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Breast Cancer—Therapeutic Challenges, Research Strategies and Novel Diagnostics
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Breast Cancer—Therapeutic Challenges, Research Strategies and Novel Diagnostics

A topical collection in Cancers (ISSN 2072-6694). This collection belongs to the section "Cancer Therapy".

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Printed Edition Available!
A printed edition of this Special Issue is available here.

Editor

Dr. Naiba Nabieva

E-Mail Website
Collection Editor
1. Department of Gynecology and Obstetrics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
2. Novartis Pharma GmbH, Nürnberg, Germany
Interests: breast cancer; chemotherapy; targeted therapy; breast surgery

Topical Collection Information

Dear Colleagues,

Thanks to the breast cancer research of recent decades, effective methods and strategies have been established, allowing the mortality rates of breast cancer patients to decrease more and more.

Compared with other subtypes, triple-negative breast cancer remains one of the most aggressive cancers. However, modern therapeutics, such as immune checkpoint inhibitors and antibody–drug conjugates, are currently changing the treatment landscape of this disease. In HER2-positive breast cancer patients, who had once been patients with an extremely poor prognosis, targeted therapies have reduced mortality rates immensely. Research has gone so far that, even decades after the discovery of the HER2 receptor, its differentiation to zero, low or positive has gained importance, as this is another target option for specific novel treatments. Additionally, when it comes to hormone-receptor-positive breast cancer, it is the class of CDK4/6 inhibitors that—after almost half a century of single-endocrine treatment—has changed usual treatment patterns, and was the first to be successfully combined even in the early therapy stage.

Despite all these advancements, we still face many challenges in breast cancer research.

On a molecular basis, the role of intrinsic subtypes, certain biomarkers or mutations is still not clear for treatment and surveillance. Novel drugs, including those mentioned above, are often associated with a different spectrum of adverse events than that seen for conventional therapies, accordingly having an impact on patients’ compliance behaviors. In breast cancer surgery, in some cases, the question remains of whether to escalate or to deescalate. Additionally, with regard to diagnostics, in a digitalized world, artificial intelligence, home-based tools and therapy monitoring options are of high importance, especially after conditions seen during the COVID-19 pandemic and supply problems.

The aim is to gather original research articles and reviews demonstrating therapeutic challenges, research strategies and novel diagnostics in breast cancer.

Dr. Naiba Nabieva
Collection Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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
  • chemotherapy
  • targeted therapy
  • breast surgery 
  • irradiation
  • adherence
  • compliance
  • side effects
  • digital health solution

Published Papers (21 papers)

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2024

Jump to: 2023, 2022

12 pages, 1252 KiB  
Article
The Safety and Efficacy of the Combination of Sacituzumab Govitecan and Palliative Radiotherapy—A Retrospective Multi-Center Cohort Study
by David Krug, Joke Tio, Ali Abaci, Björn Beurer, Sandra Brügge, Khaled Elsayad, Eva Meixner, Tjoung-Won Park-Simon, Katharina Smetanay, Franziska Winkelmann, Andrea Wittig and Achim Wöckel
Cancers 2024, 16(9), 1649; https://doi.org/10.3390/cancers16091649 - 25 Apr 2024
Viewed by 347
Abstract
Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody–drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation [...] Read more.
Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody–drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration. Full article
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21 pages, 6410 KiB  
Review
Translational Aspects in Metaplastic Breast Carcinoma
by Elizve Nairoby Barrientos-Toro, Qingqing Ding and Maria Gabriela Raso
Cancers 2024, 16(7), 1433; https://doi.org/10.3390/cancers16071433 - 7 Apr 2024
Viewed by 904
Abstract
Breast cancer is the most common cancer among women. Metaplastic breast carcinoma (MpBC) is a rare, heterogeneous group of invasive breast carcinomas, which are classified as predominantly triple-negative breast carcinomas (TNBCs; HR-negative/HER2-negative). Histologically, MpBC is classified into six subtypes. Two of these are [...] Read more.
Breast cancer is the most common cancer among women. Metaplastic breast carcinoma (MpBC) is a rare, heterogeneous group of invasive breast carcinomas, which are classified as predominantly triple-negative breast carcinomas (TNBCs; HR-negative/HER2-negative). Histologically, MpBC is classified into six subtypes. Two of these are considered low-grade and the others are high-grade. MpBCs seem to be more aggressive, less responsive to neoadjuvant chemotherapy, and have higher rates of chemoresistance than other TNBCs. MpBCs have a lower survival rate than expected for TNBCs. MpBC treatment represents a challenge, leading to a thorough exploration of the tumor immune microenvironment, which has recently opened the possibility of new therapeutic strategies. The epithelial–mesenchymal transition in MpBC is characterized by the loss of intercellular adhesion, downregulation of epithelial markers, underexpression of genes with biological epithelial functions, upregulation of mesenchymal markers, overexpression of genes with biological mesenchymal functions, acquisition of fibroblast-like (spindle) morphology, cytoskeleton reorganization, increased motility, invasiveness, and metastatic capabilities. This article reviews and summarizes the current knowledge and translational aspects of MpBC. Full article
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12 pages, 593 KiB  
Article
App-Based Lifestyle Intervention (PINK! Coach) in Breast Cancer Patients—A Real-World-Data Analysis
by Josefine Wolff, Martin Smollich, Pia Wuelfing, Jack Mitchell, Rachel Wuerstlein, Nadia Harbeck and Freerk Baumann
Cancers 2024, 16(5), 1020; https://doi.org/10.3390/cancers16051020 - 29 Feb 2024
Viewed by 1067
Abstract
Introduction: Overweight and a lack of physical activity not only increase the risk of recurrence in breast cancer patients but also negatively impact overall and long-term survival, as well as quality of life. The results presented here are the first real-world data from [...] Read more.
Introduction: Overweight and a lack of physical activity not only increase the risk of recurrence in breast cancer patients but also negatively impact overall and long-term survival, as well as quality of life. The results presented here are the first real-world data from the DiGA PINK! Coach examining the physical activity and BMI of app users. Based on the literature, an approximate weight gain of 10% over 6 months and a decrease in physical activity can be expected. The purpose of this study is to retrospectively investigate the effects of the PINK! Coach in a real-world setting on patients’ BMI and physical activity level during acute therapies. such as chemotherapy (CHT) and antihormone therapy (AHT). Material and Methods: The PINK! Coach app accompanies breast cancer patients during and after acute therapy to bring about a sustainable lifestyle change. The patients are encouraged to establish a healthy diet, become physically active, and make informed decisions. In this study, real-world data from the app were analyzed over 6 months from baseline to T1 (after 12 weeks) and T2 (after 24 weeks). The patients were under acute therapy or in follow-up care receiving either CHT or AHT. Results: The analyzed data indicate that all patients were able to maintain a consistent BMI over 6 months independent of pre-defined subgroups such as AHT, CHT, or BMI subgroups. In the subgroup of patients undergoing AHT, overweight patients were even able to significantly reduce their BMI by 1-score-point over 6 months (p < 0.01). The subgroup of patients undergoing CHT also showed an significant overall reduction in BMI (p = 0.01). All patients were also able to significantly increase their daily step count as well as their physical activity minutes per day. After the first 12 weeks, 41.4% of patients experienced weight gain, 33.4% were able to maintain their weight, and 24.2% reduced their weight. Conclusion: The presented data provides intriguing insights into the users of the PINK! Coach app and the impact of this usage in regards to BMI and physical activity. At the current time, there are only a few effective concepts for encouraging all breast cancer patients to engage in moderate physical activity and reduce body weight. Often, these concepts apply to selected patient groups. The data presented here include all age groups, tumor stages, and therapies, providing an initial insight into a comprehensive approach. Data over an even longer period would be one way to better contextualize the results in current research. Full article
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11 pages, 1844 KiB  
Article
Atypical Ductal Hyperplasia and Lobular In Situ Neoplasm: High-Risk Lesions Challenging Breast Cancer Prevention
by Luca Nicosia, Luciano Mariano, Giuseppe Pellegrino, Federica Ferrari, Filippo Pesapane, Anna Carla Bozzini, Samuele Frassoni, Vincenzo Bagnardi, Davide Pupo, Giovanni Mazzarol, Elisa De Camilli, Claudia Sangalli, Massimo Venturini, Maria Pizzamiglio and Enrico Cassano
Cancers 2024, 16(4), 837; https://doi.org/10.3390/cancers16040837 - 19 Feb 2024
Viewed by 935
Abstract
This retrospective study investigates the histopathological outcomes, upgrade rates, and disease-free survival (DFS) of high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. The study addresses the challenge [...] Read more.
This retrospective study investigates the histopathological outcomes, upgrade rates, and disease-free survival (DFS) of high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. The study addresses the challenge posed by these lesions due to their association with synchronous or adjacent Breast Cancer (BC) and increased future BC risk. The research, comprising 320 patients who underwent stereotactic VABB, focuses on 246 individuals with a diagnosis of ADH (120) or LIN (126) observed at follow-up. Pathological assessments, categorized by the UK B-coding system, were conducted, and biopsy samples were compared with corresponding excision specimens to determine upgrade rates for in situ or invasive carcinoma. Surgical excision was consistently performed for diagnosed ADH or LIN. Finally, patient follow-ups were assessed and compared between LIN and ADH groups to identify recurrence signs, defined as histologically confirmed breast lesions on either the same or opposite side. The results reveal that 176 (71.5%) patients showed no upgrade post-surgery, with ADH exhibiting a higher upgrade rate to in situ pathology than LIN1 (Atypical Lobular Hyperplasia, ALH)/LIN2 (Low-Grade Lobular in situ Carcinoma, LCIS) (38% vs. 20%, respectively, p-value = 0.002). Considering only patients without upgrade, DFS at 10 years was 77%, 64%, and 72% for ADH, LIN1, and LIN2 patients, respectively (p-value = 0.92). The study underscores the importance of a multidisciplinary approach, recognizing the evolving role of VABB. It emphasizes the need for careful follow-up, particularly for lobular lesions, offering valuable insights for clinicians navigating the complex landscape of high-risk breast lesions. The findings advocate for heightened awareness and vigilance in managing these lesions, contributing to the ongoing refinement of clinical strategies in BC care. Full article
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16 pages, 4637 KiB  
Article
Dielectric Characterization of Ex-Vivo Breast Tissues: Differentiation of Tumor Types through Permittivity Measurements
by Elizabeth G. Fernández-Aranzamendi, Patricia R. Castillo-Araníbar, Ebert G. San Román Castillo, Belén S. Oller, Luz Ventura-Zaa, Gelber Eguiluz-Rodriguez, Vicente González-Posadas and Daniel Segovia-Vargas
Cancers 2024, 16(4), 793; https://doi.org/10.3390/cancers16040793 - 15 Feb 2024
Viewed by 752
Abstract
Early analysis and diagnosis of breast tumors is essential for either quickly launching a treatment or for seeing the evolution of patients who, for instance, have already undergone chemotherapy treatment. Once tissues are excised, histological analysis is the most frequent tool used to [...] Read more.
Early analysis and diagnosis of breast tumors is essential for either quickly launching a treatment or for seeing the evolution of patients who, for instance, have already undergone chemotherapy treatment. Once tissues are excised, histological analysis is the most frequent tool used to characterize benign or malignant tumors. Dielectric microwave spectroscopy makes use of an open-ended coaxial probe in the 1–8 GHz frequency range to quickly identify the type of tumor (ductal carcinoma, lobular carcinoma, mucinous carcinoma and fibroadenoma). The experiment was undertaken with data from 70 patients who had already undergone chemotherapy treatment, which helped to electrically map the histological tissues with their electric permittivity. Thus, the variations in the permittivity of different types of tumors reveal distinctive patterns: benign tumors have permittivity values lower than 35, while malignant ones range between 40 and 60. For example, at a frequency of 2 GHz, the measured permittivity was 45.6 for ductal carcinoma, 33.1 for lobular carcinoma, 59.5 for mucinous carcinoma, and 27.6 for benign tumors. This differentiation remains consistent in a frequency range of 1 to 4.5 GHz. These results highlight the effectiveness of these measurements in the classification of breast tumors, providing a valuable tool for quick and accurate diagnosis and effective treatment. Full article
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2023

Jump to: 2024, 2022

3 pages, 186 KiB  
Editorial
Editorial for the Special Issue “Breast Cancer—Therapeutic Challenges, Research Strategies and Novel Diagnostics”
by Naiba Nabieva
Cancers 2023, 15(18), 4611; https://doi.org/10.3390/cancers15184611 - 18 Sep 2023
Viewed by 607
Abstract
Worldwide, breast cancer affects over 2 million women a year, with a rising burden [...] Full article
14 pages, 1021 KiB  
Article
Protective Factors against Fear of Cancer Recurrence in Breast Cancer Patients: A Latent Growth Model
by Gabriella Bentley, Osnat Zamir, Rawan Dahabre, Shlomit Perry, Evangelos C. Karademas, Paula Poikonen-Saksela, Ketti Mazzocco, Berta Sousa and Ruth Pat-Horenczyk
Cancers 2023, 15(18), 4590; https://doi.org/10.3390/cancers15184590 - 15 Sep 2023
Viewed by 1167
Abstract
The current study aimed to examine the fear of cancer recurrence (FCR) trajectory and protective predictors in women coping with breast cancer (BC). The study’s model investigated whether a higher coping self-efficacy and positive cognitive–emotion regulation at the time of the BC diagnosis [...] Read more.
The current study aimed to examine the fear of cancer recurrence (FCR) trajectory and protective predictors in women coping with breast cancer (BC). The study’s model investigated whether a higher coping self-efficacy and positive cognitive–emotion regulation at the time of the BC diagnosis would lead to reduced levels of FCR at six months and in later stages (12 and 18 months) post-diagnosis. The sample included 494 women with stages I to III BC from Finland, Italy, Portugal, and Israel. They completed self-report questionnaires, including the Fear of Cancer Recurrence Inventory (FCRI-SF), the Cancer Behavior Inventory-Brief Version (CBI-B), the Cognitive–Emotion Regulation Questionnaire (CERQ short), and medical–social–demographic data. Findings revealed that a higher coping self-efficacy at diagnosis predicted lower FCR levels after six months but did not impact the FCR trajectory over time. Surprisingly, positive cognitive–emotion regulation did not predict FCR levels or changes over 18 months. FCR levels remained stable from six to 18 months post-diagnosis. This study emphasizes the importance of developing specific cancer coping skills, such as coping self-efficacy. Enhancing coping self-efficacy in the first six months after BC diagnosis may lead to lower FCR levels later, as FCR tends to persist in the following year. Full article
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17 pages, 4034 KiB  
Article
LEM Domain Containing 1 Acts as a Novel Oncogene and Therapeutic Target for Triple-Negative Breast Cancer
by Xiangling Li, Shilong Jiang, Ting Jiang, Xinyuan Sun, Yidi Guan, Songqing Fan and Yan Cheng
Cancers 2023, 15(11), 2924; https://doi.org/10.3390/cancers15112924 - 26 May 2023
Cited by 1 | Viewed by 1363
Abstract
Breast cancer is the most common deadly malignancy in women worldwide. In particular, triple-negative breast cancer (TNBC) exhibits the worst prognosis among four subtypes of breast cancer due to limited treatment options. Exploring novel therapeutic targets holds promise for developing effective treatments for [...] Read more.
Breast cancer is the most common deadly malignancy in women worldwide. In particular, triple-negative breast cancer (TNBC) exhibits the worst prognosis among four subtypes of breast cancer due to limited treatment options. Exploring novel therapeutic targets holds promise for developing effective treatments for TNBC. Here, we demonstrated for the first time that LEMD1 (LEM domain containing 1) is highly expressed in TNBC and contributes to reduced survival in TNBC patients, through analysis of both bioinformatic databases and collected patient samples. Furthermore, LEMD1 silencing not only inhibited the proliferation and migration of TNBC cells in vitro, but also abolished tumor formation of TNBC cells in vivo. Knockdown of LEMD1 enhanced the sensitivity of TNBC cells to paclitaxel. Mechanistically, LEMD1 promoted the progress of TNBC by activating the ERK signaling pathway. In summary, our study revealed that LEMD1 may act as a novel oncogene in TNBC, and targeting LEMD1 may be exploited as a promising therapeutic approach to enhance the efficacy of chemotherapy against TNBC. Full article
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12 pages, 1636 KiB  
Article
Breast Digital Tomosynthesis versus Contrast-Enhanced Mammography: Comparison of Diagnostic Application and Radiation Dose in a Screening Setting
by Luca Nicosia, Anna Carla Bozzini, Filippo Pesapane, Anna Rotili, Irene Marinucci, Giulia Signorelli, Samuele Frassoni, Vincenzo Bagnardi, Daniela Origgi, Paolo De Marco, Ida Abiuso, Claudia Sangalli, Nicola Balestreri, Giovanni Corso and Enrico Cassano
Cancers 2023, 15(9), 2413; https://doi.org/10.3390/cancers15092413 - 22 Apr 2023
Cited by 8 | Viewed by 1656
Abstract
This study aims to evaluate the Average Glandular Dose (AGD) and diagnostic performance of CEM versus Digital Mammography (DM) as well as versus DM plus one-view Digital Breast Tomosynthesis (DBT), which were performed in the same patients at short intervals of time. A [...] Read more.
This study aims to evaluate the Average Glandular Dose (AGD) and diagnostic performance of CEM versus Digital Mammography (DM) as well as versus DM plus one-view Digital Breast Tomosynthesis (DBT), which were performed in the same patients at short intervals of time. A preventive screening examination in high-risk asymptomatic patients between 2020 and 2022 was performed with two-view Digital Mammography (DM) projections (Cranio Caudal and Medio Lateral) plus one Digital Breast Tomosynthesis (DBT) projection (mediolateral oblique, MLO) in a single session examination. For all patients in whom we found a suspicious lesion by using DM + DBT, we performed (within two weeks) a CEM examination. AGD and compression force were compared between the diagnostic methods. All lesions identified by DM + DBT were biopsied; then, we assessed whether lesions found by DBT were also highlighted by DM alone and/or by CEM. We enrolled 49 patients with 49 lesions in the study. The median AGD was lower for DM alone than for CEM (3.41 mGy vs. 4.24 mGy, p = 0.015). The AGD for CEM was significantly lower than for the DM plus one single projection DBT protocol (4.24 mGy vs. 5.55 mGy, p < 0.001). We did not find a statistically significant difference in the median compression force between the CEM and DM + DBT. DM + DBT allows the identification of one more invasive neoplasm one in situ lesion and two high-risk lesions, compared to DM alone. The CEM, compared to DM + DBT, failed to identify only one of the high-risk lesions. According to these results, CEM could be used in the screening of asymptomatic high-risk patients. Full article
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18 pages, 1031 KiB  
Review
CDK4/6 Inhibitors—Overcoming Endocrine Resistance Is the Standard in Patients with Hormone Receptor-Positive Breast Cancer
by Naiba Nabieva and Peter A. Fasching
Cancers 2023, 15(6), 1763; https://doi.org/10.3390/cancers15061763 - 14 Mar 2023
Cited by 3 | Viewed by 2869
Abstract
Purpose of review: Tamoxifen and aromatase inhibitors can be considered as some of the first targeted therapies. For the past 30 years, they were the endocrine treatment standard in the advanced and early breast cancer setting. CDK4/6 inhibitors, however, are the first substances [...] Read more.
Purpose of review: Tamoxifen and aromatase inhibitors can be considered as some of the first targeted therapies. For the past 30 years, they were the endocrine treatment standard in the advanced and early breast cancer setting. CDK4/6 inhibitors, however, are the first substances in almost two decades to broadly improve the therapeutic landscape of hormone receptor-positive breast cancer patients for the upcoming years. This review is designed to discuss the recent history, current role, future directions and opportunities of this substance class. Recent findings: The CDK4/6 inhibitors abemaciclib, dalpiciclib, palbociclib and ribociclib have all demonstrated a statistically significant improvement in progression-free survival in advanced disease. However, to date, abemaciclib and ribociclib are the only CDK4/6 inhibitors to have shown an improvement in overall survival in patients with metastatic breast cancer. Moreover, abemaciclib is the first CDK4/6 inhibitor to also reduce the risk of recurrence in those with early-stage disease. Further CDK inhibitors, treatment combinations with other drugs and different therapy sequences are in development. Summary: Achieving significant improvements in survival rates in the advanced and early breast cancer treatment setting, CDK4/6 inhibitors have set a new standard of care for patients with advanced breast cancer. It remains important to better understand resistance mechanisms to be able to develop novel substances and treatment sequences. Full article
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19 pages, 1623 KiB  
Article
Demographic and Clinical Features of Patients with Metastatic Breast Cancer: A Retrospective Multicenter Registry Study of the Turkish Oncology Group
by Izzet Dogan, Sercan Aksoy, Burcu Cakar, Gul Basaran, Ozlem Ercelep, Nil Molinas Mandel, Taner Korkmaz, Erhan Gokmen, Cem Sener, Adnan Aydiner, Pinar Saip and Yesim Eralp
Cancers 2023, 15(6), 1667; https://doi.org/10.3390/cancers15061667 - 8 Mar 2023
Cited by 1 | Viewed by 1850
Abstract
This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts [...] Read more.
This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0–55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options. Full article
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20 pages, 466 KiB  
Review
Use of Telemedicine to Improve Cognitive Functions and Psychological Well-Being in Patients with Breast Cancer: A Systematic Review of the Current Literature
by Andreina Giustiniani, Laura Danesin, Rachele Pezzetta, Fabio Masina, Giulia Oliva, Giorgio Arcara, Francesca Burgio and Pierfranco Conte
Cancers 2023, 15(4), 1353; https://doi.org/10.3390/cancers15041353 - 20 Feb 2023
Cited by 2 | Viewed by 2551
Abstract
The diagnosis and side effects of breast cancer (BC) treatments greatly affect the everyday lives of women suffering from this disease, with relevant psychological and cognitive consequences. Several studies have reported the psychological effects of receiving a diagnosis of BC. Moreover, women undergoing [...] Read more.
The diagnosis and side effects of breast cancer (BC) treatments greatly affect the everyday lives of women suffering from this disease, with relevant psychological and cognitive consequences. Several studies have reported the psychological effects of receiving a diagnosis of BC. Moreover, women undergoing anticancer therapies may exhibit cognitive impairment as a side effect of the treatments. The access to cognitive rehabilitation and psychological treatment for these patients is often limited by resources; women of childbearing age often encounter difficulties in completing rehabilitation programs requiring access to care institutions. Telemedicine, which provides health services using information and communication technologies, is a useful tool to overcome these limitations. In particular, telemedicine may represent an optimal way to guarantee cognitive rehabilitation, psychological support, and recovery to BC patients. Previous studies have reviewed the use of telemedicine to improve psychological well-being in BC patients, and a few have investigated the effect of telerehabilitation on cognitive deficits. This study systematically reviewed the evidence on the cognitive and psychological effects of telemedicine in BC patients. Current evidence suggests that telemedicine may represent a promising tool for the management of some psychological problems experienced by breast cancer patients, but more controlled studies are needed to clarify its effectiveness, especially for cognitive deficits. The results are also discussed in light of the intervening and modulating factors that may mediate both side effect occurrence and the success of the interventions. Full article
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24 pages, 15798 KiB  
Review
Localization Techniques for Non-Palpable Breast Lesions: Current Status, Knowledge Gaps, and Rationale for the MELODY Study (EUBREAST-4/iBRA-NET, NCT 05559411)
by Maggie Banys-Paluchowski, Thorsten Kühn, Yazan Masannat, Isabel Rubio, Jana de Boniface, Nina Ditsch, Güldeniz Karadeniz Cakmak, Andreas Karakatsanis, Rajiv Dave, Markus Hahn, Shelley Potter, Ashutosh Kothari, Oreste Davide Gentilini, Bahadir M. Gulluoglu, Michael Patrick Lux, Marjolein Smidt, Walter Paul Weber, Bilge Aktas Sezen, Natalia Krawczyk, Steffi Hartmann, Rosa Di Micco, Sarah Nietz, Francois Malherbe, Neslihan Cabioglu, Nuh Zafer Canturk, Maria Luisa Gasparri, Dawid Murawa and James Harveyadd Show full author list remove Hide full author list
Cancers 2023, 15(4), 1173; https://doi.org/10.3390/cancers15041173 - 12 Feb 2023
Cited by 15 | Viewed by 4610
Abstract
Background: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim [...] Read more.
Background: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. Methods: We performed a systematic review on localization techniques for non-palpable breast cancer. Results: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons’ and radiologists’ attitudes towards these techniques. Conclusions: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies. Full article
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28 pages, 1981 KiB  
Review
Breast Cancer Risk Assessment Tools for Stratifying Women into Risk Groups: A Systematic Review
by Louiza S. Velentzis, Victoria Freeman, Denise Campbell, Suzanne Hughes, Qingwei Luo, Julia Steinberg, Sam Egger, G. Bruce Mann and Carolyn Nickson
Cancers 2023, 15(4), 1124; https://doi.org/10.3390/cancers15041124 - 9 Feb 2023
Cited by 8 | Viewed by 2766
Abstract
Background: The benefits and harms of breast screening may be better balanced through a risk-stratified approach. We conducted a systematic review assessing the accuracy of questionnaire-based risk assessment tools for this purpose. Methods: Population: asymptomatic women aged ≥40 years; Intervention: questionnaire-based risk assessment [...] Read more.
Background: The benefits and harms of breast screening may be better balanced through a risk-stratified approach. We conducted a systematic review assessing the accuracy of questionnaire-based risk assessment tools for this purpose. Methods: Population: asymptomatic women aged ≥40 years; Intervention: questionnaire-based risk assessment tool (incorporating breast density and polygenic risk where available); Comparison: different tool applied to the same population; Primary outcome: breast cancer incidence; Scope: external validation studies identified from databases including Medline and Embase (period 1 January 2008–20 July 2021). We assessed calibration (goodness-of-fit) between expected and observed cancers and compared observed cancer rates by risk group. Risk of bias was assessed with PROBAST. Results: Of 5124 records, 13 were included examining 11 tools across 15 cohorts. The Gail tool was most represented (n = 11), followed by Tyrer-Cuzick (n = 5), BRCAPRO and iCARE-Lit (n = 3). No tool was consistently well-calibrated across multiple studies and breast density or polygenic risk scores did not improve calibration. Most tools identified a risk group with higher rates of observed cancers, but few tools identified lower-risk groups across different settings. All tools demonstrated a high risk of bias. Conclusion: Some risk tools can identify groups of women at higher or lower breast cancer risk, but this is highly dependent on the setting and population. Full article
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27 pages, 2712 KiB  
Review
Advanced Phytochemical-Based Nanocarrier Systems for the Treatment of Breast Cancer
by Vivek P. Chavda, Lakshmi Vineela Nalla, Pankti Balar, Rajashri Bezbaruah, Vasso Apostolopoulos, Rajeev K. Singla, Avinash Khadela, Lalitkumar Vora and Vladimir N. Uversky
Cancers 2023, 15(4), 1023; https://doi.org/10.3390/cancers15041023 - 6 Feb 2023
Cited by 13 | Viewed by 3237
Abstract
As the world’s most prevalent cancer, breast cancer imposes a significant societal health burden and is among the leading causes of cancer death in women worldwide. Despite the notable improvements in survival in countries with early detection programs, combined with different modes of [...] Read more.
As the world’s most prevalent cancer, breast cancer imposes a significant societal health burden and is among the leading causes of cancer death in women worldwide. Despite the notable improvements in survival in countries with early detection programs, combined with different modes of treatment to eradicate invasive disease, the current chemotherapy regimen faces significant challenges associated with chemotherapy-induced side effects and the development of drug resistance. Therefore, serious concerns regarding current chemotherapeutics are pressuring researchers to develop alternative therapeutics with better efficacy and safety. Due to their extremely biocompatible nature and efficient destruction of cancer cells via numerous mechanisms, phytochemicals have emerged as one of the attractive alternative therapies for chemotherapeutics to treat breast cancer. Additionally, phytofabricated nanocarriers, whether used alone or in conjunction with other loaded phytotherapeutics or chemotherapeutics, showed promising results in treating breast cancer. In the current review, we emphasize the anticancer activity of phytochemical-instigated nanocarriers and phytochemical-loaded nanocarriers against breast cancer both in vitro and in vivo. Since diverse mechanisms are implicated in the anticancer activity of phytochemicals, a strong emphasis is placed on the anticancer pathways underlying their action. Furthermore, we discuss the selective targeted delivery of phytofabricated nanocarriers to cancer cells and consider research gaps, recent developments, and the druggability of phytoceuticals. Combining phytochemical and chemotherapeutic agents with nanotechnology might have far-reaching impacts in the future. Full article
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17 pages, 3338 KiB  
Article
Applying Explainable Machine Learning Models for Detection of Breast Cancer Lymph Node Metastasis in Patients Eligible for Neoadjuvant Treatment
by Josip Vrdoljak, Zvonimir Boban, Domjan Barić, Darko Šegvić, Marko Kumrić, Manuela Avirović, Melita Perić Balja, Marija Milković Periša, Čedna Tomasović, Snježana Tomić, Eduard Vrdoljak and Joško Božić
Cancers 2023, 15(3), 634; https://doi.org/10.3390/cancers15030634 - 19 Jan 2023
Cited by 8 | Viewed by 2465
Abstract
Background: Due to recent changes in breast cancer treatment strategy, significantly more patients are treated with neoadjuvant systemic therapy (NST). Radiological methods do not precisely determine axillary lymph node status, with up to 30% of patients being misdiagnosed. Hence, supplementary methods for lymph [...] Read more.
Background: Due to recent changes in breast cancer treatment strategy, significantly more patients are treated with neoadjuvant systemic therapy (NST). Radiological methods do not precisely determine axillary lymph node status, with up to 30% of patients being misdiagnosed. Hence, supplementary methods for lymph node status assessment are needed. This study aimed to apply and evaluate machine learning models on clinicopathological data, with a focus on patients meeting NST criteria, for lymph node metastasis prediction. Methods: From the total breast cancer patient data (n = 8381), 719 patients were identified as eligible for NST. Machine learning models were applied for the NST-criteria group and the total study population. Model explainability was obtained by calculating Shapley values. Results: In the NST-criteria group, random forest achieved the highest performance (AUC: 0.793 [0.713, 0.865]), while in the total study population, XGBoost performed the best (AUC: 0.762 [0.726, 0.795]). Shapley values identified tumor size, Ki-67, and patient age as the most important predictors. Conclusion: Tree-based models achieve a good performance in assessing lymph node status. Such models can lead to more accurate disease stage prediction and consecutively better treatment selection, especially for NST patients where radiological and clinical findings are often the only way of lymph node assessment. Full article
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2022

Jump to: 2024, 2023

14 pages, 1362 KiB  
Article
BRCA1/2 Mutation Testing in Patients with HER2-Negative Advanced Breast Cancer: Real-World Data from the United States, Europe, and Israel
by Reshma Mahtani, Alexander Niyazov, Bhakti Arondekar, Katie Lewis, Alex Rider, Lucy Massey and Michael Patrick Lux
Cancers 2022, 14(21), 5399; https://doi.org/10.3390/cancers14215399 - 2 Nov 2022
Cited by 2 | Viewed by 2534
Abstract
Poly(adenosine diphosphate-ribose) polymerase inhibitors are approved to treat patients harboring a germline breast cancer susceptibility gene 1 or 2 mutation (BRCA1/2mut) with human epidermal growth factor receptor 2—negative (HER2−) advanced breast cancer (ABC). This study evaluated differences in patient demographics, clinical [...] Read more.
Poly(adenosine diphosphate-ribose) polymerase inhibitors are approved to treat patients harboring a germline breast cancer susceptibility gene 1 or 2 mutation (BRCA1/2mut) with human epidermal growth factor receptor 2—negative (HER2−) advanced breast cancer (ABC). This study evaluated differences in patient demographics, clinical characteristics, and BRCA1/2mut testing within the United States (US), European Union 4 (EU4; France, Germany, Italy, and Spain), and Israel in a real-world population of patients with HER2− ABC. Oncologists provided chart data from eligible patients from October 2019 through March 2020. In the US, EU4, and Israel, 73%, 42%, and 99% of patients were tested for BRCA1/2mut, respectively. In the US and the EU4, patients who were not tested versus tested for BRCA1/2mut were more likely to have hormone receptor—positive (HR+)/HER2− ABC (US, 94% vs. 74%, p < 0.001; EU4, 96% vs. 78%, p < 0.001), less likely to have a known family history of BRCA1/2-related cancer (US, 6% vs. 19%, p = 0.002; EU4, 10% vs. 28%, p < 0.001), and were older (US, 68.9 vs. 62.5 years, p < 0.001; EU4, 66.7 vs. 58.0 years, p < 0.001). Among tested patients, genetic counseling was received by 45%, 53%, and 98% with triple-negative breast cancer, and 36%, 36%, and 98% with HR+/HER2− ABC in the US, EU4, and Israel, respectively. Efforts should be made to improve BRCA1/2 testing rates in the US and Europe. Full article
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11 pages, 1649 KiB  
Article
Recurrence Score® Result Impacts Treatment Decisions in Hormone Receptor-Positive, HER2-Negative Patients with Early Breast Cancer in a Real-World Setting—Results of the IRMA Trial
by Dominik Dannehl, Tobias Engler, Lea L. Volmer, Annette Staebler, Anna K. Fischer, Martin Weiss, Markus Hahn, Christina B. Walter, Eva-Maria Grischke, Falko Fend, Florin-Andrei Taran, Sara Y. Brucker and Andreas D. Hartkopf
Cancers 2022, 14(21), 5365; https://doi.org/10.3390/cancers14215365 - 31 Oct 2022
Cited by 7 | Viewed by 1907
Abstract
Background: Patients with hormone receptor-positive (HR+), HER2-negative (HER2−) early breast cancer (eBC) with a high risk of relapse often undergo adjuvant chemotherapy. However, only a few patients will gain benefit from chemotherapy. Since classical tumor characteristics (grade, tumor size, lymph node involvement, and [...] Read more.
Background: Patients with hormone receptor-positive (HR+), HER2-negative (HER2−) early breast cancer (eBC) with a high risk of relapse often undergo adjuvant chemotherapy. However, only a few patients will gain benefit from chemotherapy. Since classical tumor characteristics (grade, tumor size, lymph node involvement, and Ki67) are of limited value to predict chemotherapy efficacy, multigene expression assays such as the Oncotype DX® test were developed to reduce over- and undertreatment. The IRMA trial analyzed the impact of Recurrence Score® (RS) assessment on adjuvant treatment recommendations. Materials and methods: The RS result was assessed in patients with HR+/HER2− unilateral eBC with 0–3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women’s Health of Tuebingen University, Germany. Therapy recommendations without knowledge of the RS result were compared to therapy recommendations with awareness of the RS result. Results: In total, 245 patients underwent RS assessment. Without knowledge of the RS result, 92/245 patients (37.6%) would have been advised to receive chemotherapy. After RS assessment, 56/245 patients (22.9%) were advised to undergo chemotherapy. Chemotherapy was waived in 47/92 patients (51.1%) that were initially recommended to receive it. Chemotherapy was added in 11/153 patients (7.2%) that were recommended to not receive it initially. Summary: Using the RS result to guide adjuvant treatment decisions in HR+/HER2− breast cancer led to a substantial reduction of chemotherapy. In view of the results achieved in prospective studies, the RS result is among other risk-factors suitable for the individualization of adjuvant systemic therapy. Full article
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19 pages, 1381 KiB  
Article
Temporal Heterogeneity of HER2 Expression and Spatial Heterogeneity of 18F-FDG Uptake Predicts Treatment Outcome of Pyrotinib in Patients with HER2-Positive Metastatic Breast Cancer
by Chengcheng Gong, Cheng Liu, Zhonghua Tao, Jian Zhang, Leiping Wang, Jun Cao, Yannan Zhao, Yizhao Xie, Xichun Hu, Zhongyi Yang and Biyun Wang
Cancers 2022, 14(16), 3973; https://doi.org/10.3390/cancers14163973 - 17 Aug 2022
Cited by 2 | Viewed by 1864
Abstract
Background: This study aimed to evaluate tumor heterogeneity of metastatic breast cancer (MBC) and investigate its impact on the efficacy of pyrotinib in patients with HER2-positive MBC. Methods: MBC patients who underwent 18F-FDG PET/CT before pyrotinib treatment were included. Temporal and spatial [...] Read more.
Background: This study aimed to evaluate tumor heterogeneity of metastatic breast cancer (MBC) and investigate its impact on the efficacy of pyrotinib in patients with HER2-positive MBC. Methods: MBC patients who underwent 18F-FDG PET/CT before pyrotinib treatment were included. Temporal and spatial tumor heterogeneity was evaluated by the discordance between primary and metastatic immunohistochemistry (IHC) results and baseline 18F-FDG uptake heterogeneity (intertumoral and intratumoral heterogeneity indexes: HI-inter and HI-intra), respectively. Progression-free survival (PFS) was estimated by the Kaplan–Meier method and compared by a log-rank test. Results: A total of 572 patients were screened and 51 patients were included. In 36 patients with matched IHC results, 25% of them had HER2 status conversion. Patients with homogenous HER2 positivity had the longest PFS, followed by patients with gained HER2 positivity, while patients with HER2 negative conversion could not benefit from pyrotinib (16.8 vs. 13.7 vs. 3.6 months, p < 0.0001). In terms of spatial heterogeneity, patients with high HI-intra and HI-inter had significantly worse PFS compared to those with low heterogeneity (10.6 vs. 25.3 months, p = 0.023; 11.2 vs. 25.3 months, p = 0.040). Conclusions: Temporal heterogeneity of HER2 status and spatial heterogeneity of 18F-FDG uptake could predict the treatment outcome of pyrotinib in patients with HER2-positive MBC, which provide practically applicable methods to assess tumor heterogeneity and guidance for treatment decisions. Full article
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9 pages, 1759 KiB  
Article
Chemotherapy Shows a Better Efficacy Than Endocrine Therapy in Metastatic Breast Cancer Patients with a Heterogeneous Estrogen Receptor Expression Assessed by 18F-FES PET
by Yizhao Xie, Xinyue Du, Yannan Zhao, Chengcheng Gong, Shihui Hu, Shuhui You, Shaoli Song, Xichun Hu, Zhongyi Yang and Biyun Wang
Cancers 2022, 14(14), 3531; https://doi.org/10.3390/cancers14143531 - 20 Jul 2022
Cited by 8 | Viewed by 2208
Abstract
Background: The heterogeneity of estrogen receptor (ER) expression has long been a challenge for the diagnosis and treatment strategy of metastatic breast cancer (MBC). A novel convenient method of ER detection using 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) offers [...] Read more.
Background: The heterogeneity of estrogen receptor (ER) expression has long been a challenge for the diagnosis and treatment strategy of metastatic breast cancer (MBC). A novel convenient method of ER detection using 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) offers a chance to screen and analyze MBC patients with ER uncertainty. Methods: MBC patients who received 18F-FES PET/CT were screened and patients with both FES positive (FES+) and negative (FES-) lesions were enrolled in this study. Progression-free survival (PFS) was estimated using the Kaplan–Meier method and was compared using the log-rank test. Results: A total of 635 patients were screened and 75 of 635 (11.8%) patients showed ER uncertainty; 51 patients received further treatment and were enrolled in this study. Among them, 20 (39.2%) patients received chemotherapy (CT), 21 (41.2%) patients received endocrine-based therapy (ET), and 10 (19.6%) patients received combined therapy (CT + ET). CT showed a better progression-free survival (PFS) compared with ET (mPFS 7.1 vs. 4.6 months, HR 0.44, 95% CI 0.20–0.93, p = 0.03). CT + ET did not improve PFS compared with either CT or ET alone (mPFS 4.4 months, p > 0.2). All three treatment options were well tolerated. Conclusions: 18F-FES PET/CT could identify patients with ER heterogeneity. Patients with bone metastasis are more likely to have ER heterogeneity. Patients with ER heterogeneity showed better sensitivity to CT rather than ET. Combined therapy of CT + ET did not improve the treatment outcome. Full article
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17 pages, 7263 KiB  
Article
High PANX1 Expression Leads to Neutrophil Recruitment and the Formation of a High Adenosine Immunosuppressive Tumor Microenvironment in Basal-like Breast Cancer
by Wuzhen Chen, Baizhou Li, Fang Jia, Jiaxin Li, Huanhuan Huang, Chao Ni and Wenjie Xia
Cancers 2022, 14(14), 3369; https://doi.org/10.3390/cancers14143369 - 11 Jul 2022
Cited by 5 | Viewed by 2031
Abstract
Background: A high adenosine level is an important characteristic of the tumor microenvironment (TME) in breast cancer. Pannexin 1 (PANX1) can release intracellular ATP to the extracellular space and elevate extracellular ATP (exATP) levels under physiological conditions. Methods: We performed public database [...] Read more.
Background: A high adenosine level is an important characteristic of the tumor microenvironment (TME) in breast cancer. Pannexin 1 (PANX1) can release intracellular ATP to the extracellular space and elevate extracellular ATP (exATP) levels under physiological conditions. Methods: We performed public database bioinformatics analysis, surgical specimen histological validation, RNA sequencing, and exATP/extracellular adenosine (exADO) assays to reveal the role of PANX1 in regulating the immune microenvironment of basal-like breast cancer. Results: Our results revealed that PANX1 acted as a poor prognostic factor for breast cancer and had high expression in basal-like breast cancer. PANX1 expression was positively correlated with exATP and exADO levels in basal-like breast cancer TME. PANX1 expression was also positively correlated with tumor-associated neutrophil (TAN) infiltration in breast cancer TME and TANs highly expressed ENTPD1 (CD39)/NT5E (CD73). Conclusions: This study suggests that high PANX1 expression is associated with high TAN infiltration and adenosine production to induce local immunosuppression in basal-like breast cancer TME. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Cognitive impairment and rehabilitation in breast cancer patients treated with endocrine therapies.
Authors: Pierfranco Conte
Affiliation: Università degli Studi di Padova, Padua, Italy

Title: Breast preservation after local recurrence of breast cancer: Comparison of length and quality of life (QoL) between breast conserving surgery with intraoperative radiotherapy (TARGIT-IORT) versus mastectomy
Authors: Kolberg
Affiliation: Clincs of Bottrop

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