Molecular profiling of advanced breast cancer tumors is beneficial in assisting clinical treatment plans

This was a retrospective review of a cohort of patients that were profiled using established IHC biomarkers, along with fragment analysis, in situ hybridization and sequencing.

Their treatments were either matched or unmatched based on whether the treatment chosen by their physician was predicted to be beneficial by Caris Life Sciences using the molecular profile of the tumor.

Comparing these two groups showed that the matched treatment group had an increase of 31% in survival compared to the average for the unmatched group, an increase of 157 days from 510 to 667 days.

When comparing the matched and unmatched groups, in terms of HER2 and ER directed therapies, there was a similar level of use in the matched group 87% of treatments were of either of these types, and in the unmatched group 83% of the treatments were one of these two types.

Figure 1: Treatments ordered by survival time for matched and unmatched patients. On the left (darker gray background) - treatment regimens followed by 43 matched patients, in ascending post-profiling survival time; on the right (lighter gray background) - 49 unmatched patients ordered by post-profiling survival time. Each column represents one patient. The y-axis is time (days) where zero is the time of profiling. Dark gray within a column shows the total time monitored from diagnosis to either death or last follow-up; a black line at the top of a column indicates death; green bars represents time on a drug of benefit; red is a lack of benefit drug; yellow is time on a combination therapy associated with both benefit and lack of benefit. Blue bars represent time on a neutral therapy associated with neither benefit nor lack of benefit.

The unmatched group received 0.32 more lines of therapy on average than the matched group, survived for less time, and had a higher mortality rate.

"The biomarker and drug associations were based on tests including fluorescent in situ hybridization and DNA sequencing, although immunohistochemistry was the main test used."

Breast cancer is the most prevalent form of cancer in women, causing approximately one in four of all cases worldwide. The genetics of sporadic breast cancer is now better understood, due to genomic sequencing of many such tumors.

Somatic driver variants and the mutational processes underlying them have now been identified, and the sequencing of 560 breast cancer genomes has furthered progression towards a complete description of the molecular events that cause these tumors.

Gene chip technologies that use gene expression profiling of the primary tumor such as Oncotype DX, have been FDA approved as a decision aid in early breast cancer to help define prognostic features.

It has been shown that tumor profiling of non-responsive breast cancer resulted in better clinical treatments, while other studies have demonstrated the benefit of profiling in other tumor types.

Patients whose drugs matched those recommended according to their tumor profile had an average overall survival of 667 days, compared to 510 days for patients that did not.

Full text - https://doi.org/10.18632/oncotarget.24564

Correspondence to - Philip Carter - phil.carter@imperial.ac.uk

Keywords - tumor profiling, breast cancer, cancer treatment