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. 2025 Feb 6;30(2):oyaf012.
doi: 10.1093/oncolo/oyaf012.

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

Carmine Valenza  1   2 , Dario Trapani  1   2 , Francesca Maria Porta  3 , Edoardo Olmeda  2   3 , Aurora Gaeta  4 , Luca Boscolo Bielo  1   2 , Federica Conversano  3 , Tommaso Martino De Pas  5 , Grazia Castellano  1   2 , Celeste Santoro  1   2 , Elena Battaiotto  1   2 , Eltjona Mane  3 , Sara Coppola  6 , Fabio Conforti  5 , Denise Mattar  7 , Sara Gandini  4 , Paolo Veronesi  2   7 , Elena Guerini Rocco  2   3 , Elisabetta Pennacchioli  6 , Giuseppe Curigliano  1   2
Affiliations

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

Carmine Valenza et al. Oncologist. .

Abstract

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.

Keywords: MED12; breast tumor; fibroadenoma; malignant phyllodes tumors of the breast.

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Conflict of interest statement

G.C. reports financial interests with AstraZeneca, Celcuity, Daiichi Sankyo, Exact Sciences, Lilly, Merck, Novartis, Pfizer, Roche, Veracyte, Ellipsis, Astellas, Blueprint Medicine, BMS, Kymab, Merck, Novartis, Philogen, Relay Therapeutics, Sanofi; and non-financial interests with the Italian National Health Council as Advisor for Ministry of Health ESMO, ESMO as Clinical Practice Guidelines Chair, Europa Donna as Member of the Scientific Council, EUSOMA as member of the Advisory Council, Fondazione Beretta, Lega Italiana Lotta ai Tumori as member of Board of Directors. All the competing interests were outside the submitted work. All other authors have no potential conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Competing risk analysis of cumulative incidence of any recurrence (A) and of distant and local recurrences (B).
Figure 2.
Figure 2.
Competing risk analysis of cumulative incidence of any recurrence (A), and distant and local recurrences (B) according to the presence of fibroadenoma-like areas. Abbreviation: FLA, fibroadenoma-like areas.
Figure 3.
Figure 3.
Genomic repertoire of malignant phyllodes tumors of the breast included in the genomic analysis.
See this image and copyright information in PMC

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