Targeted Therapies in HER2-Overexpressing Metastatic Breast Cancer

Labidi, Soumaya; Mejri, Nesrine; Lagha, Aymen; Daoud, Nouha; Benna, Houda El; Afrit, Mehdi; Boussen, Hamouda

doi:10.1159/000452194

Cited by 16 publications

(17 citation statements)

References 49 publications

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“…From today's point of view, locoregional therapy would have been beneficial, because the in-breast recurrence could likely have been prevented. As repeatedly reported in the literature, HER2-positive breast cancer is often associated with the development of brain metastases [ 4 - 5 ]. Our patient was not screened with regular imaging, consistent with national guidelines and clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…However, both patterns of disease, response to treatment, and survival are highly variable [ 3 ]. Breast cancer biology, e.g., expression of estrogen (ER), progesterone (PR) and HER2 receptors, profoundly influences the choice of systemic therapy and survival in patients with stage IV disease [ 4 ]. Patients with HER2 overexpressing metastatic breast cancer are at increased risk for development of brain metastases [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Exceptional Responses to Standard Therapy in a Patient with Metastatic HER2-Positive Breast Cancer

Nieder¹,

Mannsåker²,

Haukland³

2017

Cureus

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Patients with metastatic breast cancer involving the liver and brain often have short overall survival. Here, we report a case of de novo metastatic breast cancer with multiple liver metastases at initial diagnosis in February 2011 in a 35-year-old Caucasian female patient. The histology was poorly differentiated invasive ductal carcinoma (estrogen and progesterone receptor negative, HER2 positive) and the patient was negative for germline BRCA 1 and 2 mutations. Systemic therapy with trastuzumab and docetaxel was given for six months and then switched to trastuzumab only because of peripheral neuropathy. At that time, the patient was in complete clinical remission. She developed brain metastases in September 2012 and received whole-brain radiotherapy, which resulted in complete remission. While on continued trastuzumab, the primary tumor in the breast recurred in May 2016. A mastectomy was performed and afterwards systemic therapy was intensified (trastuzumab, pertuzumab, paclitaxel). At the last follow-up (March 06, 2017) no further recurrence was detected. This case illustrates that standard HER2-directed treatment might provide long-term disease control also in selected patients with unfavorable patterns of spread. The beneficial effect of whole-brain radiotherapy is not necessarily limited to symptom palliation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exceptional Responses to Standard Therapy in a Patient with Metastatic HER2-Positive Breast Cancer

Nieder¹,

Mannsåker²,

Haukland³

2017

Cureus

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“…Breast cancer is the most frequent cause of cancer-related death in women and the second most frequent cause of death worldwide, making it a pathology of great social and economic interest for countries worldwide. 1 In Colombia, based on a mortality rate of 12.79 per 100,000 women, the development of therapeutic alternatives has been crucial, enabling the use of anti-HER2 monoclonal therapy (such as trastuzumab), as the first-line treatment of advanced cancer, 25,26 to achieve an overall survival of more than 48 months in patients with HER2-positive advanced breast cancer. 44 Some studies have reported a 5-year overall survival of around 74.9% and 3.5 years global survival from the beginning of treatment in the metastatic stage.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, this benefit applies as well to all patients in that exposure to targeted therapies is decreased, which frequently lead to cardiotoxicity, allergic reactions, lung disease, hematotoxicity, and gastrointestinal disorders. 26 In addition, the costs of Liquid Biopsy may be reduced if it is performed by local-certified laboratories in Colombia and if the panels designed consider the most frequent mutations that confer treatment resistance in HER2-positive advanced breast cancer. Colombia is one of the leading countries in the Latin-American region in terms of installed genomic facilities, cancer genetic research groups and educational programs in genomics.…”

Section: Discussionmentioning

confidence: 99%

“…17,25 Thus, the implementation of ctDNA mutation testing during the follow-up of patients with advanced breast cancer may favor earlier change of pharmacological management and avoid prolonged treatment periods while awaiting clinical evidence of resistance, which typically occurs within less than a year of treatment with anti-HER2 drugs. 26,27 In Colombia, although the Clinical Practice Guideline for early detection, comprehensive treatment, follow-up, and rehabilitation of breast cancer has considered the inclusion of target therapies within the management of HER2-positive breast cancer, 28 it does not consider liquid biopsy as a routine test to determine change of pharmacological therapy upon detection of resistance. Considering limited health resources, it is necessary to prioritize decisions for the inclusion of new technologies in health-care systems based on proven evidence; available resources; ethical aspects; and the local, regional, national, or international context.…”

Section: Introductionmentioning

confidence: 99%

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<p>Analysis of the Cost-Effectiveness of Liquid Biopsy to Determine Treatment Change in Patients with Her2-Positive Advanced Breast Cancer in Colombia</p>

Calderón

Pedraza

Urrego

et al. 2020

CEOR

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Background: Breast cancer is highly prevalent worldwide and leads to high health-care costs. HER2-positive subtype represents 30% of all breast cancers and is associated with a poor prognosis. Patients treated with anti-HER2 therapies frequently develop resistance and require pharmacological treatment change. Liquid biopsy is a minimally invasive and an easily accessible technique, with high sensitivity and specificity, to detect molecular treatment resistance even before the onset of clinical manifestations and can thus be used to reduce unnecessary anti-HER2 treatment costs. Objective: To evaluate the cost-effectiveness of using liquid biopsy (ctDNA detection) to determine treatment change in women with HER2-positive advanced breast cancer in Colombia. Methodology: We performed an economic evaluation using decision tree modeling and deterministic analyses based on literature search for first and second lines of treatment (trastuzumab, pertuzumab, docetaxel, and TDM1); resistance; outcomes; and sensitivity and specificity of tests detecting molecular resistance. The effectiveness was measured using quality-adjusted life year (QALY) score, and costs were obtained from databases with national validity, suppliers, the Colombian Drug Price Information System (SISMED), and local studies. Results: The use of liquid biopsy (ctDNA detection) with conventional treatment was more expensive and less effective than conventional treatment without liquid biopsy (US $177,985.35 and 0.533889206 QALY, respectively). The incremental cost with liquid biopsy was US $7,333.17 and the incremental effectiveness was 0.00042256 QALY relative to the conventional method. Conclusion: Including liquid biopsy in the treatment of HER2-positive advanced breast cancer was considered currently inapplicable in Colombia because it was not cost effective. Our results open a window of opportunity to improve the development and implementation of ctDNA testing in Colombia, potentially reducing current costs. More evidence is required on the utility of this test, depending on the financial capacity of Colombia and other countries.

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Assessment of the Molecular Mechanism of Action of SB3, a Trastuzumab Biosimilar

et al. 2019

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BackgroundSB3, a biosimilar of Herceptin® (trastuzumab, hereinafter referred to as reference product) is currently approved in the EU, Korea, Australia, the USA, and Brazil for the treatment of human epidermal growth factor receptor (HER) 2-positive early and metastatic breast cancer and HER2-positive metastatic gastric cancer. Previously, the biological similarity of SB3 to EU- or US-sourced reference product was assessed using various cell-based and binding assays.ObjectiveIn this paper, as a part of its similarity assessment, SB3 was evaluated for additional characteristics related to its molecular mechanism of action (MoA).MethodsFor extracellular effects of SB3, HER2-overexpressing cancer cell lines were used to assess expression of surface HER2, shedding of the extracellular domain of HER2, and antibody-dependent cell-mediated phagocytosis (ADCP) activity. For intracellular effects, Akt phosphorylation and vascular endothelial growth factor (VEGF) release were assessed. Additionally, in vitro docetaxel or pertuzumab combination experiments were performed for further characterization; anti-proliferation, HER2/HER3 dimerization inhibition, apoptosis, and antibody-dependent cell-mediated cytotoxicity (ADCC) assays were used.ResultsIt was confirmed that SB3 is highly similar to the reference products on quality attributes related to extracellular/intracellular efficacy. This similarity was also confirmed during combination studies with docetaxel and pertuzumab.ConclusionOverall, the equivalence of SB3 with reference product in MoA-related qualities in in vitro mono- and combination therapy experiments may support clinical bioequivalence of the two substances.

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Targeted Therapies in HER2-Overexpressing Metastatic Breast Cancer

Cited by 16 publications

References 49 publications

Exceptional Responses to Standard Therapy in a Patient with Metastatic HER2-Positive Breast Cancer

Exceptional Responses to Standard Therapy in a Patient with Metastatic HER2-Positive Breast Cancer

<p>Analysis of the Cost-Effectiveness of Liquid Biopsy to Determine Treatment Change in Patients with Her2-Positive Advanced Breast Cancer in Colombia</p>

Assessment of the Molecular Mechanism of Action of SB3, a Trastuzumab Biosimilar

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