Personalized Diagnosis and Treatment of Breast Cancer

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Personalized Therapy and Drug Delivery".

Deadline for manuscript submissions: closed (25 July 2023) | Viewed by 46613

Special Issue Editors

Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
Interests: breast cancer; breast surgery; personalized medicine
Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy
Interests: thyroid cancer; breast cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Breast cancer is one of the most frequent cancers among women and is found to be highly heterogeneous. Importantly, overall survival has improved, mainly due to better medical care, early detection, and important progress of treatments. Although the 5-year overall survival rate of early breast cancer is over 90%, many patients still undergo recurrence, metastasis and drug resistance, even after standard treatment in clinical practice, besides treating breast cancer based on molecular subtypes.

This Special Issue of Journal of Personalized Medicine is focused on addressing the latest research on the diagnosis of breast cancer, including prevention, onset, and progression, as well as the potential of personalized therapies at different levels, with special attention to immunotherapy, targeted therapies, chemo and radiation therapy, and surgery, as well as resistance to treatment to improve patient prognosis.

Dr. Amabile Maria Ida
Dr. Salvatore Sorrenti
Guest Editors

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Keywords

  • breast cancer
  • molecular subtyping
  • personalized medicine
  • targeted therapy
  • breast surgery
  • predictive factors
  • prognosis

Published Papers (16 papers)

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Research

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10 pages, 839 KiB  
Article
Axillary Treatment Management in Breast Cancer during COVID-19 Pandemic (Association between ACOSOG Z0011 Criteria and OSNA Test)
by Giacomo Anedda, Federico Cappellacci, Gian Luigi Canu, Stefania Farris, Pietro Giorgio Calò, Massimo Dessena and Fabio Medas
J. Pers. Med. 2023, 13(2), 241; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm13020241 - 29 Jan 2023
Viewed by 1156
Abstract
The outbreak of the SARS-COVID-2 pandemic (COVID-19) had a significant effect on the organisation of healthcare systems. Surgical units saw a significant reduction in the volume of surgical procedures performed, with lengthening waiting lists as a consequence. We assessed the surgical activity in [...] Read more.
The outbreak of the SARS-COVID-2 pandemic (COVID-19) had a significant effect on the organisation of healthcare systems. Surgical units saw a significant reduction in the volume of surgical procedures performed, with lengthening waiting lists as a consequence. We assessed the surgical activity in relation to breast cancer that took place at the University Hospital of Cagliari, Italy, from February 2018 to March 2022. Two phases were identified based on the epidemiological circumstances: Phase 1—February 2018 to February 2020; Phase 2—March 2020 to March 2022. The surgery performed in the two phases was then compared. All the patients in our sample underwent a breast surgical procedure involving a lymph node biopsy using OSNA associated with the ACOSOG Z0011 criteria. In the study period overall at our facility, there were 4214 procedures, 417 of which involved breast surgery. In Phase 2, 91 procedures were performed using the OSNA method and ACOSOG Z0011 criteria, enabling the intraoperative staging of axillary nodes. Axillary treatment in breast cancer using this approach resulted in a significant reduction in the number of reoperations for the radicalisation of metastatic sentinel lymph nodes. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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10 pages, 1071 KiB  
Article
Analgesic Efficacies of Intraoperative Pectoralis Nerve II Block under Direct Vision in Patients Undergoing Robotic Nipple-Sparing Mastectomy with Immediate Breast Reconstruction: A Prospective, Randomized Controlled Study
by Jiae Moon, Hyung Seok Park, Jee Ye Kim, Hye Sun Lee, Soyoung Jeon, Dongwoo Lee, Sun Joon Bai and Na Young Kim
J. Pers. Med. 2022, 12(8), 1309; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12081309 - 12 Aug 2022
Viewed by 1269
Abstract
This prospective, randomized study aimed to evaluate the efficacy of an intraoperative pectoralis nerve II block (PECS II block) under direct vision in the reduction of fentanyl consumption during postoperative 24 h in patients undergoing robotic nipple-sparing mastectomy (RNSM) with immediate breast reconstruction [...] Read more.
This prospective, randomized study aimed to evaluate the efficacy of an intraoperative pectoralis nerve II block (PECS II block) under direct vision in the reduction of fentanyl consumption during postoperative 24 h in patients undergoing robotic nipple-sparing mastectomy (RNSM) with immediate breast reconstruction (IBR) using direct-to-implant (DTI) or tissue expander (TE). Thirty patients scheduled for RNSM with IBR were randomly allocated to the PECS (n = 15) or control (n = 15) groups. The PECS II block was applied under direct vision after RNSM. The primary outcome was the cumulative dose of fentanyl consumption. The secondary outcomes were pain intensity using a numerical rating scale (NRS) at rest and acting during the postoperative 24 h. The cumulative dose of fentanyl at 24 h was significantly lower in the PECS group than in the control group (p = 0.011). Patients in the PECS group showed significantly lower NRS scores during the first postoperative 2 h compared to those in the control group in both resting and acting pain (p < 0.05). An intraoperative PECS II block under direct vision can reduce opioid consumption during the postoperative 24 h and provide effective analgesia in patients undergoing RNSM with IBR using DTI or TE. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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11 pages, 745 KiB  
Article
The Role of Surgical Axillary Staging Prior to Immediate Breast Reconstruction in the Era of De-Escalation of Axillary Management in Early Breast Cancer
by Miriam Svensson and Looket Dihge
J. Pers. Med. 2022, 12(8), 1283; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12081283 - 04 Aug 2022
Viewed by 1347
Abstract
Postmastectomy radiotherapy (PMRT) following immediate breast reconstruction (IBR) is associated with postoperative complications. Although the incidence of node-positive breast cancer is declining, a separate sentinel lymph node biopsy (SLNB) is still performed before mastectomy when IBR is planned, in order to evaluate nodal [...] Read more.
Postmastectomy radiotherapy (PMRT) following immediate breast reconstruction (IBR) is associated with postoperative complications. Although the incidence of node-positive breast cancer is declining, a separate sentinel lymph node biopsy (SLNB) is still performed before mastectomy when IBR is planned, in order to evaluate nodal status and the need for PMRT. This study assessed the impact of staged SLNB on the breast reconstructive planning, and presents common clinicopathological characteristics of breast cancer with macrometastatic nodal spread where staged SLNB would be beneficial to indicate PMRT. Medical records of breast cancer patients scheduled for mastectomy and IBR at Skåne University Hospital, Sweden, from November 2014 to February 2020, were reviewed. Of 92 patients, node-positive disease was present in 15 (16%). Fifty-three patients underwent staged SLNB before mastectomy and IBR, and 10 (19%) presented with nodal metastasis. All patients with macrometastatic sentinel nodes were presented with palpable, multifocal, ER+ breast carcinoma of no special type with tumor size > 17.0 mm. Overall, four women received PMRT after verified metastasis by staged SLNB, and IBR was cancelled for three patients. These findings question the benefit of routine staged SLNB before mastectomy and IBR in breast cancer populations within established mammography screening programs with low risk of nodal metastasis. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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12 pages, 2323 KiB  
Article
Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative Phenotype
by Silvia Grassilli, Federica Brugnoli, Stefano Cairo, Nicoletta Bianchi, Jean-Gabriel Judde and Valeria Bertagnolo
J. Pers. Med. 2022, 12(6), 993; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12060993 - 17 Jun 2022
Cited by 3 | Viewed by 1890
Abstract
Triple negative breast cancer (TNBC) represents the most aggressive breast tumor, showing a high intrinsic variability in terms of both histopathological features and response to therapies. Blocking the Akt signaling pathway is a well-studied approach in the treatment of aggressive breast tumors. The [...] Read more.
Triple negative breast cancer (TNBC) represents the most aggressive breast tumor, showing a high intrinsic variability in terms of both histopathological features and response to therapies. Blocking the Akt signaling pathway is a well-studied approach in the treatment of aggressive breast tumors. The high homology among the Akt isoforms and their distinct, and possibly opposite, oncogenic functions made it difficult to develop effective drugs. Here we investigated the role of Vav1 as a potential down-regulator of individual Akt isozymes. We revealed that the over-expression of Vav1 in triple negative MDA-MB-231 cells reduced only the Akt2 isoform, acting at the post-transcriptional level through the up-modulation of miR-29b. The Vav1/miR-29b dependent decrease in Akt2 was correlated with a reduced lung colonization of circulating MDA-MB-231 cells. In cell lines established from PDX, the Vav1 induced down-modulation of Akt2 is strongly dependent on miR-29b and occurs only in some TNBC tumors. These findings may contribute to better classify breast tumors having the triple negative phenotype, and suggest that the activation of the Vav1/miR-29b axis, precisely regulating the amount of an Akt isozyme crucial for tumor dissemination, could have great potential for driving more accurate therapies to TNBCs, often not eligible or resistant to treatments. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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14 pages, 964 KiB  
Article
Association of Serum 25-Hydroxyvitamin D Concentration with Breast Cancer Risk in Postmenopausal Women in the US
by Vijay Ganji, Layan Sukik, Bushra Hoque, Linda Boutefnouchet and Zumin Shi
J. Pers. Med. 2022, 12(6), 944; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12060944 - 09 Jun 2022
Cited by 6 | Viewed by 2198
Abstract
The association between serum 25-hydroxyvitamin D [25(OH)D] concentration and breast cancer risk in postmenopausal women is not well understood. The aim of this study was to investigate the association between serum 25(OH)D concentration and breast cancer in postmenopausal women in the United States [...] Read more.
The association between serum 25-hydroxyvitamin D [25(OH)D] concentration and breast cancer risk in postmenopausal women is not well understood. The aim of this study was to investigate the association between serum 25(OH)D concentration and breast cancer in postmenopausal women in the United States using nationally representative sample surveys. We used the data from seven cycles of National Health and Nutrition Examination Surveys from 2001 to 2014. Participants were non-institutionalized postmenopausal women (n = 8108). In restricted cubic spline analysis, a significant, nonlinear, invert ‘U’ relationship was observed between serum 25(OH)D concentrations and breast cancer in postmenopausal women (p = 0.029). Overall, breast cancer risk was highest (OR = 1.5) between 70 nmol/L and 80 nmol/L of serum 25(OH)D concentration. Then after serum 25(OH)D 80 nmol/L concentration, the breast cancer risk declined. In multivariate-adjusted logistic regression, the risk of having breast cancer was significantly higher in serum 25(OH)D 75–˂100 nmol/L category compared to the 25(OH)D < 30 nmol/L category [OR and 95% CI: 2.4 (1.4–4.0)]. In conclusion, serum vitamin D concentrations ≥ 100 nmol/L are associated with reduced risk of breast cancer in postmenopausal women. Controlled trials are required to verify if serum 25(OH)D ≥ 100 nmol/L offers protection against breast cancer in postmenopausal women. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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12 pages, 834 KiB  
Article
Androgen Receptor: A New Marker to Predict Pathological Complete Response in HER2-Positive Breast Cancer Patients Treated with Trastuzumab Plus Pertuzumab Neoadjuvant Therapy
by Jiayi Li, Shuang Zhang, Chen Ye, Qian Liu, Yuanjia Cheng, Jingming Ye, Yinhua Liu, Xuening Duan, Ling Xin, Hong Zhang and Ling Xu
J. Pers. Med. 2022, 12(2), 261; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12020261 - 11 Feb 2022
Cited by 4 | Viewed by 1769
Abstract
(1) Background: Neoadjuvant therapy is the main therapeutic strategy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, and the combination of trastuzumab and pertuzumab (HP) has become a routine treatment. How to predict and screen patients who are less likely [...] Read more.
(1) Background: Neoadjuvant therapy is the main therapeutic strategy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, and the combination of trastuzumab and pertuzumab (HP) has become a routine treatment. How to predict and screen patients who are less likely to respond to neoadjuvant therapy is the focus of research. The androgen receptor (AR) is a biomarker that is widely expressed in all breast cancer subtypes and is probably related to treatment response and prognosis. In this study, we investigated the relationship between AR expression and treatment response in HER2-positive breast cancer patients treated with HP neoadjuvant therapy. (2) Methods: We evaluated early breast cancer patients treated with HP neoadjuvant therapy from Jan. 2019 to Oct. 2020 at Peking University First Hospital Breast Cancer Center. The inclusion criteria were as follows: early HER2-positive breast cancer patients diagnosed by core needle biopsy who underwent both HP neoadjuvant therapy and surgery. We compared the clinical and pathological features between pathological complete response (pCR) and non-pCR patients. (3) Results: We included 44 patients. A total of 90.9% of patients received neoadjuvant therapy of taxanes, carboplatin, trastuzumab and pertuzumab (TCHP), and the total pCR rate was 50%. pCR was negatively related to estrogen receptor (ER) positivity (OR 0.075 [95% confidence interval (CI) 0.008–0.678], p = 0.021) and positively related to high expression levels of AR (OR 33.145 [95% CI 2.803–391.900], p = 0.005). We drew a receiver operating characteristic (ROC) curve to assess the predictive value of AR expression for pCR, and the area under the curve was 0.737 (95% CI 0.585–0.889, p = 0.007). The optimal cutoff of AR for predicting pCR was 85%. (4) Conclusion: AR is a potential marker for the prediction of pCR in HER2-positive breast cancer patients treated with HP neoadjuvant therapy. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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9 pages, 1142 KiB  
Article
Breast Reconstruction after Mastectomy with the Use of an Implant and Serratus Anterior Fascia Flap—Initial Clinical Evaluation
by Mauro Tarallo, Federico Lo Torto, Fabio Ricci, Paolo Dicorato, Francesco Luca Rocco Mori, Federica Vinci, Paola Parisi, Manfredi Greco, Carlo De Masi, Alessandra Rita La Manna, Silvia Piroli and Diego Ribuffo
J. Pers. Med. 2021, 11(11), 1142; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11111142 - 03 Nov 2021
Cited by 1 | Viewed by 3303
Abstract
Prosthesis-based techniques are the predominant form of breast reconstruction worldwide. The most performed surgical technique involves the placement of the expander in a partial submuscular plane. The coverage of the implant remains a difficult management problem that can lead to complications and poor [...] Read more.
Prosthesis-based techniques are the predominant form of breast reconstruction worldwide. The most performed surgical technique involves the placement of the expander in a partial submuscular plane. The coverage of the implant remains a difficult management problem that can lead to complications and poor outcomes. The use of the serratus fascia flap may be the best choice to create a subpectoral pocket for the placement of a tissue expander, with excellent results in terms of morbidity and cost-effectiveness. A total of 20 breast reconstructions with the inferolateral coverage with the serratus fascia were performed. Patients demonstrated a low overall complication rate (9.5%), such as seroma and infection, with complete resolution during the follow-up and no major complications. The US examination of the soft tissues over the implant reported thickness measurements that demonstrated a good coverage over the inferolateral area. Our study shows that using the serratus fascia flap to create a pocket with the pectoralis major for the placement of the tissue expander is an effective technique during two-stage breast reconstruction. The resulting low rate of morbidity and the US findings collected reveal the safety of this procedure. Its success relies on appropriate patient selection and specific intraoperative technique principles. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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16 pages, 4670 KiB  
Article
Clinical Significance of Peritumoral Adipose Tissue PET/CT Imaging Features for Predicting Axillary Lymph Node Metastasis in Patients with Breast Cancer
by Jeong Won Lee, Sung Yong Kim, Sun Wook Han, Jong Eun Lee, Sung Hoon Hong, Sang Mi Lee and In Young Jo
J. Pers. Med. 2021, 11(10), 1029; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11101029 - 15 Oct 2021
Cited by 7 | Viewed by 2011
Abstract
We investigated whether textural parameters of peritumoral breast adipose tissue (AT) based on F-18 fluorodeoxyglucose (FDG) PET/CT could predict axillary lymph node metastasis in patients with breast cancer. A total of 326 breast cancer patients with preoperative FDG PET/CT were retrospectively enrolled. PET/CT [...] Read more.
We investigated whether textural parameters of peritumoral breast adipose tissue (AT) based on F-18 fluorodeoxyglucose (FDG) PET/CT could predict axillary lymph node metastasis in patients with breast cancer. A total of 326 breast cancer patients with preoperative FDG PET/CT were retrospectively enrolled. PET/CT images were visually assessed and the maximum FDG uptake of axillary lymph nodes (LN SUVmax) was measured. From peritumoral breast AT, 38 textural features of PET imaging were extracted. The diagnostic ability of PET based on visual analysis, LN SUVmax, and textural features of peritumoral breast AT for predicting axillary lymph node metastasis were assessed using the area under the receiver operating characteristic curve (AUC) values. Among the 38 peritumoral breast AT textural features, grey-level co-occurrence matrix (GLCM) entropy showed the highest AUC value (0.830) for predicting axillary lymph node metastasis. The value of GLCM entropy was higher than that of visual analysis (0.739; p < 0.05) and the AUC value was comparable to that of LN SUVmax (0.793; p > 0.05). In the subgroup analysis of patients with negative findings on visual analysis, GLCM entropy still showed a high diagnostic ability (AUC: 0.759) in predicting lymph node metastasis. The findings suggest a potential diagnostic role of PET/CT imaging features of peritumoral breast AT in predicting axillary lymph node metastasis in patients with breast cancer. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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15 pages, 32119 KiB  
Article
PRMT1 Confers Resistance to Olaparib via Modulating MYC Signaling in Triple-Negative Breast Cancer
by Wen-Jing Hsu, Cheng-Hsun Chen, Yu-Chu Chang, Chia-Hsiung Cheng, Ying-Huei TsaI and Cheng-Wei Lin
J. Pers. Med. 2021, 11(10), 1009; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11101009 - 08 Oct 2021
Cited by 9 | Viewed by 2678
Abstract
Treatment of triple-negative breast cancer (TNBC) remains an unmet clinical need owing to its lack of an efficient therapeutic target. The targeting of DNA repair by poly(ADP-ribose) polymerase (PARP) inhibitors has shown benefit for patients with the BRCA variation. However, sensitivities to the [...] Read more.
Treatment of triple-negative breast cancer (TNBC) remains an unmet clinical need owing to its lack of an efficient therapeutic target. The targeting of DNA repair by poly(ADP-ribose) polymerase (PARP) inhibitors has shown benefit for patients with the BRCA variation. However, sensitivities to the PARP inhibitors were reported regardless of BRCA status. Thus, exploring the underlying mechanisms is imperative. Herein, we identified that breast cancer cells with an elevated expression of protein arginine methyl transferase 1 (PRMT1) was associated with therapeutic sensitivity to the PARP inhibitor olaparib. The results of cell viability and colony formation assays indicated that the suppression of PRMT1 by small hairpin RNA or by the chemical inhibitor increased sensitivity to olaparib in human TNBC MDA-MB-231 and BT549 cells. Bioinformatic analysis revealed that PRMT1 expression was significantly associated with the MYC signature, and TNBC cells with higher PRMT1 and the MYC signature were associated with therapeutic sensitivity to olaparib. Mechanistic studies further demonstrated that knockdown of PRMT1 reduced the c-Myc protein level and downregulated the expression of MYC downstream targets, whereas overexpression of PRMT1 enhanced c-Myc protein expression. Moreover, the overexpression of PRMT1 promoted c-Myc protein stability, and the inhibition of PRMT1 downregulated c-Myc protein stability. Accordingly, the knockdown of PRMT1 inhibited homologous recombination gene expression. These data indicate that PRMT1 is instrumental in regulating DNA repair, at least in part, by modulating c-Myc signaling. Our data highlighted the PRMT1/c-Myc network as a potential therapeutic target in patients with TNBC. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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15 pages, 1189 KiB  
Article
Effects of Inositol Hexaphosphate and Myo-Inositol Administration in Breast Cancer Patients during Adjuvant Chemotherapy
by Maria Ida Amabile, Alessandro De Luca, Domenico Tripodi, Elena D’Alberti, Rossella Melcarne, Giovanni Imbimbo, Orietta Picconi, Vito D’Andrea, Massimo Vergine, Salvatore Sorrenti and Alessio Molfino
J. Pers. Med. 2021, 11(8), 756; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11080756 - 30 Jul 2021
Cited by 9 | Viewed by 3069
Abstract
Background: Treatment of breast cancer (BC) includes locoregional and systemic therapies depending on tumor and patient’s characteristics. Inositol hexaphosphate (IP6) is known as a strong antioxidant agent, able to improve local (i.e., breast region) side effects, functional status and quality-of-life. We investigated some [...] Read more.
Background: Treatment of breast cancer (BC) includes locoregional and systemic therapies depending on tumor and patient’s characteristics. Inositol hexaphosphate (IP6) is known as a strong antioxidant agent, able to improve local (i.e., breast region) side effects, functional status and quality-of-life. We investigated some potential beneficial effects, including hematological and local, of the combined therapy with oral myo-inositol administration and topical IP6 application in patients undergoing surgery for BC and eligible to adjuvant chemotherapy. Methods: We considered BC patients randomly assigned to the Inositol Group (oral myo-inositol + IP6 local application for the entire neoadjuvant treatment period) and to the Control Group (standard of care). The EORTC QLQ-BR23 and QLQ-C30 questionnaires were administered to both groups and blood parameters were assessed as per clinical routine practice at baseline (before starting adjuvant chemotherapy), T1 (after the first two doses of epirubicin-cyclophosphamide regimen), T2 (at the end of epirubicin-cyclophosphamide regimen), T3 (after the first six doses of paclitaxel regimen), and T4 (at the end of the paclitaxel treatment). Results: A total of 36 BC patients were considered, 18 in the Inositol Group and 18 in the Control Group. The Inositol Group showed a lower decrease in red blood cells, hemoglobin levels and white blood cells with respect to controls (p ≤ 0.02), as well as amelioration in scores related to breast and arm local symptoms (p ≤ 0.02), body image (p = 0.04) and quality-of-life related symptoms (p ≤ 0.04). Conclusions: In our cohort of BC patients, a combined treatment with oral myo-inositol + IP6 local application was able to improve local symptoms and quality-of-life related symptoms which represent clinically relevant aspects associated with patient’s prognosis. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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15 pages, 2394 KiB  
Article
High BMI1 Expression with Low CD8+ and CD4+ T Cell Activity Could Promote Breast Cancer Cell Survival: A Machine Learning Approach
by Yumin Chung, Kyueng-Whan Min, Dong-Hoon Kim, Byoung Kwan Son, Sung-Im Do, Seoung Wan Chae and Mi Jung Kwon
J. Pers. Med. 2021, 11(8), 739; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11080739 - 28 Jul 2021
Cited by 2 | Viewed by 1943
Abstract
BMI1 is known to play a key role in the regulation of stem cell self-renewal in both endogenous and cancer stem cells. High BMI1 expression has been associated with poor prognosis in a variety of human tumors. The aim of this study was [...] Read more.
BMI1 is known to play a key role in the regulation of stem cell self-renewal in both endogenous and cancer stem cells. High BMI1 expression has been associated with poor prognosis in a variety of human tumors. The aim of this study was to reveal the correlations of BMI1 with survival rates, genetic alterations, and immune activities, and to validate the results using machine learning. We investigated the survival rates according to BMI1 expression in 389 and 789 breast cancer patients from Kangbuk Samsung Medical Center (KBSMC) and The Cancer Genome Atlas, respectively. We performed gene set enrichment analysis (GSEA) with pathway-based network analysis, investigated the immune response, and performed in vitro drug screening assays. The survival prediction model was evaluated through a gradient boosting machine (GBM) approach incorporating BMI1. High BMI1 expression was correlated with poor survival in patients with breast cancer. In GSEA and in in silico flow cytometry, high BMI1 expression was associated with factors indicating a weak immune response, such as decreased CD8+ T cell and CD4+ T cell counts. In pathway-based network analysis, BMI1 was directly linked to transcriptional regulation and indirectly linked to inflammatory response pathways, etc. The GBM model incorporating BMI1 showed improved prognostic performance compared with the model without BMI1. We identified telomerase inhibitor IX, a drug with potent activity against breast cancer cell lines with high BMI1 expression. We suggest that high BMI1 expression could be a therapeutic target in breast cancer. These results could contribute to the design of future experimental research and drug development programs for breast cancer. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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14 pages, 1693 KiB  
Article
High WHSC1L1 Expression Reduces Survival Rates in Operated Breast Cancer Patients with Decreased CD8+ T Cells: Machine Learning Approach
by Hyung-Suk Kim, Kyueng-Whan Min, Dong-Hoon Kim, Byoung-Kwan Son, Mi-Jung Kwon and Sang-Mo Hong
J. Pers. Med. 2021, 11(7), 636; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11070636 - 05 Jul 2021
Cited by 7 | Viewed by 2265
Abstract
Nuclear receptor-binding SET domain protein (NSD), a histone methyltransferase, is known to play an important role in cancer pathogenesis. The WHSC1L1 (Wolf-Hirschhorn syndrome candidate 1-like 1) gene, encoding NSD3, is highly expressed in breast cancer, but its role in the development of breast [...] Read more.
Nuclear receptor-binding SET domain protein (NSD), a histone methyltransferase, is known to play an important role in cancer pathogenesis. The WHSC1L1 (Wolf-Hirschhorn syndrome candidate 1-like 1) gene, encoding NSD3, is highly expressed in breast cancer, but its role in the development of breast cancer is still unknown. The purpose of this study was to analyze the survival rates and immune responses of breast cancer patients with high WHSC1L1 expression and to validate the results using gradient boosting machine (GBM) in breast cancer. We investigated the clinicopathologic parameters, proportions of immune cells, pathway networks and in vitro drug responses according to WHSC1L1 expression in 456, 1500 and 776 breast cancer patients from the Hanyang University Guri Hospital, METABRIC and TCGA, respectively. High WHSC1L1 expression was associated with poor prognosis, decreased CD8+ T cells and high CD274 expression (encoding PD-L1). In the pathway networks, WHSC1L1 was indirectly linked to the regulation of the lymphocyte apoptotic process. The GBM model with WHSC1L1 showed improved prognostic performance compared with the model without WHSC1L1. We found that VX-11e, CZC24832, LY2109761, oxaliplatin and erlotinib were effective in inhibiting breast cancer cell lines with high WHSC1L1 expression. High WHSC1L1 expression could play potential roles in the progression of breast cancer and targeting WHSC1L1 could be a potential strategy for the treatment of breast cancer. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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Review

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21 pages, 483 KiB  
Review
Application of Artificial Intelligence Techniques to Predict Risk of Recurrence of Breast Cancer: A Systematic Review
by Claudia Mazo, Claudia Aura, Arman Rahman, William M. Gallagher and Catherine Mooney
J. Pers. Med. 2022, 12(9), 1496; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12091496 - 13 Sep 2022
Cited by 7 | Viewed by 3377
Abstract
Breast cancer is the most common disease among women, with over 2.1 million new diagnoses each year worldwide. About 30% of patients initially presenting with early stage disease have a recurrence of cancer within 10 years. Predicting who will have a recurrence [...] Read more.
Breast cancer is the most common disease among women, with over 2.1 million new diagnoses each year worldwide. About 30% of patients initially presenting with early stage disease have a recurrence of cancer within 10 years. Predicting who will have a recurrence and who will not remains challenging, with consequent implications for associated treatment. Artificial intelligence strategies that can predict the risk of recurrence of breast cancer could help breast cancer clinicians avoid ineffective overtreatment. Despite its significance, most breast cancer recurrence datasets are insufficiently large, not publicly available, or imbalanced, making these studies more difficult. This systematic review investigates the role of artificial intelligence in the prediction of breast cancer recurrence. We summarise common techniques, features, training and testing methodologies, metrics, and discuss current challenges relating to implementation in clinical practice. We systematically reviewed works published between 1 January 2011 and 1 November 2021 using the methodology of Kitchenham and Charter. We leveraged Springer, Google Scholar, PubMed, and IEEE search engines. This review found three areas that require further work. First, there is no agreement on artificial intelligence methodologies, feature predictors, or assessment metrics. Second, issues such as sampling strategies, missing data, and class imbalance problems are rarely addressed or discussed. Third, representative datasets for breast cancer recurrence are scarce, which hinders model validation and deployment. We conclude that predicting breast cancer recurrence remains an open problem despite the use of artificial intelligence. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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15 pages, 992 KiB  
Review
Thyroid Diseases and Breast Cancer
by Enke Baldini, Augusto Lauro, Domenico Tripodi, Daniele Pironi, Maria Ida Amabile, Iulia Catalina Ferent, Eleonora Lori, Federica Gagliardi, Maria Irene Bellini, Flavio Forte, Patrizia Pacini, Vito Cantisani, Vito D’Andrea, Salvatore Sorrenti and Salvatore Ulisse
J. Pers. Med. 2022, 12(2), 156; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12020156 - 25 Jan 2022
Cited by 15 | Viewed by 5677
Abstract
Epidemiological studies aimed at defining the association of thyroid diseases with extra-thyroidal malignancies (EM) have aroused considerable interest in the possibility of revealing common genetic and environmental factors underlying disease etiology and progression. Over the years, multiple lines of evidence indicated a significant [...] Read more.
Epidemiological studies aimed at defining the association of thyroid diseases with extra-thyroidal malignancies (EM) have aroused considerable interest in the possibility of revealing common genetic and environmental factors underlying disease etiology and progression. Over the years, multiple lines of evidence indicated a significant relationship between thyroid carcinomas and other primary EM, especially breast cancer. For the latter, a prominent association was also found with benign thyroid diseases. In particular, a meta-analysis revealed an increased risk of breast cancer in patients with autoimmune thyroiditis, and our recent work demonstrated that the odds ratio (OR) for breast cancer was raised in both thyroid autoantibody-positive and -negative patients. However, the OR was significantly lower for thyroid autoantibody-positive patients compared to the negative ones. This is in agreement with findings showing that the development of thyroid autoimmunity in cancer patients receiving immunotherapy is associated with better outcome and supports clinical evidence that breast cancer patients with thyroid autoimmunity have longer disease-free interval and overall survival. These results seem to suggest that factors other than oncologic treatments may play a role in the initiation and progression of a second primary malignancy. The molecular links between thyroid autoimmunity and breast cancer remain, however, unidentified, and different hypotheses have been proposed. Here, we will review the epidemiological, clinical, and experimental data relating thyroid diseases and breast cancer, as well as the possible hormonal and molecular mechanisms underlying such associations. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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14 pages, 1411 KiB  
Review
Breast Reconstruction by Exclusive Lipofilling after Total Mastectomy for Breast Cancer: Description of the Technique and Evaluation of Quality of Life
by Alexandre Piffer, Gabrielle Aubry, Claudio Cannistra, Nathalie Popescu, Maryam Nikpayam, Martin Koskas, Catherine Uzan, Jean-Christophe Bichet and Geoffroy Canlorbe
J. Pers. Med. 2022, 12(2), 153; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12020153 - 25 Jan 2022
Cited by 7 | Viewed by 3174
Abstract
Background: The objective of this work was to describe the technique of exclusive lipofilling in breast reconstruction after total mastectomy, to evaluate the satisfaction and quality of life of the patients, and to explore current literature on the subject. Methods: We conducted a [...] Read more.
Background: The objective of this work was to describe the technique of exclusive lipofilling in breast reconstruction after total mastectomy, to evaluate the satisfaction and quality of life of the patients, and to explore current literature on the subject. Methods: We conducted a retrospective observational multicentric study from January 2013 to April 2020. The modalities of surgery, esthetic result, and patient satisfaction were evaluated with the breast reconstruction module of BREAST-Q. Results: Complete data were available for 37 patients. The mean number of sessions was 2.2 (standard deviation 1.1), spread over an average of 6.8 months (SD 6.9). The average total volume of fat transferred was 566.4 mL. The complication rate was 18.9%. No severe complication was observed (Clavien–Dindo 3/4). Two patients were diagnosed with recurrence, in a metastatic mode (5.4%). The average satisfaction rate was 68.4% (SD 24.8) for psychosocial well-being and 64.5% (SD 24.1) for sexual well-being. The satisfaction rate was 60.2% (SD 20.9) for the image of the reconstructed breast and 82.7% (SD 21.9) for locoregional comfort. Conclusions: Breast reconstruction by exclusive lipofilling after total mastectomy provides satisfactory quality of life scores. The simplicity of the surgical technique and equipment required, and the high satisfaction rate confirm that lipofilling should be included in the panel of choice of breast reconstruction techniques. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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Study Protocol
Easy Scheme Outlining the Various Morphological and Vascular Abnormalities of the Lymph Node Structure Associated with Recent COVID-19 Vaccination, Each with a Different Clinical/Diagnostic Management
by Valeria Fiaschetti, Nicolò Ubaldi, Smeralda De Fazio and Elsa Cossu
J. Pers. Med. 2022, 12(9), 1371; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12091371 - 25 Aug 2022
Cited by 1 | Viewed by 7758
Abstract
Throughout this recent ongoing SARS-CoV-2 pandemic, the European Society of Breast Imaging have surely contributed in improving the management of unilateral axillary adenopathy appearance homolaterally to the side of vaccine inoculation. After considering the patient’s COVID-19 history of vaccination, our group produced a [...] Read more.
Throughout this recent ongoing SARS-CoV-2 pandemic, the European Society of Breast Imaging have surely contributed in improving the management of unilateral axillary adenopathy appearance homolaterally to the side of vaccine inoculation. After considering the patient’s COVID-19 history of vaccination, our group produced a day-to-day scheme that evaluates meticulously the probability of mammary malignancy, according to the lymph node characteristics including vascular abnormalities. It comprises of a UN (ultrasound node) score ranging from 2 to 5, that increases with the suspicion of malignancy. In this setting and in view of the additional incoming COVID-19 boost-dose vaccinations, we believe our model could be of great utility to radiologist when assessing patients whom do not have a straight forward diagnosis, in order to reduce breast cancer missed diagnosis, avoid delaying vaccinations, reduce rescheduling of breast imaging examinations and lastly avoid unnecessary lymph node biopsies. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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