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Life
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New Insights into Breast Cancer: Current Controversies and Future Perspectives
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New Insights into Breast Cancer: Current Controversies and Future Perspectives

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 5863

Special Issue Editors

Dr. Alejandro Martin Sanchez

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Guest Editor
Multidisciplinary Breast Center, Dipartimento Scienze della Salute della Donna e del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Interests: breast cancer; breast pathology; breast reconstruction; breast surgery; contralateral prophylactic mastectomy; mastectomy; oncoplastic surgery; surgical oncology
Special Issues, Collections and Topics in MDPI journals
Dr. Angela Bucaro

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Guest Editor
Multidisciplinary Breast Center—Dipartimento Scienze della Salute della donna e del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A, Gemelli IRCCS, Roma, Italia
Interests: breast surgery; surgery; surgical oncology; breast cancer management; breast cancer screening; senology; breast imaging; mammography; breast cancer; breast cancer stem cells
Dr. Flavia de Lauretis

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Guest Editor
Multidisciplinary Breast Center—Dipartimento Scienze della Salute della donna e del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A, Gemelli IRCCS, Roma, Italia
Interests: breast surgery; surgery; surgical oncology; breast cancer management; breast cancer screening; senology; breast imaging; mammography; breast cancer; breast cancer stem cells

Special Issue Information

Dear Colleagues,

Breast cancer is the most frequently diagnosed cancer and the commonest cause of cancer death among women, despite diagnostic and therapeutic advances in the last few decades.

Thanks to advances in breast imaging, prevention campaigns, and public awareness, breast cancer is mostly diagnosed at an early stage. This translates into the possibility of applying “breast conserving therapies”, resulting in very high 5-year overall survival rates.

Nevertheless, approximately 8.5% of American and 4% of European patients still present with locally advanced breast cancer, whereas 6–7% have distant metastasis at diagnosis.

In such a variable scenario, the multidisciplinary calibration of therapeutic protocols, based on recent advances in breast imaging, breast conserving and reconstructive surgical techniques, multipanel gene essays, and systemic treatments (e.g., hormone therapy, poly-chemotherapy, and molecular-targeted therapy), can lead to more efficient local and systemic control of the disease.

The aim of this Special Issue is to provide a wide range of the most recent diagnostic and therapeutic protocols in breast cancer to provide the reader with updated information regarding every aspect of recent advances and future challenges.

Dr. Alejandro Martin Sanchez
Dr. Angela Bucaro
Dr. Flavia de Lauretis
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • breast cancer treatment
  • oncoplastic surgery
  • conservative mastectomy
  • breast reconstruction
  • sentinel node biopsy
  • chemotherapy
  • radiotherapy
  • integrated therapies

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Published Papers (7 papers)

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Research

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11 pages, 2332 KiB  
Article
Immediate Breast Reconstruction with Fat-Graft-Augmented ICAP Flaps
by Francesco Klinger, Mattia Federico Cavallero, Andrea Vittorio Emanuele Lisa, Fernando Rosatti, Barbara Catania, Marco Klinger, Riccardo Di Giuli, Simone Furlan, Roberta Comunian, Stefano Vaccari and Valeriano Vinci
Life 2025, 15(7), 1017; https://doi.org/10.3390/life15071017 - 26 Jun 2025
Viewed by 200
Abstract
Background: Intercostal artery perforator (ICAP) flaps are a reliable option for volume replacement in breast-conserving surgery (BCS), particularly for lower pole defects. However, limited flap volume may reduce their applicability in selected patients. Autologous fat grafting has been proposed to enhance both volume [...] Read more.
Background: Intercostal artery perforator (ICAP) flaps are a reliable option for volume replacement in breast-conserving surgery (BCS), particularly for lower pole defects. However, limited flap volume may reduce their applicability in selected patients. Autologous fat grafting has been proposed to enhance both volume and aesthetic outcomes. Methods: This retrospective study evaluated 10 patients undergoing BCS with immediate reconstruction using fat-graft-augmented ICAP flaps. Nine anterior ICAP (AICAP) flaps and one lateral ICAP (LICAP) flap were employed. The outcomes included flap viability, complications, and aesthetic results over a 6-month follow-up. Results: Partial flap resorption occurred in 2 patients (20%), both of whom were active smokers. No cases of skin necrosis were observed. Fat grafting volumes ranged from 20 to 60 cc. Aesthetic outcomes were satisfactory, with good restoration of the breast contour and stable integration of the flap and grafted fat. Conclusions: The combined use of ICAP flaps and autologous fat grafting is a feasible and effective technique for immediate reconstruction after BCS. It allows volume enhancement, maintains natural contour, and shows low complication rates in properly selected patients. Smoking remains a significant risk factor. Full article
(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)
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15 pages, 1747 KiB  
Article
Comparative Analyses of Van Nuys Prognostic Index and NCCN Guidelines in Ductal Carcinoma In Situ Treatment in a Brazilian Hospital
by Marcelo Antonini, Raissa Barros Vasconcelos, André Mattar, Mariana Pollone Medeiros, Marina Diógenes Teixeira, Andressa Gonçalves Amorim, Odair Ferraro, Larissa Chrispim de Oliveira, Marcellus do Nascimento Moreira Ramos, Francisco Pimentel Cavalcante, Felipe Zerwes, Marcelo Madeira, Eduardo de Camargo Millen, Antonio Luiz Frasson, Fabricio Palermo Brenelli, Gil Facina, Henrique Lima Couto and Luiz Henrique Gebrim
Life 2025, 15(3), 432; https://doi.org/10.3390/life15030432 - 9 Mar 2025
Viewed by 1149
Abstract
Background: Ductal carcinoma in situ (DCIS) is a precursor of invasive breast cancer and its early diagnosis and treatment are essential to prevent progression and recurrences. Risk stratification guidelines, such as the Van Nuys Prognostic Index (VNPI) and those by the National Comprehensive [...] Read more.
Background: Ductal carcinoma in situ (DCIS) is a precursor of invasive breast cancer and its early diagnosis and treatment are essential to prevent progression and recurrences. Risk stratification guidelines, such as the Van Nuys Prognostic Index (VNPI) and those by the National Comprehensive Cancer Network (NCCN), help guide appropriate treatment. This study compares VNPI recommendations for DCIS patients treated at Hospital do Servidor Público Estadual de São Paulo (HSPE) with NCCN guidelines, focusing on treatment conducted and recurrence rates. Methods: This retrospective, cross-sectional study reviewed medical records of 145 patients treated for DCIS at HSPE between January 1996 and June 2022, with a mean follow-up of 60.3 months. Results: Based on VNPI, 38.8% were low risk, 53.2% intermediate risk, and 7.8% high risk. NCCN guidelines classified only 12.9% as low risk and 87.1% as high risk. Treatment included breast-conserving surgery (BCS) with radiotherapy (43.1%), BCS alone (38.8%), and mastectomy (18.1%). There were 18 recurrences (15.5%): 5.2% as DCIS and 10.3% as invasive cancer. Of these recurrences, 5.6% occurred in patients who, according to NCCN, would have received BCS with radiotherapy or mastectomy. Conclusion: By integrating the VNPI with NCCN treatment guidelines, the NCCN’s recommendations could potentially reduce local recurrence rates by 5.6%. However, further studies are necessary to evaluate the long-term impact of these guidelines on overall survival outcomes. Full article
(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)
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29 pages, 398 KiB  
Article
Extracting Knowledge from Machine Learning Models to Diagnose Breast Cancer
by José Manuel Martínez-Ramírez, Cristobal Carmona, María Jesús Ramírez-Expósito and José Manuel Martínez-Martos
Life 2025, 15(2), 211; https://doi.org/10.3390/life15020211 - 31 Jan 2025
Viewed by 1115
Abstract
This study explored the application of explainable machine learning models to enhance breast cancer diagnosis using serum biomarkers, contrary to many studies that focus on medical images and demographic data. The primary objective was to develop models that are not only accurate but [...] Read more.
This study explored the application of explainable machine learning models to enhance breast cancer diagnosis using serum biomarkers, contrary to many studies that focus on medical images and demographic data. The primary objective was to develop models that are not only accurate but also provide insights into the factors driving predictions, addressing the need for trustworthy AI in healthcare. Several classification models were evaluated, including OneR, JRIP, the FURIA, J48, the ADTree, and the Random Forest, all of which are known for their explainability. The dataset included a variety of biomarkers, such as electrolytes, metal ions, marker proteins, enzymes, lipid profiles, peptide hormones, steroid hormones, and hormone receptors. The Random Forest model achieved the highest accuracy at 99.401%, followed closely by JRIP, the FURIA, and the ADTree at 98.802%. OneR and J48 achieved 98.204% accuracy. Notably, the models identified oxytocin as a key predictive biomarker, with most models featuring it in their rules. Other significant parameters included GnRH, β-endorphin, vasopressin, IRAP, and APB, as well as factors like iron, cholinesterase, the total protein, progesterone, 5-nucleotidase, and the BMI, which are considered clinically relevant to breast cancer pathogenesis. This study discusses the roles of the identified parameters in cancer development, thus underscoring the potential of explainable machine learning models for enhancing early breast cancer diagnosis by focusing on explainability and the use of serum biomarkers.The combination of both can lead to improved early detection and personalized treatments, emphasizing the potential of these methods in clinical settings. The identified markers also provide additional research and therapeutic targets for breast cancer pathogenesis and a deep understanding of their interactions, advancing personalized approaches to breast cancer management. Full article
(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)
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17 pages, 2881 KiB  
Article
Immediate Diagnosis of Breast Carcinoma on Core Needle Biopsy Using Ex Vivo Fluorescence Confocal Microscopy: Feasibility in a One-Stop Breast Clinic Workflow
by Marie-Christine Mathieu, Voichita Suciu, Marie-Laure Tanguy, Neila Ines Ben Romdhane, Salma Moalla, Sana Harguem-Zayani, Remy Barbe, Corinne Balleyguier, Angelica Conversano and Muriel Abbaci
Life 2024, 14(11), 1384; https://doi.org/10.3390/life14111384 - 28 Oct 2024
Cited by 1 | Viewed by 1345
Abstract
Background: In the one-stop breast clinic setting, breast cytology traditionally provides immediate diagnosis of carcinoma. Fluorescence confocal microscopy (FCM) is an emerging optical technique enabling ex vivo analysis of breast biopsies in real-time. This study represents the first proof of concept for integrating [...] Read more.
Background: In the one-stop breast clinic setting, breast cytology traditionally provides immediate diagnosis of carcinoma. Fluorescence confocal microscopy (FCM) is an emerging optical technique enabling ex vivo analysis of breast biopsies in real-time. This study represents the first proof of concept for integrating FCM imaging into the routine workflow of breast core needle biopsies (CNB) at Gustave Roussy’s one-stop breast clinic. Methods: Fifty women with breast masses underwent consecutive enrollment. Biopsies were stained with acridine orange and fast green, followed by imaging using the Vivascope 2500M-G4 (FCM). Interpretation was conducted by two pathologists in real time (PT1) or postoperatively (PT2). Concordance with definitive histology, the duration of the FCM protocol, and its impact on conventional histopathology, immunohistochemistry, and FISH analyses were evaluated. Results: In our study of 50 biopsies, a concordant diagnosis of malignancy was performed using FCM on the malignant cases at definitive histology in 93.5% (29/31 cases) and in 90.3% (28/31 cases) according to PT1 and PT2, respectively. When the FCM suspicious cases were added, FCM identified 100% (31/31 cases) and 96.7% (30/31 cases) of the malignant cases according to PT1 and PT2, respectively. A notable false positive case was identified as a complex sclerosing lesion. The median time for sample preparation (including tissue reception) was 5 min, while the median time for imaging acquisition with interpretation was 3 min for PT1, but 1 min required for interpretation alone by PT2. Histopathological alterations were not more prevalent in FCM-imaged biopsies compared to conventionally treated biopsies. The immunophenotyping and molecular assessment of tissue were preserved after FCM protocol. Conclusions: FCM shows promise as a new histological method for the immediate diagnosis of breast carcinoma on core needle biopsies in a one-stop clinic setting, while also preserving tissue specimens for final histology. Full article
(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)
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Review

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18 pages, 337 KiB  
Review
Malignant Mesenchymal Tumors of the Breast: Current Challenges and New Perspectives on Primary Sarcomas and Malignant Phyllodes Tumors
by Flavia De Lauretis, Alejandro Martin Sanchez, Cristina Accetta, Beatrice Carnassale, Sabatino D’Archi, Alba Di Leone, Antonio Franco, Federica Gagliardi, Stefano Magno, Elena Jane Mason, Francesca Moschella, Lorenzo Scardina, Marta Silenzi, Angela Bucaro, Chiara V. Pirrottina, Nicoletta D’Alessandris, Antonino Mulè, Angela Santoro, Fabio Marazzi, Valeria Masiello, Alessandra Fabi, Armando Orlandi, Antonella Palazzo, Ida Paris, Maria Pia Foschini, Riccardo Masetti and Gianluca Franceschiniadd Show full author list remove Hide full author list
Life 2025, 15(4), 673; https://doi.org/10.3390/life15040673 - 20 Apr 2025
Viewed by 530
Abstract
Mesenchymal tumors of the breast constitute a rare and heterogeneous group of neoplasms, representing only 0.5% to 1% of all breast tumors. Originating from mesenchymal tissues, these tumors include various histological subtypes. They are particularly aggressive, characterized by a high propensity for local [...] Read more.
Mesenchymal tumors of the breast constitute a rare and heterogeneous group of neoplasms, representing only 0.5% to 1% of all breast tumors. Originating from mesenchymal tissues, these tumors include various histological subtypes. They are particularly aggressive, characterized by a high propensity for local recurrence and an overall poor prognosis. The rarity of these cases has impeded the development of comprehensive clinical studies, leading to a lack of standardized diagnostic protocols and treatment guidelines. This review provides a thorough synthesis of current knowledge on breast mesenchymal tumors with a specific focus on malignant variants such as phyllodes tumors and breast sarcomas. It also addresses the diagnostic challenges faced by clinicians, evaluates current therapeutic strategies, and emphasizes the crucial role of surgical treatment. Additionally, it examines the evolving roles of chemotherapy and radiotherapy in enhancing patient outcomes. Full article
(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)

Other

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20 pages, 7547 KiB  
Case Report
Is Sentinel Lymph Node Biopsy Feasible in Multicentric Breast Cancer? A Case Report and Literature Review
by Mihaela Camelia Tîrnovanu, Elena Cojocaru, Vlad Gabriel Tîrnovanu, Elena Țarcă, Loredana Toma, Bogdan Florin Toma, Sorana Anton, Ștefan Dragoș Tîrnovanu, Roxana Ana Covali, Cipriana Ștefănescu and Irena Cristina Grierosu
Life 2025, 15(7), 1018; https://doi.org/10.3390/life15071018 - 26 Jun 2025
Viewed by 217
Abstract
Accurate lymph node staging is crucial for both prognosis (in the event of early-stage disease) and treatment (for local control of disease) in patients with breast cancer. Sentinel lymph node biopsy (SLNB) has been studied in numerous international trials, showing that it allows [...] Read more.
Accurate lymph node staging is crucial for both prognosis (in the event of early-stage disease) and treatment (for local control of disease) in patients with breast cancer. Sentinel lymph node biopsy (SLNB) has been studied in numerous international trials, showing that it allows about 70% of axillary lymph node dissection (ALND) to be avoided and thus significantly reduces the morbidity associated with ALND. SLNB represents a necessary step in the diagnostic algorithm for breast neoplasms because the surgical treatment for breast cancer has become progressively less invasive. We present a case of a 70-year-old woman with multicentric breast cancer (MBC) treated by surgery at “Cuza Vodă” Women’s University Hospital, Iassy, Romania. In this case, only the ultrasonography established the diagnosis of left MBC with certainty. Conclusion: The detection of sentinel lymph nodes (SLNs) for MBC must be indicated. In this type of cancer, SLNB is accurate and practical, with sufficient quality control and interdisciplinary collaboration between surgical, nuclear medicine, and pathology units. Lymphoscintigraphy allows the patient to avoid axillary clearance surgery if the sentinel node is negative for metastatic disease. The variability of Ki67, PR, HER2, and ER status supports the idea that all individual foci should be tested in MBC cases to provide the best management and prognosis. Full article
(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)
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8 pages, 2412 KiB  
Case Report
Cyclin-Dependent Kinase 4/6 Inhibitors Combined with Radiotherapy in Curative Breast Cancer Patients Induced Pneumonitis: A Case Report
by Pei-Yu Hou
Life 2025, 15(5), 709; https://doi.org/10.3390/life15050709 - 27 Apr 2025
Viewed by 513
Abstract
Background: The role of CDK4/6 inhibitors (CDK4/6i) has expanded from the treatment of advanced breast cancer to early-stage disease, as recent studies have demonstrated their therapeutic benefits. However, evidence regarding the safety of combining CDK4/6i with adjuvant radiation therapy (RT) in a curative [...] Read more.
Background: The role of CDK4/6 inhibitors (CDK4/6i) has expanded from the treatment of advanced breast cancer to early-stage disease, as recent studies have demonstrated their therapeutic benefits. However, evidence regarding the safety of combining CDK4/6i with adjuvant radiation therapy (RT) in a curative setting remains limited. This study aims to present clinical experiences of pulmonary toxicity following the combined use of adjuvant RT and CDK4/6i. Case presentation: We report a case of an Asian female with left breast cancer who underwent a modified radical mastectomy followed by adjuvant chemotherapy, RT, endocrine therapy, and CDK4/6i (abemaciclib) treatment. Cancer therapy-induced grade 2 pneumonitis was impressed by clinical signs and image findings. A 57-year-old postmenopausal woman was diagnosed with left breast invasive lobular carcinoma, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−), K67 index of 5–10%, and classified as pT3N3aM0 (stage IIIC). She received adjuvant chemotherapy with FEC followed by docetaxel, endocrine therapy with letrozole, and adjuvant RT of 50.4 Gy in 28 fractions to the left chest wall and regional nodal irradiation. Abemaciclib was initiated after completing RT. Treatment-related pneumonitis developed five months after RT and abemaciclib use. Conclusions: In breast cancer patients receiving a combination of RT and CDK4/6i as curative adjuvant treatment, pulmonary toxicity is a concern and requires careful monitoring, particularly in Asian populations. Full article
(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)
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