The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial.

Abstract

In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world setting at 45 Italian cancer centers were retrospectively collected and analyzed. From 2003 to 2017, 491 HER2-positive mBC patients were included. Of these, 102 (20.7%) had been initially diagnosed as HER2-negative early BC. Estrogen and/or progesterone receptor were more expressed in patients with HER2-discordance compared to patients with HER2-concordant status (p < 0.0001 and p = 0.006, respectively). HER2-discordant tumors were characterized also by a lower rate of brain metastases (p = 0.01) and a longer disease free interval (p < 0.0001). Median overall survival was longer, although not statistically significant, in the subgroup of patients with HER2-discordant cancer with respect to patients with HER2-concordant status (140 vs 78 months, p = 0.07). Our findings suggest that patients with HER2-positive mBC with discordant HER2 status in early BC may have different clinical, biological and prognostic behavior compared to HER2-concordant patients.

• Authors: Laura Pizzuti, Maddalena Barba, Marco Mazzotta, Eriseld Krasniqi, Marcello Maugeri-Saccà, Teresa Gamucci, Rossana Berardi, Lorenzo Livi, Corrado Ficorella, Clara Natoli, Enrico Cortesi, Daniele Generali, Nicla La Verde, Alessandra Cassano, Emilio Bria, Luca Moscetti, Andrea Michelotti, Vincenzo Adamo, Claudio Zamagni, Giuseppe Tonini, Domenico Sergi, Daniele Marinelli, Giancarlo Paoletti, Silverio Tomao, Andrea Botticelli, Paolo Marchetti, Nicola Tinari, Antonino Grassadonia, Maria Rosaria Valerio, Rosanna Mirabelli, Maria Agnese Fabbri, Nicola D'Ostilio, Enzo Veltri, Domenico Corsi, Ornella Garrone, Ida Paris, Giuseppina Sarobba, Icro Meattini, Mirco Pistelli, Francesco Giotta, Vito Lorusso, Carlo Garufi, Antonio Russo, Marina Cazzaniga, Pietro Del Medico, Mario Roselli, Angela Vaccaro, Letizia Perracchio, Anna di Benedetto, Theodora Daralioti, Isabella Sperduti, Ruggero De Maria, Angelo Di Leo, Giuseppe Sanguineti, Gennaro Ciliberto, Patrizia Vici
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 13770 (07 02 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 34215766 (Publication Type: Journal Article)

Chemical References

• Receptors, Progesterone
• ERBB2 protein, human
• Receptor, ErbB-2
• Ado-Trastuzumab Emtansine

Topics

• Ado-Trastuzumab Emtansine (administration & dosage)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Brain Neoplasms (drug therapy, epidemiology, genetics, pathology)
• Breast Neoplasms (drug therapy, epidemiology, genetics, pathology)
• Disease-Free Survival
• Female
• Humans
• Middle Aged
• Neoplasm Metastasis
• Prognosis
• Receptor, ErbB-2 (genetics)
• Receptors, Progesterone (genetics)