Concurrent neoadjuvant chemotherapy and estrogen deprivation in patients with estrogen receptor–positive, human epidermal growth factor receptor 2–negative breast cancer (CBCSG‐036): A randomized, controlled, multicenter trial

Yu, Ke; Wu, Siyu; Liu, Guang Yu; Wu, Jiong; Di, Gen-Hong; Hu, Zhen; Hou, Yi; Chen, Can Ming; Fan, Lei; Tang, Li; Shen, Zhen; Wu, Ke Jin; Zhuang, Zhi; Zhang, Hong Wei; Shao, Zhi Ming

doi:10.1002/cncr.32057

Cited by 21 publications

(26 citation statements)

References 36 publications

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“… 48 However, the advantage of concurrent neoadjuvant chemotherapy and hormone therapy in ER-positive breast cancer remains controversial. 49 , 50 , 51 In light of our study, we discovered that ERα renders chemoresistance by regulating p53-dependent gene transcription from lincRNA-p21 to DDB2 for DNA repair in mutp53-expressing breast cancer cells, supporting that the addition of the ER inhibitor to neoadjuvant chemotherapy provides the improvement of the clinical response in patients with ER-positive breast cancer, especially for those individuals with p53 mutations.…”

Section: Discussionmentioning

confidence: 63%

ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions

He¹,

Yeh²,

Chen³

et al. 2021

Molecular Therapy - Nucleic Acids

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Mutant p53 (mutp53) commonly loses its DNA binding affinity to p53 response elements (p53REs) and fails to induce apoptosis fully. However, the p53 mutation does not predict chemoresistance in all subtypes of breast cancers, and the critical determinants remain to be identified. In this study, mutp53 was found to mediate chemotherapy-induced long intergenic noncoding RNA-p21 (lincRNA-p21) expression by targeting the G-quadruplex structure rather than the p53RE on its promoter to promote chemosensitivity. However, estrogen receptor alpha (ERα) suppressed mutp53-mediated lincRNA-p21 expression by hijacking mutp53 to upregulate damaged DNA binding protein 2 ( DDB2 ) transcription for subsequent DNA repair and chemoresistance. Levels of lincRNA-p21 positively correlated with the clinical responses of breast cancer patients to neoadjuvant chemotherapy and had an inverse correlation with the ER status and DDB2 level. In contrast, the carboplatin-induced DDB2 expression was higher in ER-positive breast tumor tissues. These results demonstrated that ER status determines the oncogenic function of mutp53 in chemoresistance by switching its target gene preference from lincRNA-p21 to DDB2 and suggest that induction of lincRNA-p21 and targeting DDB2 would be effective strategies to increase the chemosensitivity of mutp53 breast cancer patients.

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Section: Discussionmentioning

confidence: 63%

ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions

He¹,

Yeh²,

Chen³

et al. 2021

Molecular Therapy - Nucleic Acids

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“…Accordingly, concurrent neoadjuvant chemotherapy and estrogen deprivation had been proposed that whether NCT plus NET can convert to a higher tumor response. Several studies found that the combination neoadjuvant therapy appeared to improve the clinical response or shrinkage of tumor in ER+/HER2− BC (36)(37)(38), while inconsistent conclusion was reached that NCT plus NET as neoadjuvant therapy was not superior to NCT or NET alone in tumor response (39,40). More large-scale and high-quality prospective studies are required to follow these preliminary results to confirm the efficacy, safety and economic benefits of concurrent neoadjuvant chemotherapy and estrogen deprivation for HR+/HER2− BC patients, while in the future similar studies can involve CDK4/6 inhibitors into NET regimen to explore new fields.…”

Section: Discussionmentioning

confidence: 99%

Pharmacoeconomic evaluations of CDK4/6 inhibitors plus endocrine therapy for advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2−) breast cancer: a systematic review

Zhu¹,

Wang²,

Luo³

et al. 2022

Ann Transl Med

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Background: Hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2−) breast cancer is the most common molecular subtype of breast cancer in many countries, and endocrine therapy remains a mainstay in its treatment. Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of targeted agents administered orally that are recommended being used in combination with endocrine therapy as first and second line treatments for advanced HR+/HER2− breast cancer. However, their high prices largely hinder using these drugs in real world settings. To offer a new basis for future research, we investigated the cost-effectiveness of combinations of CDK4/6 inhibitors with endocrine therapy in the treatment of advanced HR+/HER2− breast cancer.Methods: We systematically searched several frequently used databases and identified economic evaluations published from February 2015 to April 2021. The systematic review was performed after retrieving the literatures and extracting data based on inclusion and exclusion criteria. The quality of each selected economic evaluation was assessed by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Results:The literature search yielded 161 articles, among which fourteen studies (15 articles) with CHEER scores ranging from 58.33% to 87.50% entered the final analysis. Markov models were used in most studies. Based on the currently available data, CDK4/6 inhibitors plus endocrine therapy were less costeffective in first-or second-line treatment of patients with HR+/HER2− advanced breast cancer. However, ribociclib plus letrozole was more cost-effective than palbociclib plus letrozole in the first-line treatment of postmenopausal women. The economic impacts of CDK4/6 inhibitors plus endocrine therapy in nonpostmenopausal patients or second-line therapy cannot be fully evaluated due to the limited number of studies. The three most common factors affecting economic outcomes were the prices of CDK4/6 inhibitors, hazard ratios for progression-free survival and overall survival, and health status utility values. Discussion: CDK4/6 inhibitors plus endocrine therapy have shown significantly improved efficacy outcomes in HR+/HER2− metastatic breast cancer (mBC)/advancer breast cancer (ABC) first-line and second-line treatment for endocrine-sensitive and endocrine-resistant populations, while more potential fields including neoadjuvant and adjuvant settings are being identified to benefit a wider range of breast cancer patients. Meanwhile, risk of severe adverse events that more likely to happen in patients treated with CDK4/6 inhibitors can lead to reduced life quality and higher medical costs patients need to afford. The adverse drug reaction related cost in several economic burden studies were explored to be primarily driven

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“…In the present study, only 2 patients (4.7%) achieved pCR. Recent publication by Yu et al [25] with the large cohort found the low pCR rate (7.2%) after neoadjuvant chemo-endocrine therapy in ER-positive and HER2-negaitve breast cancer. Ellis et al [26] suggested the triage to chemotherapy for patients with high Ki67 LI after neoadjuvant endocrine treatment is less effective in the American College of Surgeons Oncology Group Z1031 Trial.…”

Section: Discussionmentioning

confidence: 99%

Utility of Ki67 labeling index, cyclin D1 expression, and ER-activity level in postmenopausal ER-positive and HER2-negative breast cancer with neoadjuvant chemo-endocrine therapy

et al. 2019

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In this study, we investigated the relationships of pathological response after neoadjuvant chemo-endocrine therapy with alterations in the Ki67 labeling index (LI), expression of cyclin D1 (CCND1) and progesterone receptor (PgR), and estrogen receptor (ER) activity in breast cancer. A total of 43 Japanese post-menopausal ER-positive and human epidermal growth factor receptor 2-negative invasive breast cancer patients with tumors >2 cm or positive lymph nodes were enrolled. Exemestane alone was administered for 2 months. Neoadjuvant chemo-endocrine therapy included four cycles of doxorubicin plus paclitaxel followed by weekly paclitaxel. The immunohistochemical expression of Ki67 LI, CCND1, and PgR, and ER activity were evaluated using core needle biopsy samples at the pretreatment and post-exemestane alone stages. ER activity was evaluated through transfection of an adenovirus vector carrying an estrogen-response element-green fluorescent protein gene. In current study, marked pathological responses (including 4.7% with pathological complete response) were obtained in 34.9% of patients. Ki67 LI and PgR expression were significantly decreased after treatment. High Ki67 LI at pretreatment was a significant predictive factor of marked pathological response. At the stage of post-exemestane alone, Ki67 LI was not significantly associated with pathological response; however, high CCND1 expression was significantly correlated with high Ki67 LI. Moreover, low-level ER activity at the post-exemestane alone stage was significantly associated with marked pathological response. In conclusions, pretreatment Ki67 LI was a predictor of response to neoadjuvant chemo-endocrine therapy. CCND1 expression and ER activity at the post-endocrine therapy alone stage may be useful in determining further treatments.

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Concurrent neoadjuvant chemotherapy and estrogen deprivation in patients with estrogen receptor–positive, human epidermal growth factor receptor 2–negative breast cancer (CBCSG‐036): A randomized, controlled, multicenter trial

Cited by 21 publications

References 36 publications

ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions

ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions

Pharmacoeconomic evaluations of CDK4/6 inhibitors plus endocrine therapy for advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2−) breast cancer: a systematic review

Utility of Ki67 labeling index, cyclin D1 expression, and ER-activity level in postmenopausal ER-positive and HER2-negative breast cancer with neoadjuvant chemo-endocrine therapy

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