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Tumor Discovery Pyrotinib and capecitabine in HER2-negative recurrence

were negative in post-operative and recurrent samples, DESTINY-Breast04 study found that T-DXd significantly
confirming tumor heterogeneity. improved progression-free survival and overall survival
MDT involves a comprehensive approach that aims to with manageable safety compared to the physician’s choice
maximize therapeutic efficacy, improve survival through of treatment in low-HER2 metastatic breast cancer patients
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multimodal therapy, and ensure adherence to guidelines. who had received 1 – 2 prior lines of chemotherapy.
19
It is especially recommended for locoregional recurrent Subgroup analysis revealed that the median treatment
duration was 8.4 months with T-DXd and 3.5 months
breast cancer management. It promotes patient autonomy with the physician’s choice in 213 Asian patients. Further
20
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and collective decision-making for effectively treating clinical trials are needed to find the best treatments and
locoregional recurrence. MDT was consistently employed understand their long-term effects on patients with a
in this patient’s care, encompassing pre-neoadjuvant HER2-negative switch.
therapy, post-operative therapy, and post-locoregional
recurrent therapy plans. Following a single salvage therapy Pyrotinib efficacy in treating HER2-positive metastatic
course, the patient exhibited a partial response with notable breast cancer is well established. 31,32 A Chinese phase II
lesion reduction. Ultimately, MDT involves a customized, trial involving patients previously treated with taxanes,
synergistic strategy to enhance breast cancer outcomes. anthracyclines, and/or trastuzumab demonstrated that
pyrotinib with capecitabine exhibited a higher response
Both positive-to-negative and negative-to-positive
conversions of HER2 status were observed, with no clear rate (78.5%) and longer median progression-free
survival (18.1 months) than lapatinib. The phase III
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predominance. Typically, the transition from HER2‐ PHOEBE trial corroborated these benefits, with pyrotinib
1
negative or HER2‐equivocal primary to HER2‐positive demonstrating improved overall survival and progression-
metastatic disease is more prevalent, especially in free survival across various subgroups, regardless of
HR-positive patients. This may be the result of excluding trastuzumab resistance or prior chemotherapy. Xu et al.
14
patients with HER2-negative metastatic lesions and could advocate pyrotinib as a viable second-line treatment for
be influenced by subclonal expansion and treatment- trastuzumab-resistant cases, especially where access to
specific selective pressures in early breast cancer. Non- newer therapies is limited. Pyrotinib and capecitabine
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centralized testing may also contribute. These findings significantly decreased lesion size in the current patient.
suggest reassessing HER2 status during disease recurrence
or progression to determine therapeutic strategies. Studies 4. Conclusions
have detected HER2-positive circulating tumor cells in a
significant subset of patients with HER2-negative primary Our case emphasizes that the pyrotinib and capecitabine
tumors. While metastatic lesion biopsy may not always be combination may be beneficial in patients experiencing
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possible or informative, circulating tumor biomarkers may a HER2-negative switch following systemic therapy. This
be a non-invasive alternative for tissue-based HER2 status finding may lead to promising breast cancer research and
biomarkers. 22 the development of therapeutic strategies.
According to the fifth international consensus Acknowledgments
guidelines for advanced breast cancer by the European None.
School of Oncology and the European Society for Medical
Oncology, optimal treatment strategies following the loss Funding
of HER2 amplification remain undefined. The current
23
recommendations advocate continuing therapies targeting This work was supported by the Foundation of Basic
the HER2 signaling pathway. 24,25 Another strategy is to and Applied Basic Research of Guangdong Province,
switch to alternative HER2-targeted therapies, such as China (No. 2022A1515220202) and funds from the 2023
ADCs (T-DM1 and T-DXd), and combine other TKIs with Science and Technology Innovation Strategy Project
chemotherapy to overcome resistance to initial therapy of Guangdong Province (Big Project + Task list), China
and enhance patient outcomes. 24,26,27 The KATHERINE (No. STKJ2023009, 20230403).
study detected HER2-negative residual disease in 70 out Conflict of interest
of 845 (8.3%) patients upon retesting at surgery. Among
these, 11 invasive disease-free survival events occurred in The authors declare that they have no competing interests.
the 42 trastuzumab-treated patients (26.2%), whereas none
were observed in the 28 T-DM1-treated patients. This Author contributions
suggests that patients with HER2 status conversion may Conceptualization: Chunfa Chen, Jundong Wu
continue to benefit from HER2-targeted therapy. The Formal analysis: Bingfeng Chen, Yuling Zhang
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Volume 4 Issue 1 (2025) 117 doi: 10.36922/td.4093