Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti‐HER2 agents in the real world setting
Authors: Pizzuti Laura , Krasniqi Eriseld , Barchiesi Giacomo , Della Giulia Marina , Izzo Fiorentino , Sanguineti Giuseppe , Marchetti Paolo , Mazzotta Marco , Giusti Raffaele , Botticelli Andrea , Gamucci Teresa , Natoli Clara , Grassadonia Antonino , Tinari Nicola , Iezzi Laura , Tomao Silverio , Tomao Federica , Tonini Giuseppe , Santini Daniele , Astone Antonio , Michelotti Andrea , De Angelis Claudia , Mentuccia Lucia , Vaccaro Angela , Magnolfi Emanuela , Gelibter Alain , Magri Valentina , Cortesi Enrico , D'Onofrio Loretta , Cassano Alessandra , Rossi Ernesto , Cazzaniga Marina , Moscetti Luca , Omarini Claudia , Piacentini Federico , Fabbri Maria A. , Scinto Angelo F. , Corsi Domenico , Carbognin Luisa , Bria Emilio , La Verde Nicla , Samaritani Riccardo , Garufi Carlo , Barni Sandro , Mirabelli Rosanna , Sarmiento Roberta , Veltri Enzo M. , D'Auria Giuliana , Paris Ida , Giotta Francesco , Lorusso Vito , Cardillo Franca , Landucci Elisabetta , Mauri Maria , Ficorella Corrado , Roselli Mario , Adamo Vincenzo , Ricciardi Giuseppina R.R. , Russo Antonio , Berardi Rossana , Pistelli Mirco , Fiorio Elena , Cannita Katia , Sini Valentina , D'Ostilio Nicola , Foglietta Jennifer , Greco Filippo , Zamagni Claudio , Garrone Ornella , Di Cocco Barbara , Baldini Editta , Livi Lorenzo , Desideri Isacco , Meattini Icro , Sarobba Giuseppina , Del Medico Pietro , De Tursi Michele , Generali Daniele , De Maria Ruggero , Risi Emanuela , Ciliberto Gennaro , Sperduti Isabella , Villa Alice , Barba Maddalena , Di Leo Angelo , Vici Patrizia 
Published: July 2019

We analyzed data from 738 HER2‐positive metastatic breast cancer (mbc) patients treated with pertuzumab‐based regimens and/or T‐DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression‐free survival at first‐line (mPFS1) was 12 months. Pertuzumab as first‐line conferred longer mPFS1 compared to other first‐line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second‐line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T‐DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs‐negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T‐DM1 in second‐line after pertuzumab were significantly lower compared to pertuzumab‐naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment‐related outcomes of HER2‐positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2‐positive (mbc) patients.