Title: Pembrolizumab with chemotherapy for neoadjuvant and adjuvant treatment of untreated locally advanced non-metastatic triple negative breast cancer [ID1500]
Funder: Department of Health and Social Care

Abstract: Breast cancer arises from the tissues of the ducts or lobules of the breast. It is described as invasive when the cancer cells have grown through the lining of the ducts into the surrounding tissue. Breast cancer is described as ‘locally advanced’ if the cancer has spread from the breast to lymph nodes close to the breast, to the skin of the breast, or to the chest wall but has not spread to other parts of the body (clinical stage 3). [1]_x000D_ _x000D_ Over 46,100 people were diagnosed with breast cancer in England in 2017 [2] and there were approximately 9,600 deaths from breast cancer in England in 2018. [3] Around 15% of breast cancers are triple-negative breast cancers whereby the cancer cells test negative for oestrogen receptors and progesterone receptors (hormone-receptor-negative cancer) and human epidermal growth factor receptor 2 (HER2-negative cancer). [4] Triple-negative breast cancer is associated with poor prognosis with high risk of relapse and short progression-free survival and overall survival. As many as 50% of patients diagnosed with stage 1 to 3 triple-negative breast cancer experience disease recurrence, and 37% die in the first 5 years after surgery. [5] Depending on the stage of its diagnosis, triple-negative breast cancer can be particularly aggressive, is more likely to recur than other subtypes of breast cancer and is associated with poorer survival. It is diagnosed more frequently in younger people, black people, and in people with BRCA1 mutations (a gene on chromosome 17 that normally helps to supress cell growth, which is an inherited gene mutation that may increase the risk of breast cancer). [6]_x000D_ _x000D_ NICE guideline 101 (NG101) recommends neoadjuvant chemotherapy for people with oestrogen receptor negative invasive breast cancer as an option to reduce tumour size before surgery. It further recommends consideration of adding a platinum to an anthracycline containing neoadjuvant chemotherapy regimen for triple-negative invasive breast cancer. For adjuvant treatment after surgery, NG101 recommends offering a regimen that contains both a taxane and an anthracycline. Standard chemotherapy options used for neoadjuvant and adjuvant treatment of triple negative breast cancer include doxorubicin, epirubicin, docetaxel, paclitaxel and carboplatin._x000D_ _x000D_ References_x000D_ 1 Cancer Research UK (2020) Number stages of breast cancer. Accessed July 2021._x000D_ 2 Office for National Statistics (2019) Cancer registration statistics, England, 2017. Accessed July 2021._x000D_ 3 Cancer research UK (2018) Breast cancer mortality statistics. Accessed July 2021._x000D_ 4 The Institute of Cancer Research (2016) Promising drug target for aggressive ‘triple negative’ breast cancers identified. Accessed July 2021._x000D_ 5 Costa RLB and Gradishar WJ. Triple-negative breast cancer: current practice and future directions. Journal of Oncology Practice 13, no. 5 (May 1 2017) 301-303._x000D_ 6 Couch FJ, Hart SN, Sharma P et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. Journal of Clinical Oncology_x000D_ 2015;33(4):304-311

Lay abstract: To appraise the clinical and cost effectiveness of pembrolizumab within its marketing authorisation for the neoadjuvant and adjuvant treatment of locally advanced non-metastatic triple-negative breast cancer.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS