Over the past decade, researchers have discovered the fact that breast cancer is a disease with a variety of gene mutations that can complicate effective treatment programs. Breast cancer mutations may be germline and/or somatic forms, and understanding what type of mutation is present has a significant impact on molecular targets and appropriate treatment regimens.
Breast cancer mutations can be detected by a variety of methods, using fresh, frozen or FFPE tumor specimens. Formalin-fixed paraffin-embedded (FFPE) samples are commonly sourced to analyze breast cancer mutations. Here are a few published studies reviewing methods used to detect breast cancer mutations using FFPE samples:
BRCA1 and BRCA2 gene mutations in breast cancer
Mutations in these two genes enhance the risk of developing ovarian or breast cancer, as part of what's known as the hereditary breast-ovarian cancer syndrome. It's also been found that the BRCA1/2 genes may be implicated in the development of non-hereditary tumors because a percentage of breast cancers contain somatic BRCA1 and BRCA2 variants. In this study, researchers used FFPE specimen tissue to explore the viability of a multiplex PCR-based NGS method for detecting BRCA1 and BRCA2 mutations in fixed tumor specimens. Results indicate that this technique did detect BRCA1/2 variants in FFPE tissues, and could help determine optimal treatment regimens for breast cancer patients with this particular mutation pattern.
Triple negative breast cancer EGFR mutations
Triple negative breast cancer has one of the worst prognoses because of its lack of response to typical breast cancer treatment agents, specifically endocrine and anti-HER2 drugs. This is because triple-negative breast cancer lacks the three main hormone receptors typically targeted for cancer therapy, i.e. estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor (HER2). These tumors show a distinctive metastatic pattern, shorter recurrence time and earlier mortality. In this study, researchers focused on documenting the presence and estimating the prevalence of EGFR mutations in triple negative tumors. Researchers used a random sample of FFPE specimens from a large group of triple negative tumor samples and extracted DNA from the paraffin blocks to perform PCR and amplify the exon regions 18 to 21 of the EGFR gene. Researchers found exon 19 deletions, inversions, and exon 21 substitutions in 11 percent of specimens, which may point to new targeted treatment therapies.
PIK3CA mutations in breast cancer
Somatic mutations in the PIK3CA gene are common in breast cancer, leading researchers to study what implications such mutations have for those patients. In this study, archival FFPE samples of primary breast tumors were genotyped for PIK3CA mutations and the association between mutation site and clinicopathologic characteristics explored. Study authors found this mutation in 32% of breast cancers and an association between the mutation and older age at diagnosis, lower tumor grade and stage, and HER2 negativity. Patients with PIK3CA mutated tumors show improved survival rates.
In about 20 to 30 percent of breast cancers, there is an amplification of the HER2 receptor, due to a mutation in the ERBB2 gene. Breast cancer patients who are HER2 positive tend to have a more aggressive form of cancer, and historically, HER2 amplification has been positively linked to increased disease recurrence and a poor prognosis. The overexpression of HER2 (or ERBB2, as it is also commonly known) is a good predictor for HER2 positive breast cancer therapy. Fluorescence in situ hybridization (FISH) is a common method for detecting such mutations in tumor FFPE samples. This technique is also useful for stratifying patients for treatment with HER2-targeted therapies.
Researchers learn more each day about the genetic variations in breast cancer, and FFPE tissues procured from a reliable partner help advance drug discovery efforts.
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