Controversies and Opportunities in the Clinical Daily Use of the 21-Gene Assay for Prognostication and Prediction of Chemotherapy Benefit in HR+/HER2- Early Breast Cancer

Abstract

Several multigene assays have been developed to help clinicians in defining adjuvant treatment for patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2 (HER2)–negative early breast cancer. Despite the 21-gene assay having been available for decades, it has only recently been included in the healthcare systems of several countries. Clinical optimisation of the test remains of critical interest to achieve a greater impact of genomic information in HR+/HER2- early breast cancer. Although current guidelines recommend the use of the 21-gene assay in early breast cancer at intermediate risk of relapse, the implication of the Recurrence Score (RS) in some grey areas still remains uncertain. Our aim is to critically discuss the role of RS in peculiar circumstances. In particular, we focus on the complex integration of genomic data with clinicopathological factors; the potential clinical impact of RS in node-positive premenopausal women and in the neoadjuvant setting; the significance of RS in special histologies and in male patients; and the management and time-optimisation of test ordering. In the absence of robust evidence in these areas, we provide perspectives for improving the use of the 21-gene assay in the decision-making process and guide adjuvant treatment decisions even in challenging cases.

Adjuvant chemotherapy and survival outcomes in older women with HR+/HER2− breast cancer: a propensity score-matched retrospective cohort study using the SEER database

“…In addition, Oncotype DX is considered the genomic assay of choice worldwide and its primary purpose is to assess the risk of early HR+/ HER2− BC local and distant recurrence so that patients could be exempted from receiving ACT. However, it has the disadvantages of high price and uncertainty 23. Using data from a large sample based on the SEER database, this study concluded that further age stratification was necessary for older women with HR+/HER2− BC over 65 years of age.…”

“…However, it has the disadvantages of high price and uncertainty. 23 Using data from a large sample based on the SEER database, this study concluded that further age stratification was necessary for older women with HR+/HER2− BC over 65 years of age. According to our age classification, ACT improved the prognosis of patients aged 65–79.…”

“…Recently updated American Society of Clinical Oncology (ASCO) practice guidelines recommend the use of multigene assays in HR+/HER2− early BC adjuvant decision-making, of which the 21-gene test (Oncotype DX) is the most widely used 22. Although Oncotype DX is considered the genomic test of choice worldwide, the high cost and the remaining areas of uncertainty make the widespread use of this tool challenging 23. This paper attempts to find a more straightforward way to measure the benefits of ACT in older patients with HR+/HER2− BC by determining whether this cohort should receive ACT by age alone.…”

“… 22 Although Oncotype DX is considered the genomic test of choice worldwide, the high cost and the remaining areas of uncertainty make the widespread use of this tool challenging. 23 This paper attempts to find a more straightforward way to measure the benefits of ACT in older patients with HR+/HER2− BC by determining whether this cohort should receive ACT by age alone.…”

Ovarian Suppression: Early Menopause and Late Effects

“…An important unanswered question is whether OFS can replace adjuvant chemotherapy in intermediate-risk, endocrine-responsive early breast cancer. The use of genomic assays, such as OncotypeDX and MammaPrint, has revolutionized adjuvant treatment decisions in BC, but their applicability in premenopausal patients, especially those under 40 years with node-positive disease, is still debated [ 59 , 60 ]. This is mainly because trials testing genomic assays have had a limited representation of women under the age of 40 years and premenopausal women included in these trials predominantly received tamoxifen alone as adjuvant endocrine therapy [ 61 ].…”