Patient: 48 years – Female diagnosed with left breast cancer
Clinical Testing:
- Alterations: G12V, E298*, G386S
- Gene: KRAS, TP53, SMAD4
Treatment Options: The presence of HER2 amplification suggests that HER2 inhibitors such as trastuzumab, neratinib and lapatinib can be recommended for this patient
Indication: The patient was diagnosed with ER/PR positive and HER2 negative (by IHC) breast cancer metastasized to the bone
Research Findings: A Literature suggests that upto 25 of the HER2 negative breast cancer patients switch to HER2 positive at metastatic recurrence around 30 of these patients have bone metastases and 50 of these bone biopsy specimens have insufficient tissue for testing in case of ESR1 gene, overall conformational changes indicate that in ESR1 MUT, there is a decreased inhibitor binding, increased coactivator recruitment, and increased proteolytic stability that promotes resistance to aromatase inhibitors (AI), tamoxifen, and fulvestrant (Merenbakh Lamin, Keren et al 2013; Brett, Jamie O et al 2021)
Notes: The tumor has an ESR1 resistance mutation (D538G) suggesting that the cancer is resistant to aromatase inhibitors, tamoxifen, and fulvestrant. HER2 switch was identified from liquid biopsy which indicates recommending HER2 inhibitors. The tumor also shows loss of function in the TP53 gene, which is associated with a worse prognosis and relatively more resistant to chemotherapy and radiation.