Refining the indications for neoadjuvant chemotherapy for patients with HER2+ breast cancer: A single institution experience

Pomponio, Maria; Burkbauer, Laura; Goldbach, Macy; Nazarian, Susanna M.; Xie, Fei; Clark, Amy S.; Matro, Jennifer M.; Fox, Kevin R.; Shulman, Lawrence N.; Keele, Luke; Tchou, Julia

doi:10.1002/jso.25814

Cited by 7 publications

(4 citation statements)

References 45 publications

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“…FOXO3a is a member of the FOXO family; it enters the nucleus after binding with β-catenin, where it was reported to accelerate the self-renewal of cancer cells, thus promoting the formation of tumors ( 37 , 38 ). FOXO3a has also been discovered to combine with the transcription regulatory machinery of different target genes in the nucleus to serve a role in transcriptional regulation, in addition to participating in the proliferation, migration, invasion and apoptosis of cells ( 12 , 39 ). FOXO3a was also discovered to serve a role in abnormal activity, stress tolerance and the metabolic homeostasis of tumor cells by regulating the expression of cell cycle-related factors and apoptosis-related factors effect ( 40 , 41 ).…”

Section: Discussionmentioning

confidence: 99%

FOXO3a inhibits nephroblastoma cell proliferation, migration and invasion, and induces apoptosis through downregulating the Wnt/β‑catenin signaling pathway

Qian

Liu

2021

Mol Med Rep

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Forkhead transcription factor O subfamily 3A (FOXO3a) is an important tumor suppressor gene that is expressed in renal tissue and has been reported to be downregulated in clear cell renal cell carcinoma (CCRCC). Notably, the overexpression of FOXO3a was previously discovered to inhibit the progression of CCRCC. However, the expression levels of FOXO3a in nephroblastoma cell lines remain unknown. The present study aimed to investigate the expression levels of FOXO3a in nephroblastoma cell lines and to determine the mechanism of action of the biological functions of FOXO3a. Western blotting and reverse transcription-quantitative PCR were used to analyze the expression levels of FOXO3a in nephroblastoma cell lines. Subsequently, the effects of the overexpression of FOXO3a and the genetic knockdown of the Wnt/β-catenin signaling protein Axin-2 on the biological functions were determined through Cell Counting Kit-8, cell colony formation assays, scratch and Transwell assay and flow cytometric analysis experiments. The expression levels of FOXO3a were discovered to be downregulated in nephroblastoma cell lines. The overexpression of FOXO3a inhibited the proliferation, invasion and migration of nephroblastoma cells, while inducing apoptosis. Furthermore, the overexpression of FOXO3a downregulated the expression levels of β-catenin and Cyclin-D1 proteins involved in the Wnt/β-catenin signaling pathway. Cell proliferation and the migration and invasion ability of 17–94 cells in shRNA-Axin2-2 group were promoted. Cell apoptosis was predominantly increased by overexpressed FOXO3a, which was reversed by shRNA-Axin2-1. The biological effects of overexpressing FOXO3a on nephroblastoma were reversed after activation of Wnt/β-catenin. In conclusion, the findings of the present study suggested that FOXO3a may inhibit nephroblastoma cell proliferation, migration and invasion, while inducing apoptosis, by downregulating the Wnt/β-catenin signaling pathway. These results may provide a novel method for the early diagnosis and precise treatment of nephroblastoma.

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Section: Discussionmentioning

confidence: 99%

FOXO3a inhibits nephroblastoma cell proliferation, migration and invasion, and induces apoptosis through downregulating the Wnt/β‑catenin signaling pathway

Qian

Liu

2021

Mol Med Rep

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“…For HER2+ breast cancer patients in neoadjuvant setting, the standard regimen to date was chemotherapy and trastuzumab (AC-TH, AC-PH, or TCbH), in which the pCR rates of 50% or more can be achieved (15,(19)(20)(21). TCbH has often been preferred by clinicians due to its lower cardiotoxicity profile, in which weekly regimens are much more effective than the threeweek schedule (69% vs. 41%; p = 0.03) (15,21).…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Predictive Models for the Prediction of Pathological Complete Response to Optimize the Effectiveness for Trastuzumab Based Chemotherapy

Chen

Zheng

et al. 2021

Front. Oncol.

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BackgroundTrastuzumab shows excellent benefits for HER2+ breast cancer patients, although 20% treated remain unresponsive. We conducted a retrospective cohort study to optimize neoadjuvant chemotherapy and trastuzumab treatment in HER2+ breast cancer patients.MethodsSix hundred patients were analyzed to identify clinical characteristics of those not achieving a pathological complete response (pCR) to develop a clinical predictive model. Available RNA sequence data was also reviewed to develop a genetic model for pCR.ResultsThe pCR rate was 39.8% and pCR was associated with superior disease free survival and overall survival. ER negativity and PR negativity, higher HER2 IHC scores, higher Ki-67, and trastuzumab use were associated with improved pCR. Weekly paclitaxel and carboplatin had the highest pCR rate (46.70%) and the anthracycline+taxanes regimen had the lowest rate (11.11%). Four published GEO datasets were analyzed and a 10-gene model and immune signature for pCR were developed. Non-pCR patients were ER+PR+ and had a lower immune signature and gene model score. Hormone receptor status and immune signatures were independent predictive factors of pCR.ConclusionHormone receptor status and a 10-gene model could predict pCR independently and may be applied for patient selection and drug effectiveness optimization.

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“…This is, to our knowledge, one of the first studies to report an impact of treatment strategy (NAC vs. AC) in a subset of patients: the HER2-positive population. In a recent study of Pomponio et al, using IPTW to deal with the selection bias showed no difference between AC and NAC strategy in early HER2-postive BC [30]. Many studies have reported higher rates of breast-conserving surgery in patients treated with NAC, but a recent EBCTCG meta-analysis [13] found that NAC was as effective as AC in reducing the risk of distant recurrence and death from BC.…”

Section: Discussionmentioning

confidence: 99%

HER2-Positive Breast Cancer Patients with Pre-Treatment Axillary Involvement or Postmenopausal Status Benefit from Neoadjuvant Rather than Adjuvant Chemotherapy Plus Trastuzumab Regimens

Laas

Bresset

Féron

et al. 2021

Cancers

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Background: No survival benefit has yet been demonstrated for neoadjuvant chemotherapy (NAC) against HER2-positive tumors in patients with early breast cancer (BC). The objective of this study was to compare the prognosis of HER2-positive BC patients treated with NAC to that of patients treated with adjuvant chemotherapy (AC). Materials and methods: We retrospectively analyzed disease-free (DFS) and overall survival (OS) in 202 HER2-positive patients treated with NAC and 701 patients treated with AC. All patients received trastuzumab in addition to chemotherapy. Patient data were weighted by a propensity score to overcome selection bias. Results: After inverse probability of treatment weights (IPTW) adjustment, no difference in DFS (p = 0.3) was found between treatments for the total population. However, after multivariate analysis, an interaction was found between cN status and chemotherapy strategy (IPTW-corrected corrected Hazard ratio cHR = 0.52, 95% CI (0.3–0.9), pinteraction = 0.08) and between menopausal status and chemotherapy (CT) strategy (cHR = 0.35, 95%CI (0.18–0.7)) pinteraction < 0.01). NAC was more beneficial than AC strategy in cN-positive patients and in postmenopausal patients. Moreover, after IPTW adjustment, the multivariate analysis showed that the neoadjuvant strategy conferred a significant OS benefit (cHR = 0.09, 95%CI [0.02–0.35], p < 0.001). Conclusion: In patients with HER2-positive BC, the NAC strategy is more beneficial than the AC strategy, particularly in cN-positive and postmenopausal patients. NAC should be used as a first-line treatment for HER2-positive tumors.

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Refining the indications for neoadjuvant chemotherapy for patients with HER2+ breast cancer: A single institution experience

Cited by 7 publications

References 45 publications

FOXO3a inhibits nephroblastoma cell proliferation, migration and invasion, and induces apoptosis through downregulating the Wnt/β‑catenin signaling pathway

FOXO3a inhibits nephroblastoma cell proliferation, migration and invasion, and induces apoptosis through downregulating the Wnt/β‑catenin signaling pathway

Clinical and Genetic Predictive Models for the Prediction of Pathological Complete Response to Optimize the Effectiveness for Trastuzumab Based Chemotherapy

HER2-Positive Breast Cancer Patients with Pre-Treatment Axillary Involvement or Postmenopausal Status Benefit from Neoadjuvant Rather than Adjuvant Chemotherapy Plus Trastuzumab Regimens

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