A review of treatment options in HER2‐low breast cancer and proposed treatment sequencing algorithm

Roy, Arya Mariam; Kumarasamy, Vasanthan Muthusamy; Dhakal, Ajay; O’Regan, Ruth; Gandhi, Shipra

doi:10.1002/cncr.34904

Cited by 6 publications

(4 citation statements)

References 64 publications

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“…In addition, preclinical results provide a strong rationale for using AR as a biomarker for selecting TNBC patients for clinical trials, which would investigate the efficacy of therapeutic combinations that simultaneously target AR and PI3K. For instance, one clinical trial Phase 1 (NCT03207529) evaluates alpelisib + enzalutamide in AR-positive and PTEN-positive metastatic BC [55].…”

Section: Discussionmentioning

confidence: 99%

Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis

Martínez-Nava,

Urbina-Jara,

Lira-Albarrán

et al. 2024

Diagnostics

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(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer’s development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis

Martínez-Nava,

Urbina-Jara,

Lira-Albarrán

et al. 2024

Diagnostics

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“…As the ASCO/CAP revised the definition of HER2 positivity (the elimination of the ISH equivocal category and a change in the IHC 2+ cut-off from 30% to 10% stained cells) during and after our study period [4,41], our study may have a misclassification bias, which potentially could lead to a minor overestimation of the survival difference between HER2 IHC2+/1+ and HER2 IHC0 tumors. In addition, HER2 itself is a dynamic entity and it can vary over a period of time even within the same tumor site or within different organ sites biopsied at the same time from the same patient [12]. This might have affected the accuracy and consistency of the reported HER2 values and thereby could have affected the validity of some of the results of the study, as HER2 is a crucial variable for our study.…”

Section: Discussionmentioning

confidence: 99%

“…However, high-quality data are lacking on the clinical outcomes of breast cancers with HER2-low expression, particularly resectable disease [6,12]. Most previous studies were single-center or regional observational studies with conflicting results [13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Oncotype Dx Score, HER2 Low Expression, and Clinical Outcomes in Early-Stage Breast Cancer: A National Cancer Database Analysis

Roy,

Jiang,

Perimbeti

et al. 2023

Cancers

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Background: The interaction between HER2-low expression, oncotype recurrence score (RS), and their influence on the prognosis of HR+/HER2- breast cancer (BC) is not very well studied. Methods: We conducted a retrospective cohort study of patients diagnosed with resectable HER2-low and HER2-zero BC from the National Cancer Database. The primary outcome was overall survival (OS), and the association of RS with the clinical outcomes in HR+/HER2- BC was analyzed as an exploratory endpoint. Results: The distribution of RS was comparable between HER2-low and HER2-zero groups; however, the RSs of HER2-low tumors were more likely to be 16–25. Women with HER2-low tumors had longer 5-year OS than women with HER2-zero tumors in the HR-negative (84.3% vs. 83.9%; p < 0.001, HR: 0.87 (0.84–0.90), p < 0.001) but not in the HR-positive group (94.0% vs. 94.0%; p = 0.38, HR: 0.97 (0.95–0.99), p = 0.01). The survival advantage was observed in patients who received adjuvant/neoadjuvant chemotherapy (p-interaction (chemo vs. no chemo) < 0.001). Among those who received adjuvant chemotherapy in the group with higher RSs (26–100), those with HER2-low BC had higher 5-year OS than HER2-zero BC. Conclusions: Resectable HER2-low BC had a better prognosis than HER2-zero BC. Among those who received adjuvant chemotherapy in the higher oncotype RS group, those with HER2-low tumors had better survival.

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“…As mentioned above, there are several treatment options including endocrine therapy and chemotherapy available in HR+ BC, immunotherapy and chemotherapy in TNBC, and the ADCs in both HR+ and TNBC. Researcher and clinicians are devoted to proposing the optimal sequencing of these agents for maximum clinical benefit while maintaining the quality of life ( 43 ). With current evidence, a sequencing strategy for HR+ and HR− HER2-low MBC is recommended ( Figure 1 ).…”

Section: Advances In the Treatment Of Her2-low Advanced Bcmentioning

confidence: 99%

Challenges in HER2-low breast cancer identification, detection, and treatment

Wu,

2024

Transl Breast Cancer Res

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Recently, human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) has emerged as a novel subset within the category of HER2-negative BC, prompting a reassessment of the immunohistochemical negative scores of 0, 1+, and the 2+/in situ hybridization (ISH) negative phenotype. Recent clinical trials have provided compelling evidence of the substantial clinical advantages offered by novel antibody-drug conjugates (ADCs) that target HER2 in the treatment of these specific tumor cohorts. Notably, trastuzumab deruxtecan (T-Dxd), an ADC that specifically targets HER2, has recently received approval from the US Food and Drug Administration as the inaugural targeted therapeutic option for HER2-low BC. However, the classification of HER2-low BC as a distinct subtype, the methods for detecting HER2-low BC, and the optimal treatment approach for HER2-low BC remain subjects of ongoing debate and lack consensus. This comprehensive review aims to address these pertinent concerns, offering insights into the nuanced tumor biology underlying HER2-low BC and critically analyzing the current treatment pathways available. By synthesizing available evidence, the objective is to contribute to an enhanced understanding of HER2-low BC, providing a foundation for more informed clinical decisions and further advancements in tailored therapeutic approaches. As the medical community navigates these uncertainties, this review seeks to consolidate existing knowledge, fostering a collective effort toward establishing consensus in the diagnosis and treatment of HER2-low BC.

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A review of treatment options in HER2‐low breast cancer and proposed treatment sequencing algorithm

Cited by 6 publications

References 64 publications

Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis

Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis

Oncotype Dx Score, HER2 Low Expression, and Clinical Outcomes in Early-Stage Breast Cancer: A National Cancer Database Analysis

Challenges in HER2-low breast cancer identification, detection, and treatment

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