Genomic signature drives breast cancer treatment decisions

Fabrice Andre's research group at the Gustave Roussy Oncology Department in France recently published the article "Genomics to select treatment for patients with metastatic breast cancer" in Nature, for 1462 patients with non-HER2 overexpressing metastatic breast cancer in the SAFIR02-BREAST trial, in which 238 patients with targeted genomic variants were randomized into two groups, compared the efficacy of chemotherapy maintenance therapy with genomic alteration-matched chemotherapy.

The introduction of next-generation sequencing technology revealed that the genomic drivers of cancer differ between patients, facilitating the development of precision medicine for cancer. A tumor genomic profile is generated independently for each patient in this framework, and targeted therapies are administered accordingly. However, it is unclear how and with what effect genomic analysis is used to make responsive treatment decisions. The SAFIR02-BREAST trial is a prospective randomized trial in patients with metastatic breast cancer that compares targeted therapies matched to genomic alterations to outcomes maintained with standard chemotherapy.

The European Society of Medical Oncology's Molecular Targeted Clinical Actionability Scale, which allows for grading of breast cancer, consists of six levels, ranked according to the level of evidence for matching genomic alterations as well as drugs. level I means that drugs matching genomic alterations have been shown to be effective, and level II means that drugs matching genomic alterations have been associated with preliminary evidence of efficacy. Beyond level II, the efficacy of the matched drug as well as the genomic alteration is at best hypothetical.

In the SAFIR02-BREAST trial, the authors evaluated the clinical utility of genomic identification of therapeutic targets and the utility of the approach in the interpretation of genomic reports. Between April 2014 and October 2019, 1462 patients with human non-HER2 metastatic breast cancer signed informed consent to undergo biopsy as well as genomic testing in SAFIR02-BREAST. Of the 1462 screened patients, 646 showed targeted genomic alterations. Of these, 238 patients were subsequently randomized into a maintenance chemotherapy group totaling 81 and a targeted therapy group totaling 157.

From the results, the authors found many benefits of targeted drug therapy in patients with BRCA1/2 mutations in this trial. The analysis of targeted therapy on genomics had an impact on the progression-free survival time for patients in level I as well as level II. The median progression-free survival time was 2.9 months in the chemotherapy maintenance group compared with 5.5 months in the targeted therapy group. In addition, the authors analyzed patients on multiple variables including age, grade, number, location of metastases, and TP53 mutations, and found that patients with targeted therapy for metastatic breast cancer had a lower overall risk of disease progression. However, the authors were unable to detect evidence that scale III/IV genomic alterations were associated with sensitivity to matching therapy.

Overall, the authors' work found that new sequencing technologies provide tangible clinical benefits for targeted cancer therapy. In the current study, the authors found that DNA genomic sequencing results were beneficial for the treatment of grade I and II patients by analyzing an evaluation scale for metastatic breast cancer and grouping maintenance versus targeted therapy.

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