Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative

Abstract

Background: Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question "Should multigene tests be used in women who have early invasive breast cancer, hormone receptor-positive, HER2-negative, to guide the use of adjuvant chemotherapy?"

Methods: The European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group (GDG), a multidisciplinary guideline panel including experts and three patients, developed recommendations informed by systematic reviews of the evidence. Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision frameworks were used. Four multigene tests were evaluated: the 21-gene recurrence score (21-RS), the 70-gene signature (70-GS), the PAM50 risk of recurrence score (PAM50-RORS), and the 12-gene molecular score (12-MS).

Results: Five studies (2 marker-based design RCTs, two treatment interaction design RCTs and 1 pooled individual data analysis from observational studies) were included; no eligible studies on PAM50-RORS or 12-MS were identified and the GDG did not formulate recommendations for these tests.

Conclusions: The ECIBC GDG suggests the use of the 21-RS for lymph node-negative women (conditional recommendation, very low certainty of evidence), recognising that benefits are probably larger in women at high risk of recurrence based on clinical characteristics. The ECIBC GDG suggests the use of the 70-GS for women at high clinical risk (conditional recommendation, low certainty of evidence), and recommends not using 70-GS in women at low clinical risk (strong recommendation, low certainty of evidence).

Fig. 1. Flow charts reporting the possible uses of 21-gene recurrence score and for the 70-gene signature test to guide the use of adjuvant chemotherapy in patients with early invasive breast cancer, hormone receptor-positive, HER-2 negative.

Two strategies are proposed for 21-gene recurrence score, the first in which all women are tested for genomic risk assessment and treated accordingly, the second in which only women with high clinical risk are tested for genomic assessment, while those at low clinical risk are referred to endocrine therapy alone without genomic risk assessment. According to sub-group considerations reported by the GDG, the latter strategy is probably more cost effective and women might experience larger net desirable consequences. For the 70-gene signature only a two-step strategy is proposed where only women at high clinical risk are tested for genomic risk; testing women at low clinical risk is not recommended.