Research

23 pages, 2736 KiB

Open AccessArticle

Regulation of IGF1R by MicroRNA-15b Contributes to the Anticancer Effects of Calorie Restriction in a Murine C3-TAg Model of Triple-Negative Breast Cancer

by Ximena Bustamante-Marin, Kaylyn L. Devlin, Shannon B. McDonell, Om Dave, Jenna L. Merlino, Emma J. Grindstaff, Alyssa N. Ho, Erika T. Rezeli, Michael F. Coleman and Stephen D. Hursting

Cancers 2023, 15(17), 4320; https://doi.org/10.3390/cancers15174320 - 29 Aug 2023

Viewed by 1157

Abstract

Calorie restriction (CR) inhibits triple-negative breast cancer (TNBC) progression in several preclinical models in association with decreased insulin-like growth factor 1 (IGF1) signaling. To investigate the impact of CR on microRNAs (miRs) that target the IGF1/IGF1R pathway, we used the spontaneous murine model [...] Read more.

Calorie restriction (CR) inhibits triple-negative breast cancer (TNBC) progression in several preclinical models in association with decreased insulin-like growth factor 1 (IGF1) signaling. To investigate the impact of CR on microRNAs (miRs) that target the IGF1/IGF1R pathway, we used the spontaneous murine model of TNBC, C3(1)/SV40 T-antigen (C3-TAg). In C3-TAg mice, CR reduced body weight, IGF1 levels, and TNBC progression. We evaluated the tumoral expression of 10 miRs. CR increased the expression of miR-199a-3p, miR-199a-5p, miR-486, and miR-15b. However, only miR-15b expression correlated with tumorigenicity in the M28, M6, and M6C C3-TAg cell lines of TNBC progression. Overexpressing miR-15b reduced the proliferation of mouse (M6) and human (MDA-MB-231) cell lines. Serum restriction alone or in combination with low levels of recombinant IGF1 significantly upregulated miR-15b expression and reduced Igf1r in M6 cells. These effects were reversed by the pharmacological inhibition of IGFR with BMS754807. In silico analysis using miR web tools predicted that miR-15b targets genes associated with IGF1/mTOR pathways and the cell cycle. Our findings suggest that CR in association with reduced IGF1 levels could upregulate miR-15b to downregulate Igf1r and contribute to the anticancer effects of CR. Thus, miR-15b may be a therapeutic target for mimicking the beneficial effects of CR against TNBC. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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14 pages, 1293 KiB

Open AccessArticle

Evaluation of Cardiac Substructures Exposure of DIBH-3DCRT, FB-HT, and FB-3DCRT in Hypofractionated Radiotherapy for Left-Sided Breast Cancer after Breast-Conserving Surgery: An In Silico Planning Study

by Jordan Eber, Martin Schmitt, Nicolas Dehaynin, Clara Le Fèvre, Delphine Antoni and Georges Noël

Cancers 2023, 15(13), 3406; https://doi.org/10.3390/cancers15133406 - 29 Jun 2023

Cited by 2 | Viewed by 1084

Abstract

Left-sided breast cancer radiotherapy can lead to late cardiovascular complications, including ischemic events. To mitigate these risks, cardiac-sparing techniques such as deep-inspiration breath-hold (DIBH) and intensity-modulated radiotherapy (IMRT) have been developed. However, recent studies have shown that mean heart dose is not a [...] Read more.

Left-sided breast cancer radiotherapy can lead to late cardiovascular complications, including ischemic events. To mitigate these risks, cardiac-sparing techniques such as deep-inspiration breath-hold (DIBH) and intensity-modulated radiotherapy (IMRT) have been developed. However, recent studies have shown that mean heart dose is not a sufficient dosimetric parameter for assessing cardiac exposure. In this study, we aimed to compare the radiation exposure to cardiac substructures for ten patients who underwent hypofractionated radiotherapy using DIBH three-dimensional conformal radiation therapy (3DCRT), free-breathing (FB)-3DCRT, and FB helical tomotherapy (HT). Dosimetric parameters of cardiac substructures were analyzed, and the results were statistically compared using the Wilcoxon signed-rank test. This study found a significant reduction in the dose to the heart, left anterior descending coronary artery, and ventricles with DIBH-3DCRT and FB-HT compared to FB-3DCRT. While DIBH-3DCRT was very effective in sparing the heart, in some cases, it provided little or no cardiac sparing. FB-HT can be an interesting treatment modality to reduce the dose to major coronary vessels and ventricles and may be of interest for patients with cardiovascular risks who do not benefit from or cannot perform DIBH. These findings highlight the importance of cardiac-sparing techniques for precise delivery of radiation therapy. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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13 pages, 644 KiB

Open AccessArticle

External-Beam-Accelerated Partial-Breast Irradiation Reduces Organ-at-Risk Doses Compared to Whole-Breast Irradiation after Breast-Conserving Surgery

by Oliver J. Ott, Wilhelm Stillkrieg, Ulrike Lambrecht, Claudia Schweizer, Allison Lamrani, Tim-Oliver Sauer, Vratislav Strnad, Christoph Bert, Carolin C. Hack, Matthias W. Beckmann and Rainer Fietkau

Cancers 2023, 15(12), 3128; https://doi.org/10.3390/cancers15123128 - 09 Jun 2023

Cited by 2 | Viewed by 1328

Abstract

In order to evaluate organ-at-risk (OAR) doses in external-beam-accelerated partial-breast irradiation (APBI) compared to standard whole-breast irradiation (WBI) after breast-conserving surgery. Between 2011 and 2021, 170 patients with early breast cancer received APBI within a prospective institutional single-arm trial. The prescribed dose to [...] Read more.

In order to evaluate organ-at-risk (OAR) doses in external-beam-accelerated partial-breast irradiation (APBI) compared to standard whole-breast irradiation (WBI) after breast-conserving surgery. Between 2011 and 2021, 170 patients with early breast cancer received APBI within a prospective institutional single-arm trial. The prescribed dose to the planning treatment volume was 38 Gy in 10 fractions on 10 consecutive working days. OAR doses for the contralateral breast, the ipsilateral, contralateral, and whole lung, the whole heart, left ventricle (LV), and the left anterior descending coronary artery (LAD), and for the spinal cord and the skin were assessed and compared to a control group with real-world data from 116 patients who underwent WBI. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Compared to WBI, APBI led to reduced OAR doses for the contralateral breast (0.4 ± 0.6 vs. 0.8 ± 0.9 Gy, p = 0.000), the ipsilateral (4.3 ± 1.4 vs. 9.2 ± 2.5 Gy, p = 0.000) and whole mean lung dose (2.5 ± 0.8 vs. 4.9 ± 1.5 Gy, p = 0.000), the mean heart dose (1.6 ± 1.6 vs. 1.7 ± 1.4 Gy, p = 0.007), the LV V23 (0.1 ± 0.4 vs. 1.4 ± 2.6%, p < 0.001), the mean LAD dose (2.5 ± 3.4 vs. 4.8 ± 5.5 Gy, p < 0.001), the maximum spinal cord dose (1.5 ± 1.1 vs. 4.5 ± 5.7 Gy, p = 0.016), and the maximum skin dose (39.6 ± 1.8 vs. 49.1 ± 5.8 Gy, p = 0.000). APBI should be recommended to suitable patients to minimize the risk of secondary tumor induction and the incidence of consecutive major cardiac events. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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8 pages, 521 KiB

Open AccessCommunication

Breast Cancer: Impact of New Treatments?

by Guy A. Storme

Cancers 2023, 15(8), 2205; https://doi.org/10.3390/cancers15082205 - 08 Apr 2023

Cited by 4 | Viewed by 1675 | Correction

Abstract

Background: Breast cancer treatment has seen tremendous progress since the early 1980s, with the first findings of new chemotherapy and hormone therapies. Screening started in the same period. Methods: A review of population data (SEER and the literature) shows an increase in recurrence-free [...] Read more.

Background: Breast cancer treatment has seen tremendous progress since the early 1980s, with the first findings of new chemotherapy and hormone therapies. Screening started in the same period. Methods: A review of population data (SEER and the literature) shows an increase in recurrence-free survival until 2000 and it stagnates afterwards. Results: Over the period 1980-2000, the 15% survival gain was presented by pharma as a contribution of new molecules. The contribution of screening during that same period was not implemented by them, although screening has been accepted as a routine procedure in the States since the 1980s and everywhere else since 2000. Conclusions: Interpretation of breast cancer outcome has largely focused on drugs, whereas other factors, such as screening, prevention, biologics, and genetics, were largely neglected. More attention should now be paid to examining the strategy based on realistic global data. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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17 pages, 4432 KiB

Open AccessArticle

Transcriptome Meta-Analysis of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy

by Wei Zhang, Emma Li, Lily Wang, Brian D. Lehmann and X. Steven Chen

Cancers 2023, 15(8), 2194; https://doi.org/10.3390/cancers15082194 - 07 Apr 2023

Viewed by 2098

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease with varying responses to neoadjuvant chemotherapy (NAC). The identification of biomarkers to predict NAC response and inform personalized treatment strategies is essential. In this study, we conducted large-scale gene expression meta-analyses to identify genes associated [...] Read more.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with varying responses to neoadjuvant chemotherapy (NAC). The identification of biomarkers to predict NAC response and inform personalized treatment strategies is essential. In this study, we conducted large-scale gene expression meta-analyses to identify genes associated with NAC response and survival outcomes. The results showed that immune, cell cycle/mitotic, and RNA splicing-related pathways were significantly associated with favorable clinical outcomes. Furthermore, we integrated and divided the gene association results from NAC response and survival outcomes into four quadrants, which provided more insights into potential NAC response mechanisms and biomarker discovery. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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11 pages, 1793 KiB

Open AccessArticle

CDK4/6 Inhibitors Overcome Endocrine ESR1 Mutation-Related Resistance in Metastatic Breast Cancer Patients

by Stefania Crucitta, Martina Ruglioni, Giulia Lorenzini, Irene Bargagna, Giovanna Irene Luculli, Irene Albanese, Diana Bilancio, Francesca Patanè, Andrea Fontana, Romano Danesi and Marzia Del Re

Cancers 2023, 15(4), 1306; https://doi.org/10.3390/cancers15041306 - 18 Feb 2023

Cited by 2 | Viewed by 2142

Abstract

ESR1 mutations contribute to endocrine resistance and occur in a high percentage of hormone-receptor-positive (HR+) metastatic breast cancer (mBC) cases. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) changed the treatment landscape of HR+ mBC, as they are able to overcome estrogen resistance. The present retrospective [...] Read more.

ESR1 mutations contribute to endocrine resistance and occur in a high percentage of hormone-receptor-positive (HR+) metastatic breast cancer (mBC) cases. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) changed the treatment landscape of HR+ mBC, as they are able to overcome estrogen resistance. The present retrospective study investigates the clinical benefit of CDK4/6i in ESR1 mutant HR+ mBC patients treated with a CDK4/6i as first- or second-line therapy. Plasma was collected at baseline prior to CDK4/6i plus hormone therapy as a first- or second-line treatment. Circulating free DNA (cfDNA) was extracted from plasma, and ESR1 mutation analysis was performed on a ddPCR. Statistical analyses were performed to investigate the predictive power of ESR1 mutations and any association with clinical factors. A total of 42 patients with mBC treated with CDK4/6i plus endocrine therapy as first- (n = 35) or second-line (n = 7) were enrolled. Twenty-eight patients received hormonal therapy (AI or tamoxifen) in the adjuvant setting. ESR1 mutation status in blood was associated with shorter median disease-free survival (DFS) (30 vs. 110 months; p = 0.006). Multivariate analysis confirmed ESR1 mutations as independent factors of resistance in adjuvant hormone therapy. On the contrary, no difference in progression-free survival (PFS) was observed in the presence or absence of an ESR1 mutation in patients treated with CDK4/6i as first-line treatment (p = 0.29). No statistically significant correlation between the best response to CDK4/6i and ESR1 mutation was found (p = 0.46). This study indicates that the ESR1 mutation detected in cfDNA is an independent predictive factor of clinical recurrence in the adjuvant setting and that CDK4/6i can overcome ESR1-dependent resistance. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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16 pages, 6049 KiB

Open AccessArticle

CTTN Overexpression Confers Cancer Stem Cell-like Properties and Trastuzumab Resistance via DKK-1/WNT Signaling in HER2 Positive Breast Cancer

by So-Jeong Moon, Hyung-Jun Choi, Young-Hyeon Kye, Ga-Young Jeong, Hyung-Yong Kim, Jae-Kyung Myung and Gu Kong

Cancers 2023, 15(4), 1168; https://doi.org/10.3390/cancers15041168 - 11 Feb 2023

Cited by 5 | Viewed by 1858

Abstract

Background: Despite the therapeutic success of trastuzumab, HER2 positive (HER2+) breast cancer patients continue to face significant difficulties due to innate or acquired drug resistance. In this study we explored the potential role of CTTN in inducing trastuzumab resistance of HER2+ breast cancers. [...] Read more.

Background: Despite the therapeutic success of trastuzumab, HER2 positive (HER2+) breast cancer patients continue to face significant difficulties due to innate or acquired drug resistance. In this study we explored the potential role of CTTN in inducing trastuzumab resistance of HER2+ breast cancers. Methods: Genetic changes of CTTN and survival of HER2+ breast cancer patients were analyzed in multiple breast cancer patient cohorts (METABRIC, TCGA, Kaplan-Meier (KM) plotter, and Hanyang University cohort). The effect of CTTN on cancer stem cell activity was assessed using the tumorsphere formation, ALDEFLUOR assay, and by in vivo xenograft experiments. CTTN-induced trastuzumab resistance was assessed by the sulforhodamine B (SRB) assay, colony formation assays, and in vivo xenograft model. RNA-seq analysis was used to clarify the mechanism of trastuzumab resistance conferred by CTTN. Results: Survival analysis indicated that CTTN overexpression is related to a poor prognosis in HER2+ breast cancers (OS, p = 0.05 in the Hanyang University cohort; OS, p = 0.0014 in KM plotter; OS, p = 0.008 and DFS, p = 0.010 in METABRIC). CTTN overexpression-induced cancer stem cell-like characteristics in experiments of tumorsphere formation, ALDEFLUOR assays, and in vivo limiting dilution assays. CTTN overexpression resulted in trastuzumab resistance in SRB, colony formation assays, and in vivo xenograft models. Mechanistically, the mRNA and protein levels of DKK-1, a Wnt antagonist, were downregulated by CTTN. Treatment of the β-catenin/TCF inhibitor reversed CTTN-induced cancer stem cell-like properties in vitro. Combination treatment with trastuzumab and β-catenin/TCF inhibitor overcame trastuzumab resistance conferred by CTTN overexpression in in vitro colony formation assays. Conclusions: CTTN activates DKK-1/Wnt/β-catenin signaling to induce trastuzumab resistance. We propose that CTTN is a novel biomarker indicating a poor prognosis and a possible therapeutic target for overcoming trastuzumab resistance. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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12 pages, 2236 KiB

Open AccessArticle

Diffusion-Weighted MRI for Predicting Pathologic Complete Response in Neoadjuvant Immunotherapy

by Wen Li, Nu N. Le, Natsuko Onishi, David C. Newitt, Lisa J. Wilmes, Jessica E. Gibbs, Julia Carmona-Bozo, Jiachao Liang, Savannah C. Partridge, Elissa R. Price, Bonnie N. Joe, John Kornak, Mark Jesus M. Magbanua, Rita Nanda, Barbara LeStage, Laura J. Esserman, I-SPY Imaging Working Group, I-SPY Investigator Network, Laura J. van’t Veer and Nola M. Hylton

Cancers 2022, 14(18), 4436; https://doi.org/10.3390/cancers14184436 - 13 Sep 2022

Cited by 7 | Viewed by 1923

Abstract

This study tested the hypothesis that a change in the apparent diffusion coefficient (ADC) measured in diffusion-weighted MRI (DWI) is an independent imaging marker, and ADC performs better than functional tumor volume (FTV) for assessing treatment response in patients with locally advanced breast [...] Read more.

This study tested the hypothesis that a change in the apparent diffusion coefficient (ADC) measured in diffusion-weighted MRI (DWI) is an independent imaging marker, and ADC performs better than functional tumor volume (FTV) for assessing treatment response in patients with locally advanced breast cancer receiving neoadjuvant immunotherapy. A total of 249 patients were randomized to standard neoadjuvant chemotherapy with pembrolizumab (pembro) or without pembrolizumab (control). DCE-MRI and DWI, performed prior to and 3 weeks after the start of treatment, were analyzed. Percent changes of tumor ADC metrics (mean, 5th to 95th percentiles of ADC histogram) and FTV were evaluated for the prediction of pathologic complete response (pCR) using a logistic regression model. The area under the ROC curve (AUC) estimated for the percent change in mean ADC was higher in the pembro cohort (0.73, 95% confidence interval [CI]: 0.52 to 0.93) than in the control cohort (0.63, 95% CI: 0.43 to 0.83). In the control cohort, the percent change of the 95th percentile ADC achieved the highest AUC, 0.69 (95% CI: 0.52 to 0.85). In the pembro cohort, the percent change of the 25th percentile ADC achieved the highest AUC, 0.75 (95% CI: 0.55 to 0.95). AUCs estimated for percent change of FTV were 0.61 (95% CI: 0.39 to 0.83) and 0.66 (95% CI: 0.47 to 0.85) for the pembro and control cohorts, respectively. Tumor ADC may perform better than FTV to predict pCR at an early treatment time-point during neoadjuvant immunotherapy. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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Review

Jump to: Research, Other

11 pages, 704 KiB

Open AccessReview

Breast Cancer Treatment: To tARget or Not? That Is the Question

by Alexandra Stone, Kevin M. Lin, Ghanshyam H. Ghelani, Sanik Patel, Sam Benjamin, Stephen Graziano and Leszek Kotula

Cancers 2023, 15(23), 5664; https://doi.org/10.3390/cancers15235664 - 30 Nov 2023

Viewed by 1417

Abstract

To assess AR’s role in TNBC treatment, various existing and completed clinical trials targeting AR or co-targeting AR with other pertinent signaling molecules were analyzed. Cyclin-dependent kinase 4/6 (CDK4/6), cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17 lyase), and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling [...] Read more.

To assess AR’s role in TNBC treatment, various existing and completed clinical trials targeting AR or co-targeting AR with other pertinent signaling molecules were analyzed. Cyclin-dependent kinase 4/6 (CDK4/6), cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17 lyase), and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were some of the most prevalent biomarkers used in combination therapy with AR inhibitors in these trials. Studying how AR functions in tandem with these molecules can have increasing breakthroughs in the treatment options for TNBC. Previous studies have been largely unsuccessful in utilizing AR as the sole drug target for systemic targeted treatment in TNBC. However, there is a lack of other commonly used drug target biomarkers in the treatment of this disease, as well. Thus, analyzing the clinical benefit rate (CBR) within clinical trials that use combination therapy can prove to be imperative to the progression of improving treatment options and prognoses. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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15 pages, 3143 KiB

Open AccessReview

PD-1/PD-L1 Inhibitors Response in Triple-Negative Breast Cancer: Can Long Noncoding RNAs Be Associated?

by Carolina Mathias, Vanessa Nascimento Kozak, Jessica Maria Magno, Suelen Cristina Soares Baal, Victor Henrique Apolonio dos Santos, Enilze Maria de Souza Fonseca Ribeiro, Daniela Fiori Gradia, Mauro Antonio Alves Castro and Jaqueline Carvalho de Oliveira

Cancers 2023, 15(19), 4682; https://doi.org/10.3390/cancers15194682 - 22 Sep 2023

Viewed by 1308

Abstract

As immune checkpoint inhibitors (ICI) emerge as a paradigm-shifting treatment option for patients with advanced or metastatic cancer, there is a growing demand for biomarkers that can distinguish which patients are likely to benefit. In the case of triple-negative breast cancer (TNBC), characterized [...] Read more.

As immune checkpoint inhibitors (ICI) emerge as a paradigm-shifting treatment option for patients with advanced or metastatic cancer, there is a growing demand for biomarkers that can distinguish which patients are likely to benefit. In the case of triple-negative breast cancer (TNBC), characterized by a lack of therapeutic targets, pembrolizumab approval for high-risk early-stage disease occurred regardless of PD-L1 status, which keeps the condition in a biomarker limbus. In this review, we highlight the participation of long non-coding RNAs (lncRNAs) in the regulation of the PD-1/PD-L1 pathway, as well as in the definition of prognostic immune-related signatures in many types of tumors, aiming to shed light on molecules that deserve further investigation for a potential role as biomarkers. We also conducted a bioinformatic analysis to investigate lncRNAs already investigated in PD-1/PDL-1 pathways in other cancer types, considering the TNBC molecular context. In this sense, from the generated data, we evidence here two lncRNAs, UCA1 and HCP5, which have not yet been identified in the context of the tumoral immune response in breast cancer. These candidates can be further explored to verify their use as biomarkers for ICI response. In this article, we present an updated review regarding the use of lncRNA as biomarkers of response to ICI, highlighting the versatility of using these molecules. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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30 pages, 2324 KiB

Open AccessReview

Recent Advances with Precision Medicine Treatment for Breast Cancer including Triple-Negative Sub-Type

by Md Abdus Subhan, Farzana Parveen, Hassan Shah, Satya Siva Kishan Yalamarty, Janaína Artem Ataide and Valdimir P. Torchilin

Cancers 2023, 15(8), 2204; https://doi.org/10.3390/cancers15082204 - 08 Apr 2023

Cited by 11 | Viewed by 3872

Abstract

Breast cancer is a heterogeneous disease with different molecular subtypes. Breast cancer is the second leading cause of mortality in woman due to rapid metastasis and disease recurrence. Precision medicine remains an essential source to lower the off-target toxicities of chemotherapeutic agents and [...] Read more.

Breast cancer is a heterogeneous disease with different molecular subtypes. Breast cancer is the second leading cause of mortality in woman due to rapid metastasis and disease recurrence. Precision medicine remains an essential source to lower the off-target toxicities of chemotherapeutic agents and maximize the patient benefits. This is a crucial approach for a more effective treatment and prevention of disease. Precision-medicine methods are based on the selection of suitable biomarkers to envision the effectiveness of targeted therapy in a specific group of patients. Several druggable mutations have been identified in breast cancer patients. Current improvements in omics technologies have focused on more precise strategies for precision therapy. The development of next-generation sequencing technologies has raised hopes for precision-medicine treatment strategies in breast cancer (BC) and triple-negative breast cancer (TNBC). Targeted therapies utilizing immune checkpoint inhibitors (ICIs), epidermal growth factor receptor inhibitor (EGFRi), poly(ADP-ribose) polymerase inhibitor (PARPi), antibody–drug conjugates (ADCs), oncolytic viruses (OVs), glucose transporter-1 inhibitor (GLUT1i), and targeting signaling pathways are potential treatment approaches for BC and TNBC. This review emphasizes the recent progress made with the precision-medicine therapy of metastatic breast cancer and TNBC. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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19 pages, 907 KiB

Open AccessReview

Targeted Approaches to HER2-Low Breast Cancer: Current Practice and Future Directions

by Heng-Zhou Lai, Jie-Rong Han, Xi Fu, Yi-Feng Ren, Zhuo-Hong Li and Feng-Ming You

Cancers 2022, 14(15), 3774; https://doi.org/10.3390/cancers14153774 - 03 Aug 2022

Cited by 10 | Viewed by 4480

Abstract

HER2-low breast cancer (BC) has a poor prognosis, making the development of more suitable treatment an unmet clinical need. While chemotherapy is the main method of treatment for HER2-low BC, not all patients benefit from it. Antineoplastic therapy without chemotherapy has shown promise [...] Read more.

HER2-low breast cancer (BC) has a poor prognosis, making the development of more suitable treatment an unmet clinical need. While chemotherapy is the main method of treatment for HER2-low BC, not all patients benefit from it. Antineoplastic therapy without chemotherapy has shown promise in clinical trials and is being explored further. As quantitative detection techniques become more advanced, they assist in better defining the expression level of HER2 and in guiding the development of targeted therapies, which include directly targeting HER2 receptors on the cell surface, targeting HER2-related intracellular signaling pathways and targeting the immune microenvironment. A new anti-HER2 antibody-drug conjugate called T-DM1 has been successfully tested and found to be highly effective in clinical trials. With this progress, it could eventually be transformed from a disease without a defined therapeutic target into a disease with a defined therapeutic molecular target. Furthermore, efforts are being made to compare the sequencing and combination of chemotherapy, endocrine therapy, and HER2-targeted therapy to improve prognosis to customize the subtype of HER2 low expression precision treatment regimens. In this review, we summarize the current and upcoming treatment strategies, to achieve accurate management of HER2-low BC. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer Treatment)

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