Therapeutic approach to the management of HER2-positive breast cancer metastatic to the brain

Patil, Ajay B.; Sherbet, Gajanan V.

doi:10.1016/j.canlet.2014.12.026

Cited by 15 publications

(12 citation statements)

References 53 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over the past decades, substantial improvements in the diagnosis and treatment of BC patients have been achieved, but brain metastasis is still associated with poor outcomes, and these patients lack a sufficiently effective treatment 6,23,24 . Pyrotinib, as a novel anti-HER2 TKI, shown a potential effectiveness in patients with BM 13 .…”

Section: Discussionmentioning

confidence: 99%

Pyrotinib Treatment in Patients With HER2-positive Metastatic Breast Cancer and Brain Metastasis: Exploratory Final Analysis of Real-World, Multicenter Data

Anwar

Chen

Ouyang

et al. 2021

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC patients to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce. Experimental design:This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2+ MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR) and overall response rate (ORR) were analyzed.Results: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR). Conclusion:Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.

show abstract

Section: Discussionmentioning

confidence: 99%

Pyrotinib Treatment in Patients With HER2-positive Metastatic Breast Cancer and Brain Metastasis: Exploratory Final Analysis of Real-World, Multicenter Data

Anwar

Chen

Ouyang

et al. 2021

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Demonstrating benefits in the advanced and early disease settings, trastuzumab was also shown to improve pathological complete response rates when used in the neo-adjuvant setting, covering as expected, the whole spectrum of presentations of the disease [22]. Currently, the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network and the European Society of Medical Oncology (ESMO) as well as most other treatment guidelines for breast cancer recommend the addition of anti-HER2 agents to systemic chemotherapy or endocrine therapy for the treatment of patients with early stage, locally advanced and metastatic HER2+ breast cancer.…”

Section: Contemporary Management Of Her2+ Advanced Breast Cancermentioning

confidence: 99%

Access to high-cost drugs for advanced breast cancer in Latin America, particularly trastuzumab

Barrios¹,

Reinert²,

Werutsky³

2019

ecancer

View full text Add to dashboard Cite

Provision of high-level healthcare is a challenge for all low- to middle-income countries (LMICs) since healthcare systems are heterogeneous, face many challenges such as inadequate funding, inequitable distribution of resources and services and usually are not adequately equipped to deal with a huge problem such as breast cancer. The development of anti-HER2 therapies can be considered one of the most important examples of the translation of molecular biology knowledge into clinical benefits for cancer patients. While a variety of novel therapeutic strategies are emerging, current treatment regimens remain focussed on targeted therapy with monoclonal antibodies, mainly trastuzumab, the first agent developed in this field. While these results have revolutionised the outcome of HER2+ patients in clinical trials and in high-income countries where they are widely available, results have not impacted the natural history of this aggressive disease in most of the world. Unfortunately, the availability of these drugs is far from universal in many LMICs, and in Latin America, in particular, patients with HER2+ breast cancer are treated exclusively with standard chemotherapy, a more toxic and less efficient therapy. While the complexity of the situation and the multiple factors that have an impact in this scenario are recognised, we need to map the future and develop feasible strategies to address possible solutions to the problem of drug access. A clear and unbiased diagnosis of the situation is a good starting point. Defining healthcare priorities and a clear strategy for the allocation of resources is difficult but mandatory. In this article, we will discuss current and future challenges regarding access (and lack of access) to high-cost cancer drugs in Latin America, with a focus on anti-HER2 therapies.

show abstract

“…Another erbB2-targeted therapy, trastuzumab (Herceptin) is a humanized monoclonal antibody (Ab) binding to the extracellular domain of erbB2. Both trastuzumab and lapatinib have been successfully used in clinic to treat early and metastatic breast cancer (MBC) patients with erbB2-positive tumors [ 3 – 8 ]. However, both de novo and acquired resistance to these agents frequently occurs, representing a significant clinical problem [ 9 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

The erbB3- and IGF-1 receptor-initiated signaling pathways exhibit distinct effects on lapatinib sensitivity against trastuzumab-resistant breast cancer cells

et al. 2015

View full text Add to dashboard Cite

Both erbB3 and IGF-1 receptor (IGF-1R) have been shown to play an important role in trastuzumab resistance. However, it remains unclear whether erbB3- and IGF-1R-initiated signaling pathways possess distinct effects on the sensitivity of lapatinib, a dual tyrosine kinase inhibitor against both EGFR and erbB2, in trastuzumab-resistant breast cancer. Here, we show that the trastuzumab-resistant SKBR3-pool2 and BT474-HR20 breast cancer sublines, as compared the parental SKBR3 and BT474 cells, respectively, exhibit refractoriness to lapatinib. Knockdown of erbB3 inhibited Akt in SKBR3-pool2 and BT474-HR20 cells, significantly increased lapatinib efficacy, and dramatically re-sensitized the cells to lapatinib-induced apoptosis. In contrast, specific knockdown of IGF-1R did not alter the cells' responsiveness to lapatinib. While the levels of phosphorylated Src (P-Src) were reduced upon IGF-1R downregulation, the P-Akt levels remained unchanged. Furthermore, a specific inhibitor of Akt, but not Src, significantly enhanced lapatinib-mediated anti-proliferative/anti-survival effects on SKBR3-pool2 and BT474-HR20 cells. These data indicate that erbB3 signaling is critical for both trastuzumab and lapatinib resistances mainly through the PI-3K/Akt pathway, whereas IGF-1R-initiated Src activation results in trastuzumab resistance without affecting lapatinib sensitivity. Our findings may facilitate the development of precision therapeutic regimens for erbB2-positive breast cancer patients who become resistant to erbB2-targeted therapy.

show abstract

Therapeutic approach to the management of HER2-positive breast cancer metastatic to the brain

Cited by 15 publications

References 53 publications

Pyrotinib Treatment in Patients With HER2-positive Metastatic Breast Cancer and Brain Metastasis: Exploratory Final Analysis of Real-World, Multicenter Data

Pyrotinib Treatment in Patients With HER2-positive Metastatic Breast Cancer and Brain Metastasis: Exploratory Final Analysis of Real-World, Multicenter Data

Access to high-cost drugs for advanced breast cancer in Latin America, particularly trastuzumab

The erbB3- and IGF-1 receptor-initiated signaling pathways exhibit distinct effects on lapatinib sensitivity against trastuzumab-resistant breast cancer cells

Contact Info

Product

Resources

About