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Advances in the Diagnosis and Therapy of Breast Cancer
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Advances in the Diagnosis and Therapy of Breast Cancer

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (30 December 2020) | Viewed by 20251

Special Issue Editor

Dr. Alexander Hein

E-Mail Website
Guest Editor
Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany
Interests: gynecologic oncology; breast cancer; surgical oncology; immunotherapy; endometriosis

Special Issue Information

Dear Colleagues,

As breast cancer is the most common type of cancer in women all over the world, it is tremendously important to continue constant research on the diagnosis and treatment of the disease. Novel drugs and diagnostic techniques are capable of revolutionizing the standard of care.

Over the years, however, it has emerged that it is not always an aggressive form of treatment that benefits a breast cancer patient most, but rather therapy that is specifically adapted to each patient’s very unique tumor. Personalized approaches to treatment started a few decades ago with endocrine therapy and have led to the development of a wide range of substances targeting various specific tumor characteristics, resulting today in a significant improvement in patients becoming disease free as well as overall survival. This is an achievement that has only been possible through continuous advances in research. The aim of this Special Issue is to gather together original articles and reviews demonstrating advances in the diagnosis and treatment of breast cancer.

Dr. Alexander Hein
Guest 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 special issue 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. Journal of Clinical Medicine 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 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

  • Early breast cancer
  • Advanced/metastatic breast cancer
  • Endocrine therapy；CDK4/6 inhibitor
  • Checkpoint inhibitor
  • Antibody treatment
  • Chemotherapy
  • Osteoprotective therapy

Published Papers (6 papers)

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Research

13 pages, 1351 KiB  
Article
Discordance between Primary Breast Cancer and Ipsilateral Breast Cancer Tumor Recurrence as a Function of Distance
by Sebastian M. Jud, Reinhard Hatko, Julius Emons, Bianca Lauterbach, Carolin C. Hack, Caroline Preuß, Werner Adler, Matthias W. Beckmann and Felix Heindl
J. Clin. Med. 2020, 9(12), 4033; https://doi.org/10.3390/jcm9124033 - 13 Dec 2020
Cited by 2 | Viewed by 1656
Abstract
Background: Risk factors for ipsilateral breast cancer tumor recurrence (IBTR) are well established and include grading, nodal status, and receptor status. Little is known about the influence of the local distance between the primary tumor and recurrences on changes in tumor characteristics and [...] Read more.
Background: Risk factors for ipsilateral breast cancer tumor recurrence (IBTR) are well established and include grading, nodal status, and receptor status. Little is known about the influence of the local distance between the primary tumor and recurrences on changes in tumor characteristics and prognosis. Methods: In a retrospective setting, we analyzed primary breast cancers and their recurrences. Localizations of primary and recurrent breast cancer were recorded to calculate the relative distance in pixels. Analysis was performed regarding tumor characteristics, relative distance between both, and their impact on breast cancer prognosis. Results: In a cohort of 142 patients with ipsilateral recurrence, no statistically significant difference could be shown in the change in tumor characteristics depending on distance. Progesterone receptor (PR) and estrogene receptor (ER) status changed in 22.7% and 14.9% of cases, respectively. human epidermal growth factor receptor 2 (ERBB2, HER2) status changed in 18.3% of cases. Survival was in accordance with the literature, with luminal-A-like tumors as best and triple negative breast cancers (TNBC) as worst prognosis. With a threshold of 162 pixels, the survival was significantly better in the group with shorter distance. Conclusion: Change in tumor characteristics from primary breast cancer to recurrence occurs more often in PR than ER. In contrast to other work, in this dataset, recurrences with a larger distance to the primary tumor had a worse prognosis in univariate analysis. A Cox model might indicate the possibility that this influence is independent of other risk factors. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Breast Cancer)
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13 pages, 1590 KiB  
Article
Clinical Significance of ARID1A and ANXA1 in HER-2 Positive Breast Cancer
by Rita Silva-Oliveira, Filipa Ferreira Pereira, Sara Petronilho, Ana Teresa Martins, Ana Lameirinhas, Vera Constâncio, Inês Caldas-Ribeiro, Sofia Salta, Paula Lopes, Luís Antunes, Fernando Castro, Susana Palma de Sousa, Rui Henrique and Carmen Jerónimo
J. Clin. Med. 2020, 9(12), 3911; https://doi.org/10.3390/jcm9123911 - 2 Dec 2020
Cited by 7 | Viewed by 1934
Abstract
Background: trastuzumab is considered the standard of care for human epidermal growth factor receptor-2 (HER-2+) breast cancer patients. Regardless of the benefits of its use, many early-stage patients eventually recur, and usually, the disease progresses within a year. Since about half of the [...] Read more.
Background: trastuzumab is considered the standard of care for human epidermal growth factor receptor-2 (HER-2+) breast cancer patients. Regardless of the benefits of its use, many early-stage patients eventually recur, and usually, the disease progresses within a year. Since about half of the HER-2+ patients do not respond to trastuzumab, new biomarkers of prognosis and prediction are warranted to allow a better patient stratification. Annexin A1 (ANXA1) was previously reported to contribute to trastuzumab resistance through AKT activation. An association between adenine thymine-rich interactive domain 1A (ARID1A) loss and ANXA1 upregulation was also previously suggested by others. Methods: in this study, we examined tissue samples from 215 HER-2+ breast cancer patients to investigate the value of ARID1A and ANXA1 protein levels in trastuzumab response prediction and patient outcome. Expression of ARID1A and ANXA1 were assessed by immunohistochemistry. Results: contrary to what was expected, no inverse association was found between ARID1A and ANXA1 expression. HER-2+ (non-luminal) tumours displayed higher ANXA1 expression than luminal B-like (HER-2+) tumours. Concerning trastuzumab resistance, ARID1A and ANXA1 proteins did not demonstrate predictive value as biomarkers. Nevertheless, an association was depicted between ANXA1 expression and breast cancer mortality and relapse. Conclusions: overall, our results suggest that ANXA1 may be a useful prognostic marker in HER-2+ patients. Additionally, its ability to discriminate between HER-2+ (non-luminal) and luminal B-like (HER-2+) patients might assist in patient stratification regarding treatment strategy. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Breast Cancer)
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11 pages, 2870 KiB  
Article
Expression of MTDH and IL-10 Is an Independent Predictor of Worse Prognosis in ER-Negative or PR-Negative Breast Cancer Patients
by Pei-Yi Chu, Shin-Mae Wang, Po-Ming Chen, Feng-Yao Tang and En-Pei Isabel Chiang
J. Clin. Med. 2020, 9(10), 3153; https://doi.org/10.3390/jcm9103153 - 29 Sep 2020
Cited by 11 | Viewed by 2532
Abstract
(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote [...] Read more.
(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote tumor metastasis, the roles of HIF-1α-regulated genes and their application are not completely integrated in clinical practice. (2) Methods: We examined the correlation between HIF-1α, metadherin (MTDH), and interleukin (IL)-10 mRNA expression, as well as their expression patterns in the prognosis of breast cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) databases via a web interface; tissue microarrays (TMAs) were stained for MTDH and IL-10 protein expression using immunohistochemistry. (3) Results: HIF-1α, MTDH, and IL-10 mRNA expression are highly correlated and strongly associated with poor prognosis. MTDH and IL-10 protein expression of breast cancer patients usually harbored negative estrogen receptor (ER) or progesterone receptor (PR) status, and late-stage tumors have higher IL-10 expression. With regard to MTDH and IL-10 protein expression status for using univariate and multivariate analysis, the results showed that the protein expression of MTDH and IL-10 in ER-negative or PR-negative breast cancer patients have the worse prognosis. (4) Conclusions: we propose a new insight into hypoxia tumors in the metabolism and immune evidence for breast cancer therapy. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Breast Cancer)
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14 pages, 1641 KiB  
Article
The Value of Morphometric Measurements in Risk Assessment for Donor-Site Complications after Microsurgical Breast Reconstruction
by Muriel O. Meyer, Tristan M. Handschin, Daniel T. Boll, Frédérique Chammartin, Dirk J. Schaefer, Martin D. Haug and Elisabeth A. Kappos
J. Clin. Med. 2020, 9(8), 2645; https://doi.org/10.3390/jcm9082645 - 14 Aug 2020
Cited by 1 | Viewed by 1847
Abstract
Microsurgical abdominally-based reconstruction is considered the gold standard in autologous breast reconstruction. Despite refined surgical procedures, donor-site complications still occur, reducing patient satisfaction and quality of life. Recent work has outlined the potential of morphometric measurements in risk assessment for postoperative hernia development. [...] Read more.
Microsurgical abdominally-based reconstruction is considered the gold standard in autologous breast reconstruction. Despite refined surgical procedures, donor-site complications still occur, reducing patient satisfaction and quality of life. Recent work has outlined the potential of morphometric measurements in risk assessment for postoperative hernia development. With rising demand for personalised treatment, the goal of this study was to investigate their potential in risk assessment for any donor site complication. In this retrospective cohort study, 90 patients were included who each received microsurgical breast reconstruction at the hands of one surgeon between January 2015 and May 2017. Donor-site complications formed the primary outcome and were classified according to Clavien–Dindo. Morphometric measurements were taken on a routinely performed computed tomographic angiogram. Complications occurred in 13 of the 90 (14.4%) cases studied. All patients who developed any type of postoperative donor site complication had a history of abdominal surgery. The risk of postoperative complications increased by 3% with every square centimetre of omental fat tissue (OR 1.03, 95% CI 1.00–1.06, and p-value = 0.022). Morphometric measurements provide valuable information in risk assessment for donor-site complications in abdominally-based breast reconstruction. They may help identify personalised reconstructive options for maximal postoperative patient satisfaction and quality of life. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Breast Cancer)
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14 pages, 1212 KiB  
Article
Low Expression of miR-20a-5p Predicts Benefit to Bevacizumab in Metastatic Breast Cancer Patients Treated within the TANIA Phase III Trial
by Gabriel Rinnerthaler, Simon Peter Gampenrieder, Hubert Hackl, Markus Steiner, Claudia Monzo-Fuentes, Thomas Melchardt, Teresa Magnes, Florian Huemer, Theresa Westphal, Clemens Hufnagl, Cornelia Hauser-Kronberger, Alexander Egle and Richard Greil
J. Clin. Med. 2020, 9(6), 1663; https://doi.org/10.3390/jcm9061663 - 1 Jun 2020
Cited by 7 | Viewed by 2112
Abstract
Background: In metastatic breast cancer (MBC) patients, no biomarker predicting benefit to a bevacizumab-containing therapy has been established yet. MicroRNAs (miRNAs) are involved in angiogenesis and treatment resistance and therefore could be of predictive value. Methods: Profiling of 754 miRNAs was performed in [...] Read more.
Background: In metastatic breast cancer (MBC) patients, no biomarker predicting benefit to a bevacizumab-containing therapy has been established yet. MicroRNAs (miRNAs) are involved in angiogenesis and treatment resistance and therefore could be of predictive value. Methods: Profiling of 754 miRNAs was performed in tumor samples of 58 MBC patients treated with a bevacizumab-containing first-line regimen (learning set). Based on progression-free survival (PFS), patients were divided into responders (R) and non-responders (NR). Differentially expressed miRNAs between R and NR were analyzed in a cohort of 57 patients treated with first-line chemotherapy without bevacizumab (control set), to exclude miRNAs providing prognostic information. MiRNA candidates significantly associated with PFS in multivariate analysis were further validated in tumor samples of 203 patients treated within the phase III trial TANIA randomizing between chemotherapy either alone or with bevacizumab after progression on first-line bevacizumab. Results: Low expression of miR-20a-5p (multivariate p = 0.035) and miR-21-5p (multivariate p = 0.004) were significantly associated with longer PFS in the learning set, but not in the control set. In samples from the TANIA trial, low expression of miR-20a-5p was also significantly associated with longer PFS (hazard ration (HR) 0.60; 95%-CI 0.37–0.89; p = 0.012) and longer overall survival (OS; HR 0.54; 95%-CI 0.32–0.83; p = 0.007) in the bevacizumab arm but not in the chemotherapy-only arm (PFS: HR 0.73, p = 0.119; OS: HR 1.01; p = 0.964). For miR-21-5p no significant association with PFS or OS in both treatment arms was observed. Conclusion: MiR-20a-5p expression in breast cancer tissue was predictive for a greater benefit from bevacizumab-containing therapy in two independent cohorts. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Breast Cancer)
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15 pages, 1936 KiB  
Article
Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status
by Man Yee Keung, Yanyuan Wu, Francesca Badar and Jaydutt V. Vadgama
J. Clin. Med. 2020, 9(4), 940; https://doi.org/10.3390/jcm9040940 - 30 Mar 2020
Cited by 71 | Viewed by 9591
Abstract
Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven to be beneficial to patients with metastatic breast cancer with BRCA1/2 (BReast CAncer type 1 and type 2 genes) mutations. However, certain PARPi in pre-clinical studies have been shown to inhibit cell growth and promote the [...] Read more.
Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven to be beneficial to patients with metastatic breast cancer with BRCA1/2 (BReast CAncer type 1 and type 2 genes) mutations. However, certain PARPi in pre-clinical studies have been shown to inhibit cell growth and promote the death of breast cancer cells lacking mutations in BRCA1/2. Here, we examined the inhibitory potency of 13 different PARPi in 12 breast cancer cell lines with and without BRCA-mutations using cell viability assays. The results showed that 5 of the 8 triple-negative breast cancer (TNBC) cell lines were susceptible to PARPi regardless of the BRCA-status. The estrogen receptor (ER) negative/ human epidermal growth factor receptor 2 (HER2) positive (ER-/HER2+) cells, SKBR3 and JIMT1, showed high sensitivity to Talazoparib. Especially JIMT1, which is known to be resistant to trastuzumab, was responsive to Talazoparib at 0.002 µM. Niraparib, Olaparib, and Rucaparib also demonstrated effective inhibitory potency in both advanced TNBC and ER-/HER2+ cells with and without BRCA-mutations. In contrast, a BRCA-mutant TNBC line, HCC1937, was less sensitive to Talazoparib, Niraparib, Rucaparib, and not responsive to Olaparib. Other PARPi such as UPF1069, NU1025, AZD2461, and PJ34HCl also showed potent inhibitory activity in specific breast cancer cells. Our data suggest that the benefit of PARPi therapy in breast cancer is beyond the BRCA-mutations, and equally effective on metastatic TNBC and ER-/HER2+ breast cancers. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Breast Cancer)
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