2024

Jump to: 2023, 2022, 2021

20 pages, 1325 KiB

Open AccessReview

Hormone Receptor-Positive/HER2-Positive Breast Cancer: Hormone Therapy and Anti-HER2 Treatment: An Update on Treatment Strategies

by Chiara Tommasi, Giulia Airò, Fabiana Pratticò, Irene Testi, Matilde Corianò, Benedetta Pellegrino, Nerina Denaro, Laura Demurtas, Mariele Dessì, Sara Murgia, Giovanni Mura, Demi Wekking, Mario Scartozzi, Antonino Musolino and Cinzia Solinas

J. Clin. Med. 2024, 13(7), 1873; https://doi.org/10.3390/jcm13071873 - 24 Mar 2024

Viewed by 995

Abstract

Hormone receptor (HR)-positive/HER2-positive breast cancer represents a distinct subtype expressing estrogen and progesterone receptors with an overexpression of HER2. Approximately 14% of female breast cancer cases are HER2-positive, with the majority being HR-positive. These tumors show a cross-talk between the hormonal and HER2 [...] Read more.

Hormone receptor (HR)-positive/HER2-positive breast cancer represents a distinct subtype expressing estrogen and progesterone receptors with an overexpression of HER2. Approximately 14% of female breast cancer cases are HER2-positive, with the majority being HR-positive. These tumors show a cross-talk between the hormonal and HER2 pathways; the interaction has implications for the treatment options for the disease. In this review, we analyze the biology of HR-positive/HER2-positive breast cancer and summarize the evidence concerning the standard of care options both in neoadjuvant/adjuvant settings and in advanced disease. Additionally, we focus on new trials and drugs for HR-positive/HER2-positive breast cancer and the new entity: HER2-low breast cancer. Full article

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12 pages, 1572 KiB

Open AccessArticle

Rare Breast Cancer Histotypes—A Retrospective Study and Literature Review

by Allan Hoi Kin Lam, Michael Tiong Hong Co and Ava Kwong

J. Clin. Med. 2024, 13(3), 643; https://doi.org/10.3390/jcm13030643 - 23 Jan 2024

Viewed by 746

Abstract

Breast cancer is the most common cancer among women globally and can be classified according to various histological subtypes. Current treatment strategies are typically based on the cancer stage and molecular subtypes. This article aims to address the knowledge gap in the understanding [...] Read more.

Breast cancer is the most common cancer among women globally and can be classified according to various histological subtypes. Current treatment strategies are typically based on the cancer stage and molecular subtypes. This article aims to address the knowledge gap in the understanding of rare breast cancer. A retrospective study was conducted on 4393 breast cancer patients diagnosed from 1992 to 2012, focusing on five rare subtypes: mucinous, invasive lobular, papillary, mixed invasive and lobular, and pure tubular/cribriform carcinomas. Our analysis, supplemented by a literature review, compared patient characteristics, disease characteristics, and survival outcomes of rare breast cancer patients with invasive carcinoma (not otherwise specified (NOS)). Comparative analysis revealed no significant difference in overall survival rates between these rare cancers and the more common invasive carcinoma (NOS). However, mucinous, papillary, and tubular/cribriform carcinomas demonstrated better disease-specific survival. These subtypes presented with similar characteristics such as early detection, less nodal involvement, more hormonal receptor positivity, and less human epidermal growth factor receptor 2 (HER2) positivity. To conclude, our study demonstrated the diversity in the characteristics and prognosis of rare breast cancer histotypes. Future research should be carried out to investigate histotype-specific management and targeted therapies, given their distinct behavior. Full article

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2023

Jump to: 2024, 2022, 2021

15 pages, 1037 KiB

Open AccessEditor’s ChoiceReview

Current Treatment Landscape for Early Triple-Negative Breast Cancer (TNBC)

by Jieun Lee

J. Clin. Med. 2023, 12(4), 1524; https://doi.org/10.3390/jcm12041524 - 15 Feb 2023

Cited by 12 | Viewed by 9550

Abstract

Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancers and is characterized by an aggressive nature and a high rate of recurrence despite neoadjuvant and adjuvant chemotherapy. Although novel agents are constantly being introduced for the treatment of breast cancer, conventional [...] Read more.

Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancers and is characterized by an aggressive nature and a high rate of recurrence despite neoadjuvant and adjuvant chemotherapy. Although novel agents are constantly being introduced for the treatment of breast cancer, conventional cytotoxic chemotherapy based on anthracyclines and taxanes is the mainstay treatment option for TNBC. Based on CTNeoBC pooled analysis data, the achievement of pathologic CR (pCR) in TNBC is directly linked to improved survival outcomes. Therefore, the treatment paradigm for early TNBC has shifted to neoadjuvant treatment, and the escalation of neoadjuvant chemotherapy to improve the pCR rate and the addition of post-neoadjuvant chemotherapy to control the residual disease have been investigated. In this article, we review the current treatment landscape for early TNBC, from standard cytotoxic chemotherapy to recent data on immune checkpoint inhibitors, capecitabine, and olaparib. Full article

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23 pages, 2560 KiB

Open AccessEditor’s ChoiceReview

Predictive Biomarkers for Response to Immunotherapy in Triple Negative Breast Cancer: Promises and Challenges

by Xiaoxiao Wang, Laetitia Collet, Mattia Rediti, Véronique Debien, Alex De Caluwé, David Venet, Emanuela Romano, Françoise Rothé, Christos Sotiriou and Laurence Buisseret

J. Clin. Med. 2023, 12(3), 953; https://doi.org/10.3390/jcm12030953 - 26 Jan 2023

Cited by 13 | Viewed by 3245

Abstract

Triple negative breast cancer (TNBC) is a highly heterogeneous disease with a poor prognosis and a paucity of therapeutic options. In recent years, immunotherapy has emerged as a new treatment option for patients with TNBC. However, this therapeutic evolution is paralleled by a [...] Read more.

Triple negative breast cancer (TNBC) is a highly heterogeneous disease with a poor prognosis and a paucity of therapeutic options. In recent years, immunotherapy has emerged as a new treatment option for patients with TNBC. However, this therapeutic evolution is paralleled by a growing need for biomarkers which allow for a better selection of patients who are most likely to benefit from this immune checkpoint inhibitor (ICI)-based regimen. These biomarkers will not only facilitate a better optimization of treatment strategies, but they will also avoid unnecessary side effects in non-responders, and limit the increasing financial toxicity linked to the use of these agents. Huge efforts have been deployed to identify predictive biomarkers for the ICI, but until now, the fruits of this labor remained largely unsatisfactory. Among clinically validated biomarkers, only programmed death-ligand 1 protein (PD-L1) expression has been prospectively assessed in TNBC trials. In addition to this, microsatellite instability and a high tumor mutational burden are approved as tumor agnostic biomarkers, but only a small percentage of TNBC fits this category. Furthermore, TNBC should no longer be approached as a single biological entity, but rather as a complex disease with different molecular, clinicopathological, and tumor microenvironment subgroups. This review provides an overview of the validated and evolving predictive biomarkers for a response to ICI in TNBC. Full article

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12 pages, 2997 KiB

Open AccessArticle

Kaiso Protein Expression Correlates with Overall Survival in TNBC Patients

by Artur Bocian, Piotr Kędzierawski, Janusz Kopczyński, Olga Wabik, Anna Wawruszak, Michał Kiełbus, Paulina Miziak and Andrzej Stepulak

J. Clin. Med. 2023, 12(1), 370; https://doi.org/10.3390/jcm12010370 - 03 Jan 2023

Cited by 1 | Viewed by 1592

Abstract

Triple-negative breast cancers (TNBCs) are histologically heterogenic invasive carcinomas of no specific type that lack distinctive histological characteristics. The prognosis for women with TNBC is poor. Regardless of the applied treatments, recurrences and deaths are observed 3–5 years after the diagnosis. Thus, new [...] Read more.

Triple-negative breast cancers (TNBCs) are histologically heterogenic invasive carcinomas of no specific type that lack distinctive histological characteristics. The prognosis for women with TNBC is poor. Regardless of the applied treatments, recurrences and deaths are observed 3–5 years after the diagnosis. Thus, new diagnostic markers and targets for personalized treatment are needed. The subject of our study—the Kaiso transcription factor has been found to correlate with the invasion and progression of breast cancer. The publicly available TCGA breast cancer cohort containing Illumina HiSeq RNAseq and clinical data was explored in the study. Additionally, Kaiso protein expression was assessed in formalin-fixed and paraffin-embedded tissue archive specimens using the tissue microarray technique. In this retrospective study, Kaiso protein expression (nuclear localization) was compared with several clinical factors in the cohort of 103 patients with TNBC with long follow-up time. In univariate and multivariate analysis, high Kaiso protein but not mRNA expression was correlated with better overall survival and disease-free survival, as well as with premenopausal age. The use of radiotherapy was correlated with better disease-free survival (DFS) and overall survival (OS). However, given the heterogeneity of TNBC and context-dependent molecular diversity of Kaiso signaling in cancer progression, these results must be taken with caution and require further studies. Full article

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2022

Jump to: 2024, 2023, 2021

17 pages, 650 KiB

Open AccessReview

Long-Term Effects of Breast Cancer Therapy and Care: Calm after the Storm?

by Chiara Tommasi, Rita Balsano, Matilde Corianò, Benedetta Pellegrino, Giorgio Saba, Fabio Bardanzellu, Nerina Denaro, Matteo Ramundo, Ilaria Toma, Alessandro Fusaro, Serafina Martella, Marco Maria Aiello, Mario Scartozzi, Antonino Musolino and Cinzia Solinas

J. Clin. Med. 2022, 11(23), 7239; https://doi.org/10.3390/jcm11237239 - 06 Dec 2022

Cited by 6 | Viewed by 2770

Abstract

Breast cancer is still a lethal disease and the leading cause of death in women, undermining patients’ survival and quality of life. Modern techniques of surgery and radiotherapy allow for the obtaining of good results in terms of survival, however they cause long-term [...] Read more.

Breast cancer is still a lethal disease and the leading cause of death in women, undermining patients’ survival and quality of life. Modern techniques of surgery and radiotherapy allow for the obtaining of good results in terms of survival, however they cause long-term side effects that persist over time, such as lymphedema and neuropathy. Similarly, the advent of new therapies such as endocrine therapy revolutionized breast cancer outcomes, but side effects are still present even in years of follow-up after cure. Besides the side effects of medical and surgical therapy, breast cancer is a real disruption in patients’ lives considering quality of life-related aspects such as the distortion of body image, the psychological consequences of the diagnosis, and the impact on family dynamics. Therefore, the doctor-patient relationship is central to providing the best support both during treatment and afterwards. The aim of this review is to summarize the consequences of medical and surgical treatment on breast cancer patients and to emphasize the importance of early prevention of side effects to improve patients’ quality of life. Full article

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13 pages, 303 KiB

Open AccessArticle

Quality of Life and Sexual Satisfaction in Women with Breast Cancer Undergoing a Surgical Treatment and in Their Male Partners

by Renato Martins, Patricia Otero, Ángela J. Torres and Fernando L. Vázquez

J. Clin. Med. 2022, 11(23), 6960; https://doi.org/10.3390/jcm11236960 - 25 Nov 2022

Viewed by 1510

Abstract

This study aimed to determine the quality of life and sexual satisfaction in a sample of 389 women with breast cancer who underwent a surgical treatment and 366 men who were these women’s partners. The sample was recruited from the Portuguese League Against [...] Read more.

This study aimed to determine the quality of life and sexual satisfaction in a sample of 389 women with breast cancer who underwent a surgical treatment and 366 men who were these women’s partners. The sample was recruited from the Portuguese League Against Cancer by 10 trained psychologists who assessed the quality of life and sexual satisfaction of the participants. Data on the sociodemographic variables, diagnosis and treatment in the female participants, relationship with their partner, anxiety and depression, and body image were also collected. It was found that 76.6% and 54.2% of the women had low physical and mental health, respectively, while 100% of partners had acceptable physical and mental health. The predictors of women’s physical health were months since surgery, current treatment, completed treatments, satisfaction with the current relationship with their partner, lower anxiety and depression, and better body image. The predictors of women’s mental health were months since diagnosis and treatment completion, satisfaction with partner support during the illness, lower anxiety and depression, and better body image. The predictors of both physical and mental health of partners were lower anxiety and depression. In addition, 88.4% of women and 100% of partners presented with sexual dysfunction. The predictors of women’s sexual satisfaction were being older, satisfaction with their relationship with their partner before the illness, lower anxiety and depression, and better body image. The predictors of sexual satisfaction of the male partners were psychological/psychiatric support, satisfaction with their current relationship with their partner, and lower anxiety and depression. These findings suggest that interventions targeted at the quality of life of women and sexual satisfaction with a couple perspective are needed. Full article

20 pages, 2567 KiB

Open AccessArticle

Plasma Levels of CXC Motif Chemokine 1 (CXCL1) and Chemokine 8 (CXCL8) as Diagnostic Biomarkers in Luminal A and B Breast Cancer

by Joanna Motyka, Ewa Gacuta, Aleksandra Kicman, Monika Kulesza, Paweł Ławicki and Sławomir Ławicki

J. Clin. Med. 2022, 11(22), 6694; https://doi.org/10.3390/jcm11226694 - 12 Nov 2022

Cited by 5 | Viewed by 1335

Abstract

Chemokines are involved in the regulation of immune balance and in triggering an immune response. CXCL1 and CXCL8 belong to the ELR-motif-containing group of CXC chemokines, which, in breast cancer (BC), stimulate angiogenesis and increase migration and invasiveness of tumor cells. The aim [...] Read more.

Chemokines are involved in the regulation of immune balance and in triggering an immune response. CXCL1 and CXCL8 belong to the ELR-motif-containing group of CXC chemokines, which, in breast cancer (BC), stimulate angiogenesis and increase migration and invasiveness of tumor cells. The aim of this study was to evaluate CXCL1, CXCL8 and comparative marker CA 15-3 plasma concentrations in BC patients with luminal subtypes A and B. The study group consisted of 100 patients with BC, and the control group of 50 subjects with benign breast lesions and 50 healthy women. Chemokines concentrations were determined by ELISA method; CA15-3-by CMIA. Concentrations of CXCL8 and CA15-3 were significantly higher in BC total group and luminal B (for CA15-3 also in luminal A) subtype of BC than in healthy controls and subjects with benign lesions. In the total BC group, the highest SE, PPV and NPV were observed for CXCL8 (70%, 77.78%, 50%, resp.). A combined analysis of tested chemokines with CA 15-3 increased SE and NPV values (96%, 69.23%, resp.). The diagnostic power of the test (measured by area under ROC curve (AUC)) showed the highest value for CXCL8 in the total BC group (0.6410), luminal A (0.6120) and B subgroup of BC (0.6700). For the combined parameter, the AUC was increasing and reached the highest value for CXCL1 + CXCL8 + CA15-3 combination (0.7024). In light of these results, we suggest that CXCL8 could be used as an additional diagnostic marker that would positively influence the diagnostic utility of CA 15-3, especially in luminal B subtype of BC. Full article

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9 pages, 1912 KiB

Open AccessArticle

Is Pathologic Axillary Staging Valid If Lymph Nodes Are Less than 10 with Axillary Lymph Node Dissection after Neoadjuvant Chemotherapy?

by Hee Jun Choi, Jai Min Ryu, Jun Ho Lee, Yoonju Bang, Jongwook Oh, Byung-Joo Chae, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Se Kyung Lee and Jonghan Yu

J. Clin. Med. 2022, 11(21), 6564; https://doi.org/10.3390/jcm11216564 - 05 Nov 2022

Cited by 1 | Viewed by 1681

Abstract

Introduction: The aim of this study was to evaluate the prognostic value of the number of lymph nodes removed in breast cancer patients who undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Methods: We included patients who were diagnosed with invasive [...] Read more.

Introduction: The aim of this study was to evaluate the prognostic value of the number of lymph nodes removed in breast cancer patients who undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Methods: We included patients who were diagnosed with invasive breast cancer and cytology with proven involved axillary node metastasis at diagnosis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: Among 772 patients with NAC and ALND, there were 285 ypN0, 258 ypN1, 135 ypN2, and 94 ypN3 cases. The median follow-up duration was 69.0 months. The group with less than 10 lymph nodes number (<10 nodes group) included 123 patients and the group with 10 or more lymph nodes number (≥10 nodes group) included 649 patients. There were no significant differences in DFS (p = 0.501) or OS (p = 0.883) between the two groups. In the ypN0 subgroup, the <10 nodes group had worse DFS than ≥10 nodes group (p = 0.024). In the ypN1 subgroup, there were no significant differences in DFS (p = 0.846) or OS (p = 0.774) between the two groups. In the ypN2 subgroup, the <10 nodes group had worse DFS (p = 0.025) and OS (p = 0.031) than ≥10 nodes group Conclusion: In ypN0 and ypN2 subgroups, breast cancer patients with less than 10 lymph nodes number in ALND after NAC might be considered for additional staging or closer surveillance when compared to patients with 10 or more than lymph node. Full article

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20 pages, 1068 KiB

Open AccessReview

The Innate Immune Microenvironment in Metastatic Breast Cancer

by Chiara Tommasi, Benedetta Pellegrino, Anna Diana, Marta Palafox Sancez, Michele Orditura, Mario Scartozzi, Antonino Musolino and Cinzia Solinas

J. Clin. Med. 2022, 11(20), 5986; https://doi.org/10.3390/jcm11205986 - 11 Oct 2022

Cited by 3 | Viewed by 2209

Abstract

The immune system plays a fundamental role in neoplastic disease. In the era of immunotherapy, the adaptive immune response has been in the spotlight whereas the role of innate immunity in cancer development and progression is less known. The tumor microenvironment influences the [...] Read more.

The immune system plays a fundamental role in neoplastic disease. In the era of immunotherapy, the adaptive immune response has been in the spotlight whereas the role of innate immunity in cancer development and progression is less known. The tumor microenvironment influences the terminal differentiation of innate immune cells, which can explicate their pro-tumor or anti-tumor effect. Different cells are able to recognize and eliminate no self and tumor cells: macrophages, natural killer cells, monocytes, dendritic cells, and neutrophils are, together with the elements of the complement system, the principal players of innate immunity in cancer development and evolution. Metastatic breast cancer is a heterogeneous disease from the stromal, immune, and biological point of view and requires deepened exploration to understand different patient outcomes. In this review, we summarize the evidence about the role of innate immunity in breast cancer metastatic sites and the potential targets for optimizing the innate response as a novel treatment opportunity. Full article

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23 pages, 2361 KiB

Open AccessReview

The Present and Future of Clinical Management in Metastatic Breast Cancer

by Pauline H. Lin and George Laliotis

J. Clin. Med. 2022, 11(19), 5891; https://doi.org/10.3390/jcm11195891 - 05 Oct 2022

Cited by 6 | Viewed by 15652

Abstract

Regardless of the advances in our ability to detect early and treat breast cancer, it is still one of the common types of malignancy worldwide, with the majority of patients decease upon metastatic disease. Nevertheless, due to these advances, we have extensively characterized [...] Read more.

Regardless of the advances in our ability to detect early and treat breast cancer, it is still one of the common types of malignancy worldwide, with the majority of patients decease upon metastatic disease. Nevertheless, due to these advances, we have extensively characterized the drivers and molecular profiling of breast cancer and further dividing it into subtypes. These subgroups are based on immunohistological markers (Estrogen Receptor-ER; Progesterone Receptor-PR and Human Epidermal Growth Factor Receptor 2-HER-2) and transcriptomic signatures with distinct therapeutic approaches and regiments. These therapeutic approaches include targeted therapy (HER-2⁺), endocrine therapy (HR⁺) or chemotherapy (TNBC) with optional combination radiotherapy, depending on clinical stage. Technological and scientific advances in the identification of molecular pathways that contribute to therapy-resistance and establishment of metastatic disease, have provided the rationale for revolutionary targeted approaches against Cyclin-Dependent Kinases 4/6 (CDK4/6), PI3 Kinase (PI3K), Poly ADP Ribose Polymerase (PARP) and Programmed Death-Ligand 1 (PD-L1), among others. In this review, we focus on the comprehensive overview of epidemiology and current standard of care treatment of metastatic breast cancer, along with ongoing clinical trials. Towards this goal, we utilized available literature from PubMed and ongoing clinical trial information from clinicaltrials.gov to reflect the up to date and future treatment options for metastatic breast cancer. Full article

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19 pages, 3522 KiB

Open AccessArticle

Deep Learning and Machine Learning with Grid Search to Predict Later Occurrence of Breast Cancer Metastasis Using Clinical Data

by Xia Jiang and Chuhan Xu

J. Clin. Med. 2022, 11(19), 5772; https://doi.org/10.3390/jcm11195772 - 29 Sep 2022

Cited by 27 | Viewed by 2984

Abstract

Background: It is important to be able to predict, for each individual patient, the likelihood of later metastatic occurrence, because the prediction can guide treatment plans tailored to a specific patient to prevent metastasis and to help avoid under-treatment or over-treatment. Deep neural [...] Read more.

Background: It is important to be able to predict, for each individual patient, the likelihood of later metastatic occurrence, because the prediction can guide treatment plans tailored to a specific patient to prevent metastasis and to help avoid under-treatment or over-treatment. Deep neural network (DNN) learning, commonly referred to as deep learning, has become popular due to its success in image detection and prediction, but questions such as whether deep learning outperforms other machine learning methods when using non-image clinical data remain unanswered. Grid search has been introduced to deep learning hyperparameter tuning for the purpose of improving its prediction performance, but the effect of grid search on other machine learning methods are under-studied. In this research, we take the empirical approach to study the performance of deep learning and other machine learning methods when using non-image clinical data to predict the occurrence of breast cancer metastasis (BCM) 5, 10, or 15 years after the initial treatment. We developed prediction models using the deep feedforward neural network (DFNN) methods, as well as models using nine other machine learning methods, including naïve Bayes (NB), logistic regression (LR), support vector machine (SVM), LASSO, decision tree (DT), k-nearest neighbor (KNN), random forest (RF), AdaBoost (ADB), and XGBoost (XGB). We used grid search to tune hyperparameters for all methods. We then compared our feedforward deep learning models to the models trained using the nine other machine learning methods. Results: Based on the mean test AUC (Area under the ROC Curve) results, DFNN ranks 6th, 4th, and 3rd when predicting 5-year, 10-year, and 15-year BCM, respectively, out of 10 methods. The top performing methods in predicting 5-year BCM are XGB (1st), RF (2nd), and KNN (3rd). For predicting 10-year BCM, the top performers are XGB (1st), RF (2nd), and NB (3rd). Finally, for 15-year BCM, the top performers are SVM (1st), LR and LASSO (tied for 2nd), and DFNN (3rd). The ensemble methods RF and XGB outperform other methods when data are less balanced, while SVM, LR, LASSO, and DFNN outperform other methods when data are more balanced. Our statistical testing results show that at a significance level of 0.05, DFNN overall performs comparably to other machine learning methods when predicting 5-year, 10-year, and 15-year BCM. Conclusions: Our results show that deep learning with grid search overall performs at least as well as other machine learning methods when using non-image clinical data. It is interesting to note that some of the other machine learning methods, such as XGB, RF, and SVM, are very strong competitors of DFNN when incorporating grid search. It is also worth noting that the computation time required to do grid search with DFNN is much more than that required to do grid search with the other nine machine learning methods. Full article

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11 pages, 2132 KiB

Open AccessArticle

Adenoid Cystic Carcinoma of the Breast May Be Exempt from Adjuvant Chemotherapy

by Lixi Li, Di Zhang and Fei Ma

J. Clin. Med. 2022, 11(15), 4477; https://doi.org/10.3390/jcm11154477 - 31 Jul 2022

Cited by 3 | Viewed by 2043

Abstract

Consistent standards regarding whether postoperative adjuvant chemotherapy is required in the treatment of adenoid cystic carcinoma of the breast (ACCB) are currently lacking. Using clinical data from the Surveillance, Epidemiology, and End Results (SEER) database (1988–2015), and the National Cancer Center of China [...] Read more.

Consistent standards regarding whether postoperative adjuvant chemotherapy is required in the treatment of adenoid cystic carcinoma of the breast (ACCB) are currently lacking. Using clinical data from the Surveillance, Epidemiology, and End Results (SEER) database (1988–2015), and the National Cancer Center of China (2004–2020), we retrospectively analyzed patients with ACCB who received radical treatment. A total of 661 patients were eligible. The median age at diagnosis was 61 years; 99.5% of patients were initially diagnosed with stage I and II breast cancer, and 76.7% had triple-negative breast cancer. Only 12.4% of patients received adjuvant chemotherapy. Multivariate analysis showed that patients with lymph node metastasis and non-radiotherapy had worse overall survival (OS) (p < 0.05). Patients with lymph node metastasis, stage IIB and III, histological grade ≥ 2, and non-radiotherapy had worse breast cancer-specific survival (BCSS) (p < 0.05). Adjuvant chemotherapy did not improve the OS or BCSS. Patients treated with adjuvant chemotherapy also had no better survival outcomes after propensity score matching. External data verification confirmed that chemotherapy did not improve disease-free survival or OS. Adjuvant chemotherapy cannot improve the clinical outcomes of ACCB, even in subgroups with a high risk of recurrence and metastasis. Full article

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15 pages, 635 KiB

Open AccessReview

Fertility Counseling in BRCA1/2-Mutated Women with Breast Cancer and Healthy Individuals

by Joanna Kufel-Grabowska, Amira Podolak, Daniel Maliszewski, Mikołaj Bartoszkiewicz, Rodryg Ramlau and Krzysztof Lukaszuk

J. Clin. Med. 2022, 11(14), 3996; https://doi.org/10.3390/jcm11143996 - 10 Jul 2022

Cited by 6 | Viewed by 2565

Abstract

Breast cancer is the most commonly diagnosed cancer worldwide and the fifth leading cause of cancer death. In 2020, there were 2.3 million new cases, and 685,000 women died from it. Breast cancer among young women under 40 years of age accounts for [...] Read more.

Breast cancer is the most commonly diagnosed cancer worldwide and the fifth leading cause of cancer death. In 2020, there were 2.3 million new cases, and 685,000 women died from it. Breast cancer among young women under 40 years of age accounts for 5% to 10% of all cases of this cancer. The greater availability of multi-gene sequence analysis by next-generation sequencing has improved diagnosis and, consequently, the possibility of using appropriate therapeutic approaches in BRCA1/2 gene mutation carriers. Treatment of young breast cancer patients affects their reproductive potential by reducing ovarian reserve. It can lead to reversible or permanent premature menopause, decreased libido, and other symptoms of sex hormone deficiency. This requires that, in addition to oncological treatment, patients are offered genetic counseling, oncofertility, psychological assistance, and sexological counseling. Given the number of BRCA1/2 gene mutation carriers among young breast cancer patients, but also thanks to growing public awareness, among their healthy family members planning offspring, the possibility of benefiting from preimplantation testing and performing cancer-risk-reduction procedures: RRM (risk-reducing mastectomy) and RRSO (risk-reducing salpingo-oophorectomy) significantly increase the chance of a genetically burdened person living a healthy life and giving birth to a child not burdened by the parent’s germline mutation. The goal of this paper is to show methods and examples of fertility counselling for BRCA1/2 gene mutation carriers, including both patients already affected by cancer and healthy individuals. Full article

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19 pages, 1547 KiB

Open AccessSystematic Review

Axillary Web Syndrome in Breast Cancer Women: What Is the Optimal Rehabilitation Strategy after Surgery? A Systematic Review

by Lorenzo Lippi, Alessandro de Sire, Luigi Losco, Kamal Mezian, Arianna Folli, Mariia Ivanova, Lorenzo Zattoni, Stefano Moalli, Antonio Ammendolia, Carmine Alfano, Nicola Fusco and Marco Invernizzi

J. Clin. Med. 2022, 11(13), 3839; https://doi.org/10.3390/jcm11133839 - 01 Jul 2022

Cited by 8 | Viewed by 3495

Abstract

Background: Axillary web syndrome (AWS) is one of the most prevalent and underrecognized disorders affecting breast cancer (BC) women. However, the optimal therapeutic strategy to manage AWS is far from being fully characterized. Therefore, this systematic review aims to provide a broad overview [...] Read more.

Background: Axillary web syndrome (AWS) is one of the most prevalent and underrecognized disorders affecting breast cancer (BC) women. However, the optimal therapeutic strategy to manage AWS is far from being fully characterized. Therefore, this systematic review aims to provide a broad overview of the available rehabilitation treatments in this burdensome condition. Methods: On 13 January 2022, PubMed, Scopus, Web of Science, Cochrane, and PEDro were systematically searched for clinical studies assessing rehabilitation interventions in post-surgical BC women with AWS. The outcomes analyzed were pain, AWS clinical resolution, upper limb function, and health-related quality of life (HR-QoL). Results: The search identified 1115 records, of which 11 studies were included. A total of 174 patients were assessed (ages ranging from 37 and 66 years old). The interventions included manual lymphatic drainage, manual therapy, stretching, resistance training, mobilization techniques, and Kinesio tape. Positive improvements were reported in terms of pain relief (in 7 studies), AWS clinical resolution (in 9 studies), upper limb function (in 10 studies), and HR-QoL (in 2 studies). Conclusions: Our findings suggest that rehabilitation might be considered an effective therapeutic strategy in AWS patients. Further RCTs are needed to characterize the optimal rehabilitative interventions. Full article

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12 pages, 1218 KiB

Open AccessArticle

Growth Pattern of Hepatic Metastasis as a Prognostic Index Reflecting Liver Metastasis-Associated Survival in Breast Cancer Liver Metastasis

by Jieun Lee, Moonhyung Choi, Seungyeon Joe, Kabsoo Shin, Sung-Hak Lee and Ahwon Lee

J. Clin. Med. 2022, 11(10), 2852; https://doi.org/10.3390/jcm11102852 - 18 May 2022

Viewed by 1560

Abstract

Breast cancer with liver metastasis (BCLM) frequently cause hepatic failure owing to extensive liver metastasis compared to other cancers; however, there are no clinicopathologic or radiologic parameters for estimating BCLM prognosis. We analyzed the relationship between radiologic and clinicopathologic characteristics with survival outcomes [...] Read more.

Breast cancer with liver metastasis (BCLM) frequently cause hepatic failure owing to extensive liver metastasis compared to other cancers; however, there are no clinicopathologic or radiologic parameters for estimating BCLM prognosis. We analyzed the relationship between radiologic and clinicopathologic characteristics with survival outcomes in BCLM. During 2009–2019, baseline and final abdomen computed tomography or liver magnetic resonance imaging of BCLM patients were reviewed. Liver metastasis patterns were classified as oligometastasis (≤3 metastatic lesions), non-confluent or confluent mass formation, infiltration, and pseudocirrhosis. Thirty-one surgical or biopsy specimens for liver metastasis were immunostained for L1 adhesion molecule (L1CAM), Yes-associated protein 1/Transcriptional co-activator with PDZ-binding motif (YAP/TAZ), and β1-integrin. Out of 156 patients, 77 initially had oligometastasis, 58 had nonconfluent mass formation, 14 had confluent mass formation, and 7 had infiltrative liver metastasis. Confluent or infiltrative liver metastasis showed inferior liver metastasis-associated survival (LMOS) compared to others (p = 0.001). Positive staining for L1CAM and YAP/TAZ was associated with inferior survival, and YAP/TAZ was related to final liver metastasis. Initial hepatic metastasis was associated with LMOS, especially confluent mass formation, and infiltrative liver metastasis pattern was associated with poor survival. Positive staining for YAP/TAZ and L1CAM was associated with inferior LMOS, and YAP/TAZ was related to final liver metastasis. Full article

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11 pages, 1420 KiB

Open AccessArticle

Allostatic Load as an Insight into the Psychological Burden after Primary Treatment in Women with Breast Cancer: Influence of Physical Side Effects and Pain Perception

by Azzurra Irelli, Jessica Ranieri, Maria Maddalena Sirufo, Francesca De Pietro, Pamela Casalena, Lia Ginaldi, Katia Cannita and Dina Di Giacomo

J. Clin. Med. 2022, 11(8), 2144; https://doi.org/10.3390/jcm11082144 - 12 Apr 2022

Cited by 2 | Viewed by 1753

Abstract

Breast cancer (BC) diagnosis and treatment have become a cumulative long-standing chronic disease impairment, causing stress and turning into an allostatic load (AL) framework. This study aimed to investigate the relationship between physical issues and mental health in patients with BC after medical [...] Read more.

Breast cancer (BC) diagnosis and treatment have become a cumulative long-standing chronic disease impairment, causing stress and turning into an allostatic load (AL) framework. This study aimed to investigate the relationship between physical issues and mental health in patients with BC after medical treatment. We conducted an observational study of 61 female patients with BC, and clinical and psychological markers have been detected. We conducted descriptive statistics, ANOVA analyses, correlations, and mediation analyses to verify the effect of the comorbidity index on psychological dimensions. The findings showed high levels of distress and moderate pain, and 32.8% of the patients showed moderate physical impairment. Significant effects of “age” and “physical issues” were found. The adult group reported a higher incidence of physical issues, and the group of patients reporting moderate physical impairment seemed more depressed than patients with mild physical issues. Finally, the comorbidity condition mediated the presence of signs of depression. Patients with BC seemed to experience negative emotions related to comorbidities associated with compromised activities of daily living. Our findings highlighted allostatic overload as a predictive framework to better understand the mental health of women with BC diagnoses to tailor effective psychological treatments for enhanced recovery. Full article

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13 pages, 290 KiB

Open AccessArticle

Establishing an Expert Consensus on Key Indicators of the Quality of Life among Breast Cancer Survivors: A Modified Delphi Study

by Izidor Mlakar, Simon Lin, Jama Nateqi, Stefanie Gruarin, Lorena Diéguez, Paulina Piairo, Liliana R. Pires, Sara Tement, Ilona Aleksandraviča, Mārcis Leja, Krista Arcimoviča, Valérie Bleret, Jean-François Kaux, Philippe Kolh, Didier Maquet, Jesús Garcia Gómez, Jesus García Mata, Mercedes Salgado, Matej Horvat, Maja Ravnik, Vojko Flis and Urška Smrke Show full author list Hide full author list

J. Clin. Med. 2022, 11(7), 2041; https://doi.org/10.3390/jcm11072041 - 05 Apr 2022

Cited by 2 | Viewed by 2161

Abstract

(1) Background: The needs of cancer survivors are often not reflected in practice. One of the main barriers of the use of patient-reported outcomes is associated with data collection and the interpretation of patient-reported outcomes (PROs) due to a multitude of instruments and [...] Read more.

(1) Background: The needs of cancer survivors are often not reflected in practice. One of the main barriers of the use of patient-reported outcomes is associated with data collection and the interpretation of patient-reported outcomes (PROs) due to a multitude of instruments and measuring approaches. The aim of the study was to establish an expert consensus on the relevance and key indicators of quality of life in the clinical practice of breast cancer survivors. (2) Methods: Potential indicators of the quality of life of breast cancer survivors were extracted from the established quality of life models, depicting survivors’ perspectives. The specific domains and subdomains of quality of life were evaluated in a two-stage online Delphi process, including an international and multidisciplinary panel of experts. (3) Results: The first round of the Delphi process was completed by 57 and the second by 37 participants. A consensus was reached for the Physical and Psychological domains, and on eleven subdomains of quality of life. The results were further supported by the additional ranking of importance of the subdomains in the second round. (4) Conclusions: The current findings can serve to optimize the use of instruments and address the challenges related to data collection and interpretation as the facilitators of the adaption in routine practice. Full article

13 pages, 1875 KiB

Open AccessArticle

Triple-Negative Apocrine Breast Carcinoma Has Better Prognosis despite Poor Response to Neoadjuvant Chemotherapy

by Taobo Hu, Yiqiang Liu, Jinbo Wu, Xuejiao Lina Hu, Guiyang Zhao, Baosheng Liang, Shu Wang and Mengping Long

J. Clin. Med. 2022, 11(6), 1607; https://doi.org/10.3390/jcm11061607 - 14 Mar 2022

Cited by 4 | Viewed by 3549

Abstract

Apocrine carcinoma is a rare subtype of invasive ductal breast cancer that shows apocrine differentiation and largely triple-negative immunohistology. Triple-negative breast cancers are known to have more aggressive clinical courses. However, unlike most other subtypes, it is reported that triple-negative apocrine carcinoma (TNAC) [...] Read more.

Apocrine carcinoma is a rare subtype of invasive ductal breast cancer that shows apocrine differentiation and largely triple-negative immunohistology. Triple-negative breast cancers are known to have more aggressive clinical courses. However, unlike most other subtypes, it is reported that triple-negative apocrine carcinoma (TNAC) has a better prognosis. Due to the scarcity of reported studies, our knowledge regarding its clinical behavior, prognosis and response to therapy is very limited. In this study, we retrospectively retrieved 41 triple-negative apocrine carcinoma cases from our breast cancer database, with an average follow-up of 32.8 months. It was found that TNAC had a poorer response to neoadjuvant therapy but a better prognosis than other nonapocrine types of triple-negative breast cancer. Meanwhile, TNAC has a low proliferative nature, as indicated by its low Ki-67 index. An updated analysis of the Surveillance, Epidemiology, and End Results database showed that chemotherapy did not improve breast-cancer-specific survival in TNAC patients. Our results suggest that TNAC is a special subtype of triple-negative breast cancer with a better short-term prognosis despite poor response to neoadjuvant chemotherapy. Full article

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23 pages, 2015 KiB

Open AccessEditor’s ChoiceArticle

Oncofertility and Reproductive Counseling in Patients with Breast Cancer: A Retrospective Study

by Simona Zaami, Rossella Melcarne, Renato Patrone, Giuseppe Gullo, Francesca Negro, Gabriele Napoletano, Marco Monti, Valerio Aceti, Alessandra Panarese, Maria Carola Borcea, Chiara Scorziello, Luca Ventrone, Samira Nicole Mamedov, Maria Letizia Meggiorini, Massimo Vergine and Laura Giacomelli

J. Clin. Med. 2022, 11(5), 1311; https://doi.org/10.3390/jcm11051311 - 27 Feb 2022

Cited by 21 | Viewed by 3126

Abstract

Introduction. Improving the prognosis of breast cancer patients is of utmost importance in terms of increasing survival rates. Modern medicine has therefore prioritized better quality of life for patients, even after the disease, through a better management of the potential long-term side effects [...] Read more.

Introduction. Improving the prognosis of breast cancer patients is of utmost importance in terms of increasing survival rates. Modern medicine has therefore prioritized better quality of life for patients, even after the disease, through a better management of the potential long-term side effects induced by anticancer treatments. Fertility preservation and family planning are therefore crucial issues to be addressed in all cancer patients of reproductive age. Along those lines, a new branch of medicine with distinct multidisciplinary characteristics has developed over the years: oncofertility. Although both national and international guidelines value reproductive counseling as an essential aspect of the diagnostic-therapeutic pathway, part and parcel of the informed consent process, it is not included within the protocols adopted by the operating units for the care and management of neoplastic diseases. Objective. This study aimed to evaluate the activity of the Breast Unit of the Policlinico Umberto I Hospital, Rome, Italy, and the degree of compliance with guidelines. By knowing the strengths and weaknesses of such approaches, the standards of care offered to breast cancer patients can be improved. Materials and methods. A retrospective study based on a review of medical records was conducted between 2014 and 2021. Patients under 40 years of age diagnosed with non-metastatic malignancies were included who received chemotherapy treatment, namely neoadjuvant, adjuvant or adjuvant hormone therapy. Results. The data were extracted from the medical records of 51 patients who met the inclusion criteria, 41% of whom received reproductive counseling, and of these, 43% decided to undertake a path of fertility preservation. Factors such as the absence of children and young age reportedly favored both the interest in counseling proposals by the medical staff and the decision to undertake a path of fertility preservation. Conclusions. The study shows that there has been growing interest in the topic of oncofertility, especially in light of law 219/2017. Therefore, since 2018, multiple proposals for reproductive counseling have been set forth, but there was not an equally growing demand for fertility preservation practices, which can be explained by the invasive nature of such practices, the patients’ concern about their own state of health, and poor or inadequate information. Such impediments highlight the importance of standardized counseling and the need for a multidisciplinary medical team to support the patient in the decision-making process. The study also revealed a drop in the number of patients receiving counseling due to the COVID-19 pandemic, contrary to the positive trend that was recorded prior to the pandemic. Full article

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6 pages, 400 KiB

Open AccessArticle

Did the COVID-19 Pandemic Truly Adversely Affect Disease Progress and Therapeutic Options in Breast Cancer Patients? A Single-Centre Analysis

by Tomasz Nowikiewicz, Maria Szymankiewicz, Marta Drzewiecka, Iwona Głowacka-Mrotek, Magdalena Tarkowska, Magdalena Nowikiewicz and Wojciech Zegarski

J. Clin. Med. 2022, 11(4), 1014; https://doi.org/10.3390/jcm11041014 - 15 Feb 2022

Cited by 1 | Viewed by 1121

Abstract

Purpose: The uncontrolled spread and transmission of SARS-CoV-2 infections has disrupted most areas of social and economic life all over the world. The most important changes concern problems related to the functioning of healthcare systems. The aim of this study was to evaluate [...] Read more.

Purpose: The uncontrolled spread and transmission of SARS-CoV-2 infections has disrupted most areas of social and economic life all over the world. The most important changes concern problems related to the functioning of healthcare systems. The aim of this study was to evaluate clinical consequences associated with the COVID-19 pandemic for patients with newly diagnosed breast cancer, treated at our centre. Methods: The study participants were patients first time diagnosed with breast cancer, treated between January 2019 and March 2021, who were provided any type of cancer treatment at our centre. The study determined the grade of clinical and pathological progress of the disease and types of cancer treatment applied in patients. Results: In total, 2863 patients were included in the analysis. The number of hospitalized patients was 1228 (1123 treated surgically, 105 receiving conservative treatment) in 2019, 1318 (1206 and 112 patients, respectively) in 2020, and 317 (288 and 29 patients, respectively) in 2021. Conclusions: Despite many hazards associated with the new epidemiological situation, we were able to maintain the continuous operation of our centre. We have achieved a measurable success, and even managed to increase the number of treated breast cancer patients. Full article

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17 pages, 2979 KiB

Open AccessReview

Extracorporeal Shock Wave Therapy Combined with Complex Decongestive Therapy in Patients with Breast Cancer-Related Lymphedema: A Systemic Review and Meta-Analysis

by Yu Lin Tsai, Ting Jie I, Ya Chi Chuang, Yuan Yang Cheng and Yu Chun Lee

J. Clin. Med. 2021, 10(24), 5970; https://doi.org/10.3390/jcm10245970 - 19 Dec 2021

Cited by 3 | Viewed by 4510

Abstract

Breast cancer-related lymphedema (BCRL) is one of the most significant complications seen after surgery. Several studies demonstrated that extracorporeal shock wave therapy (ESWT), in addition to conventional complex decongestive therapy (CDT), had a positive effect on BCRL in various aspects. The systematic review [...] Read more.

Breast cancer-related lymphedema (BCRL) is one of the most significant complications seen after surgery. Several studies demonstrated that extracorporeal shock wave therapy (ESWT), in addition to conventional complex decongestive therapy (CDT), had a positive effect on BCRL in various aspects. The systematic review and meta-analysis aim to explore the effectiveness of ESWT with or without CDT on BRCL patients. We searched PubMed, Embase, PEDro, Cochrane Library Databases, and Google Scholar for eligible articles and used PRISMA2020 for paper selection. Included studies were assessed by the PEDro score, Modified Jadad scale, STROBE assessment, and GRADE framework for the risk of bias evaluation. The primary outcomes were the volume of lymphedema and arm circumference. Secondary outcome measures were skin thickness, shoulder joint range of motion (ROM), and an impact on quality-of-life questionnaire. Studies were meta-analyzed with the mean difference (MD). Eight studies were included in the systemic review and four in the meta-analysis. In summary, we found that adjunctive ESWT may significantly improve the volume of lymphedema (MD = −76.44; 95% CI: −93.21, −59.68; p < 0.00001), skin thickness (MD = −1.65; 95% CI: −3.27, −0.02; p = 0.05), and shoulder ROM (MD = 7.03; 95% CI: 4.42, 9.64; p < 0.00001). The evidence level was very low upon GRADE appraisal. ESWT combined with CDT could significantly improve the volume of lymphedema, skin thickness, and shoulder ROM in patients with BCRL. There is not enough evidence to support the use of ESWT as a replacement for CDT. This study was registered with PROSPERO: CRD42021277110. Full article

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10 pages, 3717 KiB

Open AccessArticle

The Expression of Prolactin Receptors in Benign Breast Tumors Is Not Associated with Serum Prolactin Level

by Olena Kolomiiets, Oleksandr Yazykov, Artem Piddubnyi, Mykola Lyndin, Ivan Lukavenko, Volodymyr Andryushchenko, Anatolii Romaniuk and Roman Moskalenko

J. Clin. Med. 2021, 10(24), 5866; https://doi.org/10.3390/jcm10245866 - 14 Dec 2021

Viewed by 1958

Abstract

The role of prolactin (PRL) and its receptors in the initiation and development of benign breast tumors (BBT) has not been sufficiently studied. An imbalance in the system of hormone homeostasis is crucial in the development of BBT. In particular, an association between [...] Read more.

The role of prolactin (PRL) and its receptors in the initiation and development of benign breast tumors (BBT) has not been sufficiently studied. An imbalance in the system of hormone homeostasis is crucial in the development of BBT. In particular, an association between elevated prolactin levels and the development of BBT has been reported. Our study showed no significant differences between PRL receptor (PRL-R) expression in BBT tissue under normal and elevated serum PRL levels. There was also no significant correlation between age, PRL-R expression in BBT tissue, intact tissue, and PRL level in the serum. There was a strong significant correlation (p < 0.01; r = 0.92) between PRL-R expression in BBT samples and intact breast tissue, which did not depend on the serum PRL level. There was also no significant difference in the expression of the proliferative marker Ki-67 in BBT tissues from women with normal and elevated levels of serum PRL (p > 0.05). No signs of PRL and its receptors were detected in the BBT cystic fluid women with elevated serum PRL levels. In summary, our prospective study showed that the expression of PRL-R in the tissue of BBT and physiological breast tissue does not depend on the level of serum PRL. Full article

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7 pages, 1068 KiB

Open AccessArticle

Is Sentinel Lymph Node Biopsy for Breast Cancer with Cytology-Proven Axillary Metastasis Safe? A Prospective Single-Arm Study

by Hee Jun Choi, Jai Min Ryu, Byung Joo Chae, Seok Jin Nam, Jonghan Yu, Se Kyung Lee, Jeong Eon Lee and Seok Won Kim

J. Clin. Med. 2021, 10(20), 4754; https://doi.org/10.3390/jcm10204754 - 16 Oct 2021

Viewed by 1767

Abstract

The purpose of this study was to evaluate pathologic lymph node metastasis in breast cancer with cytology-proven axillary metastasis. This study was designed prospectively. We performed axillary lymph node dissections (ALND) after lymphatic mapping by near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG). [...] Read more.

The purpose of this study was to evaluate pathologic lymph node metastasis in breast cancer with cytology-proven axillary metastasis. This study was designed prospectively. We performed axillary lymph node dissections (ALND) after lymphatic mapping by near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG). We evaluated 72 breast cancer patients with cytology-proven axillary metastasis by curative surgery at the Samsung Medical Center between May of 2016 and December of 2017. Among the 72 patients with cytology-proven axillary metastasis, 14 of 39 patients (35.9%) with one or two sentinel lymph nodes containing metastases were metastasized to post-sentinel lymph node. Thirteen of fourteen patients had additional non-sentinel lymph node metastases, seven of thirteen patients also had additional level II lymph node metastases, and one patient had only one additional level II lymph node metastasis. Of T1 or T2 stage patients, 10 of 33 patients (30.3%) with one or two sentinel lymph nodes containing metastases were metastasized to post-sentinel lymph node. Even in patients without SLN metastasis, 50% of the patients had at least three LN metastases, and 40% in the T1 or T2 stage patients. Sentinel lymph node biopsy without ALND might be not safe for patients with cytology-proven axillary metastasis. Full article

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