Gene Expression Profiling Tests to Guide Adjuvant Chemotherapy Decisions in Lymph Node?Positive Early Breast Cancer: A Systematic Review
Author(s)
Gamze Nalbant, PhD1, Katy Cooper, PhD1, Munira Essat, PhD1, Sue Harnan, MSc1, Ruth Wong, BSc, MSc, PhD1, Jean Hamilton, PhD1, Uzma Asghar, PhD2, Battisti Nicolo, MD(Res)3, Lynda Wyld, PhD1, Paul Tappenden, BA, MSc, PhD1.
1School of Medicine and Population Health, The University of Sheffield, Sheffield, United Kingdom, 2Breast Unit, Department of Medicine, Oak Cancer Centre, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, 3Breast Unit, Department of Medicine, The Royal Marsden NHS Foundation Trust, London, United Kingdom.
1School of Medicine and Population Health, The University of Sheffield, Sheffield, United Kingdom, 2Breast Unit, Department of Medicine, Oak Cancer Centre, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, 3Breast Unit, Department of Medicine, The Royal Marsden NHS Foundation Trust, London, United Kingdom.
OBJECTIVES: Breast cancer is the most common cancer among women in England. Adjuvant chemotherapy for breast cancer affects quality of life and survival. This systematic review assessed the effectiveness of four tumour profiling tests (Oncotype DX, Prosigna, EndoPredict, and MammaPrint) to guide chemotherapy decisions in people with hormone receptor-positive (HR+), early-stage breast cancer with 1-3 positive lymph nodes (LN+).
METHODS: Three databases were searched in April 2023. Randomised controlled trials (RCTs) and studies on prognostic and predictive ability, decision impact, quality of life, and anxiety conducted in the UK and Europe were included. Studies were assessed using quality assessment tools relevant to study design and were synthesised narratively.
RESULTS: Fifty-five studies were included. All four tests were prognostic for distant recurrence in LN+ patients. The RxPONDER trial found no chemotherapy benefit in post-menopausal patients with an Oncotype DX recurrence score (RS) of 0-25 but found a significant benefit in pre-menopausal patients with RS of 0-25 (5-year distant recurrence-free interval: hazard ratio (HR) (chemotherapy vs no chemotherapy) =0.64, p=0.026). The SWOG-8814 study of Oncotype DX suggested a potential predictive effect for chemotherapy benefit in post-menopausal patients (interaction between RS and effect of chemotherapy: p=0.053). Chemotherapy benefit prediction by MammaPrint in LN+ patients was inconclusive as all patients in the clinical high-risk, MammaPrint high-risk group were offered chemotherapy. Decision impact studies in LN+ populations were only available for Oncotype DX and reported a reduction of 12-75% in chemotherapy recommendations following testing. No studies were found for Prosigna or EndoPredict assessing prediction of chemotherapy benefit or for any test assessing anxiety or quality of life.
CONCLUSIONS: Testing in LN+ populations may help more low-risk patients avoid chemotherapy and its side effects. However, unless chemotherapy offers zero benefit to low-risk patients, some people who avoid chemotherapy following testing may subsequently develop cancer recurrence.
METHODS: Three databases were searched in April 2023. Randomised controlled trials (RCTs) and studies on prognostic and predictive ability, decision impact, quality of life, and anxiety conducted in the UK and Europe were included. Studies were assessed using quality assessment tools relevant to study design and were synthesised narratively.
RESULTS: Fifty-five studies were included. All four tests were prognostic for distant recurrence in LN+ patients. The RxPONDER trial found no chemotherapy benefit in post-menopausal patients with an Oncotype DX recurrence score (RS) of 0-25 but found a significant benefit in pre-menopausal patients with RS of 0-25 (5-year distant recurrence-free interval: hazard ratio (HR) (chemotherapy vs no chemotherapy) =0.64, p=0.026). The SWOG-8814 study of Oncotype DX suggested a potential predictive effect for chemotherapy benefit in post-menopausal patients (interaction between RS and effect of chemotherapy: p=0.053). Chemotherapy benefit prediction by MammaPrint in LN+ patients was inconclusive as all patients in the clinical high-risk, MammaPrint high-risk group were offered chemotherapy. Decision impact studies in LN+ populations were only available for Oncotype DX and reported a reduction of 12-75% in chemotherapy recommendations following testing. No studies were found for Prosigna or EndoPredict assessing prediction of chemotherapy benefit or for any test assessing anxiety or quality of life.
CONCLUSIONS: Testing in LN+ populations may help more low-risk patients avoid chemotherapy and its side effects. However, unless chemotherapy offers zero benefit to low-risk patients, some people who avoid chemotherapy following testing may subsequently develop cancer recurrence.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO126
Topic
Clinical Outcomes, Medical Technologies
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology