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Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation.

The definition of "no tumor on ink" is generally applied for clear resection margin (RM) after breast-conserving surgery (BCS). However, few studies reported the effect of RM in the setting of neoadjuvant chemotherapy (NAC). We investigated the association between RM status and survival outcomes for those who underwent BCS after NAC for breast cancer.We retrospectively reviewed the data of 2,803 patients who underwent BCS and whole-breast irradiation after NAC between January 2008 and December 2016 from three institutions in South Korea.The 786 patients in the pathologic complete response group (RClear RM of specimen does not have benefit on LRFS after NAC. Additionally, for the patients showing pCR with residual DCIS in the breast, margin involvement also did not affect the risk of local recurrence.

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive carcinoma. Multiple studies have shown that DCIS lesions typically possess a driver mutation associated with cancer development. Mutation in the TP53 tumour suppressor gene is present in 15-30% of pure DCIS lesions and in ~30% of invasive breast cancers. Mutations in TP53 are significantly associated with high-grade DCIS, the most likely form of DCIS to progress to invasive carcinoma. In this review, we summarise published evidence on the prevalence of mutant TP53 in DCIS (including all DCIS subtypes), discuss the availability of mouse models for the study of DCIS and highlight the need for functional studies of the role of TP53 in the development of DCIS and progression from DCIS to invasive disease.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visitNCCN.org.

INTRODUCTION: Apocrine carcinoma, a cancer of sweat glands, is very rare, with a global incidence of 0.0049 to 0.0173 cases per 100,000 persons annually. It is usually found in axilla and anogenital areas. The intraductal apocrine variety of salivary duct carcinoma in the parotid gland is very rare and aggressive and may be due to ectopic sweat glands in the parotid gland duct or metaplastic change of the salivary duct epithelium. It usually presents in an advanced stage. Even though surgery is the standard of care in most head and neck cancers, there are no standard guidelines for the treatment of intraductal apocrine parotid carcinoma, which is different from other head and neck cancers due to its rare incidence, aggressive behavior, and poor prognosis. CASE PRESENTATION: We present a rare case of intraductal apocrine salivary duct carcinoma of the left parotid gland, presented in a locally advanced stage with very high chances of recurrence after surgery, and discuss the role of volumetric modulated arc technique radiotherapy in its management. CONCLUSION: Intraductal apocrine salivary duct carcinoma usually has androgen receptor expression, and lack of expression is associated poor prognosis. Even with complete resection, it has a high recurrence rate. Volumetric modulated arc technique radiotherapy (VMAT) decreases recurrence and increases survival by irradiating the areas more likely of recurrence, with minimal toxicity to surrounding normal tissues.

Aims: Invasive cribriform and intraductal carcinoma (IDC) are associated with adverse outcome in prostate cancer patients, with the large cribriform pattern having the worst outcome in radical prostatectomies. Our objective was to determine the impact of the large and small cribriform patterns in prostate cancer biopsies. Methods and results: Pathological revision was carried out on biopsies of 1887 patients from the European Randomised Study of Screening for Prostate Cancer. The large cribriform pattern was defined as having at least twice the size of adjacent benign glands. The median follow-up time was 13.4 years. Hazard ratios for metastasis-free survival (MFS) and disease-specific survival (DSS) were calculated using Cox proportional hazards regression. Any cribriform pattern was found in 280 of 1887 men: 1.1% IDC in grade group (GG) 1, 18.2% in GG2, 57.1% in GG3, 55.4% in GG4 and 59.3% in GG5; the large cribriform pattern was present in 0, 0.5, 9.8, 18.1 and 17.3%, respectively. In multivariable analyses, small and large cribriform patterns were both (P < 0.005) associated with worse MFS [small: hazard ratio (HR) = 3.04, 95% confidence interval (CI) = 1.93–4.78; large: HR = 3.17, 95% CI = 1.68–5.99] and DSS (small: HR = 4.07, 95% CI = 2.51–6.62; large: HR = 4.13, 95% CI = 2.14–7.98). Patients with the large cribriform pattern did not have worse MFS (P = 0.77) or DSS (P = 0.96) than those with the small cribriform pattern. Conclusions: Both small and large cribriform patterns are associated with worse MFS and DSS in prostate cancer biopsies. Patients with the large cribriform pattern on biopsy have a similar adverse outcome as those with the small cribriform pattern.

The clinical significance of intraductal carcinoma of the prostate (IDC-P) in men with nonmetastatic prostate cancer (PCa) treated with high-dose external-beam radiation therapy remains unclear. The aim of this study was to evaluate the impact of IDC-P in men who received intensity-modulated radiation therapy (IMRT) for nonmetastatic PCa. All patients with high-risk (H-R) and very high–risk (VH-R) PCa who received IMRT between September 2000 and December 2013 at our institution were analyzed retrospectively. We re-reviewed biopsy cores for the presence of IDC-P. Treatment consisted of IMRT (median: 78 Gy at 2 Gy per fraction) plus 6-month neoadjuvant hormonal therapy (HT). In total, 154 consecutive patients with H-R and VH-R PCa were analyzed. Intraductal carcinoma of the prostate was present in 27.9% (n = 43). The median follow-up period was 8.4 years. The 10-year PCa-specific survival, biochemical failure (BF), clinical failure, and castration-resistant PCa rates were 90.0%, 47.8%, 27.5%, and 24.5% in patients with IDC-P, and 96.6%, 32.6%, 10.8%, and 7.0% in those without IDC-P, respectively (p = 0.12, 0.04, 0.0031, and 0.012, respectively). In multivariable analysis, IDC-P was not identified as an independent predictive factor for BF (p = 0.26). The presence of IDC-P was correlated with a significantly higher incidence of disease progression in men with H-R and VH-R PCa who received IMRT, although it was not identified as an independent predictive factor for BF. Further investigations are needed to determine the significance of IDC-P as an independent predictive factor for survival outcomes.

INTRODUCTION: As breast cancer treatment options have multiplied and biologic diversity within breast cancer has been recognized, the use of the same treatment strategies for patients with early-stage and favorable disease, and for those with biologically aggressive disease, has been questioned. In addition, as patient-reported outcome measures have called attention to the morbidity of many common treatments, and as the cost of breast cancer care has continued to increase, reduction in the overtreatment of breast cancer has assumed increasing importance. AREAS COVERED: Here we review selected aspects of surgery, radiation oncology, and medical oncology for which scientific evidence supports de-escalation for invasive carcinoma and ductal carcinoma in situ, and assess strategies to address overtreatment. EXPERT OPINION: The problems of breast cancer overtreatment we face today are based on improved understanding of the biology of breast cancer and abandonment of the “one-size-fits-all” approach. As breast cancer care becomes increasingly complex, and as our knowledge base continues to increase exponentially, these problems will only be magnified in the future. To continue progress, the move must be made from advocating the maximum-tolerated treatment to advocating the minimum-effective one.

Although great effort has been expended to understand cancer’s origins, less attention has been given to the primary cause of cancer deaths—cancer recurrences and their sequelae. This interdisciplinary review addresses mechanistic features of aggressive cancer by studying metabolic enzyme patterns within ductal carcinoma in situ (DCIS) of the breast lesions. DCIS lesions from patients who did or did not experience a breast cancer recurrence were compared. Several proteins, including phospho-Ser226-glucose transporter type 1, phosphofructokinase type L and phosphofructokinase/fructose 2,6-bisphosphatase type 4 are found in nucleoli of ductal epithelial cells in samples from patients who will not subsequently recur, but traffic to the cell periphery in samples from patients who will experience a cancer recurrence. Large coclusters of enzymes near plasmalemmata will enhance product formation because enzyme concentrations in clusters are very high while solvent molecules and solutes diffuse through small channels. These structural changes will accelerate aerobic glycolysis. Agglomerations of pentose phosphate pathway and glutathione synthesis enzymes enhance GSH formation. As aggressive cancer lesions are incomplete at early stages, they may be unrecognizable. We have found that machine learning provides superior analyses of tissue images and may be used to identify biomarker patterns associated with recurrent and nonrecurrent patients with high accuracy. This suggests a new prognostic test to predict patients with DCIS who are likely to recur and those who are at low risk for recurrence. Mechanistic interpretations provide a deeper understanding of anticancer drug action and suggest that aggressive metastatic cancer cells are sensitive to reductive chemotherapy.

Purpose Most studies regarding the value of post lumpectomy imaging (PLI) studies rely on mammography alone and are often focused on patients that present with suspicious microcalcifications or in situ disease. This way, its true benefit remains controversial, which explained the heterogeneity between centers. This is the first study to evaluate the role of mammography with breast and axillary ultrasound undertaken before radiotherapy in patients with conservatively managed invasive and/or in situ carcinoma with negative margins. Materials and Methods In this retrospective study, medical records for patients referred to our External Radiotherapy Unit between January 2018 and December 2019 were reviewed. Results A total of 1251 patients (1262 breasts) were analyzed. A total of 3.4% had suspicious findings for local residual breast disease, with 1.0% having a re-excision positive for residual malignancy. Presentation with microcalcifications alone (OR = 4.854), extension of microcalcifications > 3 cm (OR = 13.500), histologic subtype pure ductal carcinoma in situ (OR = 12.348), presence of invasive carcinoma ≤ 1 mm of the pathological margins (OR = 4.630), stage pTis (5.630), and absence of invasive component (OR = 4.629), were associated with an increased risk for residual malignancy. Only one patient (0.1%) had nodal residual involvement. Conclusion PLI detected residual local cancer in 1.0% of the patients. PLI plays an important role in the evaluation of patients undergoing breast-conserving therapy with negative margins. The major question that remains is whether it changes survival outcomes.

Background Low nuclear grade ductal carcinoma in situ (DCIS) identified at biopsy can be upgraded to intermediate to high nuclear grade DCIS at surgery. Methods that confirm low nuclear grade are needed to consider nonsurgical approaches for these patients. Purpose To develop a preoperative model to identify low nuclear grade DCIS and to evaluate factors associated with low nuclear grade DCIS at biopsy that was not upgraded to intermediate to high nuclear grade DCIS at surgery. Materials and Methods In this retrospective study, 470 women (median age, 50 years; interquartile range, 44-58 years) with 477 pure DCIS lesions at surgical histopathologic evaluation were included (January 2010 to December 2015). Patients were divided into the training set (

Introduction Breast density is an independent risk factor for the development of breast cancer. We assessed if upgrade rates to high-risk lesions and cancer were influenced by density when evaluating proliferative complex sclerosing lesions and intraductal papillomas. Methods This is a retrospective single institution study. We evaluated 168 women aged 18-86 who received a core needle biopsy revealing a breast proliferative lesion of complex sclerosing lesion (CSL) or intraductal papilloma. We analyzed the upgrade rate to high-risk atypia (HRL) and cancer. Subgroup analysis based on age and breast density was performed. Results The patient collective was well balanced—51% had dense breasts and 42% were under 50 years old. Half were diagnosed with papilloma based on CNB and the other half with CSL. For those proliferative lesions without atypia, the upgrade rate to cancer was 1.6%. CNB showed concomitant HRL in 23% of patients with non-dense breasts and in 22% with dense tissue. In 24 cases, the pathology was considered an upgrade by showing either a not prior noted HRL or carcinoma. Most patients with upgrade following surgical excision were over 50 years old. Dense breasts did not show a higher risk of upgrade following surgical excision ( P = .975). Conclusion Our data did not reveal a difference between upgrade rates of proliferative lesions excised in dense and non-dense breasts. Further evaluation is warranted to establish whether density should be considered as a meaningful factor in excision vs observation of CSL and papillomas.

Cancer cells can disseminate during very early and sometimes asymptomatic stages of tumor progression. Though biological barriers to tumorigenesis have been identified and characterized, the mechanisms that limit early dissemination remain largely unknown. We report here that the orphan nuclear receptor nuclear receptor subfamily 2, group F, member 1 (NR2F1)/COUP-TF1 serves as a barrier to early dissemination. NR2F1 expression was decreased in patient ductal carcinoma in situ (DCIS) samples. High-resolution intravital imaging of HER2+ early-stage cancer cells revealed that loss of function of NR2F1 increased in vivo dissemination and was accompanied by decreased E-cadherin expression, activation of wingless-type MMTV integration site family, member 1 (WNT)-dependent β-catenin signaling, disorganized laminin 5 deposition, and increased expression of epithelial–mesenchymal transition (EMT) genes such as twist basic helix-loop-helix transcription factor 1 (TWIST1), zinc finger E-box binding homeobox 1 (ZEB1), and paired related homeobox 1 (PRRX1). Furthermore, downregulation of NR2F1 promoted a hybrid luminal/basal phenotype. NR2F1 expression was positively regulated by p38α signaling and repressed by HER2 and WNT4 pathways. Finally, early cancer cells with NR2F1LOW/PRRX1HIGH staining were observed in DCIS samples. Together, these findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 in early-stage breast cancer cells. Significance: During early stages of breast cancer progression, HER2-mediated suppression of NR2F1 promotes dissemination by inducing EMT and a hybrid luminal/basal-like program.

The mechanism of transition of ductal carcinoma in situ (DCIS) to invasive cancer is elusive but recently changes in the myoepithelial cells (MECs) have been implicated. The aim of this study is to investigate the changes in gene profile of MECs in DCIS that could compromise their tumor suppressor function leading to promotion of tumor progression. Immuno-laser capture microdissection (LCM) was used to isolate MECs from normal and DCIS breast tissues followed by whole genome expression profiling using Affymetrix HGU-133 plus2.0 arrays. The data were analyzed using Bioconductor packages then validated by using real-time quantitative polymerase chain reaction and immunohistochemistry. Ingenuity Pathways software analysis showed clustering of most of the altered genes in cancer and cell death networks, with the Wnt/B-catenin pathway as the top canonical pathway. Validation revealed a 71.4% correlation rate with the array results. Most dramatic was upregulation of Fibronectin 1 ( FN1 ) in DCIS-associated MECs. Immunohistochemistry analysis for FN1 on normal and DCIS tissues confirmed a strong correlation between FN1 protein expression by MECs and DCIS ( P0.0001) and between high expression level and presence of invasion ( P =0.006) in DCIS. Other validated alterations in MEC expression profile included upregulation of Nephronectin and downregulation of parathyroid hormone like hormone ( PTHLH ), fibroblast growth factor receptor 2 ( FGFR2 ), ADAMTS5 , TGFBR3 , and CAV1 . In vitro experiments revealed downregulation of PTHLH in DCIS-modified MECs versus normal lines when cultured on Fibronectin matrix. This is the first study to use this in vivo technique to investigate molecular changes in MECs in DCIS. This study adds more evidences to the molecular deviations in MECs toward tumor progression in DCIS through upregulation of the tumor-promoting molecules that may lead to novel predictive and therapeutic targets.

MicroRNAs (miRNAs) control diverse biologic processes during tumor progression. This study was conducted to identify miRNAs that are implicated in progression of in situ to invasive breast cancer (IBC) and to evaluate their association with clinicopathological features of ductal carcinoma in situ (DCIS).We performed miRNA microarray analyses to find differentially expressed miRNAs between DCIS and IBC in a test set, and validated expression levels of selected miRNAs using a different set of tumors. Finally, we evaluated the relationship between clinicopathological features and the expression of selected miRNAs in DCIS samples.We found that miR-145-5p, miR-205-5p and miR-451a are significantly down-regulated in IBC compared to DCIS in the whole group, and in the estrogen receptor (ER)-positive and ER-negative subgroups. In a validation set, miR-145, miR-205, and miR-451 also showed lower expression levels in IBC than in DCIS, irrespective of ER status. Moreover, their expression levels were significantly lower in the invasive component compared to the in situ component within same tumors. MiR-145, miR-205 and miR-451 commonly showed lower expression levels in DCIS with positive HER2 status and high Ki-67 proliferation index. Especially, miR-145 and miR-205 showed lower expression levels in DCIS with microinvasion, compared to pure DCIS. In addition, lower miR-205 expression level was associated with high nuclear grade, comedo type necrosis, and hormone receptor negativity.Our study showed that miR-145, miR-205 and miR-451 expression decreased in IBC compared to DCIS, and their expression levels were low in DCIS with high-risk features for progression, implying their contributions in the progression of DCIS to invasive carcinoma as tumor suppressors.

Background: Higher circulating levels of vitamin D [25(OH)D] have been associated with reduced risk of developing invasive breast cancer. However, their association with risk of ductal carcinoma in situ (DCIS) of the breast has received little attention. Methods: We examined the association of serum vitamin D with risk of DCIS in 231,203 women, aged 40 to 69 years at enrollment in the UK Biobank cohort study. Multivariable Cox proportional hazards models were used to estimate HRs and 95% confidence intervals for the association of vitamin D with DCIS risk. Results: There was no association between serum 25(OH)D levels and risk of DCIS overall, or by menopausal status. The association was not modified by body mass index category, family history of breast cancer, or current use of menopausal hormone therapy. Conclusions: In this large prospective cohort study, we did not observe an association between circulating serum levels of vitamin D and risk of DCIS. Impact: While previous studies have suggested that serum vitamin D has an inverse association with risk of invasive breast cancer, the present results do not provide evidence for an association with DCIS, a non-obligate precursor of invasive disease.

Published MarginProbe (Dune Medical Devices Ltd., Israel) data reports ≥50% reduction in positive lumpectomy margins. We sought to determine whether adjunctive use of MarginProbe would provide value over intraoperative pathologic assessment alone.This is a retrospective chart review of 86 consecutive lumpectomies with MarginProbe from December 2018 to November 2019. Margins were considered positive using 'no ink on tumor' guideline for invasive cancer, and 2 mm or greater for ductal carcinoma in-situ. Significance was measured using Fisher's exact test.Seventy-six patients yielded 86 lumpectomies for inclusion. Mean age was 69.8 and mean tumor size was 1.09 cm. Sixty-eight invasive cancers were assessed using adjunct MarginProbe and gross assessment, while 18 ductal carcinoma in-situ cases utilized MarginProbe only. Among all cases, gross assessment alone reduced positive margins(29.2% relative reduction, p = 0.28). Utilizing both modalities, positive margins decreased from 27.9% to 9.3% (66.7% relative reduction, p 0.01) representing a 46.9% relative reduction versus gross assessment alone. After gross assessment and MarginProbe evaluation, additional excised volume averaged 2.9 cc.Synergistic use of MarginProbe and gross assessment reduces positive margins during breast conserving surgery. Surgeons can weigh its cost against it benefit with the succinct analysis we provide.

BACKGROUND: Improving diagnosis of ductal carcinoma in situ (DCIS) before surgery is important in choosing optimal patient management strategies. However, patients may harbor occult invasive disease not detected until definitive surgery. PURPOSE: To assess the performance and clinical utility of mammographic radiomic features in the prediction of occult invasive cancer among women diagnosed with DCIS on the basis of core biopsy findings. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act–compliant retrospective study, digital magnification mammographic images were collected from women who underwent breast core-needle biopsy for calcifications that was performed at a single institution between September 2008 and April 2017 and yielded a diagnosis of DCIS. The database query was directed at asymptomatic women with calcifications without a mass, architectural distortion, asymmetric density, or palpable disease. Logistic regression with regularization was used. Differences across training and internal test set by upstaging rate, age, lesion size, and estrogen and progesterone receptor status were assessed by using the Kruskal-Wallis or χ(2) test. RESULTS: The study consisted of 700 women with DCIS (age range, 40–89 years; mean age, 59 years ± 10 [standard deviation]), including 114 with lesions (16.3%) upstaged to invasive cancer at subsequent surgery. The sample was split randomly into 400 women for the training set and 300 for the testing set (mean ages: training set, 59 years ± 10; test set, 59 years ± 10; P = .85). A total of 109 radiomic and four clinical features were extracted. The best model on the test set by using all radiomic and clinical features helped predict upstaging with an area under the receiver operating characteristic curve of 0.71 (95% CI: 0.62, 0.79). For a fixed high sensitivity (90%), the model yielded a specificity of 22%, a negative predictive value of 92%, and an odds ratio of 2.4 (95% CI: 1.8, 3.2). High specificity (90%) corresponded to a sensitivity of 37%, positive predictive value of 41%, and odds ratio of 5.0 (95% CI: 2.8, 9.0). CONCLUSION: Machine learning models that use radiomic features applied to mammographic calcifications may help predict upstaging of ductal carcinoma in situ, which can refine clinical decision making and treatment planning. © RSNA, 2022

Objective The presence of an extensive intraductal component is associated to an increasing risk of relapse in the nipple-areola complex. The aim of the present study was to evaluate the outcomes of patients diagnosed with ductal carcinoma in situ (DCIS) who underwent nipple-sparing mastectomy (NSM) with immediate breast reconstruction using silicone implants. Methods We retrospectively analyzed the postoperative complications and oncological safety of 67 breast cancer patients diagnosed with pure DCIS who underwent NSM with immediate breast reconstruction using silicone implants between 2004 and 2018. Results Among the 127 NSM procedures performed, 2 hematomas (1.5%) and 1 partial nipple necrosis (0.7%) were observed. After a mean follow-up of 60months, the local recurrence rate was of 8.9%, the disease-free survival rate was of 90%, and 1 of the patients died. Conclusion Despite the local recurrence rate, we showed that NSM with immediate breast reconstruction using silicone implants is a feasible surgical approach, with a low rate of complications and high survival rates for patients with a diagnosis of pure DCIS when breast-conserving surgery is not an option. Resumo Objetivo A presença de componente intraductal extenso é associada ao risco aumentado de recorrência no complexo aréolo-mamilar. O objetivo deste estudo foi avaliar os resultados de pacientes diagnosticados com carcinoma ductal in situ (CDIS)submetidas a adenomastectomia (nipple-sparing mastectomy, NSM, em inglês) com reconstrução mamária imediata utilizando prótese de silicone. Métodos Restrospectivamente, foramanalisadas as complicações pós-operatórias e a segurança oncológica de 67 pacientes com câncer de mama diagnosticadas com CDIS puro, e submetidas a NSM com reconstrução mamária imediata utilizando prótese de silicone, entre 2004 e 2018. Resultados Entre os 127 procedimentos realizados, 2 hematomas (1,5%) e 1 necrose parcial de mamilo (0,7%) foram observados. Após um período médio de 60 meses de seguimento, a taxa de recorrência local foi de 8,9%, a sobrevida livre de doença, de 90%, e apenas 1 paciente foi a óbito. Conclusão Apesar da taxa de recorrência local, demostrou-se que NSM com reconstrução mamária imediata comprótese de silicone é umprocedimento viável, combaixa taxa de complicação e alta sobrevida para pacientes com diagnóstico de CDIS puro quando a cirurgia conservadora da mama não é uma opção.

Between 8% and 56% of pure ductal carcinoma in situ are upstaged to microinvasive or invasive carcinoma on definitive pathological examination. The first objective of this study was to perform a comprehensive review of the literature on factors associated with increased risk of pre-operative underestimation. The second objective was to perform an external validation of the predictive models developed to enable their use in daily practice if relevant.A literature search using Medline was undertaken. For each model selected, external validation within the study cohort was undertaken. The study cohort consisted of patients with histologically proven ductal carcinoma in situ who underwent surgical treatment at a French referral centre for cancer treatment between January 2007 and November 2018.Two hundred and thirteen articles were identified; of these, 34 articles focused on factors associated with pre-operative underestimation of invasive carcinoma, 11 studies were identified as predictive models, and three studies were selected for external validation within the study cohort. Four hundred and eighty-eight eligible patients were identified in the study cohort, with an underestimation rate of 9.2%. The Jakub nomogram concordance index was 0.45 [95% confidence interval (CI) 0.39-0.51], the Park nomogram concordance index was 0.57 (95% CI 0.48-0.55), and the Coufal nomogram concordance index was 0.52 (95% CI 0.48-0.55).While the literature is rich on this topic, this review clearly highlights the lack of consensus regarding parameters associated with underestimation. It was not possible to validate previously published models for use in daily practice.

Background Radial scars (RS) and complex sclerosing lesions (CSL) are breast radiologic findings described as small, stellate lesions causing architectural distortion. This can mimic malignancy. Core needle biopsy (CNB) is often performed. Advances in breast imaging have led to increased detection of RS/CSL. The upstage rate of RS/CSL to in situ or invasive disease is 0-40%. We sought to determine the upstaging rate of RS/CSL to in situ, invasive disease, or high-risk lesion at our institution to create excision guidelines. Methods The pathology database of a single center was searched for RS/CSL, from January 2013 to September 2020. We included CNB without malignancy or high-risk lesion (eg, atypical ductal hyperplasia). Patient demographics, indications for biopsy, imaging findings, biopsy procedure, and final pathology were collected. Results Forty-four patients were included. 52.3% had CNB for architectural distortion on mammography, 18.2% for mass, 11.4% for calcifications, 2.3% for abnormal MRI, and 15.9% for multiple reasons (eg, calcifications and mass). Most had an ultrasound: 43.2% had no abnormality and 34.1% had a mass. All CNB were vacuum assisted, 65.9% with 9-gauge needle, and averaged 10.0 cores. 77.3% were stereotactic biopsies, 13.6% ultrasound, and 6.8% MRI. 59.1% had excision after CNB. 82.1% of patients did not upstage. One patient upstaged to invasive ductal carcinoma (3.6%) and two patients to high-risk lesion (7.1%). Discussion There was low upstage rate of RS/CSL on excisional biopsy. Centers could consider close surveillance for RS/CSL on CNB. Longer follow-up in cases of deferred excision is needed to ensure oncologic safety.

Objective Our purpose is to evaluate the correlation of TILs with clinicopathological characteristics and disease free survival (DFS) in DCIS and DCIS-Mi breast cancer (BC) patients. Methods We retrospectively reviewed the data of 360 DCIS patients and 125 DCIS-Mi patients treated by a single institution from 2016 to 2019. TILs are regarded as continuous variables and are divided into low (≤ 5%), medium (5–40%) and high (≥ 40%) for statistical analysis. Results In DCIS and DCIS-Mi patients, larger tumor size, higher nuclear grade, hormone receptor (HR) negativity and human epidermal growth factor receptor 2(HER2) overexpression are all related to high TILs (P P P = 0.015) and high TILs (P = 0.002) compared with DCIS patients. In the survival analysis, we found that TILs had no effect on the DFS of DCIS (P = 0.938), DCIS-Mi (P = 0.807), and HER2+ (P = 0.379) BC patients. In the univariate and multivariate cox regression analysis, the correlation between TILs and the prognosis of DFS has not been confirmed in the three BC groups (P > 0.05). Conclusion TILs have played an non-negligible role in the progress of DCIS to DCIS-Mi, especially in HER2+ BC. The predictive and prognostic value of TILs still needs further research to confirm.

Randomized data support accelerated partial breast irradiation (APBI) for early-stage breast cancer with variable techniques and cosmesis outcomes. We have treated patients with 5-fraction prone external beam APBI for over a decade and herein report acute and late outcomes.Patients receiving APBI 600 cGy × 5 between 2010 and 2019 were included. APBI was primarily delivered prone, with opposed tangents targeting the tumor bed expanded by 1.5 cm (cropped 6 mm from skin). Ipsilateral breast was constrained to V50%60% and V100%35%. Survival was estimated with Kaplan-Meier. Late toxicities and clinician- and patient-rated cosmesis were evaluated for patients with6 months follow-up (FU).Of 345 patients meeting criteria, 14 were excluded due to APBI given for ipsilateral breast tumor recurrence (IBTR; n = 3), palliation (n = 9), and incomplete radiation therapy course (n = 2). Of the 331 remaining, median age was 70, 7.2% had ductal carcinoma in situ, and 94.3% were treated prone, with 32% treated every other day and 68% on consecutive days. Mean heart dose was 23.8 cGy for left-sided and 12.7 cGy for right-sided cancers. Ipsilateral lung V30% was 0.4%. At 5-year median FU, there were 7 (2.1%) IBTR, 9 (2.7%) contralateral recurrences, and 1 (0.3%) distant metastasis. Five-year local recurrence-free, disease-free, and overall survival was 99.5%, 96.7%, and 98.1%, respectively. When comparing patients with IBTR versus without, a higher proportion did not receive hormone therapy (71.4% vs. 26.2%, P = .018). Rates of acute grade 1 to 2 dermatitis, fatigue, and pain were 35.4%, 21.8%, and 9.4%, respectively, with no grade 3 toxicity. The rate of good-excellent physician- and patient-rated cosmesis (n = 199, median FU 2.8 years) was 92.5% and 89.4%, respectively. Patients experienced low rates of telangiectasia, fibrosis, and retraction/atrophy.We report excellent dosimetric, oncologic, cosmetic, and late toxicity outcomes for patients treated with 5-fraction APBI. To our knowledge this is the largest series of women treated with prone APBI.

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%.

Omission of PORT following BCS remains high among rural patients despite evidence that PORT leads to a significant reduction in the risk of local recurrence. Further research is needed to examine the impact of rural residence on treatment choices and develop methods to ensure equitable care among all breast cancer patients.Despite national guidelines, debate exists among clinicians regarding the optimal approach to treatment for patients diagnosed with ductal carcinoma in situ (DCIS). While regional variation in practice patterns has been well documented, population-based information on rural-urban treatment differences is lacking.Data from the SEER Patterns of Care studies were used to identify women diagnosed with histologically confirmed DCIS who underwent cancer-directed surgery in the years 1991, 1995, 2000, 2005, 2010, and 2015. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using weighted multivariable logistic regression to evaluate cancer-directed surgery and use of post-operative radiation therapy (PORT).Of the 3337 patients who met inclusion criteria, 27% underwent mastectomy, 26% underwent breast-conserving surgery (BCS) without PORT, and 47% underwent BCS with PORT. After adjustment for other covariates, there was no difference in the likelihood of receiving mastectomy between rural and urban patients (aOR = 0.65; 95% CI 0.37-1.14). However, rural residents were more likely than urban residents to have mastectomy during 1991/1995 (aOR = 1.78; 95% CI 1.09-2.91; pOmission of PORT following BCS remains high among rural patients despite evidence that PORT leads to a significant reduction in the risk of local recurrence. Further research is needed to examine the impact of rural residence on treatment choices and develop methods to ensure equitable care among all breast cancer patients.

Background Population breast screening services in England were suspended in March 2020 due to the COVID-19 pandemic. Here, we estimate the number of breast cancers whose detection may be delayed because of the suspension, and the potential impact on cancer deaths over 10 years. Methods We estimated the number and length of screening delays from observed NHS Breast Screening System data. We then estimated additional breast cancer deaths from three routes: asymptomatic tumours progressing to symptomatically diagnosed disease, invasive tumours which remain screen-detected but at a later date, and ductal carcinoma in situ (DCIS) progressing to invasive disease by detection. We took progression rates, prognostic characteristics, and survival rates from published sources. Results We estimated that 1,489,237 women had screening delayed by around 2–7 months between July 2020 and June 2021, leaving 745,277 outstanding screens. Depending on how quickly this backlog is cleared, around 2500–4100 cancers would shift from screen-detected to symptomatic cancers, resulting in 148–452 additional breast cancer deaths. There would be an additional 164–222 screen-detected tumour deaths, and 71–97 deaths from DCIS that progresses to invasive cancer. Conclusions An estimated 148–687 additional breast cancer deaths may occur as a result of the pandemic-related disruptions. The impact depends on how quickly screening services catch up with delays.

PURPOSE: Patients diagnosed with ductal carcinoma in situ (DCIS) face trade-offs when deciding among different treatments, including surgery, radiation, and endocrine therapy. A less chosen option is active monitoring. While evidence from clinical trials is not yet available, observational studies show comparable results for active monitoring and immediate treatment on cancer outcomes in select subgroups of patients. We developed and tested a web-based decision support tool (DST) to help patients explore current knowledge about DCIS and make an informed choice. METHODS: The DST, an interactive web application, was informed by literature reviews and formative work with patients, breast surgeons, and health communication experts. We conducted iterative interviews to evaluate the DST content among women with and without a history of breast cancer, as well as breast cancer experts. For usability testing, we conducted an online survey among women with and without a history of breast cancer. RESULTS: For content evaluation, 5 women with and 10 women without a history of DCIS were interviewed. The sample included 11 White and 4 non-White women, with a mean age of 64 years. The expert sample consisted of 5 attendings and a physician assistant. The feedback was used to add, clarify, or reorganize information in the DST. For usability testing, 22 participants with a mean age of 61 years were recruited including 15 White and 7 Black women and 6 women with a history of DCIS. The mean usability score was 3.7 out of 5. Most participants (86%) found that the DST provided unbiased information about treatments. To improve usability, we reduced the per-page content and added navigation cues. CONCLUSION: Content and usability evaluation showed that the DST helps patients explore trade-offs of active monitoring and immediate treatment. By adopting a personalized approach, the tool will enable informed decisions aligned with patients’ values and expectations.

Ductal carcinoma in situ (DCIS) often upgrade to invasive breast cancer at surgery. The current study aimed to identify factors associated with pathological underestimation and evaluate concordance rates of biomarkers between biopsy and surgery. Patients diagnosed with DCIS at needle biopsy from 2009 to 2020 were retrospectively reviewed. Univariate and multivariate analyses were performed to identify factors associated with pathological underestimation. Concordance rates between paired biopsy samples and surgical specimens were evaluated. A total of 735 patients with pure DCIS at biopsy were included, and 392 patients (53.3%) underwent pathological underestimation at surgery. Multivariate analysis demonstrated that tumor size > 5.0 cm [odds ratio (OR) 1.79], MRI BI-RADS ≥ 5 categories (OR 2.03), and high nuclear grade (OR 2.01) were significantly associated with pathological underestimation. Concordance rates of ER, PR, HER2 status and Ki-67 between biopsy and surgery were 89.6%, 91.9%, 94.8%, and 76.4% in lesions without pathological underestimation, and were 86.4%, 93.2%, 98.2% and 76.3% for in situ components in lesions with pathological underestimation. Meanwhile, in situ components and invasive components at surgery had concordance rates of 92.9%, 93.8%, 97.4%, and 86.5% for those biomarkers, respectively. In conclusion, lesions diagnosed as DCIS at biopsy have a high rate of pathological underestimation, which was associated with larger tumor size, higher MRI BI-RADS category, and higher nuclear grade. High concordances were found in terms of ER, PR, and HER2 status evaluation between biopsy and surgery, regardless of the pathological underestimation.

Ductal carcinoma in-situ (DCIS) often coexists with invasive ductal carcinoma (IDC) of the breast. DCIS is considered as a non-obligate precursor of IDC when both coexist. 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) imaging is commonly used in the staging and follow-up assessment of breast cancer. In this study, we aimed to assess if there is any correlation between primary tumor PET and histopathology findings and histopathological features of the coexisting DCIS.FDG PET/CT images and histopathology results of the patients with newly diagnosed breast cancer (IDC) with coexisting DCIS were analyzed in this retrospective study. The grade and size of the primary tumor and histopathological features of the coexisting DCIS (nuclear grade and architectural pattern) were obtained from the postoperative histopathology results. Maximum standardized uptake values (SUV: SUVmax and SULmax) of the primary tumor normalized by weight and lean body mass were measured. Statistical analysis was performed to assess the correlation between various parameters of IDC and DCIS.This study included sixty-two (62) patients with IDC-DCIS. Primary tumor grade was significantly correlated and associated with the nuclear grade of the coexisting DCIS (polychoric correlation r = 0.736, and Fisher exact test, PV0.001, respectively). Primary tumor SUV was not correlated with the nuclear grade and architectural pattern of the coexisting DCIS (polyserial correlation r = 0.172, PV = 0.155, and Point Bi-Serial correlation r = -0.009, PV = 0.955, respectively). Median primary tumor size was marginally significantly different among DCIS nuclear grades but it was not significantly different in comedo and non-comedo cases (Kruskal-Wallis test PV = 0.053, and Mann-Whitney U test PV = 0.890, respectively).Primary tumor grade is correlated with the nuclear grade of the coexisting DCIS. SUV of primary tumor does not seem to be correlated with the histopathological features of coexisting DCIS (nuclear grade and architectural pattern) but this may be further studied in a larger number of patients.

PURPOSE: Despite recommendations from national organizations supporting the use of lymph node assessment (LNA) among patients with ductal carcinoma in situ (DCIS) at time of mastectomy, variation in practice patterns across the United States has been observed. However, few studies have evaluated LNA differences and rurality. METHODS: Data from the SEER Patterns of Care (POC) studies were used to identify women who underwent mastectomy for newly diagnosed DCIS during 2000, 2005, 2010, and 2015. Weighted multivariate logistic regression was used to evaluate the association between rural-urban residence and the use of LNA. A subgroup analysis was performed comparing the use of axillary lymph node dissection (ALND) versus sentinel lymph node biopsy (SLNB). RESULTS: Of the 504 patients included in the analysis, approximately 81% underwent LNA at time of mastectomy with lower rates of use observed among rural patients (66%) versus urban patients (82%). In multivariate analysis, LNA increased over time (p

Anatomic extent of ductal carcinoma in situ (DCIS) may be uncertain in spite of clinical, pathologic, and imaging data. Consequently close/positive margins are common with lumpectomy for DCIS and often lead to a challenge in deciding whether to perform a re-excision or mastectomy.From a single health system, we identified cases of lumpectomy for DCIS with close/positive margins who underwent re-excision for the purpose of constructing a nomogram. In total, 289 patients were available for analysis. The patients were randomly divided into two sets allocating 70% to the modeling and 30% to the validation set. A multivariable logistic regression model was used to estimate the probability of overall positive margin status using multiple clinicopathologic predictors. Nomogram validation included internal tenfold cross-validation, internal bootstrap validation, and external validation for which a concordance index was calculated to assess the external validity.Significant predictors of persistent positive margins from regression modeling included necrosis at diagnosis (non-comedo or comedo); DCIS not associated with calcifications on core biopsy; high-grade DCIS; progesterone receptor positivity; and number of positive margins at initial surgery. When subjected to internal validation, the nomogram achieved an uncorrected concordance index of 0.7332, a tenfold cross-validation concordance index of 0.6795, and a bootstrap-corrected concordance index of 0.6881. External validation yielded an estimated concordance index of 0.7095.Using clinical and pathologic variables from initial diagnosis and surgery for DCIS, this nomogram predicts persistent positive margins with margin re-excision, and may be a valuable tool in surgical decision-making.

Preoperative evaluations of the size of ductal carcinoma in situ (DCIS) extension in invasive breast cancer (IBC) are problematic and markers of the actual size of DCIS remain elusive. This study aimed to quantify DCIS on core needle biopsy (CNB) and investigated its association with degree of DCIS extension on paired resection specimens, instead of with presence or absence of an extensive intraductal component or margin status as in earlier studies. This series examined 150 IBCs diagnosed from paired CNB and resection specimens. The DCIS/invasion ratio was calculated using the sum of each element size from CNB. In resection specimens, cases in which the greatest dimension of DCIS extension was longer than the greatest dimension of invasive size were defined as extended DCIS (Ext-DCIS). DCIS/invasion ratio level correlated positively with the degree of Ext-DCIS (P = 0.003). Using receiver operating characteristic curve analysis, setting cases with the subgroup of DCIS extension with greatest dimension 2.5 times that of the invasive size in the resection specimen (Ext-DCIS 2.5) as the positive class provided the best discrimination ability for DCIS/invasion ratio (0.375). In multivariate analysis, DCIS/invasion ratio 0.375 was significantly associated with Ext-DCIS 2.5 (P = 0.033). In conclusion, DCIS/invasion ratio 0.375 in CNB was identified as a predictor of Ext-DCIS 2.5 in resection specimens, suggesting that an approach combining DCIS/invasion ratio from CNB with preoperative staging may better predict the extent of DCIS and facilitate better surgical planning.

Background There is a transition from wire-guided localization (WGL) of non-palpable breast cancer to other localization techniques. Multiple prospective studies have sought to establish superior clinical outcomes for radioactive-seed localization (RSL), but consistent and congruent evidence is missing. Methods In this study, female patients with breast cancer operated with breast-conserving surgery after tumour localization of a non-palpable breast cancer or ductal carcinoma in situ (DCIS) were included. The cohort was identified from the nationwide Netherlands Breast Cancer Audit conducted between 2013 and 2018. Trends in localization techniques were analysed. Univariable and multivariable analyses were performed to assess the association between the localization technique and the probability of a reoperation. Results A total of 28 370 patients were included in the study cohort. The use of RSL increased from 15.7 to 61.1 per cent during the study years, while WGL decreased from 75.4 to 31.6 per cent. The localization technique used (RSL versus WGL) was not significantly associated with the odds of a reoperation, regardless of whether the lesion was DCIS (odds ratio 0.96 (95 per cent c.i. 0.89 to 1.03; P = 0.281)) or invasive breast cancer (OR 1.02 (95 per cent c.i. 0.96 to 1.10; P = 0.518)). Conclusion RSL is rapidly replacing WGL as the preoperative localization technique in breast surgery. This large nationwide registry study found no association between the type of localization technique and the odds of having a reoperation, thus confirming the results of previous prospective cohort studies.

Glucose and glutamine metabolism is involved in important tumor mechanisms. Metabolism-related protein expression has been previously reported to predict tumor prognosis. We aimed to investigate glucose and glutamine metabolism-related protein expression and its implication in breast ductal carcinoma in situ (DCIS). A tissue microarray was prepared for 205 DCIS cases. Glucose and glutamine metabolism-related proteins were immunostained. Based on the results of estrogen receptor, progesterone receptor, human epidermal growth factor receptor (HER)-2, and Ki-67, DCIS was classified into the luminal type, HER-2 type, and triple-negative breast cancer (TNBC). DCIS stroma was classified into non-inflammatory and inflammatory types per stromal histology. DCIS (N=205) was classified into luminal type (n=112), HER-2 type (n=81), and TNBC (n=12). Hexokinase II (p=0.044), GLS (p=0.003), and SLC7A5 (p0.001) expression rates were the highest in TNBC. Inflammatory type stroma showed higher SLC7A5 (p0.001) and SLC7A11 (p=0.008) expression rates than non-inflammatory type stroma. In summary, DCIS demonstrated differential expression of metabolism-related proteins according to the molecular subtype and stromal features. TNBC showed the highest glucose and glutamine metabolism-related protein expression, and inflammatory type stroma showed higher glutamine metabolism-related protein expression than non-inflammatory type stroma.

Background/Aim: Magnetic resonance imaging (MRI) is an important diagnostic tool in the detection of breast cancer. The Breast Center of the municipal Hospital Holweide, Cologne, annually cares for and treats patients with changes in the breast. A special problem is posed by Breast Imaging-Reporting and Data System (BI-RADS) 4 lesions. If a BI-RADS 4 finding is present, is a vacuum biopsy indicated in every case or, if there is already an indication for surgery due to other findings, can the corresponding finding be removed openly without histological clarification? We require real world data regarding the actual in-center likelihood of a BIRADS 4 lesion to be DCIS (Ductal carcinoma in situ) or invasive disease. Patients and Methods: This is a retrospective study of 1,641 patients who received MRI examination in the radiological department of the municipal hospital Holweide in 2012 and 2013. Each BI-RADS 4 finding (or higher) classified by MRI was compared with the final histological result. Results: 347 MRIs showed BI-RADS 4 findings or higher and 280 (80.7%) cases showed benign histology. In 67 (19.3%) cases, histology showed DCIS or invasive carcinoma. Conclusion: BI-RADS 4 lesions have a low probability of malignancy based on real-world data from this center. If there is already an indication for surgery due to other lesions, the patient can also be offered a simultaneous open biopsy in the context of the already initiated surgical treatment. Each center should know the sensitivity and specificity of the MRI imaging performed and counsel patients based on that.

The majority of local recurrences, after conservative surgery of breast cancer, occurs in the same anatomical area where the tumour was originally located. For the treatment of ductal carcinoma in situ (DCIS), a new medical device, named BAT-90, (BetaGlue Technologies SpA) has been proposed. BAT-90 is based on the administration of 90Y β-emitting microspheres, embedded in a bio-compatible matrix. In this work, the Geant4 simulation toolkit is used to simulate BAT-90 as a homogenous cylindrical 90Y layer placed in the middle of a bulk material. The activity needed to deliver a 20 Gy isodose at a given distance z from the BAT-90 layer is calculated for different device thicknesses, tumour bed sizes and for water and adipose bulk materials. A radiobiological analysis has been performed using both the Poisson and logistic Tumour Control Probability (TCP) models. A range of radiobiological parameters (α and β), target sizes, and densities of tumour cells were considered. Increasing α values, TCP increases too, while, for a fixed α value, TCP decreases as a function of clonogenic cell density. The models predict very solid results in case of limited tumour burden while the activity/dose ratio could be further optimized in case of larger tumour beds.

Introduction: Aurora Kinase A (AURKA/STK15) has a role in centrosome duplication and is a regulator of mitotic cell proliferation. It is over-expressed in breast cancer and other cancers, however; its role in ductal carcinoma in situ (DCIS) remains to be defined. This study aims to characterize AURKA protein expression in DCIS and evaluate its prognostic significance. Methods: AURKA was assessed immunohistochemically in a large well-characterized cohort of DCIS (n = 776 pure DCIS and 239 DCIS associated with invasive breast cancer [DCIS-mixed]) with long-term follow-up data (median = 105 months) and basic molecular characterization. Results: High AURKA expression was observed in 15% of DCIS cases and was associated with features of aggressiveness including larger tumour size, high nuclear grade, hormone receptor negativity, HER2 positivity, and high Ki67 proliferation index. AURKA expression was higher in DCIS associated with invasive breast cancer than in pure DCIS (p < 0.0001). In the DCIS-mixed cohort, the invasive component showed higher AURKA expression than the DCIS component (p < 0.0001). Outcome analysis revealed that AURKA was a predictor of invasive recurrence (p = 0.002). Conclusion: High AURKA expression is associated with poor prognosis in DCIS and might be a potential marker to predict DCIS progression to invasive disease.

INTRODUCTION: Neoadjuvant systemic therapy (NST) is increasingly applied in breast cancer to improve surgical and oncological outcome. Approximately 21% of patients receiving NST achieve pathological complete response (pCR) of the breast. There is disagreement on the definition of pCR with respect to residual DCIS (ypT0 versus ypT0/is). The aim of this retrospective study was to determine the percentage of breast pCR (ypT0) and residual DCIS (ypTis), and its association with clinicopathological variables, in patients treated with NST and surgery.MATERIALS AND METHODS: Patients with invasive breast cancer treated with neoadjuvant chemotherapy, with or without targeted therapy, in the period of 2010-2019 were selected from the Netherlands Cancer Registry (NCR). Descriptive statistics and multivariable logistic regression analyses were used to analyse the percentage of ypT0 and ypTis and its association with clinicopathological variables.RESULTS: From the NCR database, 20495 patients were included, of whom 5847 (28.5%) achieved breast pCR (ypT0) and 881 (4.3%) showed residual DCIS (ypTis). The percentage of ypTis was highest in HER2+ tumour subtypes (ER+HER2+ 7.9%, ER-HER2+ 9.8%, ER+HER2- 2.1%, triple negative 3.3%, p < 0.001). Multivariable logistic regression analyses demonstrated high tumour grade (OR 2.00, p = 0.003) and HER2+ tumour subtype (ER+HER2+ OR 3.58, ER-HER2+ OR 4.37, p < 0.001) as independent predictors for ypTis.CONCLUSION: pCR (ypT0) was achieved in 5847 (28.5%) patients receiving NST and residual DCIS (ypTis) was found in 881 (4.3%) patients. Consequently, the rate of pCR may be affected by ypTis when not excluded from the definition. The percentage of ypTis is highest in HER2+ subtypes.

An 81-year-old woman was diagnosed with corticobasal degeneration (cognitive decline and left hand posturing). Hyponatremia and bilateral faciobrachial dystonic seizures (FBDS) ensued. Neurologic examination (figure, A; video) revealed persistent involuntary continuous left 3rd and 4th finger flexor activation and delayed relaxation. EMG revealed high-frequency spontaneous discharges, including neuromyotonia and fast myokymia of the left flexor digitorum superficialis and pronator teres (figure, B). LGI1 immunoglobulin G (IgG)1 was detected, but not CASPR2-IgG (figure, C–E). Oncologic evaluation revealed breast ductal carcinoma in situ. Encephalopathy and FBDS resolved after IV immunoglobulin. Encephalopathy coexisting with peripheral nerve hyperexcitability can mimic neurodegeneration, and should prompt exclusion of LGI1/CASPR2 autoimmunity.2

Childhood and young adult survivors of Hodgkin lymphoma (HL) are at elevated risk of developing breast cancer, yet little data exist on the tumor characteristics that develop in this high-risk patient population.The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify breast cancers diagnosed between 1990 and 2016 in women who had received prior radiation therapy for HL at age 30 years or younger. Clinicopathologic features of subsequent breast cancers (breast cancer after radiation therapy for HL [BC-HL]) were examined and compared with breast cancers diagnosed in women who had no prior malignancy (breast cancer with no prior malignancy [BC-NPM]).In total, 321 breast cancers were identified in 257 women who had a history of radiation therapy for HL. The median age at HL diagnosis was 22 years (interquartile range, 18-26 years), and nearly all patients in the BC-HL group (97.9%) were diagnosed ≥8 years after radiation therapy. Overall, 56 patients in the BC-HL group (21.8%) developed bilateral breast cancer. Compared with women who had BC-NPM, those who had BC-HL were younger (43 vs 60 years; P .001) and were less likely to present with ductal carcinoma in situ (8.4% vs 14.9%; P = .001). On multivariable analysis that included adjustment for age, invasive BC-HL was associated with smaller (≤2 cm) tumor size (odds ratio, 1.64; 95% CI, 1.25-2.15) and upper outer quadrant tumors (odds ratio, 1.37; 95% CI, 1.04-1.81) compared with BC-NPM. In a subset analysis of 102 women who had HER2/neu status available, the distribution of biologic subtype was not significantly different between BC-HL and BC-NPM (P = .16).Breast cancers in women who previously received radiation therapy for HL are characterized by earlier onset disease, although most remain estrogen receptor-positive and have early stage disease at presentation.Women who have had radiation therapy for Hodgkin lymphoma at a young age are at increased risk of developing early onset breast cancer; however, most of these breast cancers are sensitive to hormones (estrogen receptor-positive) and are diagnosed at early stages. Because these breast tumors are estrogen receptor-positive, medications that prevent breast cancer by blocking the effect of or lowering hormone levels (also termed endocrine prevention) may be useful in this group of high-risk women.