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16 pages, 699 KiB

Open AccessArticle

Racial and Ethnic Disparities in European Breast Cancer Clinical Trials

by Angelina Bania, Antonis Adamou and Emmanouil Saloustros

Cancers 2024, 16(9), 1726; https://doi.org/10.3390/cancers16091726 - 29 Apr 2024

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Abstract

Breast cancer is the most prevalent female cancer worldwide with known correlations between the race and tumor characteristics of the patients and prognosis. International and US-based studies, however, have reported a disproportionate representation of Black and Hispanic patients in clinical trials. This is [...] Read more.

Breast cancer is the most prevalent female cancer worldwide with known correlations between the race and tumor characteristics of the patients and prognosis. International and US-based studies, however, have reported a disproportionate representation of Black and Hispanic patients in clinical trials. This is the first study assessing race and ethnicity reporting trends and inclusion in European breast cancer trials. The PubMed and ClinicalTrials.gov databases were systematically searched for trials on breast cancer treatment conducted exclusively in Europe between 2010 and 2022. Of the 97 identified trials, race was reported in 10.31%. Multinational participation, but not the study size or trial phase, was significantly associated with higher race reporting trends. These 10 trials featured a White-predominant population, with 1.08% Asian and 0.88% Black patients included. The acquisition of the race and ethnicity data of patients in European trials is lower compared to the U.S. or worldwide studies and does not permit extensive analysis of minority participation. In a limited analysis, the low rates of minority participation are concerning, based on population-based data on minorities in select European countries. These observations should encourage race reporting practices in European breast cancer trials and adequate minority participation to support the generalizability of the results of the studies and promote healthcare equity. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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10 pages, 7028 KiB

Open AccessArticle

Prediction of Overall Disease Burden in (y)pN1 Breast Cancer Using Knowledge-Based Machine Learning Model

by Seok-Joo Chun, Bum-Sup Jang, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin and Division for Breast Cancer, Korean Radiation Oncology Group

Cancers 2024, 16(8), 1494; https://doi.org/10.3390/cancers16081494 - 13 Apr 2024

Viewed by 385

Abstract

Background: We aimed to construct an expert knowledge-based Bayesian network (BN) model for assessing the overall disease burden (ODB) in (y)pN1 breast cancer patients and compare ODB across arms of ongoing trials. Methods: Utilizing institutional data and expert surveys, we developed a BN [...] Read more.

Background: We aimed to construct an expert knowledge-based Bayesian network (BN) model for assessing the overall disease burden (ODB) in (y)pN1 breast cancer patients and compare ODB across arms of ongoing trials. Methods: Utilizing institutional data and expert surveys, we developed a BN model for (y)pN1 breast cancer. Expert-derived probabilities and disability weights for radiotherapy-related benefit (e.g., 7-year disease-free survival [DFS]) and toxicities were integrated into the model. ODB was defined as the sum of disability weights multiplied by probabilities. In silico predictions were conducted for Alliance A011202, PORT-N1, RAPCHEM, and RT-CHARM trials, comparing ODB, 7-year DFS, and side effects. Results: In the Alliance A011202 trial, 7-year DFS was 80.1% in both arms. Axillary lymph node dissection led to higher clinical lymphedema and ODB compared to sentinel lymph node biopsy with full regional nodal irradiation (RNI). In the PORT-N1 trial, the control arm (whole-breast irradiation [WBI] with RNI or post-mastectomy radiotherapy [PMRT]) had an ODB of 0.254, while the experimental arm (WBI alone or no PMRT) had an ODB of 0.255. In the RAPCHEM trial, the radiotherapy field did not impact the 7-year DFS in ypN1 patients. However, there was a mild ODB increase with a larger irradiation field. In the RT-CHARM trial, we identified factors associated with the major complication rate, which ranged from 18.3% to 22.1%. Conclusions: The expert knowledge-based BN model predicted ongoing trial outcomes, validating reported results and assumptions. In addition, the model demonstrated the ODB in different arms, with an emphasis on quality of life. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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21 pages, 643 KiB

Open AccessArticle

Compliance with the WCRF/AICR Recommendations in Qualitative Adaptation and the Occurrence of Breast Cancer: A Case-Control Study

by Beata Stasiewicz, Lidia Wadolowska, Maciej Biernacki, Malgorzata Anna Slowinska and Ewa Stachowska

Cancers 2024, 16(2), 468; https://doi.org/10.3390/cancers16020468 - 22 Jan 2024

Viewed by 897

Abstract

Purpose: The aim of the study was twofold: (1) the qualitative adaptation of the 2018 WCRF/AICR (QAd-WCRF/AICR) score, and (2) the assessment of the association between the level of compliance with the WCRF/AICR recommendations and the occurrence of breast cancer in peri- and [...] Read more.

Purpose: The aim of the study was twofold: (1) the qualitative adaptation of the 2018 WCRF/AICR (QAd-WCRF/AICR) score, and (2) the assessment of the association between the level of compliance with the WCRF/AICR recommendations and the occurrence of breast cancer in peri- and postmenopausal women. Methods: This case–control study involved 420 women, aged 40–79 years, from northeastern Poland, including 190 newly diagnosed breast cancer cases. Data related to the WCRF/AICR recommendations were collected in face-to-face interviews with 409 women, including 179 women with breast cancer. The frequency of food consumption data were collected using the FFQ-6^® and KomPAN^® questionnaires. Body weight, height, and waist circumference were measured. The QAd-WCRF/AICR score (range: 0–8 points) was calculated on the basis of eight components, including two components from to the WCRF/AICR recommendations: (1) body mass index (BMI), and (2) waist circumference, with six components expressed qualitatively: (3) overall physical activity, as well as the frequency of the consumption of (4) vegetables/fruits/whole grains/nuts/seeds/legumes, (5) highly processed foods, including fast foods/sweets/instant soups, (6) red/processed meat, (7) sweetened/energy drinks, and (8) alcohol. Logistic regression analysis was performed to assess the occurrence of breast cancer. Results: The moderate (4–5 points) and maximal (6–8 points) compliance with the qualitative adaptation of the WRCF/AICR recommendations reduced the odds of breast cancer by 54% and 72%, respectively, compared to the results noted for minimal compliance (≤3 points). Lower odds of breast cancer were associated with moderate or high physical activity, consumption of a minimum of four serving per day of vegetables/fruits/whole grains/nuts/seeds/legumes, and limiting the consumption of highly processed food/fast foods and red/processed meat to a maximum of 1–3 times/month. Higher odds of breast cancer were associated with a higher waist circumference and alcohol abstinence. Conclusions: These findings may prove useful in establishing cancer prevention recommendations based on simple suggestions regarding the frequency of food consumption. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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11 pages, 531 KiB

Open AccessArticle

Disparities in Receipt of National Comprehensive Cancer Network Guideline-Adherent Care and Outcomes among Women with Triple-Negative Breast Cancer by Race/Ethnicity, Socioeconomic Status, and Insurance Type

by Chimezie D. Ubbaonu, Jenny Chang, Argyrios Ziogas, Rita S. Mehta, Kari J. Kansal and Jason A. Zell

Cancers 2023, 15(23), 5586; https://doi.org/10.3390/cancers15235586 - 26 Nov 2023

Viewed by 830

Abstract

Background: The National Comprehensive Cancer Network guidelines were designed to improve patient outcomes. Here, we examine factors that may contribute to outcomes and guideline adherence in patients with triple-negative breast cancer. Methods: This was a retrospective cohort study of women with triple-negative breast [...] Read more.

Background: The National Comprehensive Cancer Network guidelines were designed to improve patient outcomes. Here, we examine factors that may contribute to outcomes and guideline adherence in patients with triple-negative breast cancer. Methods: This was a retrospective cohort study of women with triple-negative breast cancer using the California Cancer Registry. Adherent treatment was defined as the receipt of a combination of surgery, lymph node assessment, adjuvant radiation, and/or chemotherapy. A multivariable logistic regression was used to determine the effects of independent variables on adherence to the NCCN guidelines. Disease-specific survival was calculated using Cox regression analysis. Results: A total of 16,858 women were analyzed. Black and Hispanic patients were less likely to receive guideline-adherent care (OR 0.82, 95%CI 0.73–0.92 and OR 0.87, 95%CI 0.79–0.95, respectively) compared to White patients. Hazard ratios adjusted for adherent care showed that Black patients had increased disease-specific mortality (HR 1.28, 95%CI 1.16–1.42, p < 0.0001) compared to White patients. Conclusions: A significant majority of breast cancer patients in California continue to receive non-guideline-adherent care. Non-Hispanic Black patients and patients from lower SES quintile groups were less likely to receive guideline-adherent care. Patients with non-adherent care had worse disease-specific survival compared to recipients of NCCN guideline-adherent care. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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18 pages, 5835 KiB

Open AccessArticle

Anticancer Effect of E26 Transformation-Specific Homologous Factor through the Induction of Senescence and the Inhibition of Epithelial–Mesenchymal Transition in Triple-Negative Breast Cancer Cells

by Soyoung Lim, Jihyun Lim, Aram Lee, Keun-Il Kim and Jong-Seok Lim

Cancers 2023, 15(21), 5270; https://doi.org/10.3390/cancers15215270 - 02 Nov 2023

Viewed by 898

Abstract

The aim of the present study was to evaluate the effect of ETS homologous factor (EHF) in malignant breast cancer cells. The overexpression and knockdown of the EHF gene in human and mouse breast cancer cells were performed, and the TCGA dataset and [...] Read more.

The aim of the present study was to evaluate the effect of ETS homologous factor (EHF) in malignant breast cancer cells. The overexpression and knockdown of the EHF gene in human and mouse breast cancer cells were performed, and the TCGA dataset and Q-omics were analyzed. We found that the tumor suppressor NDRG2 is correlated with EHF gene expression in triple-negative breast cancer cells, that EHF overexpression results in reduced cell proliferation and that apoptosis is promoted by the chemotherapeutic reagent treatment of EHF-overexpressing cells. By EHF overexpression, senescence-associated β-galactosidase activity and p21^WAF1/CIP1 expression were increased, suggesting that EHF may induce cellular senescence. In addition, the overexpression of EHF reduced the migratory ability and inhibited epithelial–mesenchymal transition (EMT). Furthermore, EHF inhibited the phosphorylation of STAT3. The overexpression of EHF also reduced the tumor size, and lung metastasis in vivo. At the tumor site, β-galactosidase activity was increased by EHF. Finally, the Kaplan–Meier-plotter analysis showed that TNBC patients with a high expression of EHF had a longer relapse-free survival rate. Our findings demonstrated that EHF inhibits breast tumor progression by inducing senescence and regulating EMT in TNBC cells. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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16 pages, 3041 KiB

Open AccessArticle

YAP1 Expression in HR+HER2− Breast Cancer: 21-Gene Recurrence Score Analysis and Public Dataset Validation

by Inho Park, Yangkyu Lee, Jee Hung Kim, Soong June Bae, Sung Gwe Ahn, Joon Jeong and Yoon Jin Cha

Cancers 2023, 15(20), 5034; https://doi.org/10.3390/cancers15205034 - 18 Oct 2023

Viewed by 995

Abstract

Background: YAP1, an oncogene in numerous cancers, is a downstream transcription factor of the Hippo pathway. This study focuses on its relationship with the Oncotype Dx (ODX) test risk score (RS) in patients with hormone-receptor-positive, HER2-negative (HR+HER2−) breast cancer. Methods: We retrospectively analyzed [...] Read more.

Background: YAP1, an oncogene in numerous cancers, is a downstream transcription factor of the Hippo pathway. This study focuses on its relationship with the Oncotype Dx (ODX) test risk score (RS) in patients with hormone-receptor-positive, HER2-negative (HR+HER2−) breast cancer. Methods: We retrospectively analyzed 401 HR+HER2− breast cancer patients from Gangnam Severance Hospital who underwent ODX tests (May 2014–April 2020). YAP1 nuclear localization was evaluated via immunohistochemical staining and its clinical correlation with clinicopathological parameters, including RS, was analyzed. Public datasets TCGA-BRCA and METABRIC validated clinical outcomes. Results: YAP1 expression negatively correlated with ODX RS (OR 0.373, p = 0.002). Elevated YAP1 mRNA levels corresponded to better clinical outcomes, specifically in ER-positive patients, with significant results in METABRIC and TCGA-BRCA datasets (p < 0.0001 OS in METABRIC, p = 0.00085 RFS in METABRIC, p = 0.040 DFS in TCGA-BRCA). In subsets with varying ESR1 mRNA expression and pronounced YAP1 expression, superior survival outcomes were consistently observed. Conclusion: YAP1 may be a valuable prognostic marker and potential therapeutic target in HR+HER2− breast cancer patients. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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10 pages, 442 KiB

Open AccessArticle

Upfront Taxane Could Be Superior to Pegylated Liposomal Doxorubicin (PLD): A Retrospective Real-World Analysis of Treatment Sequence Taxane–PLD versus PLD–Taxane in Patients with Metastatic Breast Cancer

by Till Wallrabenstein, Anton Oseledchyk, Eveline Daetwyler, Christoph Rochlitz and Marcus Vetter

Cancers 2023, 15(20), 4953; https://doi.org/10.3390/cancers15204953 - 12 Oct 2023

Viewed by 901

Abstract

Background: Patients with endocrine-resistant metastatic breast cancer (MBC) require cytostatic therapy. Single-agent taxanes and anthracyclines, including pegylated liposomal doxorubicin (PLD), are standard treatment options. There are no prospective data regarding optimal treatment sequences, and real-world data regarding both treatment options are limited. Methods: [...] Read more.

Background: Patients with endocrine-resistant metastatic breast cancer (MBC) require cytostatic therapy. Single-agent taxanes and anthracyclines, including pegylated liposomal doxorubicin (PLD), are standard treatment options. There are no prospective data regarding optimal treatment sequences, and real-world data regarding both treatment options are limited. Methods: We analyzed electronic records of all patients with Her2-negative MBC treated with either first-line PLD or first-line taxane and subsequent crossover at the University Hospital Basel between 2003 and 2021. The primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). We used the Kaplan–Meyer method and logrank test to compare time-to-event endpoints and the Fisher exact test to compare discrete variables. Results: We retrospectively identified 42 patients with Her2-negative MBC who have received either single-agent PLD or single-agent taxane as first-line chemotherapy with subsequent crossover, including 23 patients who received first-line PLD and 19 patients who received first-line taxane. Baseline characteristics were similar between treatment groups. Treatment sequence PLD–taxane was significantly inferior to taxane–PLD regarding all endpoints: median TTNC 4.9 vs. 9.9 months (p = 0.006), median OS 17.8 vs. 24.6 months (p = 0.05), median PFS 4.4 vs. 9.0 months (p = 0.005), and ORR 13% vs. 53% (p = 0.01). Conclusions: Here, we report a first retrospective head-to-head comparison of the treatment sequence PLD–taxane versus taxane–PLD in patients with MBC, showing a substantial advantage of using taxanes first, followed by PLD. An inherent treatment bias in favor of first-line taxanes cannot be excluded, thus calling for prospective validation. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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Review

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9 pages, 2006 KiB

Open AccessReview

Reducing the Risk of Needle Tract Seeding or Tumor Cell Dissemination during Needle Biopsy Procedures

by Dennis R. Holmes

Cancers 2024, 16(2), 317; https://doi.org/10.3390/cancers16020317 - 11 Jan 2024

Viewed by 2211

Abstract

Purpose: Many women fear that breast needle biopsies increase the risk of cancer spread. The purpose of this review article is to discuss the breast cancer literature regarding the risk of needle-biopsy-induced cancer cell displacement and its impact on local and regional recurrence [...] Read more.

Purpose: Many women fear that breast needle biopsies increase the risk of cancer spread. The purpose of this review article is to discuss the breast cancer literature regarding the risk of needle-biopsy-induced cancer cell displacement and its impact on local and regional recurrence and breast cancer survival. Methods: A literature review is performed to discuss the risks and mitigation of needle-biopsy-induced cancer cell displacement. Results: Needle-biopsy-induced cancer cell displacement is a common event. The risk is influenced by the biopsy technique and the breast cancer type. Evidence suggests that the risk of needle-biopsy-induced cancer cell displacement may potentially increase the odds of local recurrence but has no impact on regional recurrence and long-term survival. Conclusions: Technical modifications of needle biopsy procedures can reduce the risk of breast needle-biopsy-induced cancer cell displacement and potentially reduce the risk of local recurrence, especially in patients for whom whole breast radiation is to be omitted. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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26 pages, 375 KiB

Open AccessReview

Novel HER-2 Targeted Therapies in Breast Cancer

by Catarina Lopes Fernandes, Diogo J. Silva and Alexandra Mesquita

Cancers 2024, 16(1), 87; https://doi.org/10.3390/cancers16010087 - 23 Dec 2023

Viewed by 1022

Abstract

Human epidermal growth factor 2 (HER-2)-positive breast cancer represents 15–20% of all breast cancer subtypes and has an aggressive biological behavior with worse prognosis. The development of HER-2-targeted therapies has changed the disease’s course, having a direct impact on survival rates and quality [...] Read more.

Human epidermal growth factor 2 (HER-2)-positive breast cancer represents 15–20% of all breast cancer subtypes and has an aggressive biological behavior with worse prognosis. The development of HER-2-targeted therapies has changed the disease’s course, having a direct impact on survival rates and quality of life. Drug development of HER-2-targeting therapies is a prolific field, with numerous new therapeutic strategies showing survival benefits and gaining regulatory approval in recent years. Furthermore, the acknowledgement of the survival impact of HER-2-directed therapies on HER-2-low breast cancer has contributed even more to advances in the field. The present review aims to summarize the newly approved therapeutic strategies for HER-2-positive breast cancer and review the new and exploratory HER-2-targeted therapies currently under development. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

12 pages, 811 KiB

Open AccessReview

Optical Imaging in Human Lymph Node Specimens for Detecting Breast Cancer Metastases: A Review

by Maria Papadoliopoulou, Maria Matiatou, Spyridon Koutsoumpos, Francesk Mulita, Panagiotis Giannios, Ioannis Margaris, Konstantinos Moutzouris, Nikolaos Arkadopoulos and Nikolaos V. Michalopoulos

Cancers 2023, 15(22), 5438; https://doi.org/10.3390/cancers15225438 - 16 Nov 2023

Cited by 1 | Viewed by 937

Abstract

Assessment of regional lymph node status in breast cancer is of important staging and prognostic value. Even though formal histological examination is the currently accepted standard of care, optical imaging techniques have shown promising results in disease diagnosis. In the present article, we [...] Read more.

Assessment of regional lymph node status in breast cancer is of important staging and prognostic value. Even though formal histological examination is the currently accepted standard of care, optical imaging techniques have shown promising results in disease diagnosis. In the present article, we review six spectroscopic techniques and focus on their use as alternative tools for breast cancer lymph node assessment. Elastic scattering spectroscopy (ESS) seems to offer a simple, cost-effective, and reproducible method for intraoperative diagnosis of breast cancer lymph node metastasis. Optical coherence tomography (OCT) provides high-resolution tissue scanning, along with a short data acquisition time. However, it is relatively costly and experimentally complex. Raman spectroscopy proves to be a highly accurate method for the identification of malignant axillary lymph nodes, and it has been further validated in the setting of head and neck cancers. Still, it remains time-consuming. Near-infrared fluorescence imaging (NIRF) and diffuse reflectance spectroscopy (DFS) are related to significant advantages, such as deep tissue penetration and efficiency. Fourier-transform infrared spectroscopy (FTIR) is a promising method but has significant drawbacks. Nonetheless, only anecdotal reports exist on their clinical use for cancerous lymph node detection. Our results indicate that optical imaging methods can create informative and rapid tools to effectively guide surgical decision-making. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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