Prognosis and Management of BRAF V600E-Mutated Pregnancy-Associated Melanoma

Abstract

Background. Approximately one third of women who develop melanoma at childbearing age are diagnosed during gestation or the postpartum period, facing pregnancy-associated mela- noma (PAM). However, only some retrospective studies with heterogeneous data have analyzed the impact of pregnancy on melanoma development, and no evidence exists about the behavior and the management of BRAF-mutated disease. Subjects, Materials, and Methods. In order to better describe the evolution of BRAF V600E–mutated PAM, we present here all consecutive cases diagnosed in our site dur- ing the last 7 years, recording oncological, obstetrical, and perinatal parameters, as well as the therapeutic decisions for both melanoma and gestation. Based on our institutional experience, we weigh the current published evidence and discuss upcoming clinical considerations about the prognosis of PAM, the role of BRAF status, and the possible treatment options during pregnancy in localized or advanced/ metastatic disease. Five women were diagnosed with newly metastatic or relapsed BRAF V600E–mutated PAM (four dur- ing gestation and one in the 1st year postpartum) between 2012 and 2019. All of them developed extensive metastatic disease with multiple organ involvement, and four devel- oped brain metastases. All cases experienced melanoma progression in less than 6 months under targeted therapy and died soon independently of the followed sequence of treatments. All the neonates were delivered alive and healthy, but one developed melanoma earlier than the second year of life. Results. Reviewing the literature to confirm our unfavorable outcomes, no specificdataon BRAF-mutated PAM were retrieved and current evidence still supports that the progno- sis of PAM should be guided by the established risk factors, whereas the management of advanced/metastatic PAM should be evaluated on a case-by-case basis. Conclusion. More data are required to ascertain whether BRAF-mutated profile adversely affects PAM outcome, although the clinicians should be aware to detect any poten- tial melanoma lesion during pregnancy as soon as possible, treating it locally, regardless of its BRAF status.