The pathologic and genomic evolution of primary malignant phyllodes tumors of the breast: retrospective cohort study and case-control genomic analysis

Background: In patients with phyllodes tumors of the breast, the presence of mediator of RNA polymerase II transcription subunit 12 homolog mutations (MED12m) and a history of previous fibroadenoma may predict better outcomes. To aid in the prognostication of malignant phyllodes tumors of the breast (B-MPT), we assessed the prognostic value of fibroadenoma-like areas (supposed to have stemmed from a pre-existing fibroadenoma) and MED12m, in patients with resected primary B-MPTs. Methods: We conducted a single-center, retrospective, cohort study including all consecutive patients aged ≥18 years old, with non-metastatic B-MPT, who underwent surgery from January 2000 to December 2021. The endpoints were the cumulative incidences of all recurrences, according to the presence of fibroadenoma-like areas, reviewed by 3 reference pathologists. A nested, case-control genomic analysis was performed to evaluate the association between MED12m, the presence of fibroadenoma-like areas, and cancer recurrences. Results: Eight-nine patients were included, with 47% of tumors exhibiting Fibroadenoma-Like Areas (FLA+). These areas were not significantly associated with local recurrence (5-year cumulative incidence in FLA+ vs FLA-: 13.0, 95%CI [4.6-25.9] vs 23.6, 95%CI [11.9-37.5]; P = .14) or distant recurrence (5-year cumulative incidence in FLA+ vs FLA-: 12.5, 95%CI [4.5-25.0] vs 8.9, 95%CI [2.8-19.5], P = .61), at a median follow-up of 6.7 years. MED12m was not associated with distant recurrences or the presence of fibroadenoma-like areas. Conclusions: Half of B-MPTs are characterized by the presence of fibroadenoma-like areas. This pathologic feature is not significantly associated with lower distant and local recurrences nor with the presence of MED12 mutations.