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. 2021 Jul 2;11(1):13770.
doi: 10.1038/s41598-021-92774-z.

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

Laura Pizzuti  1 , Maddalena Barba  1 , Marco Mazzotta  2 , Eriseld Krasniqi  1 , Marcello Maugeri-Saccà  1 , Teresa Gamucci  3 , Rossana Berardi  4 , Lorenzo Livi  5 , Corrado Ficorella  6 , Clara Natoli  7 , Enrico Cortesi  8 , Daniele Generali  9 , Nicla La Verde  10 , Alessandra Cassano  11 , Emilio Bria  11 , Luca Moscetti  12 , Andrea Michelotti  13 , Vincenzo Adamo  14 , Claudio Zamagni  15 , Giuseppe Tonini  16 , Domenico Sergi  1 , Daniele Marinelli  17 , Giancarlo Paoletti  1 , Silverio Tomao  18 , Andrea Botticelli  8 , Paolo Marchetti  8   17 , Nicola Tinari  7 , Antonino Grassadonia  7 , Maria Rosaria Valerio  19 , Rosanna Mirabelli  20 , Maria Agnese Fabbri  21 , Nicola D'Ostilio  22 , Enzo Veltri  23 , Domenico Corsi  24 , Ornella Garrone  25 , Ida Paris  26 , Giuseppina Sarobba  27 , Icro Meattini  5 , Mirco Pistelli  4 , Francesco Giotta  28 , Vito Lorusso  28 , Carlo Garufi  29 , Antonio Russo  19 , Marina Cazzaniga  30 , Pietro Del Medico  31 , Mario Roselli  32 , Angela Vaccaro  33 , Letizia Perracchio  34 , Anna di Benedetto  34 , Theodora Daralioti  34 , Isabella Sperduti  35 , Ruggero De Maria  11   36 , Angelo Di Leo  37 , Giuseppe Sanguineti  38 , Gennaro Ciliberto  39 , Patrizia Vici  1
Affiliations

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

Laura Pizzuti et al. Sci Rep. .

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.

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Conflict of interest statement

MB, MM, EK, MMS, RB, CF, EC, DG, AC, VA, CZ, GT, DS, DM, GP, ST, AB, NT, AG, MRV, RM, MAF, NDO, EV, DC, GS, IM, MP, FG, VL, CG, AR, PDM, MR, AV, Let Per, AdB, TD, IS, GS and GC declare no conflicts of interest. LP received travel grants from Eisai, Roche, Pfizer, Novartis; speaker fees from Roche, Pfizer, Novartis, Gentili. TG received travel grants from Eisai, Roche, Pfizer, Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili, Lilly. CN received travel grants/personal fees from Pfizer, Eisai, Novartis, Merck Sharp &Dohme, AstraZeneca. EB is supported by the Italian Association for Cancer Research AIRC-IG 20583; he was supported by the International Association for Lung Cancer (IASLC), the LILT (Lega Italiana per la Lotta contro I Tumori) and Fondazione Cariverona; he received speakers’ and travels’ fee from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche; consultant’s fee from Roche, Pfizer; institutional research grants from Astra-Zeneca, Roche. LM received advisory board from Roche. AM received travel grants from Eisai, Celgene, Novartis Ipsen; personal fees, advisory boards from EISAI, Novartis, Astra Zeneca, Teva, Pfizer, Celgene. MC received personal fees, advisory boards from Pierre Fabre, Astra Zeneca, Celgene, Eisai, Novartis, Lilly. NLV received personal fees from Eisai and Novartis; research funding from Eisai, travel grants from Pfizer, Roche, Gentili; consulting role from Celldex. PM has/had a consultant/advisory role for BMS, Roche Genentech, MSD, Novartis, Amgen, Merck Serono, Pierre Fabre, and Incyte. IP received personal fees/advisory boards from Roche, Pfizer, Novartis, Italfarmaco, Gentili, Pierre Fabre. OG received personal fees from Celgene, Novartis, Eisai; research funding from Eisai, consulting activities with Celgene, Eisai, Pfizer, Amgen. RDM declares to be a scientific advisory board member at ExosomicsSpA (Siena IT), Hibercell Inc. (New York, NY), Kiromic Inc. (Houston, TX) and at Exiris Inc. (Rome, IT). ADL received consulting fees from Novartis and Roche. PV received travel grants from Eisai, Roche, Pfizer, Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili.

Figures

Figure 1
Figure 1
Histopathology features of a patient who switch the HER2 status from negative early breast cancer to positive in metastatic setting. In (a), at breast cancer diagnosis, HER2-assessment resulted as “Membrane staining that is incomplete and barely perceptible and within ≤ 10% of tumor cells. IHC: 0 negative”. At relapse (b), soft tissues from the left parasternal region were biopsied. HER2 expression resulted moderate, completed in > 10% of tumor cells. IHC: 2 + . The FISH resulted into gene amplification.
Figure 2
Figure 2
Histopathology example of a patient who maintained the HER2 status both in early and metastatic biopsy. At breast cancer diagnosis (a) the pathologists’ report called for “Membrane staining that is complete, intense and in ˃ 10% of tumor cells. IHC: 3 + .” At relapse (b), a cutaneous lesion in the ipsilateral breast was biopsied and the pathologists’ report exactly reproduced the prior one.
See this image and copyright information in PMC

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