Dataset Information

PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane-Based Neoadjuvant Chemotherapy.

ABSTRACT: PURPOSE:PIK3CA, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. PIK3CA mutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of PIK3CA mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy. Materials and Methods:A total of 92 patients with TNBC derived from a prospectively randomized phase II trial GeparSixto study (NCT01426880). Exon 9 and exon 20 of PIK3CA mutations were evaluated by using classical Sanger method with formalin-fixed paraffin-embedded tumor tissues. RESULTS:Seven of 90 tumors (7.8%) were detectable with a PIK3CA H1047R mutation. Overall, PIK3CA H1047R mutation was significantly associated with a lower pCR rate (14.3% vs. 56.6%; odds ratio, 0.128; 95% confidence interval [CI], 0.015 to 1.108; p=0.047). In carboplatin- containing treatment patients, H1047R mutation trended to predict a lower pCR rate (20% vs. 62.5%; p=0.146). In a multivariable analysis, H1047R mutation trended to predict a lower pCR rate (hazard ratio, 0.1; 95% CI, 0.01 to 1; p=0.056). CONCLUSION:TNBC with a PIK3CA H1047R mutation was less likely to achieve pCR after anthracycline-based neoadjuvant chemotherapy. Development of H1047R mutant selective inhibitors might be helpful to conquer this subtype of breast cancer.

SUBMITTER: Guo S

PROVIDER: S-EPMC7373870 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane-Based Neoadjuvant Chemotherapy.

Guo Sanxing S Loibl Sibylle S von Minckwitz Gunter G Darb-Esfahani Silvia S Lederer Bianca B Denkert Carsten C

Cancer research and treatment 20200204 3

<h4>Purpose</h4>PIK3CA, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. PIK3CA mutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of PIK3CA mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.<h4>Materials and methods</h4>A total of 92 patients with TNBC derived from a prospectively randomized ...[more]

PMID: 32019278

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Project description:BackgroundEribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy.MethodsPatients with primary triple negative breast cancer ≥2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study.ResultsIn stage I of the study 13 women were enrolled, median age 43 years, tumor size 2-5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR.ConclusionsDespite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial-mesenchymal transition, claims for further investigation.Trial registrationEU Clinical Trial Register, EudraCT number 2012-004956-12.

Dataset Information

PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane-Based Neoadjuvant Chemotherapy.

Publications

PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane-Based Neoadjuvant Chemotherapy.

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