Abstract PD5-06: Effects of perioperative lapatinib in early HER2+ breast cancer - The UK EPHOS-B trial (CRUK/08/002)

Author(s):  
N Bundred ◽  
D Cameron ◽  
E Kalaitzaki ◽  
R Morley ◽  
A Cramer ◽  
...  
2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6555-6555
Author(s):  
M. D. Walker ◽  
K. Lykopoulos ◽  
E. McLeod ◽  
S. Cottrell ◽  
L. Christova

6555 Background: Incidence of brain metastases (BM) are thought to be particularly high among patients with ErbB2+ (HER2+) breast cancer and have been associated with a poor survival prognosis. A previous study identified such patients as a considerable financial burden for health systems in Germany and France when compared to metastatic breast cancer (MBC) without BM. The objective of this study was to extend that analysis to estimate health care costs in Italy, Spain and the UK. Methods: Patient treatment histories, including drugs, specialist visits, procedures, inpatient stays etc, were collected retrospectively from a panel of oncologists for women with MBC across Italy, Spain and the UK, last seen by the responding oncologist during Q3-Q4 2006 or Q3-Q4 2007. To identify ErbB2+ patients they all had to have received/were receiving trastuzumab (TZ) for MBC. Patients were sampled so as to ensure the collection contained a minimum of 50 cases with BM and 200 histories overall (remainder controls). All costs within the observation period (initiation of TZ to date last seen) were calculated from a payer's perspective for patients who had developed BM and those who had not. Linear stepwise regression took into account potential confounding of time related covariates. Results: The study included 268 Italian (146 cases), 215 Spanish (126 cases) and 243 UK patients (103 cases). BM diagnosis was associated with significantly more expensive treatment histories than those patients without. Service costs such as radiotherapy and hospital visits were found to be key drivers for these differences (p<.001). Conclusions: The significantly greater cost associated with treatment of BMs in ErbB2+ MBC patients from Italy, Spain and the UK is consistent with results from identical French and German analyses. Therapies that reduce the incidence of BMs may therefore decrease the overall financial burden of ErbB2+ MBC. [Table: see text] [Table: see text]


Somatechnics ◽  
2013 ◽  
Vol 3 (1) ◽  
pp. 9-30
Author(s):  
Fiona K. O'Neill

In the UK, when one is suspected of having breast cancer there is usually a rapid transition from being diagnosed, to being told you require treatment, to this being effected. Hence, there is a sense of an abrupt transition from ‘normal’ embodiment through somatechnic engagement; from normality, to failure and otherness. The return journey to ‘embodied normality’, if indeed there can be one, is the focus of this paper; specifically the durée and trajectory of such normalisation. I offer a personal narrative from encountering these ‘normalising interventions’, supported by the narratives of other ‘breast cancer survivors’. Indeed, I havechosento become acquainted with my altered/novel embodiment, rather than the symmetrisation of prosthetication, to ‘wear my scars’,and thus subvert the trajectory of mastectomy. I broach and brook various encounters with failure by having, being and doing a body otherwise; exploring, mastering and re-capacitating my embodiment, finding the virtuosity of failure and subversion. To challenge the durée of ‘normalisation’ I have engaged in somatic movement practices which allow actual capacities of embodiment to be realised; thorough kinaesthetic praxis and expression. This paper asks is it soma, psyche or techné that has failed me, or have I failed them? What mimetic chimera ‘should’ I become? What choices do we have in the face of failure? What subversions can be allowed? How subtle must one be? What referent shall I choose? What might one assimilate? Will mimesis get me in the end? What capacities can one find? How shall I belong? Where / wear is my fidelity? The hope here is to address the intra-personal phenomenological character and the inter-corporeal socio-ethico-political aspects that this body of failure engenders, as one amongst many.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1132
Author(s):  
Javier A. Menendez ◽  
Adriana Papadimitropoulou ◽  
Travis Vander Steen ◽  
Elisabet Cuyàs ◽  
Bharvi P. Oza-Gajera ◽  
...  

The identification of clinically important molecular mechanisms driving endocrine resistance is a priority in estrogen receptor-positive (ER+) breast cancer. Although both genomic and non-genomic cross-talk between the ER and growth factor receptors such as human epidermal growth factor receptor 2 (HER2) has frequently been associated with both experimental and clinical endocrine therapy resistance, combined targeting of ER and HER2 has failed to improve overall survival in endocrine non-responsive disease. Herein, we questioned the role of fatty acid synthase (FASN), a lipogenic enzyme linked to HER2-driven breast cancer aggressiveness, in the development and maintenance of hormone-independent growth and resistance to anti-estrogens in ER/HER2-positive (ER+/HER2+) breast cancer. The stimulatory effects of estradiol on FASN gene promoter activity and protein expression were blunted by anti-estrogens in endocrine-responsive breast cancer cells. Conversely, an AKT/MAPK-related constitutive hyperactivation of FASN gene promoter activity was unaltered in response to estradiol in non-endocrine responsive ER+/HER2+ breast cancer cells, and could be further enhanced by tamoxifen. Pharmacological blockade with structurally and mechanistically unrelated FASN inhibitors fully impeded the strong stimulatory activity of tamoxifen on the soft-agar colony forming capacity—an in vitro metric of tumorigenicity—of ER+/HER2+ breast cancer cells. In vivo treatment with a FASN inhibitor completely prevented the agonistic tumor-promoting activity of tamoxifen and fully restored its estrogen antagonist properties against ER/HER2-positive xenograft tumors in mice. Functional cancer proteomic data from The Cancer Proteome Atlas (TCPA) revealed that the ER+/HER2+ subtype was the highest FASN protein expressor compared to basal-like, HER2-enriched, and ER+/HER2-negative breast cancer groups. FASN is a biological determinant of HER2-driven endocrine resistance in ER+ breast cancer. Next-generation, clinical-grade FASN inhibitors may be therapeutically relevant to countering resistance to tamoxifen in FASN-overexpressing ER+/HER2+ breast carcinomas.


Author(s):  
Slavomir Krajnak ◽  
Thomas Decker ◽  
Lukas Schollenberger ◽  
Christian Rosé ◽  
Christian Ruckes ◽  
...  

Abstract Purpose Metronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. Methods VinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2− MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. Results Between January 2017 and April 2019, nine patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1–55.0), p = 0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3–12.7). Grade 3–4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia. Conclusion VinoMetro (AGO-B-046) was closed early after nine patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2− MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population. Trial registration number and date of registration ClinicalTrials.gov Identifier: NCT03007992; December 15, 2016.


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