Breast Cancer: Pathology, Diagnosis and Treatment

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

Deadline for manuscript submissions: 16 July 2024 | Viewed by 9601

Special Issue Editor


E-Mail Website1 Website2
Guest Editor
1. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Pieve Emanuele, Milan, Italy
2. Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center—IRCCS, Humanitas Cancer Center, Via Manzoni 56, Rozzano, 20089 Rozzano, Milan, Italy
Interests: breast neoplasms; predictive and prognostic factors; radiomics; microbiota; metabolomics; neurological comorbidities; dietary patterns

Special Issue Information

Dear Colleagues,

Thanks to improvements in more accurate diagnostic tools and widespread screening programs, the incidence of breast cancer (BC) has steadily increased over the past 20 years, making it the most common female cancer, with more than 2.2 million new cases per year. At the same time, research advances in successful therapies have led to a decline in mortality rates and an increase in prevalence, with BC now affecting more than 7.7 million people.

BC risk factors include advanced age, obesity, alcohol abuse, smoking and physical inactivity, higher exposure to estrogen, and postmenopausal hormone replacement therapy. Although most cases of BC are sporadic, a third can be attributed to familial (20–30%) or hereditary (5–10%) causes.

In recent decades, basic and translational studies have led to new biological insights, that have contributed to the improvement of diagnostic and treatment options for BC, as well as to the development of predictive and prognostic biomarkers useful to avoid unnecessary treatments. Furthermore, several clinical trials have shown the possible (old and new) toxicities of cancer treatments, suggesting the best management strategies in clinical practice. However, BC management, due to the highly heterogeneity of the disease, is still a significant challenge in research.

Dr. Rita De Sanctis
Guest Editor

Manuscript Submission Information

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Keywords

  • breast cancer
  • Luminal A/B
  • HER2
  • triple negative
  • CDK4/6 inhibitors
  • multigene assays
  • antibody-drug conjugate

Published Papers (5 papers)

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Research

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17 pages, 2030 KiB  
Article
Aminosteroid RM-581 Decreases Cell Proliferation of All Breast Cancer Molecular Subtypes, Alone and in Combination with Breast Cancer Treatments
by Anna Burguin, Jenny Roy, Geneviève Ouellette, René Maltais, Juliette Bherer, Caroline Diorio, Donald Poirier and Francine Durocher
J. Clin. Med. 2023, 12(13), 4241; https://doi.org/10.3390/jcm12134241 - 24 Jun 2023
Viewed by 1533
Abstract
Breast cancer (BC) is a heterogenous disease classified into four molecular subtypes (Luminal A, Luminal B, HER2 and triple-negative (TNBC)) depending on the expression of the estrogen receptor (ER), the progesterone receptor (PR) and the human epidermal receptor 2 (HER2). The development of [...] Read more.
Breast cancer (BC) is a heterogenous disease classified into four molecular subtypes (Luminal A, Luminal B, HER2 and triple-negative (TNBC)) depending on the expression of the estrogen receptor (ER), the progesterone receptor (PR) and the human epidermal receptor 2 (HER2). The development of effective treatments for BC, especially TNBC, remains a challenge. Aminosteroid derivative RM-581 has previously shown an antiproliferative effect in multiple cancers in vitro and in vivo. In this study, we evaluated its effect in BC cell lines representative of BC molecular subtypes, including metastatic TNBC. We found that RM-581 has an antiproliferative effect on all BC molecular subtypes, especially on Luminal A and TNBC, in 2D and 3D cultures. The combination of RM-581 and trastuzumab or trastuzumab-emtansine enhanced the anticancer effect of each drug for HER2-positive BC cell lines, and the combination of RM-581 and taxanes (docetaxel or paclitaxel) improved the antiproliferative effect of RM-581 in TNBC and metastatic TNBC cell lines. We also confirmed that RM-581 is an endoplasmic reticulum (EnR)-stress aggravator by inducing an increase in EnR-stress-induced apoptosis markers such as BIP/GRP78 and CHOP and disrupting lipid homeostasis. This study demonstrates that RM-581 could be effective for the treatment of BC, especially TNBC. Full article
(This article belongs to the Special Issue Breast Cancer: Pathology, Diagnosis and Treatment)
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20 pages, 4290 KiB  
Article
Plasma Levels of Metalloproteinase 3 (MMP-3) and Metalloproteinase 7 (MMP-7) as New Candidates for Tumor Biomarkers in Diagnostic of Breast Cancer Patients
by Paweł Ławicki, Paweł Malinowski, Joanna Motyka, Michał Ławicki, Aleksandra Kicman, Monika Kulesza, Ewa Gacuta, Tomasz Guszczyn, Marcin Januszkiewicz, Monika Zbucka-Krętowska and Sławomir Ławicki
J. Clin. Med. 2023, 12(7), 2618; https://doi.org/10.3390/jcm12072618 - 30 Mar 2023
Cited by 2 | Viewed by 1362
Abstract
Matrix metalloproteinases (MMPs) are a group of enzymes that mediate both physiological and pathological processes such as carcinogenesis. The role of matrix metalloproteinase-3 (MMP-3) and (MMP-7) in the pathogenesis of breast cancer (BC) has been demonstrated, suggesting that they may be considered as [...] Read more.
Matrix metalloproteinases (MMPs) are a group of enzymes that mediate both physiological and pathological processes such as carcinogenesis. The role of matrix metalloproteinase-3 (MMP-3) and (MMP-7) in the pathogenesis of breast cancer (BC) has been demonstrated, suggesting that they may be considered as potential markers of this condition. The aim of this study was to assess plasma concentrations and diagnostic utility of MMP-3 and MMP-7 in 100 patients with early-stage breast cancer with Luminal A subtype or Luminal B HER-negative subtype, before and after surgical treatment, and in the following control groups: patients with a benign tumor (fibroadenoma) and healthy subjects. The concentrations of MMP-3 and MMP-7 were referenced to the levels of the widely recognized marker for BC diagnosis CA 15-3. MMP-3 and MMP-7 was measured by ELISA method and CA 15-3 by CMIA. Plasma levels of MMP-7 were significantly higher in Luminal A and Luminal B HER2-negative subtype breast cancer patients as compared to the healthy group. MMP-7 demonstrated comparable but mostly higher to CA 15-3 or MMP-3 values of diagnostic sensitivity, specificity, positive and negative predictive values and AUC (0.6888 for Luminal A subtype; 0.7612 for Luminal B HER2-negative; 0.7250 for BC total group, respectively) in the groups tested. The combined use of the tested parameters resulted in a further increase in diagnostic criteria and AUC. These results suggest the usefulness of combining MMP-7 with CA 15-3 in the diagnostics of breast cancer, especially in Luminal B HER2-negative subtypes patients, as a new candidate for tumor markers. Full article
(This article belongs to the Special Issue Breast Cancer: Pathology, Diagnosis and Treatment)
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11 pages, 3361 KiB  
Article
Efficacy of CDK 4/6 Inhibitors and Radiotherapy in Breast Cancer Patients with Brain Metastases
by Marcin Kubeczko, Michał Jarząb, Aleksandra Krzywon, Donata Gräupner, Anna Polakiewicz-Gilowska and Dorota Gabryś
J. Clin. Med. 2023, 12(5), 2044; https://doi.org/10.3390/jcm12052044 - 04 Mar 2023
Cited by 1 | Viewed by 1782
Abstract
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard of care for HR-positive/HER2-negative advanced breast cancer patients. However, their role in the treatment of brain metastases is currently unclear. We retrospectively evaluate the results of patients (pts) with advanced breast [...] Read more.
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard of care for HR-positive/HER2-negative advanced breast cancer patients. However, their role in the treatment of brain metastases is currently unclear. We retrospectively evaluate the results of patients (pts) with advanced breast cancer treated at our institution with CDK4/6i and radiotherapy to the brain. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC) and severe toxicity. Among 371 pts treated with CDK4/6i, 24 pts (6.5%) received radiotherapy to the brain before (11 pts), during (6 pts), or after (7 pts) CDK4/6i treatment. Sixteen pts received ribociclib, six received palbociclib, and two received abemaciclib. Six- and twelve-month PFS was 76.5% (95% CI: 60.3–96.9) and 49.7% (95% CI: 31.7–77.9), respectively, whereas six- and twelve-month LC was 80.2% (95% CI: 58.7–100) and 68.8% (95% CI: 44.5–100), respectively. With a median follow-up of 9.5 months, no unexpected toxicity was observed. We conclude that treatment with both CDK4/6i and brain radiotherapy is feasible and should not increase the toxicity compared to brain radiotherapy or CDK4/6i alone. However, the small number of individuals treated concurrently limits the conclusions about the combination of both modalities, and the results from ongoing prospective clinical trials are eagerly awaited to understand both the toxicity profile and the clinical response fully. Full article
(This article belongs to the Special Issue Breast Cancer: Pathology, Diagnosis and Treatment)
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14 pages, 2023 KiB  
Article
Sticking to the Rules: Outcome and Success Rate of Guideline-Based Diarrhea Management in Metastatic Breast Cancer Patients Treated with Abemaciclib
by Flavia Jacobs, Elisa Agostinetto, Alessandra Solferino, Rosalba Torrisi, Giovanna Masci, Armando Santoro and Rita De Sanctis
J. Clin. Med. 2023, 12(5), 1775; https://doi.org/10.3390/jcm12051775 - 23 Feb 2023
Cited by 3 | Viewed by 2236
Abstract
In clinical trials testing abemaciclib in patients with hormone-receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer, diarrhea is a very common adverse event (occurring in approximately 85% of patients, any grade). Nonetheless, this toxicity leads to abemaciclib discontinuation in a small proportion of patients [...] Read more.
In clinical trials testing abemaciclib in patients with hormone-receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer, diarrhea is a very common adverse event (occurring in approximately 85% of patients, any grade). Nonetheless, this toxicity leads to abemaciclib discontinuation in a small proportion of patients (approximately 2%) thanks to the use of effective loperamide-based supportive therapy. We aimed to determine whether the incidence of abemaciclib-induced diarrhea in real-world trials was higher than the one reported in clinical trials, where patients are highly selected, and to evaluate the success rate of standard supportive care in this setting. We conducted a retrospective, observational, monocentric study including 39 consecutive patients with HR+/HER2- advanced breast cancer treated with abemaciclib and endocrine therapy at our institution from July 2019 to May 2021. Overall, diarrhea of any grade occurred in 36 patients (92%), of whom 6 (17%) had diarrhea of grade ≥3. In 30 patients (77%), diarrhea was associated with other adverse events, including fatigue (33%), neutropenia (33%), emesis (28%), abdominal pain (20%), and hepatotoxicity (13%). Loperamide-based supportive therapy was administered to 26 patients (72%). Abemaciclib dose was reduced in 12 patients (31%) due to diarrhea, and treatment was permanently discontinued in 4 patients (10%). In 58% of patients (15/26), diarrhea was effectively managed with supportive care and did not require abemaciclib dose reduction and/or discontinuation. In our real-world analysis, we observed a higher incidence of diarrhea related to abemaciclib compared to data from clinical trials, and a higher rate of permanent treatment discontinuation due to gastrointestinal toxicity. Better implementation of guideline-based supportive care could help to manage this toxicity. Full article
(This article belongs to the Special Issue Breast Cancer: Pathology, Diagnosis and Treatment)
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Review

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21 pages, 1656 KiB  
Review
Vascular Endothelial Growth Factor Ligands and Receptors in Breast Cancer
by Klaudia Katarzyna Brogowska, Monika Zajkowska and Barbara Mroczko
J. Clin. Med. 2023, 12(6), 2412; https://doi.org/10.3390/jcm12062412 - 21 Mar 2023
Cited by 6 | Viewed by 2010
Abstract
Breast cancer (BC) is the most common malignancy responsible for the largest number of deaths in women worldwide. The risk of developing BC is predisposed by many factors such as age, presence of genetic mutations or body weight. The diagnosis is mostly made [...] Read more.
Breast cancer (BC) is the most common malignancy responsible for the largest number of deaths in women worldwide. The risk of developing BC is predisposed by many factors such as age, presence of genetic mutations or body weight. The diagnosis is mostly made relatively late, which is why patients are exposed to radical surgical treatments, long-term chemotherapy and lower survival rates. There are no sufficiently sensitive and specific screening tests; therefore, researchers are still looking for new diagnostic biomarkers that would indicate the appearance of neoplastic changes in the initial stage of neoplasm. The VEGF family of proteins (VEGF-A, VEGF-B, VEGF-C, VEGF-D, EG-VEGF, PlGF) and their receptors are significant factors in the pathogenesis of BC. They play a significant role in the process of angiogenesis and lymphangiogenesis in both physiological and pathological conditions. The usefulness of these proteins as potential diagnostic biomarkers has been initially proven. Moreover, the blockage of VEGF-related pathways seems to be a valid therapeutic target. Recent studies have tried to describe novel strategies, including targeting pericytes, use of miRNAs and extracellular tumor-associated vesicles, immunotherapeutic drugs and nanotechnology. This indicates their possible contribution to the formation of breast cancer and their usefulness as potential biomarkers and therapeutic targets. Full article
(This article belongs to the Special Issue Breast Cancer: Pathology, Diagnosis and Treatment)
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