Conference
Genomic Alterations in Breast Cancer: Insights from the 100,000 Genomes Project at a Tertiary Breast Cancer Centre
Abstract
The 100,000 Genomes Project (100KGP), a landmark British initiative exploring the genetic foundations of health and disease, including breast cancer, concluded in December 2018, with data analysis ongoing. This study aims to examine data from the 100KGP at our tertiary breast cancer centre, focusing on the relationship between somatic mutations and patient outcomes.
Methods:
We performed a detailed analysis of 100KGP reports, identifying somatic mutations in breast cancer patients. Hospital electronic records—including pathology, radiology, clinical notes, and correspondence—were reviewed to assess local recurrence, metastasis, and mortality.
Results:
116 patients were diagnosed and recruited for the 100KGP, with genomic results available for 96 patients. Among these, 43 (44.8%) patients were aged 65 or older. In this cohort, the average age of diagnosis was 74 (65–82). At the 5-year mark, 33 out of 43 patients remained alive (76.7%). At the 5-year follow-up, 82 out of 96 patients were alive (85.4%). Interestingly, patients with metastatic disease had a similar number of somatic mutations compared to those with lower-risk disease. PIK3CA (46%) was the most frequently mutated gene, followed by TP53 (36%). Among patients who died from breast cancer, half had TP53 mutations. Notably, oestrogen receptor-positive (ER+) cancers had a higher prevalence of PIK3CA mutations compared to oestrogen receptor-negative (ER-) cancers (52.5% vs. 18.7%). While age was not a significant factor in somatic mutation frequency, higher-grade cancers (grades 2 and 3) showed greater mutation counts than grade 1 cancers (19 for grade 1, 106 for grade 2, and 76 for grade 3).
Conclusions:
Our results are consistent with findings from larger genomic studies. The upcoming final national analysis of the 100KGP will provide further insights into the link between somatic mutations and breast cancer outcomes. Elderly patients demonstrated a positive willingness to participate in 100KGP.
Methods:
We performed a detailed analysis of 100KGP reports, identifying somatic mutations in breast cancer patients. Hospital electronic records—including pathology, radiology, clinical notes, and correspondence—were reviewed to assess local recurrence, metastasis, and mortality.
Results:
116 patients were diagnosed and recruited for the 100KGP, with genomic results available for 96 patients. Among these, 43 (44.8%) patients were aged 65 or older. In this cohort, the average age of diagnosis was 74 (65–82). At the 5-year mark, 33 out of 43 patients remained alive (76.7%). At the 5-year follow-up, 82 out of 96 patients were alive (85.4%). Interestingly, patients with metastatic disease had a similar number of somatic mutations compared to those with lower-risk disease. PIK3CA (46%) was the most frequently mutated gene, followed by TP53 (36%). Among patients who died from breast cancer, half had TP53 mutations. Notably, oestrogen receptor-positive (ER+) cancers had a higher prevalence of PIK3CA mutations compared to oestrogen receptor-negative (ER-) cancers (52.5% vs. 18.7%). While age was not a significant factor in somatic mutation frequency, higher-grade cancers (grades 2 and 3) showed greater mutation counts than grade 1 cancers (19 for grade 1, 106 for grade 2, and 76 for grade 3).
Conclusions:
Our results are consistent with findings from larger genomic studies. The upcoming final national analysis of the 100KGP will provide further insights into the link between somatic mutations and breast cancer outcomes. Elderly patients demonstrated a positive willingness to participate in 100KGP.
Keywords
Breast Cancer
Genomics
Somatic Mutation
