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.
Highlights
Amplification or overexpression of the human epidermal growth factor receptor 2 (HER2) is observed in approximately 20% of breast cancers (BCs) and is often associated with an aggressive clinical behavior and poor outcomes.[1]
The HER2 oncogene is the dominant driver of BC biology, and treatment strategies targeting HER2 have become the standard of care in all the disease settings since 2006.2 Currently, four anti-HER2 agents are licensed in Europe: trastuzumab, lapatinib, pertuzumab and T-DM1
We conducted a retrospective analysis on HER2-positive metastatic patients treated with pertuzumabbased regimens and/or T-DM1 according to standard clinical practice, and we focused on whether the expression of hormone receptors (HRs) defines distinct subtypes with different biological behaviors and patterns of response/resistance to novel HER2-blocking agents in HER2-positive metastatic BCs
Summary
Amplification or overexpression of the human epidermal growth factor receptor 2 (HER2) is observed in approximately 20% of breast cancers (BCs) and is often associated with an aggressive clinical behavior and poor outcomes.[1] When overexpressed, the HER2 oncogene is the dominant driver of BC biology, and treatment strategies targeting HER2 have become the standard of care in all the disease settings since 2006.2 Currently, four anti-HER2 agents are licensed in Europe: trastuzumab, lapatinib, pertuzumab and T-DM1. The use of anti-HER2 agents combined or not with chemotherapy has markedly improved prognosis in all stages of HER2-positive BC.[3,4,5,6,7]. Even though treatment with anti-HER2 agents has shown benefit independently on HR status, the cross-talk between the two downstream pathways has an impact on the natural history of the disease and magnitude of treatment-benefit
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
