Budget impact model for oncopharmacogenetics from the perspective of mandatory basic health insurance in Switzerland using the example of breast cancer

Abstract

Single-nucleotide polymorphisms (SNPs) can severely impact individual drug response and health outcomes in cancer patients. Genetic tests to screen for marker SNPs are available to adjust the drug dose of oncologicals to the patient’s needs. However, it is unclear whether the positive effects outbalance the increased costs or even lead to an overall cost reduction. This very pragmatic analysis used three frequently used oncologicals for the treatment of breast cancer to evaluate whether preemptive pharmacogenetic testing may have a cost-reducing impact on health care spending in the Swiss health care system. Our results indicate that oncopharmacogenetics might help to reduce health care costs (ie, by avoiding adverse drug effects) and to increase efficiency of drugs in oncologic patients.

Targeting Thymidylate Synthase Enhances the Chemosensitivity of Triple-Negative Breast Cancer Towards 5-FU-Based Combinatorial Therapy

“…Xenograft studies were conducted according to protocol #RD3585, under the approval of the University of Florida Institutional Animal Care and Use Committee in accordance with federal, state and local guidelines. 6-8 weeks old, female, nulliparous mice of the strain NOD/SCID (Nonobese Diabetic/ Severe Combined Immunodeficiency) gamma, the NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice, commonly known as NSG mice, underwent orthotopic, mammary fat pad injection of 4x10 6 MDA-MB-231 cells in PBS. Tumor growth was monitored by palpitation twice a week.…”

“…On the days of treatment with the combination of curcumin and 5-FU, the animals received, Lentivirus Production 5x10 6 HEK 293T cells plated in to 150 mm dishes were transfected with 10µg of TS shRNA plasmid, pLKO.1 vector or pSMPUW-GFP, 5µg psPAX (lentiviral packaging plasmid) and 5µg pMD2.G (VSV-G envelope expressing plasmid) with Fugene transfection Reagent (Qiagen), according to manufacturer's instructions. 48 h post-transfection, media containing the lentiviral particles were harvested and centrifuged at 3000 rpm at 4°C for 10 min.…”

“…The animals were separated into two groups. Group A and B underwent orthotopic, mammary fat pad injection of 4x10 6 MDA-MB-231 TS /MDA-MB-231 TScells in PBS, respectively. In both groups, tumor growth was monitored by palpitation twice a week.…”

“…5-Fluorouracil (5-FU) is the first rationally designed antimetabolite administered against a variety of solid tumors including BC, where the drug inhibits thymidylate synthase (TS), the key enzyme for de novo synthesis of 2'deoxythymidine-5'-monophosphate (dTMP) (4). Though 5-FU is not an exception to the severe side effects induced during the treatment (5), its peculiarity to target TS expression independent of BC receptor status and the cost-effectiveness compared to other chemotherapeutics (6,7), make it an absolute choice for chemotherapy for BC. However, the use of 5-FU in clinical settings is limited due to the emergence of acquired or inherent chemoresistance, an event that is mechanistically explained as a drug-induced up-regulation of its therapeutic target, TS (4).…”