Trastuzumab treatment of patients with early, HER2-positive breast cancer in 17 certified German breast cancer centers

Trastuzumab Therapy ◽

Abstract Purpose This study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment. Methods 32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab. Results UCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis. Conclusion Taken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.

Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial

British Journal of Cancer ◽

10.1038/s41416-020-0786-x ◽

2020 ◽

Vol 122 (10) ◽

pp. 1453-1460 ◽

Cited By ~ 2

Author(s):

Daniel Eiger ◽

Noam F. Pondé ◽

Dominique Agbor-Tarh ◽

Alvaro Moreno-Aspitia ◽

Martine Piccart ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Optimization ◽

Her2 Positive ◽

Trastuzumab Treatment ◽

Cardiac Outcomes ◽

De-escalating adjuvant trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer: A systemic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.524 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 524-524

Author(s):

Hadar Goldvaser ◽

Korzets Ceder Yasmin ◽

Daniel Shepshelovich ◽

Rinat Yerushalmi ◽

Michal Sarfaty ◽

...

Keyword(s):

Breast Cancer ◽

Cardiac Dysfunction ◽

Early Stage ◽

Nodal Involvement ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Trastuzumab Treatment ◽

One Year ◽

524 Background: One year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage HER2 positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results. Methods: A search of PubMed and conferences identified randomized trials that compared abbreviated trastuzumab therapy to one year of treatment in early-stage HER2 positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for disease free survival (DFS) and overall survival (OS). Data on the number of DFS and distant relapse events were also collected as were the number of patients at risk in each group. Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor (ER) expression and the duration of abbreviated trastuzumab (9-12 weeks versus 6 months). Odds ratios (ORs) and 95% CI were computed for pre-specified cardiotoxicity events including cardiac dysfunction and congestive heart failure (CHF). Results: Analysis included 6 trials comprising 11603 patients. In most studies adjuvant chemotherapy included anthracyclines and taxanes. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI 1.05-1.25, p = 0.002) and OS (HR = 1.15, 95% CI 1.02-1.29. p = 0.02). The effect on DFS was not influenced by ER status (p for the subgroup difference = 0.23), nodal involvement (p = 0.44) or the different duration of trastuzumab in the experimental arm (p = 0.08). In absolute terms, after an estimated median follow-up of 71 months, shorter treatment with trastuzumab was associated with an absolute increase in DFS events of 2.3%. Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI 0.55-0.81, p < 0.001) and CHF (OR = 0.66, 95% CI 0.50-0.86, p = 0.003). Conclusions: Compared to one year, shorter duration of adjuvant trastuzumab is associated with significantly worse DFS and OS, despite favorable cardiotoxicity profile. One year of trastuzumab should remain the standard adjuvant treatment in early-stage HER2 positive breast cancer with appropriate cardiac monitoring.

P110 9-week versus 52-week trastuzumab treatment for HER2-positive breast cancer

The Breast ◽

10.1016/s0960-9776(15)70154-2 ◽

2015 ◽

Vol 24 ◽

pp. S63

Author(s):

J. Kim ◽

J. Lee ◽

H. Jeong ◽

W. Byeon

Keyword(s):

Breast Cancer ◽

Her2 Positive ◽

Trastuzumab Treatment ◽

A Case of Small Cell Carcinoma of the Breast during Trastuzumab Treatment for HER2 Positive Breast Cancer

Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) ◽

10.3919/jjsa.78.1988 ◽

2017 ◽

Vol 78 (9) ◽

pp. 1988-1992

Author(s):

Kazushige YAMAGUCHI ◽

Ayako UENO ◽

Yuri FUJIMOTO ◽

Reo SAKURAI ◽

Kazuyuki KAWAMOTO

Keyword(s):

Breast Cancer ◽

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Small Cell ◽

Her2 Positive ◽

Carcinoma Of The Breast ◽

Trastuzumab Treatment ◽

Roles of neutrophil/lymphocyte ratio in prognosis and in differentiation of potential beneficiaries in HER2-positive breast cancer with trastuzumab therapy

10.21203/rs.2.19005/v1 ◽

2019 ◽

Author(s):

Nianhua Ding ◽

Juan Huang ◽

Ningsha Li ◽

Jiaqi Yuan ◽

Shouman Wang ◽

...

Keyword(s):

Breast Cancer ◽

Her2 Positive ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Trastuzumab Treatment ◽

Group 3 ◽

Group 2 ◽

Group 1 ◽

Abstract Purpose: The relationship of neutrophil/lymphocyte ratio (NLR) with prognosis of HER2-positive breast cancer (BC) are not well studied. We aimed to assess the prognostic role of NLR in HER2-positive BC patients treated with or without trastuzumab.Methods: The clinical data of 843 HER2-positive BC patients from July 2013 to July 2018 were collected. The difference among variables was calculated by chi-square test. The associations between clinicopathological factors, NLR and disease-free survival (DFS) were analyzed by univariate and multivariate analyses.Results : Patients were divided into three groups. In group 1 containing 255 patients without trastuzumab treatment, pretreatment NLR showed no predictive value. Patients with trastuzumab treatment were divided into two groups on equal, according to pretreatment NLR values, low NLR (group 2) and high NLR (group 3). Patients in group 2 showed significantly higher 3-year DFS rate than patients in group 1 and group 3 (95.3% vs. 91.6% vs. 90.5%, respectively, P = 0.011); patients in the group 1 and group 3 had similar 3-year DFS outcome. Multivariate analysis showed high pretreatment NLR was significantly associated with shorter DFS (HR = 2.917, 95% CI=1.055-8.062, P = 0.039) in HER2-positive BC patients treated with trastuzumab. Conclusion : Among HER2-positive trastuzumab-treated BC patients, low pretreatment NLR value was associated with better DFS, and it might help to differentiate potential beneficiaries of trastuzumab treatment.

Roles of neutrophil/lymphocyte ratio in prognosis and in differentiation of potential beneficiaries in HER2-positive breast cancer with trastuzumab therapy

10.21203/rs.2.19005/v2 ◽

2020 ◽

Author(s):

Nianhua Ding ◽

Juan Huang ◽

Ningsha Li ◽

Jiaqi Yuan ◽

Shouman Wang ◽

...

Keyword(s):

Breast Cancer ◽

Her2 Positive ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Trastuzumab Treatment ◽

Group 3 ◽

Group 2 ◽

Group 1 ◽

Abstract Purpose The relationship of neutrophil/lymphocyte ratio (NLR) to prognosis of HER2-positive breast cancer (BC) is not well studied. We aimed to assess the prognostic role of NLR in HER2-positive BC patients treated with or without trastuzumab. Methods The clinical data of 843 HER2-positive BC patients from July 2013 to July 2018 were collected. The difference among variables was calculated by chi-square test. The associations between clinicopathological factors, NLR and disease-free survival (DFS) were analyzed by univariate and multivariate analyses. Results Patients were divided into three groups. In group 1 containing 255 patients without trastuzumab treatment, pretreatment NLR showed no predictive value. Patients with trastuzumab treatment were divided into two groups on equal, according to pretreatment NLR values, low NLR (group 2) and high NLR (group 3). Patients in group 2 showed significantly higher 3-year DFS rate than patients in group 1 and group 3 (95.3% vs. 91.6% vs. 90.5%, respectively, P = 0.011); patients in the group 1 and group 3 had a similar 3-year DFS outcome. Multivariate analysis showed high pretreatment NLR was significantly associated with shorter DFS (HR = 2.917, 95% CI=1.055-8.062, P = 0.039) in HER2-positive BC patients treated with trastuzumab. Conclusion Among HER2-positive trastuzumab-treated BC patients, low pretreatment NLR value was associated with better DFS, and it might help to differentiate potential beneficiaries of trastuzumab treatment.