Treatment of primary invasive lobular breast cancer (ILBC) can be individualized, with HER2, HER3, and AKT1 mutations representing high-prevalence therapeutic targets. This according to a study of 630 ILBC primary tumors. Researchers found:

• Besides the high mutation frequency of CDH1 in 65% of tumors, alterations in 1 of the 3 key genes of the phosphatidylinositol 3-kinase pathway, PIK3CA, PTEN, and AKT1, were present in > 50% of cases.

• HER2 and HER3 were mutated in 5.1% and 3.6% of tumors, with most mutations having a proven role in activating the human epidermal growth factor receptor/ERBB pathway.

• Mutations in FOXA1 and ESR1 copy number gains were seen in 9% and 25% of tumors.

• These alterations were more frequent in ILBC than IDBC.

• ILBC’s histologic diversity was associated with specific alterations, such as enrichment for HER2 mutations in the mixed, nonclassic, and ESR1 gains in the solid subtype.

• Chromosome 1q and 11p gains showed independent prognostic value in ILBC.

• HER2 and AKT1 mutations were associated with increased relapse risk.

Citation: Desmedt C, Zoppoli G, Gundem G, et al. Genomic characterization of primary invasive lobular breast cancer. [Published online ahead of print February 29, 2016]. Clin Oncol. doi:10.1200/JCO.2015.64.0334.