Медицинская библиотека · European journal of cancer (Oxford, England : 1990) · 2026

Denosumab is associated with longer real-world progression-free survival in BRCA1/2-mutated HR+ /HER2 - breast cancer patients with bone metastases receiving CDK4/6 inhibitors: A multicenter Italian study.

Scafetta Roberta, Troiano Raffaella, Gullotta Carla, Guarino Alessandra, Fiore Cristina, Sisca Luisana, Speziale Elena, Donato Marco, Foderaro Simone, Venuti Fabio, Vilardi Francesco Antonio, Ricozzi Valentina, Iuliani Michele, Simonetti Sonia, Cavaliere Silvia, Cortellini Alessio, Cesa Annalisa La, Botticelli Andrea, Scagnoli Simone, Pisegna Simona, Criscitiello Carmen, Pedersini Rebecca, Sposetti Caterina, Tiberi Elisa, D'Auria Giuliana, Vergati Matteo, Mazzotta Marco, Caputo Roberta, Verrazzo Annarita, Garrone Ornella, Domati Federica, Piombino Claudia, Lisa Francesca Sofia Di, Filomeno Lorena, Arcuri Teresa, Puce Federica, Riva Federica, Palleschi Michela, Sirico Marianna, Piras Marta, Stucci Luigia Stefania, Lisi Delia De, Orsaria Paolo, Grasso Antonella, Ippolito Edy, Ramella Sara, Visani Luca, Livi Lorenzo, Gori Stefania, Rossi Luigi, Meattini Icro, Tagliaferri Barbara, Caffo Orazio, Bonomo Maria Vittoria, Portarena Ilaria, Irelli Azzurra, Cretella Elisabetta, Porta Camillo, Bianchini Giampaolo, Fabbri Maria Agnese, Giorgi Ugo De, Vici Patrizia, Toss Angela, Ruatta Fiorella, Laurentiis Michelino De, Villa Federica, Berardi Rossana, Minelli Mauro, Altomare Vittorio, Vernieri Claudio, Curigliano Giuseppe, Chirco Alessandra, D'Alessandro Sara, Vincenzi Bruno, Tonini Giuseppe, Santini Daniele, Pantano Francesco

СтатьяМногоцентровое исследованиеПеревод в очереди

Аннотация

BACKGROUND

Preclinical evidence suggests that BRCA1/2-mutated tumors may rely on RANKL signaling for survival and proliferation. RANKL inhibition with denosumab could disrupt tumor-bone microenvironment crosstalk and potentially limit metastatic progression. We evaluated the association between denosumab and real-world progression-free survival (rwPFS) in germline BRCA1/2-mutated hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) with bone metastases.

METHODS

We performed a retrospective, multicenter study across 24 Italian hospitals including HR+/HER2- bone mBC patients treated in first- or second-line with a CDK4/6 inhibitor plus endocrine therapy. rwPFS was estimated by Kaplan-Meier and compared with log-rank tests. Center-stratified multivariable Cox models adjusted for clinically relevant covariates were used to assess the association between denosumab exposure and rwPFS. Effect modification by BRCA status was evaluated using a denosumab×BRCA1/2 mutation status.

RESULTS

Among 1399 patients, 46 harbored germline BRCA1/2 mutations (13 BRCA1, 33 BRCA2), and 21 of these patients received denosumab. Among patients not receiving denosumab, BRCA1/2-wild-type/unknown patients had better rwPFS than BRCA1/2-mutated patients (median 28 vs 13 months; hazard ratio (HR) 0.48, 95% CI 0.32-0.73; p = 0.001). Among BRCA1/2-wild-type/unknown patients, denosumab use did not affect rwPFS (HR 0.98, 95% CI 0.85-1.12). Conversely, denosumab use was associated with longer rwPFS among patients with BRCA1/2 mutations (median 35 months, 95% CI 24-NR vs 13 months, 95% CI 9-27; HR 0.34, 95% CI 0.16-0.74; p = 0.006), with no significant difference between BRCA1 and BRCA2-mutated subgroups. Multivariable analysis confirmed the rwPFS benefit of denosumab in BRCA1/2-mutated patients (adjusted HR 0.45, 95% CI 0.21-0.99; p = 0.048).

CONCLUSION

In this real-world cohort, denosumab use was associated with longer rwPFS in germline BRCA1/2-mutated HR+/HER2- mBC with bone metastases.

Для цитирования: Scafetta Roberta, Troiano Raffaella, Gullotta Carla, Guarino Alessandra, Fiore Cristina, Sisca Luisana, Speziale Elena, Donato Marco, Foderaro Simone, Venuti Fabio, Vilardi Francesco Antonio, Ricozzi Valentina, Iuliani Michele, Simonetti Sonia, Cavaliere Silvia, Cortellini Alessio, Cesa Annalisa La, Botticelli Andrea, Scagnoli Simone, Pisegna Simona, Criscitiello Carmen, Pedersini Rebecca, Sposetti Caterina, Tiberi Elisa, D'Auria Giuliana, Vergati Matteo, Mazzotta Marco, Caputo Roberta, Verrazzo Annarita, Garrone Ornella, Domati Federica, Piombino Claudia, Lisa Francesca Sofia Di, Filomeno Lorena, Arcuri Teresa, Puce Federica, Riva Federica, Palleschi Michela, Sirico Marianna, Piras Marta, Stucci Luigia Stefania, Lisi Delia De, Orsaria Paolo, Grasso Antonella, Ippolito Edy, Ramella Sara, Visani Luca, Livi Lorenzo, Gori Stefania, Rossi Luigi, Meattini Icro, Tagliaferri Barbara, Caffo Orazio, Bonomo Maria Vittoria, Portarena Ilaria, Irelli Azzurra, Cretella Elisabetta, Porta Camillo, Bianchini Giampaolo, Fabbri Maria Agnese, Giorgi Ugo De, Vici Patrizia, Toss Angela, Ruatta Fiorella, Laurentiis Michelino De, Villa Federica, Berardi Rossana, Minelli Mauro, Altomare Vittorio, Vernieri Claudio, Curigliano Giuseppe, Chirco Alessandra, D'Alessandro Sara, Vincenzi Bruno, Tonini Giuseppe, Santini Daniele, Pantano Francesco. Denosumab is associated with longer real-world progression-free survival in BRCA1/2-mutated HR+ /HER2 - breast cancer patients with bone metastases receiving CDK4/6 inhibitors: A multicenter Italian study.. European journal of cancer (Oxford, England : 1990). 2026. DOI: 10.1016/j.ejca.2026.116703.

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