Genetic risk of rare breast cancer linked to a higher probability of missed tumors

A new study suggests ways to improve breast cancer screening and a new understanding of how genetic risk variants affect disease progression and mode of detection. The study found that the presence of some rare mutations indicated an increased risk of interval breast cancer and death.

The study was published in Research against cancer, a review of the American Association for Cancer Research.

The study focused on interval breast cancers, which are breast cancers detected between mammography screenings. The researchers said that these cancers are often aggressive and have a poor prognosis and affect about 20% of women undergoing routine mammography.

The researchers analyzed data from more than 5,000 breast cancer patients diagnosed between 2001 and 2008 in the Breast Cancer Quality Registry of the Stockholm-Gotland region. The researchers investigated associations with tumor characteristics and survival outcomes in patients with rare protein-truncating variants (PTV) in 31 cancer predisposition genes, including: BRCA1 and BRCA2.

In addition, the researchers developed a polygenic risk score (PRS) by weighting the sum of all known variants of breast cancer, also correlated with tumor characteristics and overall survival.

Dense tissues being one of the leading causes of forgotten tumors, women were stratified into risk categories based on breast density as a percentage (low risk <25%, high risk ≥ 25%).

Of the 5099 breast cancer patients analyzed, 597 were carriers of VPT. These patients were younger, had more aggressive tumor phenotypes, and had a 1.50-fold higher risk of breast cancer deaths than non-PTV patients.

After excluding 92 women with mutations in BRCA1 and BRCA2, the risk of death from breast cancer was 1.76 times higher in women with DVT than those who did not have DVT.

In women with low breast density, those with PTV mutations in genes other than BRCA1 and BRCA2 still had 1.89 times the increased risk compared to women who did not have PTV mutations.

Women whose cancer had a higher PRS score had tumors associated with less aggressive tumor characteristics. Women with low breast density and higher SRP were 23% less likely to develop breast cancer at intervals. No significant difference in survival was associated with SRP increases.

The researchers noted that heritability affects not only the risk of breast cancer, but also survival, which largely depends on the characteristics of the tumor that determine the risk of recurrence and affect the choice of adjuvant therapy. . The study found that the inheritance pattern of breast cancers with different tumor characteristics can vary, resulting in differential prognosis and survival. Estrogen receptor negativity and the basal type subtype are intrinsic properties of BRCA1Cancer-related cancers, particularly in younger diagnosed patients.

Reference

Li J, Ugalde-Morales E, Wen WX, et al. Differential load of rare and common variants on tumor characteristics, survival and mode of detection in breast cancer. Can res. 2018; 78 (21): 6329-6338. doi: 10.1158 / 0008-5472.CAN-18-1018.

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