Breast Cancer Heterogeneity in Primary and Metastatic Disease

Kalinowski, Lauren; Saunus, Jodi M.; Reed, Amy E. McCart; Lakhani, Sunil R.

doi:10.1007/978-3-030-20301-6_6

Cited by 27 publications

(20 citation statements)

References 165 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the contrary, our study has some strengths. First, we used a homogeneous cohort of primary BCs extracted from a single dataset: focusing on primary BC samples allowed us to limit the variability existing between primary tumor and metastases [ 36 , 37 , 38 ]. Second, we provided a comprehensive analysis of the impact of HER2-low status on three different clinical outcomes, based on the recommendations provided in the TCGA CDR, a standardized dataset with a transparent derivation of clinical outcome endpoints and with resolution of quality concerns.…”

Section: Discussionmentioning

confidence: 99%

HER2-Low Breast Cancer: Molecular Characteristics and Prognosis

Agostinetto

Rediti

Fimereli

et al. 2021

Cancers

137

136

View full text Add to dashboard Cite

Background: We aimed to determine the distribution of intrinsic subtypes within HER2-low breast cancer (BC), and to describe the prognostic impact of HER2-low status on survival outcomes. Methods: This is a retrospective, observational study of primary BC extracted from The Cancer Genome Atlas dataset. We described the distribution of PAM50 intrinsic subtypes within HER2-low BC subtype according to hormonal receptor status (positive (HR+) and negative (HR−)). Secondly, we assessed the impact of HER2-low on survival outcomes (progression-free interval (PFI), disease-free interval (DFI), and overall survival (OS)). Results: We analyzed 804 primary BCs, including 410 (51%) HER2-low BCs (336 HR+ and 74 HR−). The proportion of HER2-enriched tumors was higher in the HER2-low/HR− group compared to HER2-low/HR+ (13.7% versus 1.2%, respectively). HER2-enriched tumors were more frequent in HER2-low/HR− and HER2-low/HR+ subtypes, compared to HER2-negative/HR− and HER2-negative/HR+ subtypes, respectively (13.7% versus 1.6% and 1.2% versus 0.5%, respectively). We observed no significant differences in PFI, DFI, and OS between HER2-low subtypes and each non-HER2-low subtype paired by HR status. Conclusions: Our characterization of PAM50 intrinsic subtypes within HER2-low breast cancer may explain the different clinical behaviors and responses to treatment, and ultimately support further investigation of new treatment strategies in the HER2-low category. Moreover, it highlights the importance of considering HR status in the HER2-low category.

show abstract

Section: Discussionmentioning

confidence: 99%

HER2-Low Breast Cancer: Molecular Characteristics and Prognosis

Agostinetto

Rediti

Fimereli

et al. 2021

Cancers

137

136

View full text Add to dashboard Cite

show abstract

“…Besides grouping them according to neoplasm origin (ductal or lobular cancer), to metastasis occurrence (invasive BC) and staging, specific biological markers allow BCs to be clinically divided into distinct subtypes, having different prognostic and therapeutic implications. In particular, genome and transcriptome deep sequencing has led to the identification of at least four major molecular subtypes of invasive BC (luminal A and luminal B hormone receptor positive, HER2-positive, and basal-like) [9]. Among luminal BCs, approximately 80% are ER-positive (estrogen-receptor positive), and about 65% of these are also PR-positive (progesterone-receptor positive) [10].…”

Section: Breast Cancer Clinical Classificationmentioning

confidence: 99%

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Ferraro

Piccolo

Misso

et al. 2020

Cells

View full text Add to dashboard Cite

In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium-based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple-negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced next-generation metallotherapeutics, with NAMI-A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex—named AziRu—incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well-known NAMI-A complex, information on non-nanostructured Ru-based anticancer agents have been included in a precise manner.

show abstract

“…Breast cancer (BC) is currently the most common malignancy in women, both in developed and less developed countries, and the leading cause of cancer-related deaths among women worldwide, with a high incidence rate [1,2]. Every breast cancer subtype is characterized by intrinsic molecular features and metastatic lesions, and their natural heterogeneity leads to a high diversity in prognosis and clinical responses to available medical treatments, even for patients with similar diagnosis, histology and stage of disease [3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer

Díaz-Beltrán

González-Olmedo

Luque-Caro

et al. 2021

Cancers

View full text Add to dashboard Cite

Purpose: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. Methods: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. Results: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected p-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. Conclusion: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.

show abstract

Breast Cancer Heterogeneity in Primary and Metastatic Disease

Cited by 27 publications

References 165 publications

HER2-Low Breast Cancer: Molecular Characteristics and Prognosis

HER2-Low Breast Cancer: Molecular Characteristics and Prognosis

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer

Contact Info

Product

Resources

About