Precursor Lesions Of Breast Cancer Research Articles

Prediction of Subclinical and Clinical Multiple Organ Failure Dysfunction in Breast Cancer Patients-A Review Using AI Tools.

This review explores the interconnection between precursor lesions of breast cancer (typical ductal hyperplasia, atypical ductal/lobular hyperplasia) and the subclinical of multiple organ failure syndrome, both representing early stages marked by alterations preceding clinical symptoms, undetectable through conventional diagnostic methods. Addressing the question "Why patients with breast cancer exhibit a tendency to deteriorate", this study investigates the biological progression from a subclinical multiple organ failure syndrome, characterized by insidious but indisputable lesions, to an acute (clinical) state resembling a cascade akin to a waterfall or domino effect, often culminating in the patient's demise. A comprehensive literature search was conducted using PubMed, Google Scholar, and Scopus databases in October 2023, employing keywords such as "MODS", "SIRS", "sepsis", "pathophysiology of MODS", "MODS in cancer patients", "multiple organ failure", "risk factors", "cancer", "ICU", "quality of life", and "breast cancer". Supplementary references were extracted from the retrieved articles. This study emphasizes the importance of early identification and prevention of the multiple organ failure cascade at the inception of the malignant state, aiming to enhance the quality of life and extend survival. This pursuit contributes to a deeper understanding of risk factors and viable therapeutic options. Despite the existence of the subclinical multiple organ failure syndrome, current diagnostic methodologies remain inadequate, prompting consideration of AI as an increasingly crucial tool for early identification in the diagnostic process.

Papillomatous breast lesions with atypical columnar cell features

AimsColumnar cell lesions (CCLs) are recognised breast cancer precursor lesions. Intraductal papillomas are usually lined by benign (polyclonal) cells. Although papillomas with monoclonal lesions (atypical ductal hyperplasia (ADH)/ductal carcinoma in...

Investigation of breast pathologies in medical students and their families

Introduction: Breast diseases include benign and malignant pathologies. However, during the differential diagnosis, it is important to distinguish benign pathology, precursor lesions of breast cancer, and malignant breast neoplasm. We believe that research among medical students on the prevalence of breast pathologies in this population and their families is important in addition to identifying patients at high familial risk for breast and/or ovarian cancer and awakening the interest of other medical students in this topic. The objective of this study was to analyze the prevalence of benign and malignant breast pathologies among medical students and their families. Methods: This is a quantitative analytical cross-sectional study. Female medical students over 18 years old were included in the study. Data collection was carried out using an online questionnaire. It was approved by the Research Ethics Committee under CAAE Protocol No. 51338121.0.0000.5515, and each participant consented through the free and informed consent form (TCLE). Results: A total of 303 medical students responded to the questionnaire and were included in the study. Around 13.5% of participants reported having had some breast pathology, 76.2% of which were cases of breast lumps. The average age of participants was 22.9 years (ranging between 18 and 53 years). The average age of family members at diagnosis (a sample of 69 women) was 57.1 years (ranging between 29 and 84 years). There was an association between the prevalence of breast pathologies and a family history of breast cancer (OR=1.712 [0.818; 3.585]). Conclusion: From the results, it appears that 13.5% of the participants had already been diagnosed with breast pathology, and 20.8% of these reported a family history of breast cancer. In this way, we can affirm the contribution of the study in the evaluation of screening criteria for breast and neoplasms and thus increase the detection rate and carry out early therapy.

Clinical significance of pathologically detected lesions in reduction mammoplasty

Background/Aim: Breast reduction surgery is performed for various reasons, especially macromastia. Although the mammoplasty material obtained after surgery is generally accepted as normal breast tissue, incidental breast cancer or precursor lesions of breast cancer are also observed in these materials. Detection of these lesions will provide important information both for the risk developing breast cancer in the normal population and for the early treatment of these lesions. Our study aimed to investigate the rate of occurrence of high-risk lesions, such as atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and carcinoma in situ (DCIS, LCIS) and the relationship of these lesions with patient age and weight of the resected material. Methods: This study was a retrospective cohort study examining incidentally detected pathological lesions after examining reduction mammoplasty materials after breast reduction in our pathology department between 2011 and 2021. None of the cases had been previously diagnosed with breast cancer. The cases were pathologically classified as benign lesions, high-risk lesions with atypia, and in situ carcinoma. The association of atypical high-risk lesions with age (> 40 and ≤ 40 years) and resection weight was evaluated. Results: The surgical materials of 288 breasts were evaluated in a total of 144 women. The mean age of the patients was 38.9 years. Atypical high-risk lesions, such as ADH, ALH, and DCIS were detected in seven patients (4.8%). İnvasive cancer was not observed. The mean age of the patients with risky lesions was 45.98 years, and the mean weight of these lesions was 2,045 grams. Cases with high-risk lesions were older (P = 0.041) and had a higher resection weight (P = 0.003). Conclusion: The findings in our study reveal the necessity for mandatory histopathological examination of reduction mammoplasty materials. This examination is even more important in terms of high-risk lesion detection, especially in patients over 40 years and those with a high resection weight. In these cases, taking more tissue samples than used for the other situation for examination is recommended.

Nipple Adenoma Treated with Nipple Preservation in Young Female Patient: A Report of 2 Cases

Adenoma of the nipple is a rare benign type of breast that occurs most often in middle-aged women with nipple discharge, skin erosion in addition to crusting, inflammation, and pain. It can be clinically confused with Paget’s disease or breast cancer precursor lesions, such as ductal carcinoma in situ low grade. The treatment of choice for nipple adenoma is complete excision of the tumor. However in younger women, nipple preservation is required. We present two cases of nipple adenoma that were completely removed with nipple preservation.

Alternations of N-glycans recognized by Phaseolus vulgaris leucoagglutinin in the saliva of patients with breast cancer.

Breast cancer is the most frequently diagnosed cancer in most countries. Early diagnosis of breast disease is necessary for its prognosis and treatment. Altered protein glycosylation has been shown to be expressed in precursor lesions of breast cancer, making them powerful early diagnostic biomarkers. The present study validated alterations of the N-glycan profiles of their salivary glycoproteins isolated by the Phaseolus vulgaris leucoagglutinin (PHA-E+L)-magnetic particle conjugates from 141 female subjects (66 healthy volunteers (HV), and 75 patients with breast disease including breast benign cyst (BB) or breast cancer in stage I/II (BC-I/II)) were analyzed and annotated by MALDI-TOF/TOF-MS. The results showed that there were 11, 20, 16, and 17 N-glycans recognized by PHA-E+L identified and annotated from the pooled salivary samples of HV, BB, BC-I, and BC-II, respectively. There were 3 N-glycans peaks (m/z 2459.8799, 2507.9139, and 2954.0547), 2 N-glycans peaks (m/z 1957.7265 and 2794.0427), and 2 N-glycans peaks (m/z 1866.6608 and 2240.8056) recognized by PHA-E+L that existed only in BB, BC-I, and BC-II, respectively. The present study compared the alternations of N-glycans from the salivary proteins isolated by PHA-E+L-magnetic particle conjugates among HV, BB, BC-I, and BC-II, which could provide information on N-glycans during the development of breast cancer in saliva to promote the study of its biomarkers.

Detection of breast cancer precursor lesions by autofluorescence ductoscopy

PurposeAutofluorescence is an image enhancement technique used for the detection of cancer precursor lesions in pulmonary and gastrointestinal endoscopy. This study evaluated the feasibility of addition of autofluorescence to ductoscopy for the detection of intraductal breast cancer precursor lesions.MethodsAn autofluorescence imaging system, producing real-time computed images combining fluorescence intensities, was coupled to a conventional white light ductoscopy system. Prior to surgery, ductoscopy with white light and autofluorescence was evaluated under general anaesthesia in women scheduled for therapeutic or prophylactic mastectomy. Endoscopic findings in both modes were compared, marked and correlated with histology of the surgical specimen.ResultsFour breast cancer patients and five high-risk women, with a median age of 47 years (range 23–62) were included. In autofluorescence mode, two intraductal lesions were seen in two breast cancer patients, which had an increase in the red-to-green fluorescence intensity compared with the surrounding tissue. One lesion had initially been missed by white light ductoscopy but was clearly visible in subsequent autofluorescence mode. One endoscopic finding was classified as suspicious by white light, but was negative in autofluorescence mode and showed normal histology.ConclusionsThis study demonstrates for the first time the in vivo feasibility of autofluorescence ductoscopy to detect pathologically confirmed breast cancer precursor lesions in both breast cancer patients and high-risk women that were occult under white light.

Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer

BackgroundInsights into the molecular pathogenesis of breast cancer might come from molecular analysis of tissue from early stages of the disease.MethodsWe conducted a case–control study nested in a cohort of women who had biopsy-confirmed benign breast disease (BBD) diagnosed between 1971 and 2006 at Kaiser Permanente Northwest and who were followed to mid-2015 to ascertain subsequent invasive breast cancer (IBC); cases (n = 218) were women with BBD who developed subsequent IBC and controls, individually matched (1:1) to cases, were women with BBD who did not develop IBC in the same follow-up interval as that for the corresponding case. Targeted sequence capture and sequencing were performed for 83 genes of importance in breast cancer.ResultsThere were no significant case–control differences in mutation burden overall, for non-silent mutations, for individual genes, or with respect either to the nature of the gene mutations or to mutational enrichment at the pathway level. For seven subjects with DNA from the BBD and ipsilateral IBC, virtually no mutations were shared.ConclusionsThis study, the first to use a targeted multi-gene sequencing approach on early breast cancer precursor lesions to investigate the genomic basis of the disease, showed that somatic mutations detected in BBD tissue were not associated with breast cancer risk.

Male breast cancer precursor lesions: analysis of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program

In men, data regarding breast cancer carcinogenesis are limited. The aim of our study was to describe the presence of precursor lesions adjacent to invasive male breast cancer, in order to increase our understanding of carcinogenesis in these patients. Central pathology review was performed for 1328 male breast cancer patients, registered in the retrospective joint analysis of the International Male Breast Cancer Program, which included the presence and type of breast cancer precursor lesions. In a subset, invasive breast cancer was compared with the adjacent precursor lesion by immunohistochemistry (n=83) or targeted next generation sequencing (n=7). Additionally, we correlated the presence of ductal carcinoma in situ with outcome. A substantial proportion (46.2%) of patients with invasive breast cancer also had an adjacent precursor lesion, mainly ductal carcinoma in situ (97.9%). The presence of lobular carcinoma in situ and columnar cell-like lesions were very low (<1%). In the subset of invasive breast cancer cases with adjacent ductal carcinoma in situ (n=83), a complete concordance was observed between the estrogen receptor, progesterone receptor, and HER2 status of both components. Next generation sequencing on a subset of cases with invasive breast cancer and adjacent ductal carcinoma in situ (n=4) showed identical genomic aberrations, including PIK3CA, GATA3, TP53, and MAP2K4 mutations. Next generation sequencing on a subset of cases with invasive breast cancer and an adjacent columnar cell-like lesion showed genomic concordance in two out of three patients. A multivariate Cox model for survival showed a trend that the presence of ductal carcinoma in situ was associated with a better overall survival, in particular in the Luminal B HER2+ subgroup. In conclusion, ductal carcinoma in situ is the most commonly observed precursor lesion in male breast cancer and its presence seems to be associated with a better outcome, in particular in Luminal B HER2+ cases. The rate of lobular carcinoma in situ and columnar cell-like lesions adjacent to male breast cancer is very low, but our findings support the role of columnar cell-like lesions as a precursor of male breast cancer.

Adenoma of the nipple: A clinicopathological report of 13 cases.

Adenoma of the nipple (AN) represents a rare benign mammary proliferation of lactiferous ducts. It appears as an erosive or ulcerative lesion, which in a number of cases is associated with a serous/hematic secretion. AN may be clinically confused with Paget’s disease and histologically with invasive breast carcinoma or breast cancer precursor lesions. Therefore, the histological and immunophenotypic analysis is essential for the differential diagnosis. The present study describes the histopathological characteristics of a first case series of AN.

Prognostic value of molecular markers and cytogenetic alterations that characterize breast cancer precursor lesions (Review)

The understanding of the molecular mechanisms that underlie all stages of tumor progression in breast cancer (BC) represents an important goal in the biomedical research of this disease, particularly for the identification of more specific targeted therapies. In this context, BC preinvasive and precursor lesions represent a major dilemma. These lesions are well characterized under the phenotypic and genotypic profile, but it is not clear if they represent obligatory passages of a multistep process determining breast cancer evolution. In fact, the numerous cytogenetic and molecular alterations identified are not always representative of the progression into invasive phenotypes.

Abstract P3-04-02: Promoter CpG Island Hypermethylation along Multistep Carcinogenesis of Breast Cancer

Abstract Background: In breast cancer, promoter CpG island hypermethylation has been described for various genes in all aspects of cellular function. However, most studies focused on the methylation status in tumor-related genes in invasive breast cancer, compared to normal breast tissue, and methylation studies of potential precursor lesions of breast cancer were sparse. We investigated the changes in promoter CpG islands hypermethylation during breast cancer progression from intraductal proliferative lesions [usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS)] to invasive ductal carcinoma (IDC) of breast, and tried to find the specific changes in each step of tumorigenesis. Materials and Methods: We performed MethyLight analyses for methylation status of 57 CpG island loci in 20 IDCs and its paired normal breast tissues. After selecting 15 CpG island loci showing cancer-specific DNA methylation, another sets of normal breast tissue from non-cancer patients (n=10), UDH (n=10), ADH (n=20), DCIS (n=30) and IDC (n=30) were analyzed for these loci. Results: By this approach, we found six new methylation markers of breast cancer including DLEC1, GRIN2B, HOXA1, MT1G, SFRP4 and TMEFF2, as well as APC, GSTP1, HOXAIO, IGF2, RARB, RASSF1A, RUNX3, SCGB3A1 (HIN-1) and SFRP1. The number of methylated genes showed stepwise increase from normal breast to ducal hyperplasia (DH) and DCIS, while IDC showed no difference with DCIS (median, 1 for normal breast, 2 for DH, 5 for DCIS, 6 for IDC; P&amp;lt;0.001). Of the 15 CpG island loci tested, nine loci already showed methylation in normal breast tissue. Methylation of RASSF1A, DLEC1 and SCGB3A1 (HIN-1) promoter CpG islands was significantly higher in DH than in normal breast tissues. Eight CpG island loci (APC, GRIN2B, GSTP1, HOXA1, RARB, RUNX3, SFRP1 and TMEFF2) showed higher methylation frequency and levels in DCIS compared to DH. DICS and IDC showed no difference in the methylation levels or frequency in the 14 CpG islands except HOXA10. Discussion: Our results indicated that CpG island methylation of tumor-related genes is an early event and accumulate with breast cancer progression. CpG island methylation was significantly changed during the progression of DH to DCIS, and DCIS showed similar CpG island methylation with IDC, suggesting that the transition of DH to DCIS is a critical step for breast cancer tumorigenesis associated with promoter CpG islands hypermethylation. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-04-02.

Molekulare Pathologie beim Mammakarzinom

Die Analyse der Genexpressionsmuster beim Mammakarzinom hat eine Klassifikation dieser Tumoren in funf verschiedene molekulare Subtypen (luminal A und B, HER2-Uberexpression, basaler Phanotyp und normaler Phanotyp) ermoglicht, die sich durch prognostische und therapeutische Unterschiede auszeichnen. Diese molekulare Klassifikation des Mammakarzinoms kann mit einer begrenzten Zahl immunhistochemischer Marker annaherungsweise reproduziert werden, allerdings gibt es noch keinen Konsens, was die Selektion der Marker und die Schwellenwerte betrifft. Der Einsatz dieser Klassifikation wird in Zukunft helfen, zielgerichtete Therapien mit den tumorbiologisch klar definierten Subgruppen zu korrelieren, und dadurch die Aussagekraft klinischer Studien verbessern. Die verschiedenen molekularen Subtypen gehen aus histologisch unterschiedlichen Vorlauferlasionen und Differenzierungswegen hervor. Zu den Vorlauferlasionen mit geringem Risiko zahlen atypische Zylinderepithelveranderungen, atypische duktale Epithelhyperplasien und lobulare Neoplasien. Diese Lasionen stellen fakultative prakanzerose Lasionen des niedrigmalignen Mammakarzinoms dar.

GSTP1 promoter hypermethylation during breast cancer development.

Abstract Abstract #5042 Background. Promoter hypermethylation in precursor lesions of the breast cancer may be biomarkers of cancer risk and targets for cancer chemoprevention. GSTP1 is inactivated by promotor hypermethylation in invasive breast cancers. However, little is known about epigenetic silencing of GSTP1 gene by promoter hypermethylation in precursor lesions.&amp;#x2028; Method. To determine the significance of GSTP1 promoter hypermethylation in breast carcinogenesis, methylation status of GSTP1 gene was studied by nested methylation-specific PCR and GSTP1 expression was studied by immunohistochemistry in invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), usual ductal hyperplasia (UDH) and normal breast tissue.&amp;#x2028; Results. GSTP1 promoter hypermethylation was detected in 4/24 (16.7%) of UDH, 18/49 (36.7%) of DCIS, and 14/36 (38.9%) of IDC. No hypermethylation was detected in normal breast tissues. GSTP1 promoter hypermethylation was found to be progressively elevated during breast carcinogenesis (P &amp;lt; 0.01). GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (P &amp;lt; 0.01 for UDH, P &amp;lt; 0.001 for DCIS and IDC).&amp;#x2028; Conclusion. Our results suggest that GSTP1 promoter hypermethylation is an early event in breast carcinogenesis and appears to functionally silence GSTP1 expression. GSTP1 promoter hypermethylation in the precursor lesions of breast cancer may be used as a target for cancer chemoprevention. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5042.

GSTP1 promoter hypermethylation is an early event in breast carcinogenesis

Promoter hypermethylation in precursor lesions of the breast cancer may be biomarkers of cancer risk and targets for cancer chemoprevention. Pi-class glutathione-S-transferases (GSTP1) is inactivated by promoter hypermethylation in invasive breast cancers. However, little is known about epigenetic silencing of GSTP1 gene by promoter hypermethylation in precursor lesions. To determine the significance of GSTP1 promoter hypermethylation in breast carcinogenesis, methylation status of GSTP1 gene was studied by nested methylation-specific polymerase chain reaction, and GSTP1 expression was studied by immunohistochemistry in invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), usual ductal hyperplasia (UDH), and normal breast tissue. GSTP1 promoter hypermethylation was detected in 4/24 (16.7%) of UDH, 18/49 (36.7%) of DCIS, and 14/36 (38.9%) of IDC. No hypermethylation was detected in normal breast tissues. GSTP1 promoter hypermethylation was found to be progressively elevated during breast carcinogenesis (p < 0.01). GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (p < 0.01 for UDH, p < 0.001 for DCIS and IDC). Our results suggest that GSTP1 promoter hypermethylation is an early event in breast carcinogenesis and appears to functionally silence GSTP1 expression. GSTP1 promoter hypermethylation in the precursor lesions of breast cancer may be used as a target for cancer chemoprevention.

Ductal-lobar organisation of human breast tissue, its relevance in disease and a research objective: vector mapping of parenchyma in complete breasts (the Astley Cooper project)

A human breast has many lobes, which are highly variable in size and shape, each with one central duct, its peripheral branches and their associated glandular tissues. Realising the potential of new endoductal approaches to breast diagnosis and improving our understanding of breast cancer precursors will require greatly improved knowledge of this ductal-lobar anatomy and the distribution of cancer precursors within it. This architecture is very challenging to study in its entirety: whole-breast lobe mapping has only been achieved for two human breasts. Clearly, much more efficient techniques are required. Streamlined data capture and visualisation of breast parenchymal anatomy from thin and thick sections in a vector format would allow integrated mapping of whole-breast structure with conventional histology and molecular data. The 'Astley Cooper digital breast mapping project' is proposed as a name for this achievable research objective. Success would offer new insights into the development of breast cancer precursor lesions, allow testing of the important 'sick lobe' hypothesis, improve correlation with imaging studies and provide 'ground truth' for mathematical modelling of breast growth.

Telomere length abnormalities occur early in the initiation of epithelial carcinogenesis.

Telomeres help maintain chromosomal integrity. Dysfunctional telomeres can cause genetic instability in vitro and an increased cancer incidence in telomerase knock out mouse models. We recently reported that telomere shortening was a prevalent alteration in human prostate, pancreas, and breast cancer precursor lesions. In the present study, we address whether the previous findings are broadly applicable to human epithelial cancer precursors in general. Surgical specimens of epithelial cancer precursor lesions from the urinary bladder, esophagus, large intestine, oral cavity, and uterine cervix were examined using a recently developed technique for direct in situ telomere length assessment in formalin-fixed human tissue specimens. Widespread telomere length abnormalities were nearly universal (97.1% of cases) in the preinvasive stages of human epithelial carcinogenesis in all sites examined in this series, with telomere shortening the predominant abnormality (88.6% of cases). Telomere length abnormalities appear to be one of the earliest and most prevalent genetic alterations acquired in the multistep process of malignant transformation. These findings support a model whereby telomere dysfunction induces chromosomal instability as an initiating event in many, perhaps most, human epithelial cancers. Together with previous findings from the prostate and pancreas, the percentage of intraepithelial neoplasia lesions showing telomere length abnormalities is 95.6%. The implications of these findings include the potential that telomere length assessment in situ may be a widely useful biomarker for monitoring disease prevention strategies and for improved early diagnosis.

C- erbB-2 amplification in breast cancer: Detection in formalin-fixed, paraffin-embedded tissue by in situ hybridization

We describe a sensitive and practical in situ hybridization method, using a digoxigenin-labeled probe, for the detection of c- erbB-2 amplification in breast cancer in formalin-fixed, paraffin-embedded tissue sections. Forty-six primary breast carcinomas were studied. Nuclear hybridization signal was observed in 36 of 46 carcinomas. Signal was confined to malignant cells. Normal breast epithelium and stromal and inflammatory cells were uniformally negative. DNase predigestion, no-probe preparations, and competitive hybridization confirmed the specificity of the reaction. The hybridization reaction was localized to multiple discrete foci in tumor cell nuclei, suggesting multiple sites of gene copy and transcriptional activity in the nucleus. Considerable cell-to-cell variation in hybridization signal was evident within individual tumors and positive reactions were observed in several cases in which amplification could not be detected by either Southern or slot blot analysis. The high sensitivity and specificity of the reaction and its use in a tissue-based system will allow the study of a range of possible precursor lesions of breast cancer for evidence of c- erbB-2 amplification.

Detection of c-erbB-2 amplification in breast cancer by in situ hybridization

An in situ hybridization method, using digoxigenin labelling, for the detection of c-erbB-2 amplification in breast cancer is described. 16 primary breast carcinomas were selected for study. Nuclear hybridization signal was observed in nine cases with amplification detected by both Southern and slot blotting and in only one of seven cases without detected amplification. The hybridization reaction was punctate and multifocal in tumour cell nuclei, suggesting multiple sites of gene copy and transcriptional activity in the nucleus. The hybridization reaction was negative in three cases in which overexpression of oncoprotein (detected by immunocytochemistry and ELISA) occured without amplification. The method described is a reliable means of detecting c-erbB-2 amplification. The high sensitivity and specificity of the reaction and its use in a tissue based system will allow study of a range of possible precursor lesions of breast cancer for evidence of c-erbB-2 amplification.