Outcomes of atypical lobular hyperplasia managed by active surveillance or immediate surgery.

BACKGROUND: Atypical lobular hyperplasia (ALH) is typically diagnosed via needle core biopsy (NCB) and is commonly removed surgically in light of upgrade to malignancy rates of 1%-5%. As studies on radiographic outcomes of ALH managed by active surveillance (AS) are limited, we investigated the upgrade rates of surgically excised ALH as well as radiographic progression during AS. METHODS: In this retrospective study, 125 patients with 127 ALH lesions diagnosed via NCB at Weill Cornell Medicine from 2015 to 2021 were included. The upgrade rate to cancer was determined for patients who had surgical management ≤6 months after biopsy. Among patients with ALH managed by AS, we investigated radiographic progression on 6-month interval imaging. RESULTS: Of 127 ALH lesions, 75% (n = 95) were immediately excised and 25% (n = 32) were observed under AS. The upgrade rate of immediately excised ALH was 2.1% (n = 2; invasive ductal carcinoma [IDC], T1N0 and IDC, and T1Nx). In the AS cohort, no ALH lesions progressed radiographically during the follow-up period of 22.5 months (median), with all remaining stable (50%, n = 16), resolving (47%, n = 15), or decreasing in size (3%, n = 1). CONCLUSIONS: In this study, NCB-diagnosed ALH had a low upgrade to malignancy rate (2.1%), and no ALH lesions managed by AS progressed radiographically during the follow-up period of 22.5 months. These results support AS as the favorable option for patients with pure ALH on biopsy, with surgical excision for lesions that progress on surveillance.

Identification of Glandular (Acinar)/Tubule Formation in Invasive Carcinoma of the Breast: A Study to Determine Concordance Using the World Health Organization Definition.

CONTEXT.­: The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. OBJECTIVE.­: To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. DESIGN.­: A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. RESULTS.­: Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. CONCLUSIONS.­: We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

Active Surveillance of Atypical Ductal Hyperplasia of the Breast.

BACKGROUND: When needle core biopsy (NCB) of the breast yields atypical ductal hyperplasia (ADH), excision is typically recommended. The natural history of ADH undergoing active surveillance (AS) is not well described. We investigate the rates of upgrade to malignancy of excised ADH and the rates of radiographic progression under AS. MATERIALS AND METHODS: We retrospectively reviewed records of 220 cases of ADH on NCB. Of patients who had surgery within 6 months of NCB, we examined the malignancy upgrade rate. In the AS cohort, we examined rates of radiographic progression on interval imaging. RESULTS: The malignancy upgrade rate among patients who underwent immediate excision (n = 185) was 15.7%: 14.1% (n = 26) ductal carcinoma in situ (DCIS) and 1.6% (n = 3) invasive ductal carcinoma (IDC). Upgrade to malignancy was less common in lesions <4 mm in size (0%) or with focal ADH (5%), and more common among lesions presenting with a radiographic mass (26%). Among the 35 patients who underwent AS, median follow-up was 20 months. Two lesions progressed on imaging (incidence 3.8% at 2 years). One patient without radiographic progression was found to have IDC at delayed surgery. The remaining lesions remained stable (46%), decreased in size (11%), or resolved (37%). CONCLUSIONS: Our findings suggest that AS is a safe approach to managing ADH on NCB for most patients. This could spare many patients with ADH from unnecessary surgery. Given that AS is being investigated for low-risk DCIS in multiple international prospective trials, these results suggest that AS should also be investigated for ADH.

Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy.

Black, compared to white, women with residual estrogen receptor-positive (ER+) breast cancer after neoadjuvant chemotherapy (NAC) have worse distant recurrence-free survival (DRFS). Such racial disparity may be due to difference in density of portals for systemic cancer cell dissemination, called TMEM doorways, and pro-metastatic tumor microenvironment (TME). Here, we evaluate residual cancer specimens after NAC from 96 Black and 87 white women. TMEM doorways are visualized by triple immunohistochemistry, and cancer stem cells by immunofluorescence for SOX9. The correlation between TMEM doorway score and pro-metastatic TME parameters with DRFS is examined using log-rank and multivariate Cox regression. Black, compared to white, patients are more likely to develop distant recurrence (49% vs 34.5%, p = 0.07), receive mastectomy (69.8% vs 54%, p = 0.04), and have higher grade tumors (p = 0.002). Tumors from Black patients have higher TMEM doorway and macrophages density overall (p = 0.002; p = 0.002, respectively) and in the ER+/HER2- (p = 0.02; p = 0.02, respectively), but not in the triple negative disease. Furthermore, high TMEM doorway score is associated with worse DRFS. TMEM doorway score is an independent prognostic factor in the entire study population (HR, 2.02; 95%CI, 1.18-3.46; p = 0.01), with a strong trend in ER+/HER2- disease (HR, 2.38; 95%CI, 0.96-5.95; p = 0.06). SOX9 expression is not associated with racial disparity in TME or outcome. In conclusion, higher TMEM doorway density in residual breast cancer after NAC is associated with higher distant recurrence risk, and Black patients are associated with higher TMEM doorway density, suggesting that TMEM doorway density may contribute to racial disparities in breast cancer.

Long-Term Maintenance of Projection of Nipples Reconstructed Using Three-Dimensionally Printed Poly-4-Hydroxybutyrate Bioabsorbable Scaffolds.

BACKGROUND: For patients who are unable to undergo nipple-sparing mastectomy, reconstruction of the nipple-areola complex has been shown to promote greater satisfaction in cosmetic outcome, body image, and sexual relationships. Although a variety of techniques have been developed to optimize the shape, size, and mechanical properties of the reconstructed nipple-areola complex, maintenance of sustained nipple projection over time remains a challenge for plastic surgeons. METHODS: Three-dimensionally printed poly-4-hydroxybutyrate (P4HB) scaffolds were designed and fabricated filled with either mechanically minced or zested patient-derived costal cartilage, designed with an internal P4HB lattice (rebar) to provide interior structure to foster tissue ingrowth, or left unfilled. All scaffolds were wrapped within a C-V flap on the dorsa of a nude rat. RESULTS: One year after implantation, neonipple projection and diameter were well preserved in all scaffolded groups compared with nonscaffolded neonipples ( P < 0.05). Histologic analysis showed significant vascularized connective tissue ingrowth at 12 months in both empty and rebar-scaffolded neonipples and fibrovascular cartilaginous tissue formation in mechanically processed costal cartilage-filled neonipples. The internal lattice promoted more rapid tissue infiltration and scaffold degradation and best mimicked the elastic modulus of the native human nipple after 1 year in vivo. No scaffolds extruded or caused any mechanical complications. CONCLUSIONS: Three-dimensionally printed biodegradable P4HB scaffolds maintain diameter and projection while approximating the histologic appearance and mechanical properties of native human nipples after 1 year with a minimal complication profile. These long-term preclinical data suggest that P4HB scaffolds may be readily translated for clinical application. CLINICAL RELEVANCE STATEMENT: The authors' unique, three-dimensionally printed P4HB scaffolds can be used to create custom nipple scaffolds that contour to any nipple shape and size, enabling the fabrication of tissue-engineered neonipples with significantly greater projection maintenance and closely approximating desired nipple biomechanical properties.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

Recognition Awards in Pathology Specialty Societies.

OBJECTIVES: Recognition awards build physician reputation and facilitate career advancement. We hypothesize women physicians are underrepresented as award recipients by pathology medical societies compared with representation in the specialty. METHODS: We analyzed publicly available online information about physician recipients (January 2015 to December 2021) from three general pathology society websites. Recipient gender was determined by pronoun use, first name, and photograph. Representation was compared with Association of American Medical Colleges (AAMC) specialty data from 2015 and 2019, which showed a minimum of 36.7% women pathologists in 2015 and up to 43.4% in 2019. RESULTS: Twenty-six awards and 230 physician recipients were included in the analysis. A total of 159 (69.1%) men physicians and 71 (30.9%) women physicians received awards. Overall, women physicians were underrepresented in recognition awards compared with AAMC benchmarks. Prestigious awards (defined as those that recognize a person's body of work over time) showed a similar disparity with 22 (30.1%) of 73 recipients being women. Men physicians were more likely to receive multiple awards. CONCLUSIONS: Women physicians are underrepresented overall for recognition awards by pathology medical societies. Disparities are greater for prestigious awards. Further research is needed to better understand the reasons for these findings and how they affect women physicians' careers.

Combining TMEM Doorway Score and MenaCalc Score Improves the Prediction of Distant Recurrence Risk in HR+/HER2- Breast Cancer Patients.

PURPOSE: to develop several digital pathology-based machine vision algorithms for combining TMEM and MenaCalc scores and determine if a combination of these biomarkers improves the ability to predict development of distant metastasis over and above that of either biomarker alone. METHODS: This retrospective study included a subset of 130 patients (65 patients with no recurrence and 65 patients with a recurrence at 5 years) from the Calgary Tamoxifen cohort of breast cancer patients. Patients had confirmed invasive breast cancer and received adjuvant tamoxifen therapy. Of the 130 patients, 86 cases were suitable for analysis in this study. Sequential sections of formalin-fixed paraffin-embedded patient samples were stained for TMEM doorways (immunohistochemistry triple staining) and MenaCalc (immunofluorescence staining). Stained sections were imaged, aligned, and then scored for TMEM doorways and MenaCalc. Different ways of combining TMEM doorway and MenaCalc scores were evaluated and compared to identify the best performing combined marker by using the restricted mean survival time (RMST) difference method. RESULTS: the best performing combined marker gave an RMST difference of 5.27 years (95% CI: 1.71-8.37), compared to 3.56 years (95% CI: 0.95-6.1) for the associated standalone TMEM doorway analysis and 2.94 years (95% CI: 0.25-5.87) for the associated standalone MenaCalc analysis. CONCLUSIONS: combining TMEM doorway and MenaCalc scores as a new biomarker improves prognostication over that observed with TMEM doorway or MenaCalc Score alone in this cohort of 86 patients.

Concordance in Breast Cancer Grading by Artificial Intelligence on Whole Slide Images Compares With a Multi-Institutional Cohort of Breast Pathologists.

CONTEXT.­: Breast carcinoma grade, as determined by the Nottingham Grading System (NGS), is an important criterion for determining prognosis. The NGS is based on 3 parameters: tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC). The advent of digital pathology and artificial intelligence (AI) have increased interest in virtual microscopy using digital whole slide imaging (WSI) more broadly. OBJECTIVE.­: To compare concordance in breast carcinoma grading between AI and a multi-institutional group of breast pathologists using digital WSI. DESIGN.­: We have developed an automated NGS framework using deep learning. Six pathologists and AI independently reviewed a digitally scanned slide from 137 invasive carcinomas and assigned a grade based on scoring of the TF, NP, and MC. RESULTS.­: Interobserver agreement for the pathologists and AI for overall grade was moderate (κ = 0.471). Agreement was good (κ = 0.681), moderate (κ = 0.442), and fair (κ = 0.368) for grades 1, 3, and 2, respectively. Observer pair concordance for AI and individual pathologists ranged from fair to good (κ = 0.313-0.606). Perfect agreement was observed in 25 cases (27.4%). Interobserver agreement for the individual components was best for TF (κ = 0.471 each) followed by NP (κ = 0.342) and was worst for MC (κ = 0.233). There were no observed differences in concordance amongst pathologists alone versus pathologists + AI. CONCLUSIONS.­: Ours is the first study comparing concordance in breast carcinoma grading between a multi-institutional group of pathologists using virtual microscopy to a newly developed WSI AI methodology. Using explainable methods, AI demonstrated similar concordance to pathologists alone.

3D-printed poly-4-hydroxybutyrate bioabsorbable scaffolds for nipple reconstruction.

Nearly all autologous tissue techniques and engineered tissue substitutes utilized for nipple reconstruction are hindered by scar contracture and loss of projection of the reconstructed nipple. The use of unprocessed costal cartilage (CC) as an internal support for the reconstructed nipple has not been widely adopted because of the excessively firm resultant construct. Herein we use a 3D-printed Poly-4-Hydroxybutyrate (P4HB) bioabsorbable scaffold filled with mechanically processed patient-derived CC to foster ingrowth of tissue in vivo to protect the regenerated tissue from contractile forces as it matures. After 6 months in vivo, newly formed spongy fibrovascular cartilaginous tissue was noted in processed CC filled 3D-printed scaffolds, which maintained significantly greater projection than reconstructions without scaffolds. Interestingly, 3D-printed P4HB scaffolds designed with an internal 3D lattice of P4HB filaments (without CC) displayed the fastest material absorption and vascularized adipose-fibrous tissue as demonstrated by SEM and histological analysis, respectively. Using 3D-printed P4HB scaffolds filled with either processed CC, a 3D P4HB lattice or no fills, we have engineered neo-nipples that maintain projection over time, while approximating the biomechanical properties of the native human nipple. We believe that this innovative 3D-printed P4HB nipple reconstruction scaffold will be readily translatable to the clinic. STATEMENT OF SIGNIFICANCE: Nearly all autologous tissue techniques and engineered tissue substitutes utilized for nipple reconstruction are hindered by scar contracture and substantial loss of projection of the reconstructed nipple, leading to significant patient dissatisfaction. Using 3D-printed P4HB scaffolds filled with either processed costal cartilage or 3D P4HB lattices, we have engineered neo-nipples that resist the forces induced by scar contracture, resulting in maintenance of neo-nipple projection over time and biomechanically approximating human nipples after 6 months in vivo implantation. This novel 3D-printed bioabsorbable P4HB scaffold will be readily translatable to the clinic to reconstruct nipples with patient-specific dimensions and long-lasting projection.

Mucocele-like Lesion of the Breast Diagnosed on Core Biopsy.

CONTEXT.­: Mucocele-like lesion of the breast (MLL) is an uncommon entity, and recent studies show low rates of upgrade from core needle biopsy (CNB) to excision. OBJECTIVE.­: To evaluate features associated with upgrade of MLLs diagnosed on CNB. DESIGN.­: Seventy-eight MLLs diagnosed on CNB from 1998-2019 and subsequent excisions were reviewed. Histologic parameters evaluated included the presence of atypia, presence and morphology of calcifications, and morphologic variant (classic [C-MLL], duct ectasia-like [DEL-MLL], or cystic mastopathy-like [CML-MLL]). RESULTS.­: Overall, 45 MLLs lacked atypia and 33 were associated with atypia (atypical ductal hyperplasia, 32; atypical lobular hyperplasia, 1). Most were C-MLLs (61) with fewer DEL-MLLs (14) and CML-MLLs (3). Half showed both coarse and fine calcifications, with fewer showing only coarse or fine calcifications, and some showing none. Subsequent excision or clinical follow-up was available for 25 MLLs without atypia-of which 2 (8.0%) were upgraded to ductal carcinoma in situ (DCIS)-and 23 with atypia, of which 4 (17.4%) were upgraded to DCIS. No cases were upgraded to invasive carcinoma. All upgraded cases showed coarse calcifications on CNB, and all upgraded cases were associated with residual calcifications on post-CNB imaging. CONCLUSIONS.­: Most MLLs present as calcifications and nearly half are associated with atypia. Upgrade to DCIS is twice as frequent in MLLs with atypia versus those without. A predominance of coarse calcifications and the presence of residual targeted calcifications following core biopsy may be associated with higher upgrade rates.

Subareolar Tissue Biopsy Predicts Occult Nipple Involvement in Nipple-Sparing Mastectomies.

OBJECTIVES: Subareolar tissue is examined during nipple-sparing mastectomy (NSM) to minimize the risk of occult malignancy within the preserved nipple. A positive subareolar tissue biopsy typically warrants subsequent nipple excision. We study the factors associated with a positive subareolar tissue biopsy, the rate of residual malignancy in subsequent nipple excisions, and the value of subareolar tissue biopsy intraoperative frozen section (IOF). METHODS: We identified 1,026 consecutive NSMs with separately submitted subareolar tissue biopsies over a 5.5-year period. Clinicopathologic data were reviewed. We examined concordance rates between subareolar tissue biopsy and subsequent nipple excisions as well as IOF diagnosis and permanent control diagnosis. RESULTS: Among cases of therapeutic NSM, the rate of a positive subareolar tissue biopsy was 7.2%. Multifocal/multicentric disease (P = .0005), presence of lymphovascular invasion (P = .033), and nodal involvement (P = .006) were significantly associated with a positive subareolar tissue biopsy. Thirty-nine of 41 cases with positive subareolar biopsies underwent subsequent nipple excision, with 20 (51%) showing residual carcinoma. Among all IOF samples, 9 (3.3%) showed a discrepancy between the IOF and permanent diagnoses, mostly because of false-negatives. CONCLUSIONS: A positive subareolar tissue biopsy predicts residual carcinoma in the excised nipples in 51% of cases. IOF is accurate and reliable.

Merkel cell carcinoma of the breast: A case report.

Merkel cell carcinoma (MCC) of the breast is a very rare and aggressive type of neuroendocrine carcinoma of the breast (NECB) that typically occurs in older and immunocompromised individuals often presenting as a large palpable mass (Albright et al., 20181). Imaging features of MCC are similar to other NECBs, typically appearing as an oval circumscribed mass on mammography and as an irregular mass with increased vascularity on sonography (Jeon et al., 20142). While both MCC and primary NECB demonstrate positive immunostaining for synaptophysin, obtaining immunohistochemical stains for specific markers, such as CK7 and CK20 is imperative to confirm the diagnosis of MCC (Albright et al., 20181). We present a case of a 57-year-old female patient with no personal or family history of breast cancer, who presented for evaluation of a palpable abnormality in her left breast. Initial diagnostic mammogram demonstrated a circumscribed mass in the upper outer quadrant of the left breast corresponding to the palpable area of concern, which correlated to an irregular mass with increased vascularity on targeted ultrasound, similar to other NECBs. Pathologic results after tissue sampling yielded poorly differentiated primary NECB. Following neoadjuvant chemotherapy, the patient underwent a lumpectomy and further immunohistochemical stains of the lumpectomy specimen demonstrated diffusely positive synaptophysin, negative CK7, and positive CK20, consistent with MCC of the breast.

Ink on the move: tattoo pigment resembling axillary lymph node calcifications.

High-density foci within axillary lymph nodes are associated with a number of potential diagnoses. In this case series, we present four tattooed patients who had mammographic findings that demonstrated high-density material in axillary lymph nodes, indicative of tattoo pigment migration. The aim of presenting these cases is to highlight the importance of recognizing such pigment migration in order to help breast radiologists form an appropriate differential diagnosis that might include this entity.

Investigation of triple-negative breast cancer risk alleles in an International African-enriched cohort.

Large-scale efforts to identify breast cancer (BC) risk alleles have historically taken place among women of European ancestry. Recently, there are new efforts to verify if these alleles increase risk in African American (AA) women as well. We investigated the effect of previously reported AA breast cancer and triple-negative breast cancer (TNBC) risk alleles in our African-enriched International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort. Using case-control, case-series and race-nested approaches, we report that the Duffy-null allele (rs2814778) is associated with TNBC risk (OR = 3.814, p = 0.001), specifically among AA individuals, after adjusting for self-indicated race and west African ancestry (OR = 3.368, p = 0.007). We have also validated the protective effect of the minor allele of the ANKLE1 missense variant rs2363956 among AA for TNBC (OR = 0.420, p = 0.005). Our results suggest that an ancestry-specific Duffy-null allele and differential prevalence of a polymorphic gene variant of ANKLE1 may play a role in TNBC breast cancer outcomes. These findings present opportunities for therapeutic potential and future studies to address race-specific differences in TNBC risk and disease outcome.

Radial Scars and Complex Sclerosing Lesions of the Breast: Prevalence of Malignancy and Natural History Under Active Surveillance.

BACKGROUND: When needle core biopsies (NCBs) of the breast reveal radial scar or complex sclerosing lesions (RSLs), excision is often recommended despite a low risk of malignancy in the modern era. The optimal management of NCBs revealing RSLs is controversial, and understanding of the natural history of unresected RSLs is limited. METHODS: We retrospectively analyzed pathology and imaging data from 148 patients with NCB revealing RSL without atypia from 2015 to 2019 to determine the prevalence of malignancy and the behavior of RSLs undergoing active surveillance (AS). RESULTS: The mean age of patients was 52 years, and most lesions were screen-detected (91%). The median lesion size was 6.0 mm (range 2-39). Most patients (66%, n = 98) underwent immediate surgery, while 34% (n = 50) of patients underwent AS, with a median follow-up of 16 months (range 6-51). Of the excised RSLs, 99% (n = 97) were benign and 1% (n = 1) revealed ductal carcinoma in situ (DCIS). In 17% (n = 17) of cases, additional high-risk lesions were discovered upon excision. Among the 50 patients undergoing AS, no lesions progressed on interval imaging. CONCLUSIONS: In this cohort, 99% of RSLs undergoing excision were benign, 1% revealed DCIS, and there were no invasive cancers. In the first study of patients with RSLs undergoing AS, we found that all lesions either remained stable or resolved. We propose that the vast majority of patients with RSL on NCB can be safely offered AS, and that routine excision is a low-value intervention.

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.