.016). CCLs as a whole (p = 0.005) and also CCC (p = 0.006) and FEA (p = 0.048) and LGDCIS (p < 0.001) showed significant associations with low NG tumours. High NG tumours showed a significant association with HGDCIS (p < 0.001). Microglandular adenosis was not identified in our study population. CONCLUSION: These morphological findings support the multistep molecular based pathogenetic pathways of breast carcinoma in the studied setting in South Asia. Identification of these proliferative epithelial components in a core biopsy that is negative for BCa, should prompt for close clinicoradiological correlation, and if necessary re-biopsy of women suspected of harbouring a BCa.

Upgrade rate of percutaneously diagnosed pure flat epithelial atypia: systematic review and meta-analysis of 1,924 lesions.

CONTEXT: Management remains controversial due to the risk of upgrade for malignancy from flat epithelial atypia (FEA). Data about the frequency and malignancy upgrade rates are scant. Namely, observational follow-up is advised by many studies in cases of pure FEA on core biopsy and in the absence of an additional surgical excision. For cases of pure FEA, the American College of Surgeons no longer recommends surgical excision but rather recommends observation with clinical and imaging follow-up. OBJECTIVES: The aim of this study is to perform a systematic review and meta-analysis to calculate the pooled upgrade of pure FEA following core needle biopsies. METHODS: A search of MEDLINE and Embase databases were conducted in December 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A fixed- or random-effects model was utilized. Heterogeneity among studies was estimated by utilizing the I2 statistic and considered high if the I2 was greater than 50%. The random-effects model with the DerSimonian and Laird method was utilized to calculate the pooled upgrade rate and its 95% confidence interval. RESULTS: A total of 1924 pure FEA were analyzed among 59 included studies. The overall pooled upgrade rate to malignancy was 8.8%. The pooled upgrade rate for mammography only was 8.9%. The pooled upgrade rate for ultrasound was 14%. The pooled upgrade rate for mammography and ultrasound combined was 8.8%. The pooled upgrade rate for MRI-only cases was 27.3%. CONCLUSIONS: Although the guidelines for the management of pure FEA are variable, our data support that pure FEA diagnosed at core needle biopsy should undergo surgical excision since the upgrade rate >2%.

Rates and Outcomes of Breast Lesions of Uncertain Malignant Potential (B3) benchmarked against the National Breast Screening Pathology Audit; Improving Performance in a High Volume Screening Unit.

INTRODUCTION: Our breast screening unit was identified as high outlier for B3 lesions with a low positive predictive value (PPV) compared to the England average. This prompted a detailed internal audit and review of B3 lesions and their outcomes to identify causes and address any variation in practice. PATIENTS AND METHODS: The B3 rate was calculated in 4168 breast core biopsies from 2019, using the subsequent excision to determine the PPV. Atypical intraductal epithelial proliferation (AIDEP) cases were subject to microscopic review to reassess the presence of atypia against published criteria. The B3 rate was re-audited in 2021, and the results compared. RESULTS: Screening cases had a high B3 rate of 12.4% (30% above the national average), and a PPV of 7.7% (9.7% with atypia). AIDEP was identified as a possible cause of this outlier status. On review and by consensus, AIDEP was confirmed in only 66% of cases reported as such, 17% were downgraded, and 16% did not reach consensus, the latter highlighting the difficulty and subjectivity in diagnosis of these lesions. Repeat audit of B3 rates after this extended review revealed a reduction from 12.4% to 9.11%, which is more in line with national standards. CONCLUSION: Benchmarking against national reporting standards is critical for service improvement. Through a supportive environment, team working, rigorous internal review and adherence to guidelines, interobserver variation and outlier status in breast pathology screening outliers can both be addressed. This study can serve as a model to other outlier units to identify and tackle underlying causes.

Risk-Associated Lesions of the Breast in Core Needle Biopsies: Current Approaches to Radiological-Pathological Correlation.

Image-guided core needle biopsies (CNBs) of the breast frequently result in a diagnosis of a benign or atypical lesion associated with breast cancer risk. The subsequent clinical management of these patients is variable, reflecting a lack of consensus on criteria for selecting patients for clinical and radiological follow-up versus immediate surgical excision. In this review, the evidence from prospective studies of breast CNB with radiological-pathological correlation is evaluated and summarized. The data support an emerging consensus on the importance of radiologic-pathologic correlation in standardizing the selection of patients for active surveillance versus surgery.

Breast Cancer and Secondary Cancer Recurrences After Autologous Tissue Reconstruction.

BACKGROUND: The medical literature defining breast cancer recurrence and secondary cancers after autologous tissue reconstruction for breast cancer is sparse. We sought to identify and analyze occurrences at our institution. PATIENTS AND METHODS: A 20-year retrospective review of cancer recurrences and atypical breast neoplasms after autologous tissue breast reconstruction at Roswell Park Comprehensive Cancer Center was conducted after being granted a waiver from the institutional review board. RESULTS: Eighteen locoregional recurrences among 337 cases were identified and analyzed. Overall recurrence rate was 5.3%. Four secondary cancers (1.2%) were radiation-induced angiosarcoma, undifferentiated pleomorphic sarcoma, and metaplastic carcinoma. One case of flat epithelial atypia was identified. CONCLUSION: Our retrospective review found incidence and survival after treatment of breast cancer concordant with reports in the literature. We also identified and analyzed secondary neoplasms, including a unique case of undifferentiated pleomorphic sarcoma and metachronous recurrence of breast carcinoma. A case of recurrence as metaplastic carcinoma was identified.

Management of High-Risk Breast Lesions.

High-risk breast lesions (HRLs) are a group of heterogeneous lesions that can be associated with a synchronous or adjacent breast cancer and that confer an elevated lifetime risk of breast cancer. Management of HRLs after core needle biopsy may include close imaging and clinical follow-up or excisional biopsy to evaluate for cancer. This article reviews histologic features and clinical presentation of each of the HRLs, current evidence with regard to management, and guidelines from the American Society of Breast Surgeons and National Comprehensive Cancer Network. In addition, imaging surveillance and risk-reduction strategies for women with HRLs are discussed.