Abstract P3-07-02: Increased risk of secondary cancers in patients with breast cancer under age 50 and the identification of non-BRCA inherited cancer syndromes using multi-gene hereditary cancer panels
Authors: Diab S , Stuenke A , Kagey J , Hamlington B , Keiles S , Freivogel M , Asmar L , Langer L 
Published: August 2014

Women with breast cancer (BC) under age 50 are at elevated risk of secondary cancers (SC), in part, due to a higher prevalence of inherited gene mutations. Hereditary genetic panels may be effective in identifying genetic mutations other in genes other than BRCA1/2. The objective of this study is to quantify the risk and spectrum of SC in women with BC under age 50 and to report on national data generated with commercially available next generation sequencing panels. In the Surveillance, Epidemiology, and End Results database, we analyzed the observed to expected (O/E) risk of SC in patients with a first BC diagnosis under age 50 in all patients and then stratified by hormone receptor status. The statistically significant (P &lt; 0.05) O/E risk and absolute excess risk (AER) per 10,000 patients per year are presented in this table:

Risk of second cancers in patients with breast cancer diagnosed under age 50 years. All ptsER- and PR -ER + or PR + (N = 108,985)(N = 15,921)(N = 45,145)Type of CancersO/EAERO/EAERO/EAERAll solid tumors1.6740.872.5470.691.7436.96Breast2.3332.773.7354.992.3429.31Oral cavity and pharynx1.270.302.621.221.540.44Salivary Glands2.470.224.490.423.050.26Peritoneum/mesentery1.620.096.640.54 Respiratory system1.272.241.642.731.401.88Bones and Joints2.040.09  Skin excluding basal and squamous1.220.61 1.471.34Soft tissue including heart2.100.372.750.522.060.32Leukemia and lymphoma1.251.082.063.251.41.32Female Genital system1.403.682.369.661.342.63Esophagus1.550.15 0-0.16Stomach1.370.22  Pancreas1.190.23 1.420.33Bladder1.360.43 1.890.64Kidney/renal pelvis0.80-0.28  Brain and other nervous system  1.510.3ER: Estrogen Receptor. PR: Progesterone Receptor.

This wide spectrum of increased SC is in part related to inherited gene mutations. The identification of specific inherited cancer syndromes may allow the implementation of individualized surveillance protocols. BreastNext™ is a next generation sequencing panel that simultaneously analyzes 14 genes that contribute to increased risk for BC beyond BRCA1 and BRCA2. OvaNext™ is a panel that analyzes 19 genes that contribute to increased risk for breast, ovarian, and/or uterine cancers. CancerNext™ is a panel that analyzes 22 genes that contribute to increased risk for breast, colon, ovarian, uterine and other cancers. These panels were used to evaluate 1523 subjects (874 BreastNext, 224 OvaNext, and 425 CancerNext) with a positive mutation rate of 8.79% and an inconclusive rate of 38.8%. Pathogenic mutations were identified in ATM, BARD1, BRIP1, CDH1, PTEN, CHK2, MLH1, PALB2, TP53, RAD51, and other genes were identified.. Conclusion: Women under age 50 with BC have an increased risk of a wide spectrum of second cancers. Hereditary genetic panels can identify gene mutations that may not be apparent by clinical history alone and might lead to individualized surveillance recommendations.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-02.