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PIK3CA mutations and first-line outcomes in endocrine-resistant HR+/HER2- metastatic breast cancer: A multicentric
Maria Vittoria Dieci1, Grazia Vernaci2, Chiara Colangelo3
1Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
Background:
Outcomes and characteristics of endocrine-resistant, PIK3CA-mutated HR+ /HER2- advanced breast cancer patients in real-world are poorly investigated. Here, we explored the role of circulating PIK3CA mutations in endocrine-resistant patients in the ongoing prospective, multicentric CHAMBER study.
Methods:
PIK3CA was analyzed by NGS panel covering the full exonic region of PIK3CA gene. Endocrine resistance was defined as: i) primary: relapse during the first 2 years of adjuvant ET, or ii) secondary: relapse after 2 years of starting or within 1 year of completing ET. Overall survival (OS) was calculated from the start of first-line to death from any cause. Progression free survival 1 (PFS1) was calculated from the start of first-line to progression or death.
Results:
Among the overall CHAMBER population, 22 % patients met the criteria for endocrine-resistance (74/337). The study population consisted in 95 % women and 5 % men; median age at diagnosis was 50 years (IQR 44-63); 75 % of the women was postmenopausal;86 % of the total population presented with a secondary endocrine-resistance, 64 % had visceral relapse, 74 % had less than 3 metastatic sites, 79 % had received first-line CDK4/6 inhibitor. PIK3CA status was available for 63/74 pts, with a 29 % prevalence of mutation. PIK3CAmut was a negative prognostic factor for OS (median 65 [wt] vs 36 months [mut], log-rank p 0.024 HR 2.61 [95 % CI 1.10-6.22]) and PFS1 (median 22 [wt] vs 10 months [mut], log-rank p 0.012, HR 2.24 [95 % CI 1.18-4.26]).
Conclusion:
The co-occurrence of endocrine-resistance and PIK3CAmut identifies a population with unfavorable prognosis, reinforcing the rationale of escalated therapies.
Insights
In advanced breast cancer, PIK3CA mutations in endocrine-resistant patients indicate a worse prognosis. This finding supports the use of escalated therapies for this patient group.
Area of Science:
- Oncology
- Genetics
- Clinical Research
Background:
- Limited data exists on endocrine-resistant, PIK3CA-mutated HR+/HER2- advanced breast cancer in real-world settings.
- The CHAMBER study prospectively investigates circulating PIK3CA mutations in these patients.
Purpose of the Study:
- To explore the role of circulating PIK3CA mutations in endocrine-resistant HR+/HER2- advanced breast cancer patients.
- To assess the prognostic significance of PIK3CA mutations in this population.
Main Methods:
- Next-generation sequencing (NGS) was used to analyze the PIK3CA gene.
- Endocrine resistance was defined by primary or secondary relapse criteria.
- Overall survival (OS) and progression-free survival 1 (PFS1) were calculated from first-line therapy start.
Main Results:
- 22% of the CHAMBER population had endocrine resistance; 29% of these had PIK3CA mutations.
- PIK3CA mutation was associated with significantly shorter OS (36 vs. 65 months) and PFS1 (10 vs. 22 months).
- Patients often had secondary endocrine resistance, visceral relapse, and received first-line CDK4/6 inhibitors.
Conclusions:
- Co-occurrence of endocrine resistance and PIK3CA mutation identifies a high-risk population.
- These findings support the rationale for escalated treatment strategies in this subgroup.
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