Data from The Breast Cancer Susceptibility Mutation <i>PALB2 1592delT</i> Is Associated with an Aggressive Tumor Phenotype

Abstract

<div>Abstract<p><b>Purpose:</b> To determine the effect of the breast cancer susceptibility mutation <i>PALB2 1592delT</i> on tumor phenotype and patient survival.</p><p><b>Experimental Design:</b> We defined the <i>PALB2</i> mutation status in 947 familial and 1,274 sporadic breast cancer patients and 1,079 population controls, and compared tumor characteristics and survival in mutation carriers relative to other familial and sporadic cases and to 79 <i>BRCA1</i> and 104 <i>BRCA2</i> mutation carrier cases.</p><p><b>Results:</b> The <i>PALB2 1592delT</i> mutation was found in 19 familial [2.0%; odds ratio, 11.03; 95% confidence interval (95% CI), 2.65-97.78; <i>P</i> < 0.0001] and eight sporadic patients (0.6%; odds ratio, 3.40; 95% CI, 0.68-32.95; <i>P</i> = 0.1207) compared with two (0.2%) control individuals. Tumors of the <i>PALB2</i> mutation carriers presented triple negative (estrogen receptor negative/progesterone receptor negative/HER negative) phenotype more often (54.5%; <i>P</i> < 0.0001) than those of other familial (12.2%) or sporadic (9.4%) breast cancer patients. They were also more often of higher grade (<i>P</i> = 0.0027 and <i>P</i> = 0.0017, respectively) and had higher expression of Ki67 (<i>P</i> = 0.0004 and <i>P</i> = 0.0490, respectively). Carrying a <i>PALB2</i> mutation was also associated with reduced survival, especially in familial cases (hazard ratio, 2.30; 95% CI, 1.01-5.24; <i>P</i> = 0.0466) and among familial patients with HER2-negative tumors (hazard ratio, 4.57; 95% CI, 1.96-10.64; <i>P</i> = 0.0004). Carrying a <i>BRCA2</i> mutation was also found to be an independent predictor of poor survival at 10-year follow-up (<i>P</i> = 0.04).</p><p><b>Conclusions:</b> The <i>PALB2 1592delT</i> mutation has a strong effect on familial breast cancer risk. The tumors rising in patients carrying this mutation manifest a phenotype associated with aggressive disease. Our results also suggest a significant impact of carrying a <i>BRCA2</i> mutation on long-term breast cancer survival.</p></div>