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The effect of targeted DNA sequencing on cancer treatment options in metastatic breast cancer

The effect of targeted DNA sequencing on cancer treatment options in metastatic breast cancer

Evaluation of multiple somatic mutations in metastatic breast cancer

Among patients diagnosed with breast cancer, about 30% will eventually develop into metastatic breast cancer (MMC). It is estimated that approximately 150,000 stage IV breast cancer patients in the United States undergo relative research. Evaluation of multiple somatic mutations in MMK; determine the mechanism of resistance, prognostic genomic markers, or molecular targets to be developed. Personalized cancer medicine adapted to medical decision making by combining clinical features and demographic factors with genetic information is promising, but its value is in ambiguous forms such as breast cancer, which includes some truly predictable. Genomic changes. They noted that most researchers' understanding of somatic genome changes in breast cancer came from primary breast cancer research, but that their understanding of MMK genome data was not complete.
In the largest MMK clinical genome analysis to date, a prospective DNA panel sequencing of tumors was performed, with frequently altered gene mutations, triple-negative breast cancer (TNBC), human epidermal growth factor receptor 2 TP53, and hormone receptor (HR) positive. It has been noted to be similar to mutations in primary cancers such as PIK3CA and CDH1 in (HER2) negative patients.

Treatment recommendations based on genomic changes and available clinical literature

Studies have shown that the total number of changes in MMC tumors in HR-positive / HER2-negative patients is only moderately higher than that of the primary tumor. A recent assessment of breast cancer genomic targets revealed 9 changes with evidence of level I / II mobility. These changes include ERBB2 amplification (grade IA), germline pathogenic BRCA1 or BRCA2 mutations (IA), missense mutations (IA) activating PIK3CA hotspots, microsatellite instability (IC), NTRK fusion (IC), false activating ESR1 hotspot The mutation (IIA), PTEN (IIA) activating the ERBB2 hotspot, AKT1 mutation (IIB), and a missense mutation (IIB) disappear. Clinical tumor genome analysis often relies on targeted next-generation sequencing (NGS) of a set of specific, often activated cancer-related genes to analyze somatic genetic changes in biopsy samples. Clinical tumor genome analysis often relies on targeted next-generation sequencing (NGS) of a set of specific, often activated cancer-related genes to analyze somatic genetic changes in biopsy samples. This research provides treatment recommendations based on the most commercially targeted panel sequencings methods, such as genome modification and existing clinical literature (including FoundationOne CDx). The researchers noted that this prospective, single-center, single-arm study recruited MMC patients within 10 weeks of starting their new treatment. At the time of enrollment, FoundationOne CDx was used to deep sort tumor samples (> 500 ×) of any of the 315 cancer-associated genes, and the sequencing results were left to the provider at the time of disease progression, and the questionnaire evaluated the doctor's treatment recommendations. The researchers evaluated three predetermined questions to evaluate patients' genomic test perceptions. A total of 100 patients were tested for genomics and the average number of mutations in each patient was 5 (ranging from 0 to 13 mutations). Genomic testing showed that 98% of patients had one or more potential therapies and 60% of patients received one or more recommended treatments with evidence of level I / II activity. In the published 94 genome text reports, it is stated that 87 patients have doctor survey data and 31.0% of patients have the treatment changes recommended by the doctor. Additionally, 37.0% of the patients underwent genomic testing. The researchers said there was no statistically significant difference between patients with varying treatment and duration of treatment or overall survival compared to patients who underwent genomic testing.

Confidence in treatment success decreased significantly in patients who completed the questionnaire before and after genome testing, especially in patients who did not receive treatment changes supported by genome testing. As a result, research results show that NGS with tools such as FoundationOne CDx can provide valuable information to doctors and patients when determining the best treatment plan for MMC patients with disease progression. Additionally, the researchers pointed out that there are obvious clinical difficulties in integrating NGS into the MMC framework of care, including barriers to preferred treatment options and the complex interplay between genomic testing and patient cognition, which requires further investigation.

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