Cancer Research and Treatment

Original Articles

Breast cancer

PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients: Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park; Cancer Res Treat. 2023;55(2):531-541. Published online September 7, 2022; DOI: https://doi.org/10.4143/crt.2022.221

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Purpose
Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer.
Materials and Methods
We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment.
Results
Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors.
Conclusion
Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Citations

Citations to this article as recorded by

Safety and efficacy of pyrotinib for HER‑2‑positive breast cancer in the neoadjuvant setting: A systematic review and meta‑analysis
Qian Ma, Bai Wei, Bi-Cheng Wang, Ganxin Wang, Xuan Zhou, Yan Wang
Oncology Letters.2024;[Epub] CrossRef
A novel PIK3CA hot-spot mutation in breast cancer patients detected by HRM-COLD-PCR analysis
Saoussen Debouki-Joudi, Wala Ben Kridis, Fatma Trifa, Wajdi Ayadi, Abdelmajid Khabir, Tahia Sellami-Boudawara, Jamel Daoud, Afef Khanfir, Raja Mokdad-Gargouri
Breast Disease.2024; 43(1): 213. CrossRef
Liquid Biopsy in the Clinical Management of Cancers
Ho-Yin Ho, Kei-See (Kasey) Chung, Chau-Ming Kan, Sze-Chuen (Cesar) Wong
International Journal of Molecular Sciences.2024; 25(16): 8594. CrossRef
Modeling the management of patients with human epidermal growth factor receptor 2-positive breast cancer with liquid biopsy: the future of precision medicine
Eleonora Nicolò, Caterina Gianni, Giuseppe Curigliano, Carolina Reduzzi, Massimo Cristofanilli
Current Opinion in Oncology.2024; 36(6): 503. CrossRef
Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer
Li Yin, Gui-lai Chen, Zhuo Xiang, Yu-lin Liu, Xing-yu Li, Jing-wang Bi, Qiang Wang
Biomedicine & Pharmacotherapy.2023; 162: 114648. CrossRef
Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
Scientific Reports.2023;[Epub] CrossRef
Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data
Haizhu Chen, Xingbin Hu, Daquan Wang, Ying Wang, Yunfang Yu, Herui Yao
Translational Oncology.2023; 37: 101738. CrossRef
Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer—A Literature Review
Danilo Giffoni de Mello Morais Mata, Rania Chehade, Malek B. Hannouf, Jacques Raphael, Phillip Blanchette, Abdullah Al-Humiqani, Monali Ray
Cancers.2023; 15(17): 4336. CrossRef
The clinical significance of HER2 expression in DCIS
Ioanna Akrida, Francesk Mulita
Medical Oncology.2022;[Epub] CrossRef

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Clinical Outcomes of Local Excision Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Nam Kwon Lee, Dae Yong Kim, Sun Young Kim, Jae Hwan Oh, Won Park, Doo Ho Choi, Taek-Keun Nam, Kyung-Ja Lee; Cancer Res Treat. 2014;46(2):158-164. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.158

Abstract PDF PubReader ePub

Purpose

To evaluate the treatment outcomes of local excision following preoperative chemoradiotherapy in patients with locally advanced rectal cancer who have not undergone radical surgery for any reason.

Materials and Methods

The data of 27 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy followed by local excision were analyzed retrospectively. The primary endpoint was the 5-year relapse-free survival rate, and the secondary endpoint was the pattern of recurrence.

Results

The median follow-up time was 81.8 months (range, 28.6 to 138.5 months). The 5-year local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were 88.9%, 81.1%, 77.8%, and 85.0%, respectively. Six (22%) patients developed treatment failure; one (4%) patient had local recurrence only, three (11%) patients had distant recurrence only, and two (7%) patients had both. The 5-year LRFS, DMFS, RFS, and OS for patients with ypT0-1 compared with ypT2-3 were 94.1% vs. 77.8% (p=0.244), 94.1% vs. 55.6% (p=0.016), 88.2% vs. 55.6% (p=0.051), and 94.1% vs. 66.7% (p=0.073), respectively.

Conclusion

Local excision following preoperative chemoradiotherapy may be an alternative treatment for highly selected patients with locally advanced rectal cancer who have achieved ypT0-1 after preoperative chemoradiotherapy.

Citations

Citations to this article as recorded by

Organ‐saving surgery for rectal cancer after neoadjuvant chemoradiation: Analysis of failures and long‐term results
Maurizio Cosimelli, Pietro Ursi, Raffaello Mancini, Giada Pattaro, Pasquale Perri, Chiara Parrino, Valerio De Peppo, Maria Grazia Diodoro, Andrea Balla, Gian Luca Grazi
Journal of Surgical Oncology.2020; 121(2): 375. CrossRef
Local excision for ypT2 rectal cancer following preoperative chemoradiation therapy: it should not be justified
Kwan Mo Yang, Seok-Byung Lim, Jong Lyul Lee, Chan Wook Kim, Yong Sik Yoon, In Ja Park, Chang Sik Yu, Jin Cheon Kim
International Journal of Colorectal Disease.2018; 33(4): 487. CrossRef
Are We Predicting Disease Progress of the Rectal Cancer Patients without Surgery after Neoadjuvant Chemoradiotherapy?
Bo Young Oh, Jung Wook Huh, Woo Yong Lee, Yoon Ah Park, Yong Beom Cho, Seong Hyeon Yun, Hee Cheol Kim, Ho-Kyung Chun
Cancer Research and Treatment.2018; 50(3): 634. CrossRef
Total Mesorectal Excision Versus Local Excision After Favorable Response to Preoperative Chemoradiotherapy in “Early” Clinical T3 Rectal Cancer: A Propensity Score Analysis
Young Seob Shin, Chang Sik Yu, Jin-hong Park, Jin Cheon Kim, Seok-Byung Lim, In Ja Park, Tae Won Kim, Yong Sang Hong, Kyu-pyo Kim, Sang Min Yoon, Ji Hyeon Joo, Jong Hoon Kim
International Journal of Radiation Oncology*Biology*Physics.2017; 99(1): 136. CrossRef
Controversial issues in radiotherapy for rectal cancer: a systematic review
Jong Hoon Kim
Radiation Oncology Journal.2017; 35(4): 295. CrossRef
Local excision of low rectal cancer treated by chemoradiotherapy: is it safe for all patients with suspicion of complete tumor response?
Clotilde Debove, Nathalie Guedj, Ecoline Tribillon, Léon Maggiori, Magaly Zappa, Yves Panis
International Journal of Colorectal Disease.2016; 31(4): 853. CrossRef
Seven low-mass ions in pretreatment serum as potential predictive markers of the chemoradiotherapy response of rectal cancer
Kangsan Roh, Seung-Gu Yeo, Byong Chul Yoo, Kyung-Hee Kim, Sun Young Kim, Min-Jeong Kim
Anti-Cancer Drugs.2016; 27(8): 787. CrossRef
A Systematic Review of Local Excision After Neoadjuvant Therapy for Rectal Cancer: Are ypT0 Tumors the Limit?
Sally Hallam, David E. Messenger, Michael G. Thomas
Diseases of the Colon & Rectum.2016; 59(10): 984. CrossRef
Definitive high-dose radiotherapy with concurrent chemotherapy for locally advanced rectal cancer
Min-Jeong Kim, Eun Seok Kim, Seung-Gu Yeo
Medicine.2016; 95(40): e5059. CrossRef
Association of pretreatment serum carcinoembryonic antigen levels with chemoradiation-induced downstaging and downsizing of rectal cancer
SEUNG-GU YEO
Molecular and Clinical Oncology.2016; 4(4): 631. CrossRef
The Role of Fibrinogen as a Predictor in Preoperative Chemoradiation for Rectal Cancer
Jong Hoon Lee, Jong Hee Hyun, Dae Yong Kim, Byong Chul Yoo, Ji Won Park, Sun Young Kim, Hee Jin Chang, Byung Chang Kim, Tae Hyun Kim, Jae Hwan Oh, Dae Kyung Sohn
Annals of Surgical Oncology.2015; 22(1): 209. CrossRef
Oncologic Outcomes according to the Treatment Strategy in Radiologic Complete Responders after Neoadjuvant Chemoradiation for Rectal Cancer
Soo Young Lee, Chang Hyun Kim, Young Jin Kim, Hyeong Rok Kim
Oncology.2015; 89(6): 311. CrossRef

13,541 View
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