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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Modified MVAC as a Second-Line Treatment for Patients with Metastatic Urothelial Carcinoma after Failure of Gemcitabine and Cisplatin Treatment: Jung Hyun Lee, Sung Gu Kang, Seung Tae Kim, Seok Ho Kang, In Keun Choi, Young Je Park, Sang Chul Oh, Deuk Jae Sung, Jae Hong Seo, Jun Cheon, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim, Kyong Hwa Park; Cancer Res Treat. 2014;46(2):172-177. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.172

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Purpose

There is no established standard second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and cisplatin (GC) chemotherapy. This study was conducted in order to investigate the efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with metastatic UC previously treated with GC.

Materials and Methods

We retrospectively analyzed 28 patients who received modified MVAC between November 2004 and November 2012. All patients failed prior, first-line GC chemotherapy.

Results

The median age of patients was 64.0 years (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The overall response rate and the disease control rate were 36.0% and 64.0%, respectively. After a median follow-up period of 38 weeks (range, 5 to 182 weeks), median progression free survival was 21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or 4 non-hematological toxicities did not occur and there was no treatment-related death.

Conclusion

Modified MVAC appears to be a safe and active chemotherapy regimen in patients with stable physical status and adequate renal function after GC treatment.

Citations

Citations to this article as recorded by

Chronological transition in outcome of second-line treatment in patients with metastatic urothelial cancer after pembrolizumab approval: a multicenter retrospective analysis
Teruki Isobe, Taku Naiki, Yosuke Sugiyama, Aya Naiki-Ito, Takashi Nagai, Toshiki Etani, Satoshi Nozaki, Keitaro Iida, Yusuke Noda, Nobuhiko Shimizu, Nami Tomiyama, Rika Banno, Hiroki Kubota, Shuzo Hamamoto, Ryosuke Ando, Noriyasu Kawai, Takahiro Yasui
International Journal of Clinical Oncology.2022; 27(1): 165. CrossRef
SIU-ICUD recommendations on bladder cancer: systemic therapy for metastatic bladder cancer
Axel S. Merseburger, Andrea B. Apolo, Simon Chowdhury, Noah M. Hahn, Matthew D. Galsky, Matthew I. Milowsky, Daniel Petrylak, Tom Powles, David I. Quinn, Jonathan E. Rosenberg, Arlene Siefker-Radtke, Guru Sonpavde, Cora N. Sternberg
World Journal of Urology.2019; 37(1): 95. CrossRef
Efficacy of Different Second-line Therapy Regimens in Metastatic Urothelial Carcinoma
Lukas Barwitz, Anne Berger, Stefanie Zschaebitz, Max Jenzer, Cathleen Nientiedt, Stefan Duensing, Dirk Jäger, Dogu Teber, Markus Hohenfellner, Carsten Grüllich
The Open Urology & Nephrology Journal.2017; 10(1): 52. CrossRef
Cisplatin- Versus Non–Cisplatin-based First-Line Chemotherapy for Advanced Urothelial Carcinoma Previously Treated With Perioperative Cisplatin
Jennifer A. Locke, Gregory Russell Pond, Guru Sonpavde, Andrea Necchi, Patrizia Giannatempo, Ravi Kumar Paluri, Guenter Niegisch, Peter Albers, Carlo Buonerba, Giuseppe Di Lorenzo, Ulka N. Vaishampayan, Scott A. North, Neeraj Agarwal, Syed A. Hussain, Sum
Clinical Genitourinary Cancer.2016; 14(4): 331. CrossRef
Second Line Chemotherapy for Advanced and Metastatic Urothelial Carcinoma: Vinflunine and Beyond—A Comprehensive Review of the Current Literature
Christoph Oing, Michael Rink, Karin Oechsle, Christoph Seidel, Gunhild von Amsberg, Carsten Bokemeyer
Journal of Urology.2016; 195(2): 254. CrossRef
Predicting the response of patients with advanced urothelial cancer to methotrexate, vinblastine, Adriamycin, and cisplatin (MVAC) after the failure of gemcitabine and platinum (GP)
Ki Hong Kim, Sung Joon Hong, Kyung Seok Han
BMC Cancer.2015;[Epub] CrossRef

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Docetaxel and Cisplatin Combination Chemotherapy in Patients with Squamous Cell Carcinomas of the Head and Neck: Jung Hyun Lee, Kyung Woo Lee, Young Jin Choi, Jae Hoon Choi, Ho Jin Shin, Joo Seop Chung, Goon Jae Cho, Byung Ju Lee, Soo Geun Wang; Cancer Res Treat. 2003;35(3):261-266. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.261

Abstract PDF

PURPOSE
The objective of this phase II study was to assess the clinical antitumor activity and toxicities of docetaxel and cisplatin chemotherapy, in patients with locally advanced and metastatic, recurrent squamous cell carcinomas of the head and neck (SCCHN). MATERIALS AND METHODS: All eligible patients with locally advanced and metastatic, recurrent SCCHN had received two courses of chemotherapy followed by repeated head and neck examinations and computed tomography. Patients who had received prior chemotherapy with taxanes were ineligible. If the patients achieved a response (either CR or PR), they received one more course of chemotherapy prior to undergoing definitive local treatment. The combination chemotherapy consisted of docetaxel, 70 mg/m2, and cisplatin, 75 mg/m2, on day 1, with the cycles repeated every 3~4 weeks. RESULTS: All 32 patients were assessable for response and toxicity analyses. The most common grade 3/4 adverse event was neutropenia, which occurred in 11% of cases. No febrile neutropenia was noticed. The other grade 3/4 adverse events included: anemia (2%) and stomatitis (3%). The response rate in patients with locally advanced cancer was 19/21 (90%). Fifteen patients (71%) achieved a CR and 4 (19%) a PR. Out of the 4 patients presenting with a distant metastatic disease, 1 each achieved CR and PR, with 2 stable disease (SD). Out of the 7 patients with a recurrence at a distant site, 1 each achieved PR and SD, and 5 (71%) had a progression of the disease (PD). The overall response rate was 22/32 (69%).
CONCLUSION
Docetaxel plus cisplatin is an effective regimen with an acceptable toxicity profile. This regimen may offer high antitumor activity on short outpatient administration, with a low incidence of severe toxicity.

Citations

Citations to this article as recorded by

The Analysis of Induction Chemotherapy Using Docetaxel and Platinum in Treatment of Hypopharyngeal Carcinoma
Jongseung Kim, Kyengsuk Lee, Byungeon Hwang, Sangho Lim, Sunho Ryu, Ilwoo Ha, Eun Jung Lee, Kihwan Hong, Yunsu Yang
Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2010; 53(11): 706. CrossRef
The Efficacy of an Induction Chemotherapy Combination with Docetaxel, Cisplatin, and 5-FU Followed by Concurrent Chemoradiotherapy in Advanced Head and Neck Cancer
Jae-Sook Ahn, Sang-Hee Cho, Ok-Ki Kim, Joon-Kyoo Lee, Deok-Hwan Yang, Yeo-Kyeoung Kim, Je-Jung Lee, Sang-Chul Lim, Hyeoung-Joon Kim, Woong-Ki Chung, Ik-Joo Chung
Cancer Research and Treatment.2007; 39(3): 93. CrossRef

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