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Breast Surgery
Published in Tjun Tang, Elizabeth O'Riordan, Stewart Walsh, Cracking the Intercollegiate General Surgery FRCS Viva, 2020
Gaural Patel, Lucy Kate Satherley, Animesh JK Patel, Georgina SA Phillips
What other drugs are being developed to treat breast cancer?CDK4/6 inhibitors (e.g. palbociclib, ribociclib, abemaciclib) disrupt cancer cell growth by inhibiting CDK4 and CDK6, which are enzymes involved in cell division. Adverse effects include neutropenia, infections, fatigue and GI toxicity. They have been recommended by NICE in combination with an aromatase inhibitor for locally advanced or metastatic ER+, HER2 –ve cancers and are being evaluated in combination with fulvestrant for women who have had previous endocrine therapy.PARP inhibitors – targeted therapy for BRCA gene carriers (HER2 –ve)Bevacizumab (Avastin): This antiangiogenic monoclonal antibody inhibits vascular endothelial growth factor A (VEGF-A).It slows progression of metastatic disease but has no effect on overall survival or quality of life, and has significant side effects including hypertension.It is not recommended by NICE for metastatic breast cancer.It can be prescribed off licence via the Cancer Drugs Fund for triple-negative recurrent tumours and cancers which have progressed despite prior taxane treatment.Trastuzumab emtansine (Kadcyla): Recurrent HER2 +ve cancers, given with a taxane.NeuVax: This is a combination of a synthetic derivative of HER2 peptide and GMCSF which targets CD4 T cells to HER2-overexpressing cells.Phase 3 clinical trials are ongoing.Serum HER2 levels can be used to monitor response to treatment.43PI3K/Akt/mTOR pathway has been implicated in trastuzumab resistance in HER2+ breast cancer. There are a number of trials of mTOR and Akt inhibitors ongoing.Several other novel therapies targeting cellular signalling proteins including PD-L1, tyrosine kinase and TGFβ R1 are currently being evaluated in clinical trials.
Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence
Published in Expert Review of Vaccines, 2022
Maryam Abbaspour, Vajihe Akbari
NeuVax is a BC vaccine that contains peptides derived from extracellular domain of HER2/neu which is called Nelipepimut-S (E75). HER2-derived E75 peptide in combination with the GM-CSF can increase the antitumor activity of the vaccine. NeuVax exhibits a stimulatory effect on CTLs and CD8 memory cells against E75. More specifically, the activated CTLs are bound to HLA-A2/A3 molecule in the APCs, thus, they can recognize, neutralize and eliminate HER2, and prevent the spread of cancer [82,83]. NeuVax clinical trial data in phase II show the effectiveness of this vaccine in BC patients (HER2 1+/2+) with minimal toxicity [84].
Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives
Published in Expert Opinion on Investigational Drugs, 2018
Enrique Soto-Perez-De-Celis, Kah Poh Loh, Capucine Baldini, Nicolò Matteo Luca Battisti, Yanin Chavarri-Guerra, Nienke A. De Glas, Tina Hsu, Arti Hurria
NeuVax™ is the most studied vaccine against the HER2 protein. It is composed by the HER2-derived peptide E75 (nelipepimut-S) combined with the immune-adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) and induces CD8+ and CD4+ Th1 responses against HER2 [95]. One of the limitations of treatment development with E75 vaccines is its restriction to HLA-A2 and HLA–A3 subtypes [96]. In the adjuvant setting, a phase I/II study enrolled node-positive and high-risk node-negative patients with tumors expressing any degree of HER2. HLA-A2/3+ patients (n = 108) were vaccinated, while HLA-A2/3-negative patients (n = 79) were followed prospectively as controls. The median age of patients in the vaccination arm was 57 years (range 28–78). Five-year DFS was 89.7% in the vaccinated group versus 80.2% in controls (p = 0.08), giving a 48% reduction in the relative risk of recurrence [97]. The vaccine caused mainly local toxicities, most commonly injection site erythema and pruritus, all grade 1 (83.3%) and grade 2 (16.7%). Systemic toxicities, such as bone pain, influenza-like symptoms, and fatigue, were mild. Unfortunately, a RCT (PRESENT, NCT01479244) of NeuVax™ in early-stage BC was stopped early due to futility, although results have not been published. Two additional studies are ongoing in combination with trastuzumab: a phase IIb trial in node-positive (or HR negative, node negative) patients with HER2+ BC (NCT01570036); and a phase II trial in patients with high-risk node-positive or -negative HER2+ tumors (NCT02297698). Other vaccines currently under development are summarized in Figure 4. Age-specific analyses will be relevant to understand if anti-HER2 vaccines can generate an efficacious antibody response in the context of the aging immune system of older adults, who may have a decline in adaptive immunity and in vaccine longevity [98].