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

Laura Pizzuti, Eriseld Krasniqi, Giacomo Barchiesi, Marina Della Giulia, Fiorentino Izzo, Giuseppe Sanguineti, Paolo Marchetti, Marco Mazzotta, Raffaele Giusti, Andrea Botticelli, Teresa Gamucci, Clara Natoli, Antonino Grassadonia, Nicola Tinari, Laura Iezzi, Silverio Tomao, Federica Tomao, Giuseppe Tonini, Daniele Santini, Antonio AstoneAndrea Michelotti, Claudia De Angelis, Lucia Mentuccia, Angela Vaccaro, Emanuela Magnolfi, Alain Gelibter, Valentina Magri, Enrico Cortesi, Loretta D'Onofrio, Alessandra Cassano, Ernesto Rossi, Marina Cazzaniga, Luca Moscetti, Claudia Omarini, Federico Piacentini, Maria A. Fabbri, Angelo F. Scinto, Domenico Corsi, Luisa Carbognin, Emilio Bria, Nicla La Verde, Carlo Garufi, Ida Paris, Francesco Giotta, Vito Lorusso, Ruggero De Maria, Gennaro Ciliberto, Isabella Sperduti, Maddalena Barba, Patrizia Vici

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusAccepted/In press - Jan 1 2019

Keywords

  • advanced breast cancer
  • HER2 positive
  • pertuzumab
  • real world
  • T-DM1
  • trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / 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; Garufi, Carlo; Paris, Ida; Giotta, Francesco; Lorusso, Vito; De Maria, Ruggero; Ciliberto, Gennaro; Sperduti, Isabella; Barba, Maddalena; Vici, Patrizia.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Pizzuti, L, Krasniqi, E, Barchiesi, G, Della Giulia, M, Izzo, F, Sanguineti, G, Marchetti, P, Mazzotta, M, Giusti, R, Botticelli, A, Gamucci, T, Natoli, C, Grassadonia, A, Tinari, N, Iezzi, L, Tomao, S, Tomao, F, Tonini, G, Santini, D, Astone, A, Michelotti, A, De Angelis, C, Mentuccia, L, Vaccaro, A, Magnolfi, E, Gelibter, A, Magri, V, Cortesi, E, D'Onofrio, L, Cassano, A, Rossi, E, Cazzaniga, M, Moscetti, L, Omarini, C, Piacentini, F, Fabbri, MA, Scinto, AF, Corsi, D, Carbognin, L, Bria, E, La Verde, N, Garufi, C, Paris, I, Giotta, F, Lorusso, V, De Maria, R, Ciliberto, G, Sperduti, I, Barba, M & Vici, P 2019, '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', International Journal of Cancer. https://doi.org/10.1002/ijc.32583
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 ; Garufi, Carlo ; Paris, Ida ; Giotta, Francesco ; Lorusso, Vito ; De Maria, Ruggero ; Ciliberto, Gennaro ; Sperduti, Isabella ; Barba, Maddalena ; Vici, Patrizia. / 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. In: International Journal of Cancer. 2019.
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abstract = "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-na{\"i}ve 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.",
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T1 - 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

AU - Pizzuti, Laura

AU - Krasniqi, Eriseld

AU - Barchiesi, Giacomo

AU - Della Giulia, Marina

AU - Izzo, Fiorentino

AU - Sanguineti, Giuseppe

AU - Marchetti, Paolo

AU - Mazzotta, Marco

AU - Giusti, Raffaele

AU - Botticelli, Andrea

AU - Gamucci, Teresa

AU - Natoli, Clara

AU - Grassadonia, Antonino

AU - Tinari, Nicola

AU - Iezzi, Laura

AU - Tomao, Silverio

AU - Tomao, Federica

AU - Tonini, Giuseppe

AU - Santini, Daniele

AU - Astone, Antonio

AU - Michelotti, Andrea

AU - De Angelis, Claudia

AU - Mentuccia, Lucia

AU - Vaccaro, Angela

AU - Magnolfi, Emanuela

AU - Gelibter, Alain

AU - Magri, Valentina

AU - Cortesi, Enrico

AU - D'Onofrio, Loretta

AU - Cassano, Alessandra

AU - Rossi, Ernesto

AU - Cazzaniga, Marina

AU - Moscetti, Luca

AU - Omarini, Claudia

AU - Piacentini, Federico

AU - Fabbri, Maria A.

AU - Scinto, Angelo F.

AU - Corsi, Domenico

AU - Carbognin, Luisa

AU - Bria, Emilio

AU - La Verde, Nicla

AU - Garufi, Carlo

AU - Paris, Ida

AU - Giotta, Francesco

AU - Lorusso, Vito

AU - De Maria, Ruggero

AU - Ciliberto, Gennaro

AU - Sperduti, Isabella

AU - Barba, Maddalena

AU - Vici, Patrizia

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - advanced breast cancer

KW - HER2 positive

KW - pertuzumab

KW - real world

KW - T-DM1

KW - trastuzumab

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