Written by Dr Jonathan Briody & Amina Babar
Dr Jonathan Briody is a health economist conducting an economic evaluation of intervention in, and prevention of, diabetes at RCSI University of Medicine and Health Sciences. He is supervising the MSc in Health Economics of co-author Amina Babar at the University of York.
Breast cancer accounts for 30% of all female cancer cases and is the most common cancer in women worldwide, constituting just under 10% of annual cancer diagnoses in Ireland. On average, 88.3% of women diagnosed with breast cancer are expected to survive for at least five years. Triple-negative breast cancer (TNBC) is a subtype characterized by a lack of expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2).
One in every eight breast cancer cases diagnosed in Ireland is triple negative. TNBC is more common in younger women, with the highest rates occurring in women under 40. TNBC can be more resistant to chemotherapy, often the primary treatment option for this breast cancer subtype. Cancer cells similarly do not respond to hormone therapies, such as tamoxifen and aromatase inhibitors. These factors make it more difficult to achieve a complete response to treatment and prolonged periods of remission when treating this disease.
This disease is also more likely to spread. Breast cancer is described as being locally advanced when it is limited to the breast and nearby lymph nodes. When the cancer extends to an area of the body other than the original site, it is said to have metastasized. The risk ratio for developing metastasis in triple-negative disease is particularly high in the first five years following diagnosis compared to other breast tumours. Within ten years of diagnosis, triple-negative breast cancer patients are significantly more likely (23%) than other breast cancer patients to develop a visceral metastasis as the primary site of distant recurrence.
Five-year survival rates are 11% in TNBC that has metastasized to the bones, lungs, or liver.
Targeted immunotherapies, targeting specific proteins or pathways in cancer cells, are critical in treating many breast cancers and have dramatically altered the survival landscape once the disease metastasizes. However, there are currently no targeted therapies that are expressly approved for the treatment of TNBC. Nevertheless, some targeted therapies used to treat other types of cancer, such as PARP inhibitors and immune checkpoint inhibitors, are being studied in clinical trials to treat TNBC.
Much of the promise in improving treatment outcomes for TNBC comes from such clinical trials. In the IMpassion130 study, atezolizumab with nab-paclitaxel was more effective than nab-paclitaxel alone in extending progression-free survival for patients with metastatic triple-negative breast cancer. The phase III KEYNOTE-355 trial found that in patients with locally recurrent inoperable or metastatic PD-L1-positive TNBC, the combination of pembrolizumab and chemotherapy significantly improved overall and progression-free survival. A phase III clinical trial (GeparQuinto) found that the combination of paclitaxel and carboplatin was more effective at improving PFS compared to docetaxel in patients with TNBC.
Establishing emerging therapy options is only one of many steps required for adoption in the clinic. The effectiveness and the efficiency of interventions in health are quickly becoming of equal importance in increasingly constrained healthcare systems. National policy requires a health economic analysis to assess the best use of limited resources and provides a definite structure in which investments in treatment strategies which maximize the overall health produced in the care system are prioritized. Subsequently, the highest degree of net health the system can provide can be realized.
Ireland’s Health Service Executive (HSE) provides guidance on the cost-effectiveness of treatment options for TNBC. According to HSE recommendations, treatments are most commonly considered cost-effective for treating TNBC in Ireland if an incremental cost-effectiveness ratio (ICER) of €45,000 per quality-adjusted life year (QALY) is met. That is, the cost difference between a suggested novel therapy and standard of care, divided by the difference in outcomes between these therapies, must be less than or equal to €45,000 per QALY gained. When the proposed intervention cost exceeds the cost-effectiveness threshold, the applicant company may enter into confidential negotiations with the HSE to reduce the initially proposed drug or technology price.
As the prevalence of TNBC increases with advances in screening and shifts in population dynamics, this suggests an increasing demand for novel therapies in a disease that is challenging to treat under standard of care. Such interventions are expected to present a higher cost burden. Where the benefits of novel strategies are not balanced with costs, the burden to the Irish healthcare system will be passed onto patients via financially diminished service provision and declines in access to other forms of care. Ongoing health economic analysis for the treatment of TNBC can help guide such treatment decisions to ensure that healthcare resources are utilized in such a way as to maximize the overall level of health produced by the health system, resulting in a net gain for all users.
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