Written by Isobel Young.
Breast cancer is one of the most common forms of cancer, with 1 in 7 UK women being diagnosed with the disease in their lifetime. This form of cancer is widely known to be caused by a mutation in the BRCA gene, which provides a target for breast cancer treatment.
A new study by a team of researchers from Gustave Roussy, France, indicates that using targeted drugs in metastatic breast cancer (mBC) patients, matched with their unique genomic profile, could provide a higher chance of survival compared to traditional means of treatment.
Metastasis and chemotherapy resistance
Nearly 30% of women diagnosed with early-stage breast cancer will develop mBC, which results in a poorer clinical outcome. According to the European Society of Medical Oncology (ESMO), the recommended method of treatment for mBC is chemotherapy. However, this doesn’t work for everyone, as some tumour cells can be resistant to it. This highlights a need to find alternative treatment options that could improve the clinical outcome of those with chemo-resistant mBC.
Targeted therapy for mBC
The aim of the current study was to determine if targeted therapies, based on genomic alterations within the DNA of mBC patients, could improve clinical outcomes. The team gathered a large cohort of participants, all with metastatic HER2-negative breast cancer, and all having no more than one round of chemotherapy before participating in the study. Biopsies or blood samples were taken, and genetic testing was conducted.
Next generation sequencing and comparative genomic hybridization were used to identify patients with targetable molecular alterations within their DNA. Those identified to have these alterations were then randomized and either given maintenance chemotherapy or targeted therapy matched to their specific genomics profile – for example, olaparib, capivasertib or vistusertib. Participants without targetable genomic alterations were again randomized and given standard non-targeted treatment of either durvalumab or maintenance chemotherapy.
Targeted or non-targeted?
The team found that patients with genomic alterations classified as ESCAT I/II (based on the ESMO scale for clinical actionability of molecular targets) benefited from significantly improved progression-free survival scores compared to those on chemotherapy. However, it was found that the same could not be said for those with genomic alterations classified beyond level II. This suggests that the future of precision medicine for breast cancer treatment should include the integration of patient data from multiple sources for the prediction of drug sensitivity.
The study also presented new support for olaparib as a maintenance treatment, which is typically used as a form of maintenance treatment in individuals with BRCA mutation-related cancers. Previous studies have suggested the use of olaparib as a frontline treatment of breast cancer. However, the present study shows that the drug has a higher efficacy in the maintenance of cancer in individuals with gBRCA1 and gBRCA2 mutations, compared to its use as a frontline treatment.
Despite these findings, the author notes how the field of targeted therapy for cancer is in its infancy: “Our study suggests that, besides the companion diagnostics validated in therapeutic trials, we do not yet have the biological knowledge to identify a target in each individual.” Hopefully, with the advancement of biological knowledge, targeted therapy for cancer patients could be used in the future as a better treatment option.
Limitations and future directions
It is also worth noting several limitations with this study. For example, the trial was not a true test of precision medicine because the control arm of the study included chemotherapy. To get a true indication of the efficiency of targeted therapy as a treatment for cancer, the control group would need to be treated with alternative drugs to chemotherapy.
Additionally, the study group may be biased. The participants involved in this study were all sensitive to chemotherapy, which suggests that these results may not be applicable to individuals who do not have chemotherapy resistance.
While the results may not be applicable to all breast cancer patients, it does provide hope for alternative treatments for patients whose cancer isn’t responding to chemotherapy. Future studies are necessary to understand the true nature of the relationship between targeted therapy and metastatic breast cancer survival.
