Molecular profiling in breast cancer—ready for clinical routine?

Abstract

The herald of genomic testing opened novel diagnostic and therapeutic possibilities for many tumor entities. For breast cancer, molecular profiling has become an integral part of disease management on multiple levels. Genetic testing allows for the identification of hereditary cancer syndromes in patients with a family history of malignancies and contributes to the successful prevention of breast cancer. In early breast cancer, several prospective randomized trials demonstrated the prognostic significance of commercially available mRNA-based gene expression analyses, which now have become part of standard of care in the adjuvant setting. In advanced breast cancer, testing for targetable mutations ensures personalized cancer treatment. Poly-ADPribose polymerase (PARP) inhibitors provide the first targeted alternative for patients with BRCA 1/2-associated breast cancer. In advanced breast cancer of luminal type, the detection of Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) mutations provides a novel treatment option with alpelisib, a PIK3CA inhibitor. Further targetable mutations include NTRK3 in rare cases of secretory breast carcinoma and human epidermal growth factor receptor 2 (HER2). Recent data support the importance of the analysis of circulating tumor cells and cell-free DNA. These "liquid biopsies" open novel possibilities of molecular profiling. However, clinical benefit of such analyses remains to be confirmed.

Incorporating Genomic and Genetic Testing into the Treatment of Metastatic Luminal Breast Cancer

“…Therefore, testing should be performed on EDTA blood or salvia. Testing of tumor tissue samples for BRCA 1/2 mutations is still challenging, as a germline mutation cannot be confirmed from these samples and certain types of large genomic rearrangements might be missed [7]. In terms of germline testing, pretest genetic counseling is preferable; however, according to the German genetic diagnostics law, it is sufficient to impart information on germline testing by the treating physician if the referral concerns a therapeutic indication.…”

“…Compared to this, the application of selective, isoform-specific inhibitors such as alpelisib has mainly overcome these limitations [7]. Results from the phase 3 SO-LAR I trial indicate that male and postmenopausal female luminal breast cancer patients carrying PIK3CA mutations benefit from treatment with alpelisib in combination with fulvestrant [18].…”

“…Emphasizing the high frequency of PIK3CA mutations and the biological relevance of the signaling pathway, PIK3CA mutations seem to be promising with regard to targeted therapies [7]. However, several clinical studies investigating the effectiveness of broad-spectrum pan-PIK3CA inhibitors like buparlisib have frequently reported adverse events (AE).…”

“…However, several clinical studies investigating the effectiveness of broad-spectrum pan-PIK3CA inhibitors like buparlisib have frequently reported adverse events (AE). Particularly AE like diarrhea, transaminitis, hyperglycemia, mood disorders, and rash limited the treatment response regarding discontinuation of use [7].…”

Molecular profiling—ready for clinical routine

“…In this special issue of the Magazine of European Medical Oncology (MEMO) multidisciplinary experts summarize and discuss recent developments and future perspectives of comprehensive molecular profiling spanning from specific cancer entities to agnostic approaches [1][2][3].…”