Multigene signatures for early breast cancer in clinical practice: A report of the Lombardy genomic assays for breast cancer working group

Abstract

The increasing understanding of breast cancer biology has provided the basis for the development of multigene signatures aimed to improve the capability of clinicians to assess patients’ prognostication and risk stratification. Incorporating these tools in clinical practice has profoundly impacted on the decision-making process for the adjuvant therapy of patients with ER+/HER2- early breast cancer and the results from prospective adjuvant trials have strengthened the clinical utility of multigene signatures in this setting. In July 2019, Lombardy was the first Region in Italy to reimburse genomic testing for patients with ER+/HER2- early breast cancer. Three years later, a group of investigators from six referral Cancer Centers in Lombardy convened to debate the use of multigene signatures in clinical practice and share their own experience with the tests after reimbursement. Here, we reviewed relevant data on the role of multigene signatures in tailoring adjuvant chemotherapy for patients with ER+/HER2- early breast cancer and discussed about the optimal use of these assays in current clinical practice. As the treatment landscape of early breast cancer evolves and novel questions about the possible additional applications of multigene assays arise, we also provide our viewpoint on the potential implementation of the assays in the evolving scenario ER+/HER2- early breast cancer treatment.

Real-world use of multigene signatures in early breast cancer: differences to clinical trials

“…These findings likely reflect that clinicians perceive the predictive information for chemotherapy benefit provided by Oncotype DX as one of the most relevant aspects driving their choice of assay. They also indicate that prescribing oncologists generally adhere to Guidelines recommendations [ 26 ]. Indeed, Oncotype DX is the only test recommended by current Guidelines with a level of evidence and a grade of recommendation of I, A for both node-negative and node-positive postmenopausal patients and for node-negative premenopausal patients [ 18 ].…”

“…These data indicate that, although Guidelines do not recommend the use of Oncotype DX or other genomic assays to tailor adjuvant therapy decisions in node-positive premenopausal patients (or patients ≤ 50 years), the oncologists prescribing Oncotype DX considered the test informative also in this population [ 26 ]. The role of age and menopausal status has been quite neglected in the development of Oncotype DX and other MGAs.…”

Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy

“…Estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2−) breast cancers are biologically and clinically heterogeneous [1]. Molecular tools that partially capture this heterogeneity are currently utilized in clinical practice to tailor adjuvant treatment [2,3]. Genomic signatures offer valuable prognostic information and help in estimating adjuvant chemotherapy benefits [4].…”