Intercepting Premalignant, Preinvasive Breast Lesions Through Vaccination

Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and chemoprevention remain the main risk-reducing modalities for those with hereditary cancer syndromes, as well as high-risk non-hereditary breast lesions such as ADH, ALH, or LCIS. Ductal carcinoma in situ (DCIS) is a preinvasive malignant lesion of the breast that closely mirrors IBC and, if left untreated, develops into IBC in up to 50% of lesions. Certain high-risk patients with DCIS may have a 25% risk of developing recurrent DCIS or IBC, even after surgical resection. The development of breast cancer elicits a strong immune response, which brings to prominence the numerous advantages associated with immune-based cancer prevention over drug-based chemoprevention, supported by the success of dendritic cell vaccines targeting HER2-expressing BC. Vaccination against BC to prevent or interrupt the process of BC development remains elusive but is a viable option. Vaccination to intercept preinvasive or premalignant breast conditions may be possible by interrupting the expression pattern of various oncodrivers. Growth factors may also function as potential immune targets to prevent breast cancer progression. Furthermore, neoantigens also serve as effective targets for interception by virtue of strong immunogenicity. It is noteworthy that the immune response also needs to be strong enough to result in target lesion elimination to avoid immunoediting as it may occur in IBC arising from DCIS. Overall, if the issue of vaccine targets can be solved by interrupting premalignant lesions, there is a potential to prevent the development of IBC.

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RETROSPECTIVE ANALYSIS OF MAMMOGRAM, SONOMAMMOGRAM AND ITS HISTOPATHOLOGICAL CORRELATION AS AN AID FOR DIAGNOSIS OF BREAST LESIONS

10.36106/ijsr/2803236 ◽

2021 ◽

pp. 1-4

Author(s):

Sathish babu ◽

Arifkhan Sainudeen ◽

Abdul Eksana

Keyword(s):

Breast Cancer ◽

Breast Imaging ◽

Ductal Carcinoma ◽

Histopathological Examination ◽

Benign Lesion ◽

Malignant Lesion ◽

Breast Lesions ◽

Care Hospital ◽

Malignant Breast ◽

Malignant Lesions

INTRODUCTION: Breast cancer is the most common cancer impacting 2.1 million women each year and also relates to the most cancer related deaths in women. In 2018, it was estimated that 627,000 women died from breast cancer which approximates to 15 % of all cancer related deaths among women [1]. The triple test– clinical examination, mammography and core biopsy helps in differentiating benign and malignant lesions. Histopathological examination is considered being the gold standard test for confirming malignant lesions and forms the basis of management. AIM: To assess sensitivity of mammogram with ultrasonography in diagnosing various breast lesions and to correlate the categorized breast lesions (BI-RADS) with histopathology reports and thereby obtain specificity and NPV of evaluation using Mammogram and ultrasonography. STUDY DESIGN: Retrospective analytical study. Study Period: July 2018 – July 2019. METHODS: The results of ultrasonography and mammography of 72 cases diagnosed clinically with breast lesions over the period of one year in tertiary health care hospital were compared with histopathology reports. RESULTS: The mean age of the patients was 45.65 ± 3.19. Our results showed that in histopathology reports in 20 patients (27.78%) were malignant, 51 cases (70.83%) had benign disease and 1 case 1.39% was borderline malignant. Fibroadenoma was the commonest benign lesion whereas infiltrating ductal carcinoma was the most common malignant lesion. Breast Imaging – Reporting and Data System (BIRADS) by mammogram revealed category II in 54.1%, III in 20.8%, IV in 16.6% and V in 8.3%. The specificity of mammography alone in diagnosing malignant breast lesions was 90.1%. When combined (ultrasound and mammogram), the specificity in diagnosing malignant breast lesion was 98.5% CONCLUSION: Mammography and sono-mammogram plays an important role in the diagnostic and surgical management of breast lesions with correlative histopathology evaluation. The diagnostic accuracy shows significant improvement when mammogram was combined with ultrasound correlation and thereby improving sensitivity and specificity of diagnosing malignant breast lesions.

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High Prevalence of Premalignant Lesions in Prophylactically Removed Breasts From Women at Hereditary Risk for Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2003.02.137 ◽

2003 ◽

Vol 21 (1) ◽

pp. 41-45 ◽

Cited By ~ 86

Author(s):

N. Hoogerbrugge ◽

P. Bult ◽

L.M. de Widt-Levert ◽

L.V. Beex ◽

L.A. Kiemeney ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Ductal Carcinoma In Situ ◽

Odds Ratio ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Prophylactic Mastectomy ◽

Premalignant Lesions ◽

Ductal Hyperplasia

Purpose: Women with a hereditary predisposition for breast cancer have an extremely high risk of developing invasive breast carcinoma, and many women consider prophylactic mastectomy to avoid this risk. The use of prophylactic mastectomy is still debated. Identification of frequent premalignant lesions in mastectomy specimens would support the preventive concept of prophylactic mastectomy. Patients and Methods: We performed a prospective study of breast specimens from 67 women at extremely high genetic risk of breast cancer, with or without previous breast cancer, who were undergoing prophylactic mastectomy (66% were carriers of a BRCA1 or BRCA2 mutation). Breast specimens were studied by radiographic and macroscopic examination of 5-mm tissue slices, with subsequent histology of suspicious lesions and random samples from each quadrant of the breast and the nipple area. Results: In 57% of the women, one or more different types of high-risk histopathologic lesions were present: 37% atypical lobular hyperplasia, 39% atypical ductal hyperplasia, 25% lobular carcinoma-in-situ, and 15% ductal carcinoma-in-situ. A 4-mm invasive ductal carcinoma was found in one woman with ductal carcinoma-in-situ. None of these lesions was detected at palpation or mammography, which were performed before the mastectomy. The presence of high-risk lesions was independently related to age older than 40 years (odds ratio, 6.6; P = .01) and to bilateral oophorectomy before prophylactic mastectomy (odds ratio, 0.2; P = 0.02). Conclusion: Many women at high risk of hereditary breast cancer develop high-risk histopathologic lesions, especially after the age of 40 years. Surveillance does not detect such high-risk histopathologic lesions.

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Invasive Mammary Paget Disease Without an Underlying Breast Cancer: A Case Report

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz113.016 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S43-S44 ◽

Cited By ~ 1

Author(s):

Alexis Bousamra ◽

Nazia Khatoon ◽

Ariel Sandhu ◽

Jan Silverman ◽

Mary Beth Malay

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Ductal Carcinoma ◽

Malignant Lesion ◽

Sentinel Lymph Nodes ◽

Fish Analysis ◽

Nipple Areolar Complex ◽

Paget Disease ◽

Areolar Complex ◽

Skin Punch Biopsy

Abstract Mammary Paget disease (MPD) is a malignant lesion of the nipple-areolar complex and considered an intraepidermal sign of an underlying invasive or in situ carcinoma. In rare instances, mammary Paget cells can invade the dermis. Comprehensive literature review identified 33 such cases. Here, we report a case of a 48-year-old female with invasive MPD, without an associated underlying breast cancer. Only five such presentations are reported. With a presentation of right nipple-areolar excoriation for 2 years, skin punch biopsy was performed and reported as “Paget disease.” Further evaluation with bilateral mammograms failed to show any primary mass or calcifications. Bilateral breast MRI revealed focal nonmass enhancement in upper outer quadrant in both breast, the biopsy of which showed benign breast tissue. Right breast nipple areolar complex resection demonstrated MPD extensively involving the epidermis. Multiple foci of invasive ductal carcinoma are present, growing downward into the nipple dermis, the largest focus being 0.2 cm in greatest dimension. No lymphovascular invasion is identified. The mammary Paget cells are positive for Cam 5.2 and epithelial membrane antigen (EMA) and negative for keratins 7 and 20. The invasive tumor cells are strongly positive for estrogen receptor (100%) and progesterone receptor (75%) and equivocal (2+) for Her2/Neu. FISH analysis showed amplification for HER2 (HER2/CEP17 ratio: 2.75). Four right axillary sentinel lymph nodes are negative for carcinoma. Two of the five patients with invasive MPD described in the literature, and without underlying breast cancer, had a sentinel lymph node biopsy performed. Isolated tumor clusters were present in one of these two cases. In summary, we describe a rare case of invasive MPD without an underlying breast cancer. Although sentinel lymph nodes are important to assess metastasis, further cases are required to evaluate the significance and prognosis of this rare entity.

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Histological Assessment of Breast Lesions Identified Exclusively by Magnetic Resonance

The American Surgeon ◽

10.1177/000313481408001007 ◽

2014 ◽

Vol 80 (10) ◽

pp. 944-947

Author(s):

Victoria O'connor ◽

Elizabeth Arena ◽

Joslyn Albright ◽

Nefertiti Brown ◽

Ryan O'connor ◽

...

Keyword(s):

Breast Cancer ◽

Magnetic Resonance ◽

Breast Biopsy ◽

Ductal Carcinoma ◽

Low Grade ◽

Breast Lesions ◽

Significant Family History ◽

Ductal Hyperplasia ◽

Significant Pathology

Radiologic–pathologic correlation of lesions diagnosed by magnetic resonance (MR) is precluded by insufficient data on histological characteristics of lesions suspicious on MR but not visible on concurrent mammogram or ultrasound. The objective of this study was to describe histological features of breast lesions diagnosed exclusively by MR. The participants underwent MR-guided breast biopsy between 2007 and 2012 for a suspicious lesion not identified by mammography or ultrasound. Histology slides were interpreted retrospectively by a breast pathologist. Of 126 patients (126 lesions), 34 (27%) had new breast cancer, 51 (40.5%) previous breast cancer, and 41 (32.5%) dense breasts or a significant family history of breast cancer. MR identified 23 (18.3%) invasive cancers: 20 were Grade 1 and 17 were ductal. Of the 126 lesions, 16 (13%) were ductal carcinoma in situ (DCIS), four were atypical ductal hyperplasia and atypical lobular hyperplasia (3%), and 68 (54%) were benign. Fifteen biopsies (12%) had no significant pathology. Five DCIS lesions were upgraded to T1 invasive cancers. Approximately 30 per cent of suspicious lesions detected exclusively by MR are invasive or in situ cancers that are predominantly low grade. Further studies are needed to determine if malignant lesions can be prospectively distinguished by MR characteristics.

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Serum ANGPTL2 Levels Reflect Clinical Features of Breast Cancer Patients: Implications for the Pathogenesis of Breast Cancer Metastasis

The International Journal of Biological Markers ◽

10.5301/jbm.5000080 ◽

2014 ◽

Vol 29 (3) ◽

pp. 239-245 ◽

Cited By ~ 22

Author(s):

Motoyoshi Endo ◽

Yutaka Yamamoto ◽

Masahiro Nakano ◽

Tetsuro Masuda ◽

Haruki Odagiri ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Clinical Features ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

Ductal Carcinoma ◽

Breast Cancer Metastasis ◽

Breast Cancer Patients

Introduction Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression. Methods We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients. Results Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades. Conclusions These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.

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Promoter Hypermethylation and Suppression of Glutathione Peroxidase 3 Are Associated with Inflammatory Breast Carcinogenesis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2014/787195 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 22

Author(s):

Mona M. Mohamed ◽

Salwa Sabet ◽

Dun-Fa Peng ◽

M. Akram Nouh ◽

Mohamed El-Shinawi ◽

...

Keyword(s):

Breast Cancer ◽

Glutathione Peroxidase ◽

Cancer Progression ◽

Epigenetic Regulation ◽

Ductal Carcinoma ◽

Methylation Status ◽

Promoter Hypermethylation ◽

Normal Breast ◽

Glutathione Peroxidase 3 ◽

Breast Tissues

Reactive oxygen species (ROS) play a crucial role in breast cancer initiation, promotion, and progression. Inhibition of antioxidant enzymes that remove ROS was found to accelerate cancer growth. Studies showed that inhibition of glutathione peroxidase-3 (GPX3) was associated with cancer progression. Although the role of GPX3 has been studied in different cancer types, its role in breast cancer and its epigenetic regulation have not yet been investigated. The aim of the present study was to investigate GPX3 expression and epigenetic regulation in carcinoma tissues of breast cancer patients’ in comparison to normal breast tissues. Furthermore, we compared GPX3 level of expression and methylation status in aggressive phenotype inflammatory breast cancer (IBC) versus non-IBC invasive ductal carcinoma (IDC). We found that GPX3 mRNA and protein expression levels were downregulated in the carcinoma tissues of IBC compared to non-IBC. However, we did not detect significant correlation between GPX3 and patients’ clinical-pathological prosperities. Promoter hypermethylation of GPX3 gene was detected in carcinoma tissues not normal breast tissues. In addition, IBC carcinoma tissues showed a significant increase in the promoter hypermethylation of GPX3 gene compared to non-IBC. Our results propose that downregulation of GPX3 in IBC may play a role in the disease progression.

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Upgrade of high-risk breast lesions detected on mammography in the Breast Cancer Surveillance Consortium

The American Journal of Surgery ◽

10.1016/j.amjsurg.2013.05.014 ◽

2014 ◽

Vol 207 (1) ◽

pp. 24-31 ◽

Cited By ~ 45

Author(s):

Tehillah S. Menes ◽

Robert Rosenberg ◽

Steven Balch ◽

Shabnam Jaffer ◽

Karla Kerlikowske ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Surveillance ◽

Breast Lesions ◽

Breast Cancer Surveillance Consortium ◽

High Risk Breast

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Breast Cancer Chemoprevention among High-risk Women and those with Ductal Carcinoma In Situ

The Breast Journal ◽

10.1111/tbj.12418 ◽

2015 ◽

Vol 21 (4) ◽

pp. 377-386 ◽

Cited By ~ 21

Author(s):

Laura L. Reimers ◽

Parijatham S. Sivasubramanian ◽

Dawn Hershman ◽

Mary Beth Terry ◽

Heather Greenlee ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Ductal Carcinoma In Situ ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Cancer Chemoprevention ◽

High Risk Women ◽

Breast Cancer Chemoprevention

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Prevalence of c-myc expression in breast lesions associated with microcalcifications detected by routine mammography

Sao Paulo Medical Journal ◽

10.1590/s1516-31802009000200003 ◽

2009 ◽

Vol 127 (2) ◽

pp. 66-70 ◽

Cited By ~ 2

Author(s):

Renato Coimbra Mazzini ◽

Simone Elias ◽

Afonso Celso Pinto Nazário ◽

Cláudio Kemp ◽

Ângela Flávia Logullo

Keyword(s):

Breast Imaging ◽

Ductal Carcinoma ◽

Percutaneous Biopsy ◽

Screening Mammography ◽

University Hospital ◽

Premalignant Lesions ◽

Breast Lesions ◽

Benign Lesions ◽

Cross Sectional ◽

Malignant Lesions

CONTEXT AND OBJECTIVE: Genetic abnormalities in cell proliferation-regulating genes have been described in premalignant lesions. The aims here were to evaluate c-myc protein expression in non-palpable breast lesions associated with microcalcifications, detected by screening mammography, and to compare these results with histopathological, clinical and epidemiological variables. DESIGN AND SETTING: Analytical cross-sectional study, with retrospective data collection, in a university hospital in São Paulo. METHODS: Seventy-nine female patients who underwent routine mammography between 1998 and 2004 were studied. Lesions classified by the Breast Imaging Reporting and Data System (BI-RADS) as 4 or 5 underwent percutaneous biopsy using a large-core needle. Ninety-eight lesions were studied anatomopathologically. Paraffin blocks properly representing the lesions were selected for immunohistochemical analyses using the streptavidin-biotin-peroxidase technique with monoclonal mouse c-myc antibodies. RESULTS: Among the 98 lesions, 29 (29.6%) contained malignant neoplasia; 40 (40.8%) had a positive immunohistochemical reaction for c-myc. When the groups were divided between lesions without atypias versus atypical lesions plus malignant lesions, 31.03% of the 58 lesions without atypias were positive for c-myc and 55% of the 40 malignant and atypical lesions (P = 0.018). Comparing the atypical lesions with ductal carcinoma in situ versus the benign lesions without atypias, c-myc was present in 51.61% of the 31 atypical lesions and 31.03% of the benign lesions without atypias (P = 0.057). CONCLUSION: C-myc protein was more frequently expressed in atypical and malignant lesions than in benign lesions without atypias. C-myc expression correlated with the presence of atypias (P = 0.018).

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Transcriptome and genome evolution during HER2-amplified breast neoplasia

Breast Cancer Research ◽

10.1186/s13058-021-01451-6 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Peipei Lu ◽

Joseph Foley ◽

Chunfang Zhu ◽

Katherine McNamara ◽

Korsuk Sirinukunwattana ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Ductal Carcinoma ◽

Copy Number Variations ◽

Neoplastic Progression ◽

Interferon Signaling ◽

Her2 Amplification ◽

Cancer Multiple ◽

Spatially Oriented

Abstract Background The acquisition of oncogenic drivers is a critical feature of cancer progression. For some carcinomas, it is clear that certain genetic drivers occur early in neoplasia and others late. Why these drivers are selected and how these changes alter the neoplasia’s fitness is less understood. Methods Here we use spatially oriented genomic approaches to identify transcriptomic and genetic changes at the single-duct level within precursor neoplasia associated with invasive breast cancer. We study HER2 amplification in ductal carcinoma in situ (DCIS) as an event that can be both quantified and spatially located via fluorescence in situ hybridization (FISH) and immunohistochemistry on fixed paraffin-embedded tissue. Results By combining the HER2-FISH with the laser capture microdissection (LCM) Smart-3SEQ method, we found that HER2 amplification in DCIS alters the transcriptomic profiles and increases diversity of copy number variations (CNVs). Particularly, interferon signaling pathway is activated by HER2 amplification in DCIS, which may provide a prolonged interferon signaling activation in HER2-positive breast cancer. Multiple subclones of HER2-amplified DCIS with distinct CNV profiles are observed, suggesting that multiple events occurred for the acquisition of HER2 amplification. Notably, DCIS acquires key transcriptomic changes and CNV events prior to HER2 amplification, suggesting that pre-amplified DCIS may create a cellular state primed to gain HER2 amplification for growth advantage. Conclusion By using genomic methods that are spatially oriented, this study identifies several features that appear to generate insights into neoplastic progression in precancer lesions at a single-duct level.

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