A new study offers insights into ways to improve breast cancer screening with a new understanding of how genetic risk variants affect disease progression and mode of detection. The study found that the presence of certain rare mutations was indicative of increased risk from interval breast cancers and death.
The study was published in Cancer Research, a journal 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 these cancers are often aggressive and have a poor prognosis, and affect about 20% of women who get routine mammographies.
Researchers analyzed data from over 5000 patients with breast cancer diagnosed between 2001 and 2008 through the Stockholm-Gotland Regional Breast Cancer quality register. The researchers studied associations with tumor characteristics and survival outcomes for patients with rare protein-truncating variants (PTVs) in 31 cancer predisposition genes, including BRCA1 and BRCA2.
In addition, the researchers developed a polygenic risk score (PRS) through the weighted sum of all known common breast cancer variants, which was also correlated with tumor characteristics and overall survival.
Because dense tissue is one of the main reasons for missed tumors, women were stratified into risk categories based on percent breast density (low risk < 25%; high risk ≥25%).
Of the 5099 breast cancer patients analyzed, 597 carried PTVs. These patients were younger, had more aggressive tumor phenotypes, and had 1.65 times the risk of death from breast cancer compared to those who did not carry PTVs.
After excluding 92 women that carried mutations in BRCA1 and BRCA2, women with PTVs had 1.76 times the risk of death from breast cancer compared to those without PTVs.
Among women with low breast density, those who carried PTV mutations in genes other than BRCA1 and BRCA2 still had 1.89 times increased risk compared to women who did not carry PTV mutations.
Those women whose cancers had a higher PRS score had tumors that were associated with less aggressive tumor characteristics. Women with low breast density and a higher PRS had a 23% decreased risk for developing interval breast cancer. There were no significant survival differences associated with increases in PRS.
The researchers noted that heritability affects not only breast cancer risk but also breast cancer survival, which is largely dependent on tumor characteristics that determine risk of recurrence and influence choice of adjuvant therapy. The study noted that the inheritance pattern for breast cancers of different tumor characteristics may vary, resulting in differential prognosis and survival. Estrogen-receptor negativity and basal-like subtype are intrinsic properties of BRCA1-related cancers, particularly among patients diagnosed at a younger age.
Li J, Ugalde-Morales E, Wen WX, et al. Differential burden 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.