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The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients

BACKGROUND: There is pressing needs to find the biomarker in the selection of neoadjuvant therapy in postmenopausal luminal breast cancer patients. We examined the hypothesis that PIK3CA mutations and low phosphatase and tensin homolog (PTEN) expression affect the response to neoadjuvant therapy and...

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Autores principales: Hayama, Shouko, Nakamura, Rikiya, Ishige, Takayuki, Sangai, Takafumi, Sakakibara, Masahiro, Fujimoto, Hiroshi, Ishigami, Emi, Masuda, Takahito, Nakagawa, Ayako, Teranaka, Ryotaro, Ota, Satoshi, Itoga, Sakae, Yamamoto, Naohito, Nagashima, Takeshi, Otsuka, Masayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134571/
https://www.ncbi.nlm.nih.gov/pubmed/37106324
http://dx.doi.org/10.1186/s12885-023-10853-y
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author Hayama, Shouko
Nakamura, Rikiya
Ishige, Takayuki
Sangai, Takafumi
Sakakibara, Masahiro
Fujimoto, Hiroshi
Ishigami, Emi
Masuda, Takahito
Nakagawa, Ayako
Teranaka, Ryotaro
Ota, Satoshi
Itoga, Sakae
Yamamoto, Naohito
Nagashima, Takeshi
Otsuka, Masayuki
author_facet Hayama, Shouko
Nakamura, Rikiya
Ishige, Takayuki
Sangai, Takafumi
Sakakibara, Masahiro
Fujimoto, Hiroshi
Ishigami, Emi
Masuda, Takahito
Nakagawa, Ayako
Teranaka, Ryotaro
Ota, Satoshi
Itoga, Sakae
Yamamoto, Naohito
Nagashima, Takeshi
Otsuka, Masayuki
author_sort Hayama, Shouko
collection PubMed
description BACKGROUND: There is pressing needs to find the biomarker in the selection of neoadjuvant therapy in postmenopausal luminal breast cancer patients. We examined the hypothesis that PIK3CA mutations and low phosphatase and tensin homolog (PTEN) expression affect the response to neoadjuvant therapy and prognosis in postmenopausal luminal breast cancer patients. METHODS: Postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, up to stage II, who underwent neoadjuvant chemotherapy (NAC; n = 60) or neoadjuvant endocrine therapy (NAE; n = 55) were selected. PIK3CA exon 9 and exon 20 mutations were screened by high resolution melting analysis and confirmed by Sanger sequence. PTEN expression was evaluated by immunohistochemistry. The relationships among PIK3CA mutations, PTEN expression, clinicopathological features, the pathological effect of neoadjuvant therapy, recurrence-free survival (RFS) and overall survival were analyzed. RESULTS: Among 115 patients, PIK3CA mutations and low PTEN expression before treatment were detected in 35 patients (30.4%) and in 28 patients (24.3%), respectively. In the NAC group, tumor with PIK3CA mutations showed significantly poorer response than tumor with PIK3CA wild-type (p = 0.03). On the other hand, in the NAE group, there was no significant difference in pathological therapeutic effect between tumor with PIK3CA mutations and tumor with PIK3CA wild-type (p = 0.54). In the NAC group, the log-rank test showed no difference in RFS between patients with PIK3CA mutations and PIK3CA wild-type (p = 0.43), but patients with low PTEN expression showed significantly worse RFS compared to patients with high PTEN expression (5 year RFS 0.64 vs. 0.87, p = 0.01). In the Cox proportional hazards model for RFS, PTEN expression, progesterone receptor, and pathological therapeutic effect were predictive factors for time to recurrence (All p < 0.05). CONCLUSIONS: PIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10853-y.
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spelling pubmed-101345712023-04-28 The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients Hayama, Shouko Nakamura, Rikiya Ishige, Takayuki Sangai, Takafumi Sakakibara, Masahiro Fujimoto, Hiroshi Ishigami, Emi Masuda, Takahito Nakagawa, Ayako Teranaka, Ryotaro Ota, Satoshi Itoga, Sakae Yamamoto, Naohito Nagashima, Takeshi Otsuka, Masayuki BMC Cancer Research BACKGROUND: There is pressing needs to find the biomarker in the selection of neoadjuvant therapy in postmenopausal luminal breast cancer patients. We examined the hypothesis that PIK3CA mutations and low phosphatase and tensin homolog (PTEN) expression affect the response to neoadjuvant therapy and prognosis in postmenopausal luminal breast cancer patients. METHODS: Postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, up to stage II, who underwent neoadjuvant chemotherapy (NAC; n = 60) or neoadjuvant endocrine therapy (NAE; n = 55) were selected. PIK3CA exon 9 and exon 20 mutations were screened by high resolution melting analysis and confirmed by Sanger sequence. PTEN expression was evaluated by immunohistochemistry. The relationships among PIK3CA mutations, PTEN expression, clinicopathological features, the pathological effect of neoadjuvant therapy, recurrence-free survival (RFS) and overall survival were analyzed. RESULTS: Among 115 patients, PIK3CA mutations and low PTEN expression before treatment were detected in 35 patients (30.4%) and in 28 patients (24.3%), respectively. In the NAC group, tumor with PIK3CA mutations showed significantly poorer response than tumor with PIK3CA wild-type (p = 0.03). On the other hand, in the NAE group, there was no significant difference in pathological therapeutic effect between tumor with PIK3CA mutations and tumor with PIK3CA wild-type (p = 0.54). In the NAC group, the log-rank test showed no difference in RFS between patients with PIK3CA mutations and PIK3CA wild-type (p = 0.43), but patients with low PTEN expression showed significantly worse RFS compared to patients with high PTEN expression (5 year RFS 0.64 vs. 0.87, p = 0.01). In the Cox proportional hazards model for RFS, PTEN expression, progesterone receptor, and pathological therapeutic effect were predictive factors for time to recurrence (All p < 0.05). CONCLUSIONS: PIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10853-y. BioMed Central 2023-04-27 /pmc/articles/PMC10134571/ /pubmed/37106324 http://dx.doi.org/10.1186/s12885-023-10853-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hayama, Shouko
Nakamura, Rikiya
Ishige, Takayuki
Sangai, Takafumi
Sakakibara, Masahiro
Fujimoto, Hiroshi
Ishigami, Emi
Masuda, Takahito
Nakagawa, Ayako
Teranaka, Ryotaro
Ota, Satoshi
Itoga, Sakae
Yamamoto, Naohito
Nagashima, Takeshi
Otsuka, Masayuki
The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients
title The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients
title_full The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients
title_fullStr The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients
title_full_unstemmed The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients
title_short The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients
title_sort impact of pik3ca mutations and pten expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134571/
https://www.ncbi.nlm.nih.gov/pubmed/37106324
http://dx.doi.org/10.1186/s12885-023-10853-y
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