scholarly journals Emerging treatment strategies for breast cancer brain metastasis: from translational therapeutics to real-world experience

2020 ◽  
Vol 12 ◽  
pp. 175883592093615 ◽  
Author(s):  
Ding Ren ◽  
Hao Cheng ◽  
Xin Wang ◽  
Monika Vishnoi ◽  
Bin S. Teh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Difficult Problem ◽  
Therapeutic Strategies ◽  
Her2 Positive ◽  
Whole Brain Radiation ◽  
Breast Cancer Brain Metastasis

Systemic therapies for primary breast cancer have made great progress over the past two decades. However, oncologists confront an insidious and particularly difficult problem: in those patients with metastatic breast cancer, up to 50% of human epidermal growth factor 2 (HER2)-positive and 25–40% of triple-negative subtypes, brain metastases (BM) kill most of them. Fortunately, standard- of-care treatments for BM have improved rapidly, with a decline in whole brain radiation therapy and use of fractionated stereotactic radiosurgery as well as targeted therapies and immunotherapies. Meanwhile, advances in fundamental understanding of the basic biological processes of breast cancer BM (BCBM) have led to many novel experimental therapeutic strategies. In this review, we describe the most recent clinical treatment options and emerging experimental therapeutic strategies that have the potential to combat BCBM.

scholarly journals Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)

Breast Cancer ◽  
2021 ◽  
Author(s):  
Takamichi Yokoe ◽  
Sasagu Kurozumi ◽  
Kazuki Nozawa ◽  
Yukinori Ozaki ◽  
Tetsuyo Maeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Real World ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Breast Cancer Patients ◽  
Her2 Positive

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.

scholarly journals Use of HER2-Directed Therapy in Metastatic Breast Cancer and How Community Physicians Collaborate to Improve Care

2020 ◽  
Vol 9 (6) ◽  
pp. 1984 ◽  
Author(s):  
Joanne E. Mortimer ◽  
Laura Kruper ◽  
Mary Cianfrocca ◽  
Sayeh Lavasani ◽  
Sariah Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Research Network ◽  
Her2 Positive ◽  
Community Partners ◽  
Significant Prolongation ◽  
Positive Breast Cancer

The development of new HER2-directed therapies has resulted in a significant prolongation of survival for women with metastatic HER2-positive breast cancer. Discoveries in the laboratory inform clinical trials which are the basis for improving the standard of care and are also the backbone for quality improvement. Clinical trials can be completed more rapidly by expanding trial enrollment to community sites. In this article we review some of the challenges in treating metastatic breast cancer with HER2-directed therapies and our strategies for incorporating our community partners into the research network.

scholarly journals Differential expression of the G0/G1 switch gene 2, G0S2, in the brain metastases of patients with breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Differential Expression ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Breast Cancer Brain Metastasis ◽  
Microarray Datasets ◽  
The Brain

In patients with breast cancer, brain metastasis provides limited treatment options (1-3). To discover genes associated with brain metastases in patients with metastatic breast cancer, we mined published microarray datasets, comparing global transcription in brain metastases and primary tumors of the breast (4, 5). Using this methodology, we identified significant differential expression of the G0/G1 switch gene 2, encoded by G0S2, in the brain metastases of patients with breast cancer as compared to primary tumors of the breast. The G0S2 gene product could be of relevance to any one of the numerous processes by which tumor cells in breast cancer metastasize, including exit of the breast, entry into the periphery, breach of the blood brain barrier or colonization of and survival in the brain.

scholarly journals Therapy Algorithms for the Diagnosis and Treatment of Patients with Early and Advanced Breast Cancer

Breast Care ◽  
2020 ◽  
Vol 15 (6) ◽  
pp. 608-618
Author(s):  
Andreas Schneeweiss ◽  
Ingo Bauerfeind ◽  
Tanja Fehm ◽  
Wolfgang Janni ◽  
Christoph Thomssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Evidence Based ◽  
Complex Treatment ◽  
Her2 Positive ◽  
Evidence Based Treatment

<b><i>Background:</i></b> In order to offer optimal treatment approaches based on available evidence, the Commission Breast of the Working Group Gynecologic Oncology (AGO) of the German Cancer Society developed therapy algorithms for eight complex treatment situations in primary and advanced breast cancer. <b><i>Summary:</i></b> Therapy algorithms for the following complex treatment situations are outlined in this paper: (neo)adjuvant therapy of human epidermal growth factor receptor 2 (HER2)-positive breast cancer; axillary surgery and neoadjuvant chemotherapy; adjuvant endocrine therapy in premenopausal patients; adjuvant endocrine therapy in postmenopausal patients; hormone receptor (HR)-positive/HER2-negative metastatic breast cancer: strategies; HR-positive/HER2-negative metastatic breast cancer: endocrine-based first-line treatment; HER2-positive metastatic breast cancer: first to third-line; metastatic triple-negative breast cancer. <b><i>Key Messages:</i></b> The therapy options shown in these algorithms are based on the current AGO recommendations updated in January 2020 but cannot represent all evidence-based treatment options. Prior therapies, performance status, comorbidities, patient preference, etc. must be taken into account for the actual treatment choice. Therefore, in individual cases, other evidence-based treatment options not listed here may also be appropriate and justified.

A prognostic factor (PF) index for overall survival in a HER2-negative endocrine-resistant metastatic breast cancer (MBC) population: Analysis from the ATHENA trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 555-555 ◽  
Author(s):  
Antonio Llombart-Cussac ◽  
Xavier B. Pivot ◽  
Laura Biganzoli ◽  
Hernan Cortes-Funes ◽  
Kathleen I. Pritchard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Population Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Her2 Positive ◽  
Soft Tissue Involvement

555 Background: Chemotherapy is the standard of care for patients (pts) with HER2-negative endocrine-resistant MBC. The considerable variability in overall survival (OS) within this population relates essentially to prognostic factors (PF). Increasingly, large studies based on progression-free survival (PFS) as a primary endpoint are now being questioned. An accurate PF index may help in designing innovative trials with appropriate pts selection according to overall survival (OS) prognosis. Methods: The ATHENA trial assessed the safety of first-line bevacizumab combined with non-anthracycline-containing therapy in 2264 pts treated in 37 countries from 2006 to 2009. Pt characteristics, safety, and efficacy have been reported [Breast Cancer Res Treat 2011;130:133-43]. Sixty-one HER2-positive pts were excluded. A multivariate Cox regression model selected PF generating a simple PF index. Of note, skin, lymph node, ipsi-/contra- breast, or other soft tissue involvement was scored as a single organ. Results: After a median follow-up of 20.1 months and 1171 OS events (53% of pts), median OS for the entire sample and triple-negative (TNBC) and non-TNBC subgroups was 25.2 (95% CI 23.9–26.3), 18.3 (16.3–19.7) and 27.3 (26.3–29.3) months, respectively. PF most closely associated with poorer OS were: liver mets or >2 involved organs (HR 1.6; 95% CI 1.5–1.8); DFI ≤24 months (HR 1.7; 1.5–2.0); adjuvant anthracyline and/or taxane (HR 1.1; 1.2–1.4); and TNBC (HR 1.6; 1.4–1.8). A predictive model was designed stratifying by number of PF present (0/1 vs 2 vs 3/4). The model was consistent in both TNBC and non-TNBC populations (Table). Conclusions: A PF index may estimate figures and balance arms in future trials considering OS as primary objective. A well-defined group of non-TNBC accounting for 37% of patients has an OS estimate similar to the most aggressive TNBC. [Table: see text]

scholarly journals Targeted Therapies in HER2-Positive Breast Cancer - a Systematic Review

Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Amelie Schramm ◽  
Nikolaus De Gregorio ◽  
Peter Widschwendter ◽  
Visnja Fink ◽  
Jens Huober
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Increased Risk ◽  
Positive Breast Cancer

About 20% of all breast cancer patients have a human epidermal growth factor receptor 2 (HER2)-positive breast tumor. This entity underwent an impressive change in prognosis, with notable improvement of progression-free survival and overall survival. Due to more aggressive tumors and no specific therapy, HER2 overexpression was historically seen as a negative prognostic marker, with worse prognosis and increased risk of recurrent disease. Trastuzumab, the first anti-HER2 antibody, revolutionized the systemic therapy options in HER2-positive breast cancer and initiated several targeted therapies and more personalized treatment strategies. Over the years, multiple HER2-targeting drugs stepped into clinical practice, for the curative as well as the metastatic situation. This review summarizes the targeted treatment options in HER2-positive breast cancer and their current impact in the clinical routine. Results of the most outstanding trials in HER2-targeted therapies and important ongoing trials are subsequently described for an up-to-date overview.

scholarly journals Treatment Landscape for Patients with HER2-Positive Metastatic Breast Cancer: A Review on Emerging Treatment Options

2020 ◽  
Vol Volume 12 ◽  
pp. 10615-10629
Author(s):  
Simon Peter Gampenrieder ◽  
Vanessa Castagnaviz ◽  
Gabriel Rinnerthaler ◽  
Richard Greil
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Her2 Positive

scholarly journals New Therapeutic Strategies in Advanced Nonoperable or Metastatic HER2-positive Breast Cancer

2021 ◽  
Vol 81 (06) ◽  
pp. 666-678
Author(s):  
Diana Lüftner ◽  
Matthias Peipp
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Antibody Engineering ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
The Us ◽  
Positive Breast Cancer

AbstractDespite therapeutic gains in the treatment of HER2-positive (HER2: human epidermal growth factor receptor 2) advanced/metastatic breast cancer, there remains an urgent need for more effective treatment options. At present, there is no definitive approved standard therapy beyond second-line treatment. One of the major challenges is overcoming treatment resistance. Depending on the underlying resistance mechanism, different strategies are being pursued for new innovative treatment concepts in HER2-positive breast cancer. Specifically designed antibodies for targeted therapy are one important focus to successfully meet these challenges. Trastuzumab deruxtecan (T-DXd, DS-8201a), an optimised antibody drug conjugate (ADC) is in clinical trials, showing promising outcomes in patients with advanced, nonoperable or metastatic HER2-positive breast cancer who had already undergone intensive prior treatment. Based on this data, T-DXd has already been approved in the US and Japan for HER2-positive advanced nonoperable and metastatic breast cancer – in the US after at least two prior anti-HER2 targeted treatment lines and in Japan after prior chemotherapy. T-DXd represents successful “antibody engineering”. Since the beginning of the year, T-DXd has also been approved in Europe as monotherapy for inoperable or metastatic HER2-positive breast cancer in patients who are pretreated with at least two anti-HER2 directed therapies. This paper presents strategies for improving treatment options in advanced nonoperable and metastatic HER2-positive breast cancer, with the development of T-DXd as an example.

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