Germline PALB2 Variants and PARP Inhibitors in Endometrial Cancer

PARP inhibitors are orally administered antineoplastic agents that affect the homologous recombination (HR) repair pathway, and are approved by the FDA for the treatment of ovarian, breast, pancreatic, and prostate cancers. This report presents a case of recurrent endometrial carcinoma occurring in a woman with a germline pathogenic PALB2 whole-exon deletion. This uncommon finding in a patient with endometrial carcinoma provided the opportunity to use a management strategy of PARP inhibition with olaparib, resulting in a prolonged response to treatment; however, disease progression eventually occurred. Further studies are required to elucidate the mechanisms underlying resistance to PARP inhibition, and the potential future treatment options in this setting. Current recommendations for risk management of female carriers of PALB2 variants focus on breast and ovarian cancer risk. This case raises the additional question of a potential role for risk-reducing hysterectomy in female carriers of PALB2 variants.