Treatment Strategies for Patients With Anthracycline- and Taxane-Pretreated Metastatic Breast Cancer

Abstract Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

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Cost-effectiveness of HER2 testing and trastuzumab therapy for metastatic breast cancer (MBC) patients in Sweden

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1088 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1088-1088

Author(s):

M. Lidgren ◽

C. Rehnberg ◽

N. Wilking ◽

B. Jönsson

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cost Effectiveness ◽

Treatment Strategies ◽

Metastatic Breast ◽

Chemotherapy Treatment ◽

Her2 Testing ◽

Trastuzumab Treatment ◽

Life Years ◽

The Cost

1088 Background: Trastuzumab is a monoclonal antibody that together with chemotherapy significantly improves time to progression and overall survival for MBC patients with tumours overexpressing HER2. The aim of this study was to analyse the cost- effectiveness of HER2 testing and trastuzumab in combination with chemotherapy compared with chemotherapy alone from a societal perspective in a Swedish setting. Methods: We used a Markov state transition model to simulate HER2 testing and subsequent treatment in a hypothetical cohort of 65 year old metastatic breast cancer patients based on the study by Marty et al (Marty et al, J Clin Oncol. Jul 1 2005;23(19):4265–4274). Outcomes included life-time costs, quality adjusted life years (QALY), and cost per QALY gained. Five different testing and treatment strategies were evaluated. Results: We estimated the cost per QALY gained to be about 485,000 SEK (approximately 70,000 USD) and the cost per life year (LY) gained to be about 332,000 SEK (approximately 47,000 USD) for the strategy of IHC testing for all patients, with FISH confirmation of 2+ and 3+, and trastuzumab and chemotherapy treatment for FISH positive patients. For the strategy of FISH testing for all patients, with trastuzumab and chemotherapy for FISH positive patients, we estimated the cost per QALY gained to about 561,000 SEK (approximately 80,000 USD) and the cost per LY gained to be 384,000 SEK (approximately 55,000 USD). The remaining testing and treatment strategies were dominated. Results were sensitive to changes in the quality adjustment of life years with metastatic disease, the risk of breast cancer related death, and test characteristics. Conclusions: Our analysis indicate that the present Swedish guidelines of IHC testing for all patients with metastatic breast cancer, with FISH confirmation of 2+ and 3+, followed by trastuzumab and chemotherapy treatment for FISH positive patients is a cost-effective treatment option. However, further research on budget impact of trastuzumab treatment and patient accessibility to trastuzumab treatment is needed. No significant financial relationships to disclose.

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Optimal treatment strategies in postmenopausal women with hormone-receptor-positive and HER2-negative metastatic breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-008-0232-x ◽

2008 ◽

Vol 112 (S1) ◽

pp. 53-66 ◽

Cited By ~ 12

Author(s):

Joseph Gligorov ◽

Jean-Pierre Lotz

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Postmenopausal Women ◽

Hormone Receptor ◽

Treatment Strategies ◽

Metastatic Breast ◽

Optimal Treatment ◽

Hormone Receptor Positive

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PREVENTION AND MONITORING OF CARDIOVASCULAR COMPLICATIONS IN PATIENTS WITH LUMINAL HER2-NEGATIVE METASTATIC BREAST CANCER

Tumors of female reproductive system ◽

10.17650/1994-4098-2018-14-2-61-71 ◽

2018 ◽

Vol 14 (2) ◽

pp. 61-71

Author(s):

N. A. Kozyavin ◽

T. Yu. Semiglazova

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Systemic Treatment ◽

Myocardial Dysfunction ◽

Treatment Strategies ◽

Metastatic Breast ◽

Cardiovascular Complications ◽

New Drugs ◽

Qtc Interval ◽

Optimal Patient Management

Myocardial dysfunction, heart failure and prolongation of the QTc interval are dangerous cardiovascular complications associated with systemic treatment for luminal HER2-negative metastatic breast cancer. Special monitoring is required to control such complications, especially when introducing new drugs. Understanding the mechanisms underlying the development of cardiovascular complications as well as diagnostic, prevention, and treatment strategies is important for optimal patient management.

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Treatment strategies in patients with Metastatic Breast Cancer: real-world practice in the United Kingdom (UK) and Italy

Annals of Oncology ◽

10.1093/annonc/mdw337.15 ◽

2016 ◽

Vol 27 ◽

pp. iv63

Author(s):

L. Ferrari ◽

L. Gerratana ◽

M. Jove ◽

M. Bonotto ◽

M. Cinausero ◽

...

Keyword(s):

Breast Cancer ◽

United Kingdom ◽

Metastatic Breast Cancer ◽

Real World ◽

Treatment Strategies ◽

Metastatic Breast ◽

The United Kingdom

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Hormone therapy for premenopausal women with metastatic breast cancer: combinations with cyclin-dependent kinase inhibitors

Tumors of female reproductive system ◽

10.17650/1994-4098-2019-15-2-30-41 ◽

2019 ◽

Vol 15 (2) ◽

pp. 30-41

Author(s):

E. V. Artamonova ◽

E. I. Kovalenko

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Hormone Therapy ◽

Randomized Trials ◽

Kinase Inhibitors ◽

Treatment Strategies ◽

Metastatic Breast ◽

Premenopausal Women ◽

Cyclin Dependent Kinase ◽

Ovarian Suppression

This article discusses the problems associated with the search of the most effective treatment strategies for HER2-negative metastatic breast cancer in premenopausal women. Until recently, ovarian suppression and hormone therapy had been the main treatments used in this group of patients. The development of palbociclib, called a “breakthrough therapy”, as well as promising results of trials evaluating the efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors added to hormone therapy in postmenopausal women suggested a need for the assessment of this treatment regimen in combination with ovarian suppression in younger patients.According to the results of randomized trials and subgroup analysis, the addition of a CDK4/6 inhibitor to ovarian suppression and hormonal therapy significantly increases survival. The safety profile is similar to that of older patients. Randomized trials comparing the efficacy of palbociclib + ovarian suppression + aromatase inhibitor vs. chemotherapy in premenopausal women demonstrated significant benefits of a new treatment strategy: a CDK4/6 inhibitor as a part of combination therapy reduced the risk of progression by 36 % compared to capecitabine.

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First- and second-line treatment strategies for hormone-receptor (HR)-positive HER2-negative metastatic breast cancer: A real-world study

The Breast ◽

10.1016/j.breast.2021.02.015 ◽

2021 ◽

Vol 57 ◽

pp. 104-112

Author(s):

Debora Basile ◽

Lorenzo Gerratana ◽

Carla Corvaja ◽

Giacomo Pelizzari ◽

Giorgia Franceschin ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Real World ◽

Hormone Receptor ◽

Treatment Strategies ◽

Metastatic Breast ◽

Line Treatment ◽

Second Line

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ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target

Frontiers in Oncology ◽

10.3389/fonc.2021.759577 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xuan Cheng ◽

Jian-Xiong Zhao ◽

Feng Dong ◽

Xu-Chen Cao

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Therapeutic Potential ◽

Endocrine Resistance ◽

Hdac Inhibitors ◽

Treatment Strategies ◽

Disease Free Survival ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Luminal A

Distant metastasis is the principal cause of mortality for breast cancer patients. Targeting specific mutations that have been acquired during the evolution process of advanced breast cancer is a potential means of enhancing the clinical efficacy of treatment strategies. In metastatic breast cancer, ARID1A is the most prevalent mutation of the SWI/SNF complex, which regulates DNA repair, recombination, and gene transcription. The low expression of ARID1A is associated with poor disease-free survival and overall survival of patients with luminal A or HER2-rich breast cancer. In addition, ARID1A plays a prominent role in maintaining luminal characteristics and has an advantage for identifying responses to treatment, including endocrine therapies, HDAC inhibitors and CDK4/6 inhibitors. The therapeutic vulnerabilities initiated by ARID1A alterations encourage us to explore new approaches to cope with ARID1A mutant-related drug resistance or metastasis. In this review, we describe the mutation profiles of ARID1A in metastatic breast cancer and the structure and function of ARID1A and the SWI/SNF complex as well as discuss the potential mechanisms of ARID1A-mediated endocrine resistance and therapeutic potential.

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