Assessment of Human Epidermal Growth Factor Receptor 2 HER 2 Status for Management of Breast Cancer Patients

Abstract

Breast cancer has been a pioneer in translating molecular biology knowledge to clinical practice. This happened with the use of the flagship drug trastuzumab (anti HER2 therapy. These patients will receive treatment with trastuzumab. This is also combined with chemotherapy. PCR based methods on the other hand can detect HER2 positive tumors at DNA or RNA level. These tests are quantitative. They are independent from interobserver variation. As the primary objective of this study we performed testing of breast cancer samples on RTPCR. Going further we also analyzed few samples on Droplet Digital PCR (DDPCR) to see if a more sensitive PCR machine would yield better results in terms of clinical benefit to the patient. The secondary objective of this thesis was also to do deep sequencing in breast cancer cases. ER, PR and HER2 testing were available for 105 breast cancer patients. However, 115 patients got tested by 3 methods of IHC, FISH and RTPCR. FISH results were taken to be the response variable, (ROC). Curves were prepared and analyzed for RTPCR. The cases were labeled as HER2 negative, positive or equivocal RTPCR score of 1, 2 and 3 respectively. Relationships between RTPCR, FISH and IHC were established. 115 patients were included in the study. None of the patients who had IHC score of 0 or 1 was FISH positive for HER2 testing; also all the cases, which had IHC score of 3, were also FISH positive. 43 patients were designated an IHC score of 2. In total 72 patients gained from the initial IHC testing [clinical benefit 62.6%]. RTPCR results were not at par to IHC. Incorporating DDPCR in the current clinical diagnostic paradigm has the potential to improve its cost effectiveness and benefit. Molecular tests can be utilized in breast cancer especially in TNBC group. BRCA1 and BRCA2 NGS testing can be done in select group of TNBC and/or with family history. newline