HER-2 positive

Emerging treatments in HER2-positive breast cancer aim to tackle the disease by acting on different targets, including not only HER2 (both at the extra- and intracellular level), but also HER3, PD-(L)1, CTLA4, NKG2A, AKT, PI3K, and, in triple-positive tumors, the estrogen receptors and the cyclin-dependent kinases 4/6. This review describes the evolving treatment landscape of HER2-positive breast cancer, from the current approved therapies to the future perspectives, with a focus on the new agents which are likely to get approved in the next future.

Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Within HR-negative breast cancer, those with low HER2 expression exhibit a less aggressive profile compared to HER2-zero tumors.

In conclusion, minor modifications in HER2 IHC staining conditions significantly affected the frequency of HER2-low BC but had little impact on the HER2-positivity rate. Each pathology laboratory should verify IHC conditions using control slides (including 1+) to enable the accurate identification of HER2-low BC.

No abstract available

Additionally, OS was higher in patients treated at private institutions compared to public ones. This study demonstrates the disparity in oncological treatment efficacy between clinical trials and clinical reality in Uruguay, emphasizing the importance of authentic environment research for more representative and effective medicine in Latin America.

This has provoked many discussions on HER2-low breast cancer, such as quality control prior to HER2-low expression detection, the latest progress of tumor heterogeneity, and the application of AI. In this paper, we discuss the latest testing guidelines and advances on HER2-low breast cancer, aiming to standardize and improve the pathological testing of HER2-low breast cancer.

Common non-hematological toxicity occurred in abemaciclib group was diarrhea (27.4%), and were increased aspartate aminotransferase (AST) (26.3%), nausea (25.0%), vomiting (11.8%) and hypokalemia (13.2%) in tucidinostat group. Our study suggests superiority of abemaciclib-based therapy over tucidinostat-based therapy in patients progressed on palbociclib, which merits further assessment in larger and prospective trials.

Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

P2, N=174, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Oct 2024

P3, N=190, Active, not recruiting, National Cancer Institute (NCI) | N=600 --> 190 | Trial completion date: Apr 2024 --> May 2025

P1/2, N=154, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=320 --> 154 | Trial completion date: Jan 2026 --> Mar 2025

P2, N=60, Recruiting, MedSIR | Trial primary completion date: Apr 2024 --> Dec 2025

Our findings suggest that MSN and ARFIP2 could serve as promising biomarkers for predicting response to Tz, offering valuable insights for future research in the identification of diagnostic and therapeutic targets for BC patients with Tz resistance.

CCNE1 amplification may confer primary resistance to T-DXd in HER2-positive G/GEJ cancer, suggesting that the cell cycle could be a potential therapeutic target in CCNE1/ERBB2 coamplified tumors. ERBB2-activating mutation may also attenuate T-DXd efficacy in HER2-positive G/GEJ cancer.

ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.

Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

Our findings showed a significant decrement in utility scores among metastatic breast cancer patients. Patients' health-state utility differed by their demographic characteristics (age, education level, and income) and clinical characteristics (stage of cancer and distress). Their utility scores may support further cost-effectiveness analysis in Vietnam.

P1/2, N=13, Terminated, Precirix | Active, not recruiting --> Terminated; Per Strategic Sponsor decision

P2/3; Trial completion date: Mar 2024 --> Jun 2025

The calibration curve showed that the multimodal radiomics model had a high consistency with the actual results in predicting HER-2 expression. T2WI, ADC and early-delayed phase DCE-MRI imaging histology models for HER-2 expression status in breast cancer are expected to provide a non-invasive virtual pathological basis for decision-making on preoperative neoadjuvant regimens in breast cancer.

The most common adverse effect of T-DM1 was thrombocytopenia, with an incidence of 69.31% (70/101), and the probability of Grade ≥ 3 thrombocytopenia was 11.88% (12/101). This real-world study demonstrated that T-DM1 had good efficacy and was well tolerated by both HER2-positive early-stage BC and mBC patients.

In the present study, PCR was the only modifiable parameter that changed breast cancer outcomes with brain metastasis and leptomeningeal metastasis was associated with the worst outcomes. Our study favors that PCR has prognostic importance.

P2; Trial primary completion date: Dec 2023 --> Dec 2026

P=N/A, N=72, Active, not recruiting, University of Birmingham | Recruiting --> Active, not recruiting | N=150 --> 72

P2/3, N=136, Active, not recruiting, Caigang Liu | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Dec 2028

From a large, registry-based study, we observed that patients with ERBB2 + and triple negative BC have the highest incidence of BrM. Our data supports prospective surveillance brain MRI studies. Given advancements in BrM treatment, clinicians should have a low threshold for brain imaging in BC patients with high risk subtypes.

Since 3D models such as cancer cell spheroids are superior to 2D cultures in predicting in vivo responses of tumors to anticancer therapies, spheroid co-cultures of EGFP-expressing HER2+ JIMT-1 breast cancer cells and the NK92.CD16 cell lines were set up and induced with Trastuzumab, a monoclonal antibody clinically approved against HER2-positive breast cancer. The applicability of our assay to identify ADCC-modulating molecules is demonstrated by showing that Sunitinib, a receptor tyrosine kinase inhibitor approved by the FDA against metastatic cancer, almost completely abolishes ADCC. The generation of the spheroids and image acquisition and analysis pipelines are compatible with high-throughput screening for ADCC-modulating compounds in cancer cell spheroids.

However, challenges such as methodological heterogeneity and transparency in utility valuation persist, underscoring the need for standardized guidelines and collaborative efforts among stakeholders. PROSPERO ID: CRD42021259826.

This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

The DESTINY-Breast04 trial results showed that trastuzumab deruxtecan (T-DXd) significantly prolonged the survival of patients with HER2-low breast cancer, thus presenting a paradigm shift in anti-HER2 therapy...We inferred that the HER2-low and HER2-zero statuses do not affect the RFS and OS of patients with ER-positive breast cancer. The prognostic significance of HER2-low or HER2-zero status in luminal A- and B-like breast cancers might differ, and a new treatment strategy is required for the HER2-low subgroup.

P2, N=240, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2024 --> Mar 2025

P1/2, N=188, Recruiting, Cancer Research UK | N=114 --> 188 | Trial completion date: Sep 2025 --> Jun 2027 | Trial primary completion date: Sep 2025 --> Jun 2027

P2, N=70, Active, not recruiting, Hope Rugo, MD | Recruiting --> Active, not recruiting

In this trial, SC trastuzumab was preferred over IV trastuzumab. The duration of SC trastuzumab administration was significantly shorter than that of IV trastuzumab, saving patients and HCPs time. Safety and efficacy results were consistent with other published trials and were not associated with any new safety signal.

Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.

This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.

In this early access program in patients with heavily pretreated HER2-positive metastatic/unresectable breast cancer, T-DXd had antitumor activity with a similar response to that reported in previous clinical studies. T-DXd was well tolerated and no new safety signals were observed.

Encapsulated polyphenolic extract was also found to be cytotoxic against drug-resistant doxorubicin-induced senescent breast cancer cells that were accompanied by increased levels of apoptotic and necrotic markers, cell cycle inhibitor p21 and proinflammatory cytokine IL8. Furthermore, diverse responses to the stimulation with encapsulated polyphenolic extract in senescent breast cancer cells were observed, as in the encapsulated polyphenolic extract-treated non-proliferating AU565 cells, the autophagic pathway, here cytotoxic autophagy, was also induced, as judged by elevated levels of beclin-1 and LC3b. We show for the first time the anti-breast cancer activity of encapsulated polyphenolic extract of pearl millet and postulate that microencapsulation may be a useful approach for potentiating the anticancer effects of phytochemicals with limited bioavailability.

Trastuzumab deruxtecan, an antibody-drug conjugate, has shown positive results even in later-line treatment and has become new standard treatment. In first-line therapy, combination therapy with pembrolizumab and trastuzumab plus chemotherapy demonstrated a dramatic response rate...The emergence of combination therapy including immunotherapy with HER2-targeting agents and the development of HER2 targeting agents with or without immunotherapy have been advancing for treating HER2-positive gastric cancer. In this review, we will discuss the current status of treatment development and future perspectives for HER2-positive gastric cancer.

Strikingly, HER2 transcript and protein levels were both significantly downregulated by 1E5. Taken together, these findings indicate the therapeutic potential of targeting HER2 overexpression and associated metabolic reprogramming via the modulation of LXR in HER2-positive breast cancers.

Pyrotinib-based therapy is effective and tolerable in human epidermal growth factor receptor 2-positive metastatic breast cancer with BMs. Patients who underwent radiotherapy for BMs, particularly those who received pyrotinib concurrently with radiotherapy, exhibited a more favorable prognosis.

The joint sequence model had the highest AUC value. The MRI radiomics models can be used to effectively predict the HER2 expression in breast cancer and provide a non-invasive and early assistant method for clinicians to formulate individualized and accurate treatment plans.