Prognosis and Management of BRAF V600E-Mutated Pregnancy-Associated Melanoma
Open Access
- 1 August 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in The Oncologist
- Vol. 25 (8), E1209-E1220
- https://doi.org/10.1634/theoncologist.2019-0747
Abstract
Background Approximately one third of women who develop melanoma at childbearing age are diagnosed during gestation or the postpartum period, facing pregnancy-associated melanoma (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 ofBRAF-mutated disease. Subjects, Materials, and Methods In order to better describe the evolution ofBRAFV600E-mutated PAM, we present here all consecutive cases diagnosed in our site during 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 ofBRAFstatus, and the possible treatment options during pregnancy in localized or advanced/metastatic disease. Five women were diagnosed with newly metastatic or relapsedBRAFV600E-mutated PAM (four during 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 developed 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 specific data onBRAF-mutated PAM were retrieved and current evidence still supports that the prognosis 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 whetherBRAF-mutated profile adversely affects PAM outcome, although the clinicians should be aware to detect any potential melanoma lesion during pregnancy as soon as possible, treating it locally, regardless of itsBRAFstatus. Implications for Practice The prognosis and management of pregnancy-associated melanoma whetherBRAF-mutated or wild type, is currently guided by the same parameters as in the nonpregnant condition. In this special nontrial subpopulation,BRAF-mutated status seems to have a detrimental effect on disease outcome, independently of the following treatments. In early stage melanoma, wide local excision with or without sentinel lymph node dissection may be curative at any trimester of gestation, while in advanced/metastatic setting, therapeutic strategy including immune-checkpoint or BRAF/MEK inhibitors, is more challenging, regardless ofBRAFstatus, and should be based on an individualized decision in each case at a multidisciplinary level.This publication has 62 references indexed in Scilit:
- Concordance of preclinical and clinical pharmacology and toxicology of therapeutic monoclonal antibodies and fusion proteins: cell surface targetsBritish Journal of Pharmacology, 2012
- BRAF Mutations in Advanced Cancers: Clinical Characteristics and OutcomesPLOS ONE, 2011
- Spontaneous regression of transplacental metastases from maternal melanoma in a newborn: case report and review of the literatureMelanoma Research, 2010
- Rapidly progressing malignant melanoma influenced by pregnancyInternational Journal of Dermatology, 2010
- Cancer and Pregnancy: Parallels in Growth, Invasion, and Immune Modulation and Implications for Cancer Therapeutic AgentsMayo Clinic Proceedings, 2009
- Melanoma in relation to reproductive and hormonal factors in women: current review on controversial issuesCancer Causes & Control, 2008
- Extended somatic support for a pregnant woman with brain death from metastatic malignant melanoma: A case reportThe Journal of Maternal-Fetal & Neonatal Medicine, 2008
- Cancer in pregnancyAnnals of Oncology, 2003
- Pregnancy and early‐stage melanomaCancer, 2003
- Melanoma and pregnancyThe Lancet, 1991