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Advances in Breast Disease: From Screening to Diagnosis and Therapy

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (1 December 2023) | Viewed by 24296

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Dr. Giada Maria Vecchio

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Anatomic Pathology, Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy
Interests: surgical pathology; breast pathology; immunohistochemistry; oncology; gynecopathology

Dr. Isabella Castellano

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Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Interests: breast pathology; immunohistochemistry; molecular biology; oncology
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Dr. Lorenzo Memeo

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Pathology Unit, Department of Experimental Oncology, Mediterranean Institute of Oncology, 95029 Catania, Italy
Interests: gastrointestinal tumors; endocrine tumors; urological tumors; breast tumors
Special Issues, Collections and Topics in MDPI journals

Dr. Antonio Rizzo

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Guest Editor Assistant

Humanitas Clinical Institute, 95029 Catania, Italy
Interests: gastrointestinal tumors; thoracic tumors; urological tumors; breast tumors

Special Issue Information

Dear Colleagues,

Research in the field of breast pathology is a currently evolving topic. There are many innovations in the diagnosis of both benign and malignant breast lesions. Although it is advisable to identify more and more biological factors with prognostic value or acting as predictors of therapeutic response, mainly in the field of breast carcinoma, there is also the need to focus on fibroepithelial entities that represent a well-defined but heterogeneous spectrum of lesions (i.e., phylloidtumors) or underrecognized/not well-defined non-fibroadenomas/phylloid tumors’ stromo-epithelial lesions. Accordingly, this Special Issue is dedicated to updates in breast cancer and phylloid tumors from radiological/pathological diagnosis to therapy. In addition, proposals for new benign and/or malignant entities are welcomed.

Dr. Giada Maria Vecchio
Dr. Isabella Castellano
Dr. Lorenzo Memeo
Guest Editors

Dr. Antonio Rizzo
Guest Editor Assistant

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Keywords

prognostic and predictive factors
breast carcinoma
phylloid tumor
immunohistochemistry
molecular biology
stromo-epithelial lesion
diagnosis
therapy

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Published Papers (10 papers)

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Research

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15 pages, 1632 KiB

Open AccessArticle

Digital Mammography (DM) vs. Dynamic Contrast Enhancement-Magnetic Resonance Imaging (DCE-MRI) in Microcalcifications Assessment: A Radiological–Pathological Comparison

by Federica Cicciarelli, Elisa Guiducci, Francesca Galati, Giuliana Moffa, Paolo Ricci, Federica Pediconi and Veronica Rizzo

Diagnostics 2024, 14(11), 1063; https://doi.org/10.3390/diagnostics14111063 - 21 May 2024

Viewed by 1224

Abstract

The aim of this study was to compare the characteristics of breast microcalcification on digital mammography (DM) with the histological and molecular subtypes of breast cancer and to identify the predictive value of DM and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing microcalcifications for radiologic–pathologic correlation. We relied on our prospectively maintained database of suspicious microcalcifications on DM, from which data were retrospectively collected between January 2020 and April 2023. We enrolled 158 patients, all of whom were subjected to biopsy. Additionally, 63 patients underwent breast DCE-MRI. Microcalcifications with a linear branched morphology were correlated with malignancies (p < 0.001), among which an association was highlighted between triple negatives (TNs) and segmental distribution (p < 0.001). Amorphous calcifications were correlated with atypical ductal hyperplasia (ADH) (p = 0.013), coarse heterogeneous (p < 0.001), and fine-pleomorphic (p = 0.008) with atypical lobular hyperplasia (ALH) and fine pleomorphic (p = 0.009) with flat epithelial atypia (FEA). Regarding DCE-MRI, no statistical significance was observed between non-mass lesions and ductal carcinoma in situ (DCIS). Concerning mass lesions, three were identified as DCIS and five as invasive ductal carcinoma (IDC). In conclusion, microcalcifications assessed in DM exhibit promising predictive characteristics concerning breast lesion subtypes, leading to a reduction in diagnostic times and further examination costs, thereby enhancing the clinical management of patients. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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15 pages, 5396 KiB

Open AccessArticle

Optical Emission Spectroscopy for the Real-Time Identification of Malignant Breast Tissue

by Selin Guergan, Bettina Boeer, Regina Fugunt, Gisela Helms, Carmen Roehm, Anna Solomianik, Alexander Neugebauer, Daniela Nuessle, Mirjam Schuermann, Kristin Brunecker, Ovidiu Jurjut, Karen A. Boehme, Sascha Dammeier, Markus D. Enderle, Sabrina Bettio, Irene Gonzalez-Menendez, Annette Staebler, Sara Y. Brucker, Bernhard Kraemer, Diethelm Wallwiener, Falko Fend and Markus Hahn Show full author list Hide full author list

Diagnostics 2024, 14(3), 338; https://doi.org/10.3390/diagnostics14030338 - 4 Feb 2024

Cited by 1 | Viewed by 1503

Abstract

Breast conserving resection with free margins is the gold standard treatment for early breast cancer recommended by guidelines worldwide. Therefore, reliable discrimination between normal and malignant tissue at the resection margins is essential. In this study, normal and abnormal tissue samples from breast cancer patients were characterized ex vivo by optical emission spectroscopy (OES) based on ionized atoms and molecules generated during electrosurgical treatment. The aim of the study was to determine spectroscopic features which are typical for healthy and neoplastic breast tissue allowing for future real-time tissue differentiation and margin assessment during breast cancer surgery. A total of 972 spectra generated by electrosurgical sparking on normal and abnormal tissue were used for support vector classifier (SVC) training. Specific spectroscopic features were selected for the classification of tissues in the included breast cancer patients. The average classification accuracy for all patients was 96.9%. Normal and abnormal breast tissue could be differentiated with a mean sensitivity of 94.8%, a specificity of 99.0%, a positive predictive value (PPV) of 99.1% and a negative predictive value (NPV) of 96.1%. For 66.6% patients all classifications reached 100%. Based on this convincing data, a future clinical application of OES-based tissue differentiation in breast cancer surgery seems to be feasible. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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12 pages, 3614 KiB

Open AccessArticle

Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy

by Stefano Marletta, Alexandra Giorlandino, Enrico Cavallo, Michele Dello Spedale Venti, Giorgia Leone, Maria Grazia Tranchina, Lucia Gullotti, Claudia Lucia Bonanno, Graziana Spoto, Giusi Falzone, Irene Tornabene, Carmelina Trovato, Marco Maria Baron, Giuseppe Di Mauro, Lucia Falsaperna, Giuseppe Angelico, Sarah Pafumi and Antonio Rizzo

Diagnostics 2024, 14(3), 259; https://doi.org/10.3390/diagnostics14030259 - 25 Jan 2024

Cited by 1 | Viewed by 1514

Abstract

Background: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. Methods: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-operative core needle biopsies (CNBs). Phenotypical findings were correlated to morphological features and their clinical implications. Results: Divergent expression between PTs and ALNs was found in 10% of the tumors, often involving multiple biomarkers (12/31, 39%). Most (52%) displayed significant differences in ER and PR staining. HER2 divergences were observed in almost three-quarters of the cases (23/31, 74%), with five (16%) switching from negativity to overexpression/amplification in ALNs. Roughly 90% of disparities reflected significant morphological differences between PTs and ALN metastases. Less than half of the discrepancies (12/31, 39%) modified pre/post-operative treatment options. Conclusions: We observed relevant discrepancies in biomarker expression between PTs and metastatic ALNs in a noteworthy proportion (10%) of preoperative BC CNBs, which were often able to influence therapies. Hence, our data suggest routine preoperative assessment of biomarkers in both PTs and ALNs in cases showing significant morphological differences. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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12 pages, 3192 KiB

Open AccessArticle

Peritumoural Strain Elastography of Newly Diagnosed Breast Tumours: Does Maximum Peritumoural Halo Depth Correlate with Tumour Differentiation and Grade?

by Leonhard Gruber, Johannes Deeg, Daniel Egle, Afschin Soleiman, Valentin Ladenhauf, Anna Luger, Birgit Amort and Martin Daniaux

Diagnostics 2023, 13(12), 2064; https://doi.org/10.3390/diagnostics13122064 - 14 Jun 2023

Cited by 2 | Viewed by 1208

Abstract

To evaluate the diagnostic utility of the maximum ultrasound strain elastography (SE) halo depth in newly diagnosed and histologically confirmed breast lesions, a retrospective study approval was granted by the local Ethical Review Board. Overall, the maximum strain elastography peritumoural halos (SEPHmax)—the maximum distance between the SE stiffening area and the B-mode lesion size—in 428 cases with newly diagnosed breast lesions were retrospectively analysed alongside patient age, affected quadrant, tumour echogenicity, size, acoustic shadowing, and vascularity. Statistical analysis included an ordinary one-way ANOVA to compare the SEPHmax between BI-RADS 2, 3, and 5 groups and between tumour grades 1, 2, and 3. A binary regression analysis was used to determine the correlation between tumour malignancy and the above-mentioned demographic and imaging factors. SEPHmax was significantly higher in BI-RADS 5 tumours (5.5 ± 3.9 mm) compared to BI-RADS 3 (0.9 ± 1.7 mm, p < 0.0001) and 2 (0.6 ± 1.4 mm, p < 0.0001). The receiver operating characteristic area under the curve was 0.933 for the detection of BI-RADS 5 lesions. Furthermore, tumour grades 2 (5.6 ± 3.6 mm, p = 0.001) and 3 (6.8 ± 4.2 mm, p < 0.0001) exhibited significantly higher SEPHmax than grade 1 tumours (4.0 ± 3.9 mm). Similarly, St. Gallen Ki67-stratified low-risk (p = 0.005) and intermediate-risk (p = 0.013) tumours showed smaller SEPHmax than high-risk tumours. Multivariate analysis revealed a significant correlation between malignant differentiation and SEPHmax (standardized regression coefficient 3.17 [95% confidence interval (CI) 2.42–3.92], p < 0.0001), low tumour echogenicity (1.68 [95% CI 0.41–3.00], p = 0.03), and higher patient age (0.89 [95% CI 0.52–1.26], p < 0.0001). High SEPHmax is a strong predictor for tumour malignancy and a higher tumour grade and can be used to improve tumour characterisation before histopathological evaluation. It may also enable radiologists to identify lesions warranting observation rather than immediate biopsy. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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16 pages, 2501 KiB

Open AccessArticle

Role of Circ-ITCH Gene Polymorphisms and Its Expression in Breast Cancer Susceptibility and Prognosis

by Sara F. Saadawy, Nermin Raafat, Walaa M. Samy, Ahmed Raafat and Aliaa Talaat

Diagnostics 2023, 13(12), 2033; https://doi.org/10.3390/diagnostics13122033 - 12 Jun 2023

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Abstract

Introduction/Objective: Breast cancer (BC) is the first leading cause of cancer-related mortality in females worldwide. We have investigated the correlation between circ-ITCH gene polymorphisms, circ-ITCH expression, and their effect on β-catenin levels and BC development. Methods: Participants included 62 BC and 62 controls matched in terms of age. The circ-ITCH polymorphisms rs10485505 and rs4911154 were genotyped using whole blood samples. In addition, mRNA expression analysis of circ-ITCH was performed on BC tissues. The β-catenin levels in serum samples were measured using ELISA. Results: The qRT-PCR results demonstrated that circ-ITCH was significantly downregulated in BC compared to normal healthy tissues. The genotype distribution of rs10485505 and rs4911154 were significantly associated with BC risk. For rs10485505, genotype CT and TT were significantly associated with an increased BC risk. In contrast, there was a significant association between rs4911154, genotypes GA and AA, and an increased BC risk. Regarding the rs10485505 genotype, carriers of the T allele frequently have a poor prognosis compared to carriers of the CC genotype. Serum β-catenin in the BC patients’ group was significantly higher than in the control group. The relative expression levels of circ-ITCH were remarkably decreased in the BC samples of patients carrying the A allele at rs4911154 compared to patients with a GG genotype. Conversely, β-catenin protein levels were increased in patients carrying the A allele, while rs10485505 genotype carriers of the CT and TT genotypes showed downregulation of circ-ITCH expression fold compared to the CC genotype. Contrarily, β-catenin levels markedly increased in TT and CT genotypes compared with the CC genotype. Conclusions: Our research showed that the rs10485505 polymorphism (T allele) and the rs4911154 polymorphism (A allele) are associated with the risk and prognosis of BC. This finding may be due to the effect on the level of circ-ITCH mRNA expression in BC tissues as well as the level of β-catenin in BC patients. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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9 pages, 477 KiB

Open AccessArticle

Evaluation of the RDW Index (Red Cell Distribution Width) in Women with Breast Cancer Treated with Doxorubicin in a One-Year Follow-Up Study

by Ricardo Simões, Amanda Cambraia Ferreira, Luciana Maria Silva, Adriano de Paula Sabino, Maria das Graças Carvalho and Karina Braga Gomes

Diagnostics 2023, 13(9), 1552; https://doi.org/10.3390/diagnostics13091552 - 26 Apr 2023

Cited by 2 | Viewed by 4159

Abstract

Breast cancer is the most common cancer and the most frequent cause of death in women. Doxorubicin, an anthracycline, is an important drug due to its efficacy in treating solid cancers, especially breast cancer. However, this drug is often responsible for cardiotoxicity that may affect more than 25% of patients. This study aimed to evaluate the red cell distribution width (RDW) in women with breast cancer to monitor adverse events associated with the use of doxorubicin. A prospective study of 80 women with breast malignancy undergoing neoadjuvant doxorubicin-based chemotherapy was conducted. The patients were evaluated at baseline (T0), just after the last cycle of chemotherapy with doxorubicin (T1), and 1 year after the treatment (T2). There was a significant increase over the time points for the RDW (p < 0.001). There was a negative correlation between the RDW and C-reactive protein (CRP) levels at T1. The RDW did not show a significant difference between the groups classified according to cardiotoxicity. Based on these results, the RDW is a cost-effective test that shows a relationship with the doxorubicin response, but not with cardiotoxicity. It is a potential biomarker to evaluate patients with breast cancer after they receive chemotherapy with doxorubicin. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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12 pages, 1253 KiB

Open AccessArticle

Involvement of APOBEC3A/B Deletion in Mouse Mammary Tumor Virus (MMTV)-like Positive Human Breast Cancer

by Nathália de Sousa Pereira, Glauco Akelinghton Freire Vitiello and Marla Karine Amarante

Diagnostics 2023, 13(6), 1196; https://doi.org/10.3390/diagnostics13061196 - 22 Mar 2023

Cited by 2 | Viewed by 2288

Abstract

The association between mouse mammary tumor virus (MMTV)-like sequences and human breast cancer (BC) is largely documented in the literature, but further research is needed to determine how they influence carcinogenesis. APOBEC3 cytidine deaminases are viral restriction factors that have been implicated in cancer mutagenesis, and a germline deletion that results in the fusion of the APOBEC3A coding region with the APOBEC3B 3′-UTR has been linked to increased mutagenic potential, enhanced risk of BC development, and poor prognosis. However, little is known about factors influencing APOBEC3 family activation in cancer. Thus, we hypothesized that MMTV infection and APOBEC3-mediated mutagenesis may be linked in the pathogenesis of BC. We investigated APOBEC3A/B genotyping, MMTV-like positivity, and clinicopathological parameters of 209 BC patients. We show evidence for active APOBEC3-mediated mutagenesis in human-derived MMTV sequences and comparatively investigate the impact of APOBEC3A/B germline deletion in MMTV-like env positive and negative BC in a Brazilian cohort. In MMTV-like negative samples, APOBEC3A/B deletion was negatively correlated with tumor stage while being positively correlated with estrogen receptor expression. Although APOBEC3A/B was not associated with MMTV-like positivity, samples carrying both MMTV-like positivity and APOBEC3A/B deletion had the lowest age-at-diagnosis of all study groups, with all patients being less than 50 years old. These results indicate that APOBEC3 mutagenesis is active against MMTV-like sequences, and that APOBEC3A/B deletion might act along with the MMTV-like presence to predispose people to early-onset BC. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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Review

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30 pages, 940 KiB

Open AccessReview

Updates on Triple-Negative Breast Cancer in Type 2 Diabetes Mellitus Patients: From Risk Factors to Diagnosis, Biomarkers and Therapy

by Sabine Matou-Nasri, Maram Aldawood, Fatimah Alanazi and Abdul Latif Khan

Diagnostics 2023, 13(14), 2390; https://doi.org/10.3390/diagnostics13142390 - 17 Jul 2023

Cited by 10 | Viewed by 2884

Abstract

Triple-negative breast cancer (TNBC) is usually the most malignant and aggressive mammary epithelial tumor characterized by the lack of expression for estrogen receptors and progesterone receptors, and the absence of epidermal growth factor receptor (HER)2 amplification. Corresponding to 15–20% of all breast cancers and well-known by its poor clinical outcome, this negative receptor expression deprives TNBC from targeted therapy and makes its management therapeutically challenging. Type 2 diabetes mellitus (T2DM) is the most common ageing metabolic disorder due to insulin deficiency or resistance resulting in hyperglycemia, hyperinsulinemia, and hyperlipidemia. Due to metabolic and hormonal imbalances, there are many interplays between both chronic disorders leading to increased risk of breast cancer, especially TNBC, diagnosed in T2DM patients. The purpose of this review is to provide up-to-date information related to epidemiology and clinicopathological features, risk factors, diagnosis, biomarkers, and current therapy/clinical trials for TNBC patients with T2DM compared to non-diabetic counterparts. Thus, in-depth investigation of the diabetic complications on TNBC onset, development, and progression and the discovery of biomarkers would improve TNBC management through early diagnosis, tailoring therapy for a better outcome of T2DM patients diagnosed with TNBC. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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7 pages, 908 KiB

Open AccessBrief Report

Brain Metastases from Breast Cancer Histologically Exhibit Solid Growth Pattern with at Least Focal Comedonecrosis: A Histopathologic Study on a Monocentric Series of 30 Cases

by Jessica Farina, Giuseppe Angelico, Giada Maria Vecchio, Lucia Salvatorelli, Gaetano Magro, Lidia Puzzo, Andrea Palicelli, Magda Zanelli, Roberto Altieri, Francesco Certo, Saveria Spadola, Maurizio Zizzo, Giuseppe Maria Vincenzo Barbagallo, Rosario Caltabiano and Giuseppe Broggi

Diagnostics 2023, 13(19), 3141; https://doi.org/10.3390/diagnostics13193141 - 6 Oct 2023

Viewed by 1463

Abstract

Since there are no morphological clues capable of making a pathologist suspect a possible mammary origin of a metastatic lesion without adequate clinical information, the histologic diagnosis of brain metastasis from BC is still based on the immunohistochemical expression of mammary gland markers such as GATA-3, ERs, PgRs and HER-2. The present retrospective study aimed to select purely morphological features capable of suggesting the mammary origin of a metastatic carcinoma in the brain. The following histological features were collected from a series of 30 cases of brain metastases from breast cancer: (i) a solid growth pattern; (ii) the presence of comedonecrosis; and (iii) glandular differentiation. Our results showed that most cases histologically exhibited a solid growth pattern with at least focal comedonecrosis, producing an overall morphology closely reminiscent of mammary high-grade ductal carcinoma in situ. Although the above-mentioned morphological parameters are not strictly specific to a mammary origin, they may have an important diagnostic utility for leading pathologists to suspect a possible breast primary tumor and to include GATA-3, ERs, PgRs and HER-2 in the immunohistochemical panel. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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8 pages, 2367 KiB

Open AccessCase Report

What Can Trigger Spontaneous Regression of Breast Cancer?

by Nicoletta D’Alessandris, Angela Santoro, Damiano Arciuolo, Giuseppe Angelico, Michele Valente, Giulia Scaglione, Stefania Sfregola, Angela Carlino, Elena Navarra, Antonino Mulè and Gian Franco Zannoni

Diagnostics 2023, 13(7), 1224; https://doi.org/10.3390/diagnostics13071224 - 24 Mar 2023

Cited by 5 | Viewed by 5499

Abstract

Background: Spontaneous regression of tumors is a rare phenomenon in which cancer volume is reduced or, alternatively, a tumor completely disappears in the absence of any pharmacological treatment. This phenomenon has previously been described in several tumors, such as neuroblastomas, testicular malignancies, renal cell carcinomas, melanomas, and lymphomas. Spontaneous remission has also been documented in breast cancer; however, it represents an extremely rare and poorly understood phenomenon, with only a few reported cases in the literature. Methods: We herein report two cases of breast cancer that showed spontaneous tumor regression in the surgical specimen after a pathologically confirmed diagnosis of invasive breast cancer in core needle biopsy samples. Results: Macroscopically, both the surgical samples revealed a whitish, fibrous area with a rubbery consistency. On histological examination, diffuse fibrous tissue, hemosiderin deposition, and chronic inflammation were observed. The first case showed the complete disappearance of the tumor, whereas the second case showed just a small (3 mm), residual nest of neoplastic cells. Conclusions: Although spontaneous regression of breast cancer is a rare event, it is important to know that it might happen. It is also of great importance to try to better explain, over time, its underlying mechanism. This knowledge could help us to further develop cancer prevention methods and predict the clinical course of these kinds of neoplasms. Full article

(This article belongs to the Special Issue Advances in Breast Disease: From Screening to Diagnosis and Therapy)

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