The value of MRI contrast enhancement in biopsy decision of suspicious mammographic microcalcifications: a prospective multicenter study.

OBJECTIVES: To investigate the inclusion of breast MRI in radiological assessment of suspicious, isolated microcalcifications detected with mammography. METHODS: In this prospective, multicenter study, cases with isolated microcalcifications in screening mammography were examined with dynamic contrast-enhanced MRI (DCE-MRI) before biopsy, and contrast enhancement of the relevant calcification localization was accepted as a positive finding on MRI. Six experienced breast radiologists evaluated the images and performed the biopsies. Imaging findings and histopathological results were recorded. Sensitivity, specificity, NPV, and PPV of breast MRI were calculated and compared with histopathological findings. RESULTS: Suspicious microcalcifications, which were detected by screening mammograms of 444 women, were evaluated. Of these, 276 (62.2%) were diagnosed as benign and 168 (37.8%) as malignant. Contrast enhancement was present in microcalcification localization in 325 (73.2%) of the cases. DCE-MRI was positive in all 102 invasive carcinomas and in 58 (87.9%) of 66 DCIS cases. MRI resulted in false negatives in eight DCIS cases; one was high grade and the other seven were low-to-medium grade. The false-negative rate of DCE-MRI was 4.76%. The sensitivity, specificity, PPV, and NPV for DCE-MRI for mammography-detected suspicious microcalcifications were 95.2%, 40.2%, 49.2%, and 93.3%, respectively. CONCLUSIONS: In this study, all invasive cancers and all DCIS except eight cases (12.1%) were detected with DCE-MRI. DCE-MRI can be used in the decision-making algorithm to decrease the number of biopsies in mammography-detected suspicious calcifications, with a tradeoff for overlooking a small number of DCIS cases that are of low-to-medium grade. KEY POINTS: • All invasive cancer cases and 87.8% of all in situ cancer cases were detected with MRI, showing a low false-negative rate of 4.7%. • Dynamic contrast-enhanced MRI can be used in the decision-making algorithm to decrease the number of biopsies in mammography-detected suspicious calcifications, with a tradeoff for overlooking a small number of DCIS cases that are predominantly low-to-medium grade. • If a decision for biopsy were made based on MRI findings in mammography-detected microcalcifications in this study, biopsy would not be performed to 119 cases (26.8%).

Modeling the natural history of ductal carcinoma in situ based on population data.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased substantially since the introduction of mammography screening. Nevertheless, little is known about the natural history of preclinical DCIS in the absence of biopsy or complete excision. METHODS: Two well-established population models evaluated six possible DCIS natural history submodels. The submodels assumed 30%, 50%, or 80% of breast lesions progress from undetectable DCIS to preclinical screen-detectable DCIS; each model additionally allowed or prohibited DCIS regression. Preclinical screen-detectable DCIS could also progress to clinical DCIS or invasive breast cancer (IBC). Applying US population screening dissemination patterns, the models projected age-specific DCIS and IBC incidence that were compared to Surveillance, Epidemiology, and End Results data. Models estimated mean sojourn time (MST) in the preclinical screen-detectable DCIS state, overdiagnosis, and the risk of progression from preclinical screen-detectable DCIS. RESULTS: Without biopsy and surgical excision, the majority of DCIS (64-100%) in the preclinical screen-detectable state progressed to IBC in submodels assuming no DCIS regression (36-100% in submodels allowing for DCIS regression). DCIS overdiagnosis differed substantially between models and submodels, 3.1-65.8%. IBC overdiagnosis ranged 1.3-2.4%. Submodels assuming DCIS regression resulted in a higher DCIS overdiagnosis than submodels without DCIS regression. MST for progressive DCIS varied between 0.2 and 2.5 years. CONCLUSIONS: Our findings suggest that the majority of screen-detectable but unbiopsied preclinical DCIS lesions progress to IBC and that the MST is relatively short. Nevertheless, due to the heterogeneity of DCIS, more research is needed to understand the progression of DCIS by grades and molecular subtypes.

Does sentinel lymph node biopsy for screening high-grade ductal carcinoma in situ of the breast cause more harm than good?

PURPOSE: Ductal carcinoma in situ (DCIS) of the breast does not metastasize to axillary lymph nodes. Yet high-grade DCIS (HgDCIS) is often subjected to Sentinel Lymph Node Biopsy (SLNB) concomitant with definitive surgery. This is to avoid further axillary surgery in the event of upstaging to invasive carcinoma, which often entails Axillary Lymph Node Dissection (ALND). We wished to examine the validity of this approach. METHODS: This study includes a retrospective analysis of consecutive pre-operatively diagnosed HgDCIS patients from a single screening unit between December/2014 and August/2016. The main outcomes were the overall incidence of upstaging and the independent predictors of upstaging on multivariable analysis. The rates of various complications of SLNB vs ALND in four RCTs were used to calculate the upstaging rate below which SLNB could be safely omitted. RESULTS: There were 224 eligible patients of whom 26 (11.6%) were upstaged. Axillary metastasis (pN1) occurred in two patients (0.9%). On Univariable analysis, upstaged patients were significantly younger (median (IQR) = 56.0 (51.0-63) vs 60.0 (54.0-65.0); p = 0.019). Radiological size, pathological size, type of biopsy, type of operation, and comedo-necrosis were not significant (p > 0.05). On multivariable analysis, age as a continuous variable (OR 0.93; p = 0.031) and core biopsy (OR 2.62; p = 0.036) were the only independent predictors of upstaging. Chi-square test showed that patients < 55 years whose pre-operative diagnosis was made on core biopsy were at significantly higher risk of upstaging than the others (31.8% vs 9.4%; p = 0.002). CONCLUSION: Upstaging of HgDCIS is infrequent. According to the known rates of complications of SLNB relative to ALND, routine SLNB concomitant with surgery seems to be more harmful than its routine omission. A selective approach based on age and type of biopsy could be considered.

Risk of invasive breast cancer in relatives of patients with breast carcinoma in situ: a prospective cohort study.

BACKGROUND: Wide implementation of mammography screening has resulted in increased numbers of women diagnosed with breast carcinoma in situ. We aimed to determine the risk of invasive breast cancer in relatives of patients with breast carcinoma in situ in comparison to the risk in relatives of patients with invasive breast cancer. METHODS: We analyzed the occurrence of cancer in a nationwide cohort including all 5,099,172 Swedish women born after 1931 with at least one known first-degree relative. This was a record linkage study of Swedish family cancer datasets, including cancer registry data collected from January 1, 1958, to December 31, 2015. We calculated standardized incidence ratios (SIRs) and 10-year cumulative risk of breast cancer diagnosis for women with a family history of in situ and invasive breast cancer. RESULTS: Having one first-degree relative with breast carcinoma in situ was associated with 50% increased risk of invasive breast cancer (SIR = 1.5, 95% CI 1.4-1.7) when compared to those who had no family history of invasive breast cancer or breast carcinoma in situ in either first- or second-degree relatives. Similarly, having one first-degree relative with invasive breast cancer was associated with 70% (1.7, 1.7-1.8) increased risk. The 10-year cumulative risk for women at age 50 with a relative with breast carcinoma in situ was 3.5% (2.9-3.9%) and was not significantly different from 3.7% (3.6-3.8%) risk for 50-year-old women with a relative with invasive breast cancer (95% confidence intervals overlapped). CONCLUSIONS: The risk of invasive breast cancer for women with a family history of breast carcinoma in situ was comparable to that for women with a family history of invasive breast cancer. Therefore, family history of breast carcinoma in situ should not be overlooked in recommendations for breast cancer prevention for women with a family history of breast cancer.

Risk of breast cancer by prior screening results among women participating in BreastScreen Norway.

BACKGROUND: A premalignant lesion in the breast is associated with an increased risk of breast cancer. The aim of this article was to identify women with an increased risk of breast cancer based on prior screening results (PSRs). METHODS: This registry-based cohort study followed women who participated in the organized breast cancer screening program in Norway, BreastScreen Norway, in 1995-2016. Incidence rates and incidence rate ratios were used to estimate absolute and relative risks of breast cancer associated with PSRs. Histopathological characteristics of subsequent breast cancers were presented by PSRs. RESULTS: This study included 762,643 women with up to 21 years of follow-up. In comparison with negatively screened women, increased incidence rate ratios of 1.8, 2.0, 2.9, and 3.8 were observed after negative additional imaging, for benign biopsy, for hyperplasia with atypia, and for carcinoma in situ, respectively. Subsequent breast cancers did not differ in tumor diameter or histological grade, whereas the proportion of lymph node-positive breast cancers decreased as the presumed malignancy potential of PSRs increased. CONCLUSIONS: The risk of subsequent breast cancer increased with the presumed malignancy potential of PSRs, whereas the tumor characteristics of subsequent cancers did not differ except for the lymph node status. Women with screen-detected benign lesions or hyperplasia with atypia might benefit from more frequent screening.

Comparison of performance metrics with digital 2D versus tomosynthesis mammography in the diagnostic setting.

OBJECTIVES: To compare performance metrics between digital 2D mammography (DM) and digital breast tomosynthesis (DBT) in the diagnostic setting. METHODS: Consecutive diagnostic examinations from August 2008 to February 2011 (DM group) and from January 2013 to July 2015 (DM/DBT group) were reviewed. Core biopsy and surgical pathology results within 365 days after the mammogram were collected. Performance metrics, including cancer detection rate (CDR), abnormal interpretation rate (AIR), positive predictive value (PPV) 2, PPV3, sensitivity, and specificity were calculated. Multivariable logistic regression models were fit to compare performance metrics in the DM and DM/DBT groups while adjusting for clinical covariates. RESULTS: A total of 22,883 mammograms were performed before DBT integration (DM group), and 22,824 mammograms were performed after complete DBT integration (DM/DBT group). After adjusting for multiple variables, the CDR was similar in both groups (38.2 per 1,000 examinations in the DM/DBT group versus 31.3 per 1,000 examinations in the DM group, p = 0.14); however, a higher proportion of cancers were invasive rather than in situ in the DM/DBT group [83.7% (731/873) versus 72.3% (518/716), p < 0.01]. The AIR was lower in the DM/DBT group (p < 0.01), and PPV2, PPV3, and specificity were higher in the DM/DBT group (all p = 0.01 or p < 0.01). CONCLUSIONS: Complete integration of DBT into the diagnostic setting is associated with improved diagnostic performance. Increased utilization of DBT may thus result in better patient outcomes and lead to a shift in the benchmarks that have been established for DM. KEY POINTS: • Integration of tomosynthesis into the diagnostic setting is associated with improved performance. • A higher proportion of cancers are invasive rather than in situ with digital breast tomosynthesis. • Increased utilization of tomosynthesis may lead to a shift in established benchmarks.

Diffusion-tensor imaging as an adjunct to dynamic contrast-enhanced MRI for improved accuracy of differential diagnosis between breast ductal carcinoma in situ and invasive breast carcinoma.

OBJECTIVE: To determine the value of diffusion-tensor imaging (DTI) as an adjunct to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for improved accuracy of differential diagnosis between breast ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). METHODS: The MRI data of 63 patients pathologically confirmed as breast cancer were analyzed. The conventional MRI analysis metrics included enhancement style, initial enhancement characteristic, maximum slope of increase, time to peak, time signal intensity curve (TIC) pattern, and signal intensity on FS-T2WI. The values of apparent diffusion coefficient (ADC), directionally-averaged mean diffusivity (Davg), exponential attenuation (EA), fractional anisotropy (FA), volume ratio (VR) and relative anisotropy (RA) were calculated and compared between DCIS and IBC. Multivariate logistic regression was used to identify independent factors for distinguishing IBC and DCIS. The diagnostic performance of the diagnosis equation was evaluated using the receiver operating characteristic (ROC) curve. The diagnostic efficacies of DCE-MRI, DWI and DTI were compared independently or combined. RESULTS: EA value, lesion enhancement style and TIC pattern were identified as independent factor for differential diagnosis of IBC and DCIS. The combination diagnosis showed higher diagnostic efficacy than a single use of DCE-MRI (P=0.02), and the area of the curve was improved from 0.84 (95% CI, 0.67-0.99) to 0.94 (95% CI, 0.85-1.00). CONCLUSIONS: Quantitative DTI measurement as an adjunct to DCE-MRI could improve the diagnostic performance of differential diagnosis between DCIS and IBC compared to a single use of DCE-MRI.

Repercussions of the COVID-19 pandemic on breast cancer actions in a Brazilian state.

Objective: To analyze whether the COVID-19 pandemic had an impact on the screening, diagnosis and treatment of breast cancer in women up to 50 years of age in the state of Pará. Methods: Retrospective, cross-sectional study with a quantitative approach, using data from the Information Technology Department of the Brazilian Unified Health System. (DATASUS). The number of exams carried out in the pre-pandemic (2018-2019) and pandemic (2020-2021) period was analyzed based on the percentage variation, application of the chi-square test and G test for the time of exams and start time of treatment. Results: During the pandemic period, there was a greater number of screening mammograms (+3.68%), cytological (+23.68%), histological (+10.7%) and a lower number of diagnostic mammograms (-38.7%). The time interval for carrying out the exams was up to 30 days for screening and diagnostic exams and more than 60 days to start treatment during the pandemic period. Conclusion: Although the results indicate an increase in the number of screening and diagnostic procedures for breast cancer during the pandemic period, with the exception of diagnostic mammography, when considering probability values, the study points out that statistically the COVID-19 pandemic did not interfere with actions of breast cancer, in women over 50 years of age, in the state of Pará. Considering the autonomy of nursing and its role in public health, it is up to the professionals who are in charge of primary care programs to implement contingency plans in periods of crisis so that the population is not left unassisted.

Effect of Ambrosia arborescens Mill. ethanolic extract on breast cancer induced in rats.

Background and Aims: Ambrosia arborescens Mill. (A. arborescens) is an aromatic plant used in traditional medicine as an anti-inflammatory, anti-tussive, anti-rheumatic, and anti-diarrheal agent. This study aimed to evaluate the effect of A. arborescens Mill. on a Rattus norvegicus var. albinus-induced breast cancer model. Materials and Methods: We collected A. arborescens from the province of Julcán, La Libertad Region, Per, and prepared an ethanolic extract using pulverized leaves macerated in 96° ethanol for 72 h with magnetic stirring. In the evaluation of anticancer activity, four experimental groups with 10 female rats each were formed: Group I (Control-7,12-dimethylbenz[a]anthracene [DMBA]), which received DMBA (single dose) and physiological saline solution for 4 months, and Groups II, III, and IV, which received DMBA (single dose) and 200, 400, and 600 mg/kg/day of the ethanolic extract of A. arborescens, respectively, for 4 months. Results: The DMBA control group presented histological characteristics of ductal carcinoma in situ with necrotic and inflammatory areas, whereas the A. arborescens extract group showed a decrease in tumor volume and recovery of the ductal duct. Conclusion: Ethanol extract of A. arborescens leaves decreases tumor development in rats with induced breast cancer, and this effect is dose-dependent.

Real-World Evidence on the Use of Endocrine Therapy for Ductal Carcinoma In Situ in Patients Treated With Breast-Conserving Surgery Followed by Postoperative Radiation Therapy: A Brazilian Retrospective Cohort Study.

INTRODUCTION/BACKGROUND: This study aims to evaluate the reproducibility of findings from randomized controlled trials regarding adjuvant hormone therapy (HT) for breast ductal carcinoma in situ (DCIS) in a real-life scenario. MATERIALS/METHODS: This retrospective cohort study used Fundação Oncocentro de São Paulo database. It included DCIS patients DCIS who received breast-conserving surgery and postoperative radiation therapy. The endpoints were local control (LC), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: We analyzed 2192 patients treated between 2000 and 2020. The median FU was 48.99 months. Most patients (53.33%; n = 1169) received adjuvant HT. Patients not receiving adjuvant HT tend to be older (P = .021) and have a lower educational level (P < .001). At the end of FU, 1.5% of patients had local recurrence, and there was no significant difference between groups (P = .19). The 10-year OS and BCSS were 89.4% and 97.5% for adjuvant HT versus 91.5% and 98.5% for no adjuvant HT, respectively, and there were no significant differences between groups. The 10-year OS was 93.25% for medium/high education level versus 87.31% for low (HR for death 0.51; 95% CI, 0.32-0.83; P = .007). CONCLUSIONS: The benefits of adjuvant HT for DCIS were not reproduced in a Brazilian cohort. Education significantly impacted survival and HT usage, reflecting the influence of socioeconomic factors. These findings can allow for more precise interventions.

The natural history of ductal carcinoma in situ (DCIS) in simulation models: A systematic review.

OBJECTIVE: Assumptions on the natural history of ductal carcinoma in situ (DCIS) are necessary to accurately model it and estimate overdiagnosis. To improve current estimates of overdiagnosis (0-91%), the purpose of this review was to identify and analyse assumptions made in modelling studies on the natural history of DCIS in women. METHODS: A systematic review of English full-text articles using PubMed, Embase, and Web of Science was conducted up to February 6, 2023. Eligibility and all assessments were done independently by two reviewers. Risk of bias and quality assessments were performed. Discrepancies were resolved by consensus. Reader agreement was quantified with Cohen's kappa. Data extraction was performed with three forms on study characteristics, model assessment, and tumour progression. RESULTS: Thirty models were distinguished. The most important assumptions regarding the natural history of DCIS were addition of non-progressive DCIS of 20-100%, classification of DCIS into three grades, where high grade DCIS had an increased chance of progression to invasive breast cancer (IBC), and regression possibilities of 1-4%, depending on age and grade. Other identified risk factors of progression of DCIS to IBC were younger age, birth cohort, larger tumour size, and individual risk. CONCLUSION: To accurately model the natural history of DCIS, aspects to consider are DCIS grades, non-progressive DCIS (9-80%), regression from DCIS to no cancer (below 10%), and use of well-established risk factors for progression probabilities (age). Improved knowledge on key factors to consider when studying DCIS can improve estimates of overdiagnosis and optimization of screening.

Can we improve breast cancer management using an image-guided histopathology workup supported by larger histopathology sections?

PURPOSE: Breast radiologists examine the entire breast in full-size images, while breast pathologists examine small tissue samples at high magnification. The diagnostic information from these complementary imaging approaches can be difficult to integrate for a more clinically relevant evaluation of malignancies spanning several centimetres. We have explored the advantages and disadvantages of imaging guided larger section pathology techniques compared with the standard 2 × 2.5 cm. small section technique. METHODS: We compared the ability of conventional small section histopathology with larger section histopathology techniques to examine surgical resection margins and full disease extent. We evaluated the pre-surgical imaging workup and use of microfocus magnification radiography of sliced surgical specimens in the histopathologic evaluation of disease extent and status of surgical margins. RESULTS: Image assisted large section histopathology of excised breast tissue enables comprehensive examination of an approximately tenfold larger contiguous tissue area than is provided by conventional small section technology. Attempting to cover the full area of each consecutive slice of resected tissue is more labour-intensive and expensive with the small section approach and poses challenges in reconstituting three-dimensional tumour architecture after morcellation and sectioning. Restricting histopathologic examination to a limited number of samples provides an incomplete evaluation of surgical margins. CONCLUSIONS: A considerably improved documentation of breast cancer and a more reliable assessment of tissue margins is provided by using larger sized histopathology samples to correlate with breast imaging findings. These in turn can enable more appropriate treatment planning, improved surgical performance, fewer recurrences, and better patient outcome. Uncertainty of surgical margin evaluation inherent to the standard small section technique can lead to inappropriate decisions in surgical management and adjunctive therapy. Progress in breast diagnosis and treatment will largely depend on whether histopathology terminology and technique will undergo a revolution similar to the one that has already occurred in breast imaging.

Lobular Carcinoma In Situ during Preoperative Biopsy and the Rate of Upgrade.

PURPOSE: There is a potential risk that lobular carcinoma in situ (LCIS) on preoperative biopsy might be diagnosed as ductal carcinoma in situ (DCIS) or invasive carcinoma in the final pathology. This study aimed to evaluate the rate of upgrade of LCIS on preoperative biopsy to DCIS or invasive carcinoma. MATERIALS AND METHODS: Data of 55 patients with LCIS on preoperative biopsy were analyzed. All patients underwent surgery between 1991 and 2016 at Severance Hospital in Seoul, Korea. We analyzed the rate of upgrade of preoperative LCIS to DCIS or invasive cancer in the final pathology. The clinicopathologic features related to the upgrade were evaluated. RESULTS: The rate of upgrade of LCIS to DCIS or invasive carcinoma was 16.4% (9/55). In multivariate analysis, microcalcification and progesterone receptor expression were significantly associated with the upgrade of LCIS (p=0.023 and p=0.044, respectively). CONCLUSION: The current study showed a relatively high rate of upgrade of LCIS on preoperative biopsy to DCIS or invasive cancer. The presence of microcalcification and progesterone receptor expression may be potential predictors of upgradation of LCIS on preoperative biopsy. Surgical excision of the LCIS during preoperative biopsy could be a management option to identify the concealed malignancy.

Imaging biomarkers of breast cancers originating from the major lactiferous ducts: Ductal adenocarcinoma of the breast, DAB.

PURPOSE: As we have previously demonstrated, breast cancers originating in the major lactiferous ducts and propagating through the process of neoductgenesis are a distinct subtype of invasive breast cancers, although by current practice they are placed within the group termed ductal carcinoma in situ (DCIS) and are consequently underdiagnosed and undertreated. Imaging biomarkers provide a reliable indication of the site of origin of this breast cancer subtype (Ductal Adenocarcinoma of the breast, DAB) and have excellent concordance with long-term patient outcome. In the present paper, the imaging biomarkers of DAB are described in detail to encourage and facilitate its recognition as a distinct, invasive breast cancer subtype. METHODS: Correlation of breast imaging biomarkers with the corresponding histopathological findings using large format technology, with additional evidence from subgross, thick section histopathology to demonstrate the complex three-dimensional structure of the newly formed duct-like structures, neoducts. RESULTS: There are six imaging biomarkers (mammographic tumour features) of DAB. Four subgroups have characteristic malignant-type calcifications on the mammogram. Two of these are characterized by intraluminal necrosis producing fragmented or dotted casting type calcifications on the mammogram; another two subgroups are characterized by intraductal fluid production which may eventually calcify, producing skipping stone-like or string of pearl-like calcifications. A fifth DAB subgroup presents with bloody or serous nipple discharge and is usually occult on mammography but is detectable with galactography and magnetic resonance imaging (MRI). The sixth subgroup presents as architectural distortion on the mammogram without associated calcifications. CONCLUSIONS: Radiologists can use these well-defined imaging biomarkers to readily detect Ductal Adenocarcinoma of the Breast, DAB. Immunochemical biomarkers are generally not determined from the DAB itself, due to the erroneous assumption that DAB is non-invasive. MRI plays a crucial role in determining disease extent and guiding surgical management. The accumulating evidence that this disease subtype is, in fact, an invasive cancer, necessitates an urgent re-evaluation of the diagnostic and management criteria for this poorly understood malignancy.

Breast cancers originating from the major lactiferous ducts and the process of neoductgenesis: Ductal Adenocarcinoma of the Breast, DAB.

PURPOSE: To call attention to a highly fatal breast cancer subtype arising from the major lactiferous ducts that is currently underdiagnosed as ductal carcinoma in situ (DCIS) with or without microinvasion. METHOD: All breast cancers diagnosed at the Department of Mammography, Falun Central Hospital, Sweden, since 1977 have been classified according to their mammographic tumour features (imaging biomarkers) and followed up at regular intervals for the past four decades. The imaging biomarkers characteristic of breast cancers apparently arising from the major lactiferous ducts have been correlated with large format thin and thick section histopathology and long-term patient outcome. RESULTS: Breast cancers arising within the major lactiferous ducts propagate intraductally and produce continuously branching neoducts through epithelial-mesenchymal transformation (EMT), an invasive process termed neoductgenesis, which eventually forms a massive tumour burden. The high fatality of this breast cancer subtype indicates its truly invasive nature, although it is conventionally termed ductal carcinoma in situ, DCIS, terminology which is at odds with its poor long-term patient outcome. The neoducts are filled with multiple layers of malignant cells, have no attached lobules, and propagate by forming multiple invasive side branches. These newly formed duct-like structures are surrounded by a desmoplastic reaction (cancer associated fibroblasts, CAFs) and periductal lymphocytic infiltration. The neoducts are tightly packed together in irregular formations bearing no resemblance to the paniculate branching structure of normal lactiferous ducts. Cancers originating from the major ducts have six imaging biomarkers which can be easily recognized at breast imaging. These are described in detail in an accompanying article. CONCLUSIONS: Neoductgenesis in the breast, DAB, is similar in appearance and prognosis to ductal adenocarcinoma of the prostate, DAP. We propose the term ductal adenocarcinoma of the breast, DAB, to facilitate its recognition as a distinct invasive breast cancer subtype. The high fatality rates associated with neoductgenesis reflect the failure of current histopathologic diagnostic criteria to effectively guide therapeutic practice. When the neoducts are associated with small stellate/spiculated or spherical/oval-shaped invasive cancers arising from the terminal ductal lobular units (TDLUs), the prognosis and management are erroneously estimated according to the smaller invasive tumour(s), giving a false sense of security often resulting in undertreatment. Recognition that neoductgenesis is an invasive malignancy is a prerequisite for preventing treatment failure.

Breast cancers originating from the terminal ductal lobular units: In situ and invasive acinar adenocarcinoma of the breast, AAB.

PURPOSE: To use mammographic tumour features (imaging biomarkers) to identify and investigate breast cancers originating from the terminal ductal lobular units (TDLUs) of the breast in order to overcome the confusion arising from the current histopathology terminology, which calls cancers arising from the TDLUs either "ductal" or "lobular". METHOD: Prospectively collected data from a randomized controlled mammography screening trial with more than four decades of follow up, and data from the subsequent population-based service screening program in Dalarna County, Sweden, provided the database necessary for studying nonpalpable, primarily screen-detected breast cancer cases in their earliest detectable phases. Large format thick (subgross) and thin section histopathologic images of breast cancers originating from the TDLUs were correlated with their mammographic tumour features (imaging biomarkers) and long-term patient outcome. RESULTS: This systematic correlation indicates that imaging biomarkers can reliably determine the site of origin of breast cancers arising from the terminal ductal lobular units (TDLUs). This breast cancer subgroup has four specific mammographic tumour features: the in situ carcinomas developing from the TDLUs appear as powdery or crushed stone-like calcifications, while the invasive carcinomas appear as stellate/spiculated or circular/oval shaped tumour masses. These features are easily identified with breast imaging, either alone or in combination, unifocal or multifocal. We propose calling breast cancers of TDLU origin acinar adenocarcinoma of the breast (AAB). CONCLUSIONS: The era of early detection necessitates rectifying the current, confusing histopathological nomenclature to one that is based on the anatomical site of origin of breast cancers. Invasive cancers originating from the TDLUs are either stellate/spiculated or circular, irrespective of the complex WHO histopathologic terminology. The mortality reduction accomplished by participation in mammography screening is mostly accomplished by identifying and treating the AABs in their non-palpable, early phase. AABs detected when < 15 mm diameter with no associated carcinoma originating from the major lactiferous ducts (ductal adenocarcinoma of the breast, DAB) have a good to excellent long-term outcome, irrespective of the current terminology, which tends to lead to overtreatment of these early invasive tumours. The conventionally used prognostic factors, including immunohistochemical biomarkers, fail to identify those 1-14 mm invasive AABs tumours that are eventually fatal. This identification can be made preoperatively by including the characteristic mammographic tumour features, imaging biomarkers, in primary diagnosis, treatment planning, and predicting long-term patient outcome. Forthcoming articles will address breast malignancies originating from structures of the breast other than the TDLUs.

A new approach to breast cancer terminology based on the anatomic site of tumour origin: The importance of radiologic imaging biomarkers.

PURPOSE: To use mammographic tumour features (imaging biomarkers) to classify breast cancer according to its apparent anatomic site of origin in the new era where tumours are found at their nonpalpable, earliest detectable phase. METHOD: Large format, subgross, three-dimensional histopathologic images of breast cancer subtypes and their corresponding imaging biomarkers were correlated with large format thin section histopathology and long-term patient outcome. RESULTS: This systematic correlation indicates that breast cancers arise from three separate fibroglandular tissue components: the terminal ductal lobular units (TDLUs), the major lactiferous ducts, and in the stem cells of the mesenchyme. The resulting three cancer subgroups have distinctly different clinical, histopathological and mammographic presentations and different long-term outcomes. The relative frequency of these three breast cancer subgroups is approximately 75%, 20% and 5%, respectively. Classification of breast cancers according to their anatomic site of origin, as demonstrated with breast imaging and confirmed by subgross histopathology, correlates closely with the long-term patient outcome. CONCLUSIONS: Classification of breast cancers according to their site of origin helps overcome the inconsistencies in the current histopathologic terminology with its ductal-lobular dichotomy. The ability of the imaging biomarkers to determine the site of tumour origin and serve as a prognostic indicator emphasizes the increasingly crucial role of breast imaging in the management of breast cancer. Basing breast cancer management upon anatomically relevant terminology challenges the conventional mindset. Our proposals are based on research results from an unprecedented number of prospectively collected nonpalpable breast cancers diagnosed at their earliest detectable phases and followed up for several decades. This article is a general introduction to a series of forthcoming articles describing in detail the breast malignancies originating from the three sites of origin.

When is Sentinel Lymph Node Biopsy Useful in Ductal Carcinoma In Situ? The Experience at a Latin American Cancer Center.

Introduction Ductal carcinoma in situ (DCIS) accounts for 15% of breast cancers. Surgery is the main treatment, and the use of sentinel node biopsy (SLNB) is restricted to patients at risk of infiltration, which is estimated to be around 26%. Materials and methods Aimed at evaluating the benefit of SLNB in patients with DCIS at the Breast and Soft Tissue Functional Unit of the National Cancer Institute (INC for its initials in Spanish), a descriptive observational study of a retrospective cases series was conducted between August 1, 2013, and September 30, 2018. Results A total of 40 patients with a median age of 57 years were included in the study; 62.5% of them underwent mastectomy with SLNB, and the remaining 37.5% underwent conservative surgery with SLNB. 100% of sentinel nodes were identified, by using lymphoscintigraphy in 95%. Sentinel node was positive in four patients (10%), three of whom had infiltration in the surgical specimen reported. With a follow-up of 49 months, only one patient had a local relapse. None of the patients had axillary or distant recurrence. Conclusions SLNB in DCIS should be limited to patients with risk factors for infiltration (tumor size greater than 3 cm, comedo-type histology, and high-grade DCIS), and patients with an indication for mastectomy. Its percentage of complications is low, and a high identification percentage in surgical groups with adequate training.

Evaluation and management of pathological nipple discharges without using intraductal imaging methods.

BACKGROUND: The most common cause of pathological nipple discharge (PND) is single papilloma, which is a benign intraductal lesion (BIL). However, underlying malign (MIL) or high-risk intraductal lesions (HIL) should be considered during examination. AIM: To reveal the value of conventional imaging methods (CIM), discharge characteristics, and cytology in lack of intraductal imaging methods to detect intraductal lesions (IL) and MIL that cause PND. METHODS: We compared the pathological findings with the characteristics of discharge, CIM, and cytology findings of the patients who admitted to our clinic with nipple discharge and underwent duct excision (n = 111). RESULTS: IL were detected in 69 (62.2%) patients as BIL (n = 31), HIL (n = 23), and MIL (n = 15). Most of the IL was observed with bloody, serosanguineous, and serous discharges (83.3%, 76.2%, and 69.2%, respectively). The sensitivities of ultrasonography, MRI, and cytology in detecting IL were found to be 50.7%, 42.6%, and 74.1%, while their specificities were found to be 73.8%, 88.2%, and 48.6%, respectively. None of the CIM was sufficient to detect MIL in 5 (33.3%) patients. The appearance of red blood cells detailed in cytology was significantly related to IL (p < 0.01), whereas the presence of inflammatory cells was related to ductal ectasia and periductal mastitis (p < 0.001). CONCLUSIONS: Although patients' physical examinations, CIM, and cytology findings were normal, duct excision procedures should be applied to exclude MIL or HIL, which can be a cause of discharge in case of suspicious color. The details in cytology reports have a role in increasing the value of cytology.

Breast Microinvasive Carcinoma With Different Morphologies: Analysis of Clinicopathologic Features of 121 Cases.

PURPOSE: To investigate the clinicopathological features of patients with breast microinvasive carcinoma (MI). METHODS: The clinical data of 121 cases with breast MI were retrospectively collected. The whole tumor in each case was stained with hematoxylin and eosin (H&E) for pathological evaluation. The relationships among size of tumor, histological grade, tumor-infiltrating lymphocytes (TILs), the number of MIs, type of MI, and lymph node metastasis were analyzed. RESULTS: It was revealed that 86% of the cases had high-grade ductal carcinoma in situ (DCIS) and 63.6% had multiple MIs. The larger size of the tumors, the higher the grade of DCIS, the more the number of MIs; 3.3% of cases had rich TILs (lymphocyte/stroma > 30%) in the DCIS, and 26.5% had rich TILs in MIs. The type A of MIs is characterized by single cells and small clusters of solid cells. Tumor cells in type B of MIs can form glandular ducts. Formal grading of microinvasive is challenging/impossible due to its limited size precluding a representative mitotic count. But nuclear grade and tubule (differentiation) grades can be reported. In addition, 72.7% of cases had type A of MIs and 27.3% of cases had type B of MIs. Type B was found to be highly accompanied by moderate-grade DCIS. Only 6.6% of patients with MI had lymph node metastasis, which was mainly related to MIs with less TILs. CONCLUSION: Breast MI is easy to occur in high-grade DCIS, and multiple infiltration foci may be observed in case with tumor size of higher than 3.5 cm. Microinvasive carcinoma with poor TILs maybe a risk factor for lymph node metastasis in patient with DCIS-Mi.