• 18F-FES PET-CT
• Breast neoplasms
• ER+/HER2–
• Fulvestrant
• Metabolites
• Neoadjuvant therapy

• Humans
• Female
• Breast Neoplasms/drug therapy
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Breast Neoplasms/diagnostic imaging
• Positron Emission Tomography Computed Tomography/methods
• Middle Aged
• Neoadjuvant Therapy/methods
• Receptor, ErbB-2/metabolism
• Receptors, Estrogen/metabolism
• Adult
• Fulvestrant/administration & dosage
• Fulvestrant/therapeutic use
• Fulvestrant/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Aged
• Treatment Outcome
• Estradiol/analogs & derivatives
• Estradiol/administration & dosage

• 2021MSXM291 Chongqing Science and Health Joint Medical Research Project
• 2022MSXM004 Chongqing Science and Health Joint Medical Research Project
• CB23003 Beijing Health Alliance Charitable Foundation
• National Key Clinical Specialty Construction Project
• 2019NLTS005 Chongqing Municipal Health and Health Commission
• CQYC20200303137 Talent Program of Chongqing

• Breast cancer
• Chemotherapy
• Combination therapy
• Endocrine therapy
• Sequential therapy

• Humans
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Female
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Antineoplastic Agents, Hormonal/therapeutic use
• Antineoplastic Agents, Hormonal/administration & dosage
• Receptors, Estrogen/metabolism

• chemotherapy
• early breast cancer
• endocrine therapy
• hormone-receptor positive breast cancer
• neoadjuvant treatment

• Breast cancer
• chemotherapy
• endocrine therapy
• hormone receptor-positive/human epidermal growth factor receptor 2-negative
• immunotherapy
• neoadjuvant
• network meta-analysis

• Humans
• Female
• Neoadjuvant Therapy/methods
• Bayes Theorem
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Network Meta-Analysis
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2/metabolism
• Antineoplastic Combined Chemotherapy Protocols/pharmacology
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Clinical Trials, Phase III as Topic
• Clinical Trials, Phase II as Topic

• Asian patients
• Biomarkers
• Breast cancer
• Genetic variation
• Molecular subtypes
• Neoadjuvant treatment
• Pathological complete response
• Systematic review

• Female
• Humans
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Breast Neoplasms/drug therapy
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Bridged-Ring Compounds
• Class I Phosphatidylinositol 3-Kinases
• Genetic Variation
• Ki-67 Antigen/metabolism
• Receptor, ErbB-2/genetics
• Receptor, ErbB-2/metabolism
• Receptors, Estrogen/genetics
• Receptors, Estrogen/metabolism
• Taxoids/therapeutic use
• Triple Negative Breast Neoplasms/drug therapy
• Triple Negative Breast Neoplasms/genetics

• Breast cancer
• chemotherapy
• concomitant
• endocrine therapy
• meta-analysis
• neoadjuvant

• Humans
• Female
• Neoadjuvant Therapy/adverse effects
• Receptor, ErbB-2
• Breast Neoplasms/drug therapy
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Hormones/therapeutic use
• Chemotherapy, Adjuvant
• Antineoplastic Combined Chemotherapy Protocols/adverse effects

• Chemotherapy
• Concurrent therapy
• Early breast cancer
• Endocrine therapy

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.

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).

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 cost-effective 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 non-postmenopausal 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.

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 by hospitalizations and outpatient, and assessment of cost associated with CDK4/6 inhibitors adverse events is worth further developing. Drug wastage costs were found higher in palbociclib regimen than ribociclib regimen due to different dosing patterns. Moreover, current economic evaluations showed that ribociclib plus letrozole had better economic benefits than palbociclib plus letrozole for first-line treatment of postmenopausal women with HR+/HER2− ABC.

• CDK4/6 inhibitors
• breast cancer
• pharmacoeconomic evaluation
• systematic review

• DDB2
• G-quadruplex
• chemotherapy
• estrogen receptor
• lincRNA-p21
• mutant p53

Studies have shown that neoadjuvant anti-HER-2 therapy and chemotherapy can increase pathologic complete response (pCR) rate in HER-2-positive breast cancer patients and improve prognosis. However, data from Chinese patients are limited. Therefore, we conducted a single-center retrospective study to evaluate the effects of neoadjuvant single or dual anti-HER-2 therapy and chemotherapy in Chinese HER-2-positive breast cancer patients and to explore the prognostic indicators of pCR and progression-free survival (PFS).

We included patients with HER-2-positive breast cancer treated with neoadjuvant anti-HER-2 therapy and chemotherapy at the First Affiliated Hospital of Chongqing Medical University in China from January 2016 to July 2020. We analyzed the relationship between patient characteristics and the pCR rate or PFS.

Forty-seven patients with HER-2-positive breast cancer receiving neoadjuvant anti-HER-2 therapy and chemotherapy were included. Univariate analysis suggested that compared with patients receiving neoadjuvant single anti-HER-2 therapy, patients receiving neoadjuvant dual anti-HER-2 therapy tended to have a higher pCR rate and better PFS. Patients who achieved pCR also tended to have longer PFS. Multivariate analysis indicated that patients with greater systemic inflammation response index (SIRI) reduction (>0.54) during neoadjuvant treatment (NAT) and patients with a lower T stage were more likely to achieve pCR. Patients aged ≤60 years with lower Ki-67 had longer PFS.

Greater SIRI reduction during NAT was an independent influencing factor for pCR. Patients receiving neoadjuvant dual anti-HER-2 therapy and chemotherapy tended to have higher pCR rates and longer PFS. Patients who achieved pCR also tended to have longer PFS.

• HER-2-positive
• Pathologic complete response
• Progression-free survival
• anti-HER-2 targeted therapy
• breast cancer

Does a paclitaxel-plus-carboplatin (PCb) as adjuvant treatment in women with operable triple-negative breast cancer offer superior benefit compared with a standard-dose CEF-T regimen (cyclophosphamide, epirubicin, and fluorouracil followed by docetaxel)?

In this randomized phase 3 clinical trial conducted at 9 cancer centers and hospitals in China and including 647 patients, after a median follow-up of 62 months, 5-year disease-free survival rate was statistically significantly higher in the PCb group compared with the CEF-T group.

Results of this study suggest that a paclitaxel-plus-carboplatin regimen may be an alternative adjuvant chemotherapy choice for patients with operable triple-negative breast cancer.

The value of platinum-based adjuvant chemotherapy in patients with triple-negative breast cancer (TNBC) remains controversial, as does whether BRCA1 and BRCA2 (BRCA1/2) germline variants are associated with platinum treatment sensitivity.

To compare 6 cycles of paclitaxel plus carboplatin (PCb) with a standard-dose regimen of 3 cycles of cyclophosphamide, epirubicin, and fluorouracil followed by 3 cycles of docetaxel (CEF-T).

This phase 3 randomized clinical trial was conducted at 9 cancer centers and hospitals in China. Between July 1, 2011, and April 30, 2016, women aged 18 to 70 years with operable TNBC after definitive surgery (having pathologically confirmed regional node-positive disease or node-negative disease with tumor diameter >10 mm) were screened and enrolled. Exclusion criteria included having metastatic or locally advanced disease, having non-TNBC, or receiving preoperative anticancer therapy. Data were analyzed from December 1, 2019, to January 31, 2020, from the intent-to-treat population as prespecified in the protocol.

Participants were randomized to receive PCb (paclitaxel 80 mg/m² and carboplatin [area under the curve = 2] on days 1, 8, and 15 every 28 days for 6 cycles) or CEF-T (cyclophosphamide 500 mg/m², epirubicin 100 mg/m², and fluorouracil 500 mg/m² every 3 weeks for 3 cycles followed by docetaxel 100 mg/m² every 3 weeks for 3 cycles).

The primary end point was disease-free survival (DFS). Secondary end points included overall survival, distant DFS, relapse-free survival, DFS in patients with germline variants in BRCA1/2 or homologous recombination repair (HRR)–related genes, and toxicity.

A total of 647 patients (mean [SD] age, 51 [44-57] years) with operable TNBC were randomized to receive CEF-T (n = 322) or PCb (n = 325). At a median follow-up of 62 months, DFS time was longer in those assigned to PCb compared with CEF-T (5-year DFS, 86.5% vs 80.3%, hazard ratio [HR] = 0.65; 95% CI, 0.44-0.96; P = .03). Similar outcomes were observed for distant DFS and relapse-free survival. There was no statistically significant difference in overall survival between the groups (HR = 0.71; 95% CI, 0.42-1.22, P = .22). In the exploratory and hypothesis-generating subgroup analyses of PCb vs CEF-T, the HR for DFS was 0.44 (95% CI, 0.15-1.31; P = .14) in patients with the BRCA1/2 variant and 0.39 (95% CI, 0.15-0.99; P = .04) in those with the HRR variant. Safety data were consistent with the known safety profiles of relevant drugs.

These findings suggest that a paclitaxel-plus-carboplatin regimen is an effective alternative adjuvant chemotherapy choice for patients with operable TNBC. In the era of molecular classification, subsets of TNBC sensitive to PCb should be further investigated.

ClinicalTrials.gov Identifier: NCT01216111

• Antineoplastic Agents, Hormonal/therapeutic use
• Breast Neoplasms/mortality
• Breast Neoplasms/therapy
• Chemotherapy, Adjuvant
• Female
• Gonadotropin-Releasing Hormone/agonists
• Humans
• Premenopause
• Randomized Controlled Trials as Topic
• Survival Analysis
• Tamoxifen/therapeutic use
• Treatment Outcome

A potential strategy for patients with estrogen receptor (ER)-positive breast cancer is necessary to replace neoadjuvant chemotherapy which has limited benefit. Neoadjuvant endocrine therapy (NAE) has been indicated to be a favorable alternate approach to downstage large or locally advanced breast cancer in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-) patients, especially postmenopausal women. Previous studies have demonstrated the efficacy of various endocrine agents in NAE. Aromatase inhibitors (AIs) have proven superiority over tamoxifen as a suitable choice to optimize treatment efficacy. Fulvestrant was recently reported as an effective agent, similar to AIs. Furthermore, the addition of targeted agents exerts synergistic antiproliferative effects with endocrine agents and rapidly improves response rates in both endocrine sensitive and resistant tumors. The neoadjuvant platform provides a unique opportunity to define the appropriate strategy and address the mechanisms of endocrine resistance. In addition, the predictive value of biomarkers and genomic assays in NAE is under investigation to evaluate individual effects and validate biomarker-based strategies. In this review, we discuss the most relevant evidence on the potential of NAE for ER+ breast cancer. The current understanding also offers new insights into the identification of the optimal settings and valuable predictive tools of NAE to guide clinical treatment decisions and achieve beneficial therapeutic effects.

• Breast cancer
• Neoadjuvant endocrine therapy
• Neoadjuvant chemotherapy
• Aromatase inhibitor
• Palbociclib
• Ki67
• Genomic assay

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.

• Aged
• Breast Neoplasms/drug therapy
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Cyclin D1/metabolism
• Female
• Humans
• Ki-67 Antigen/metabolism
• Middle Aged
• Neoadjuvant Therapy
• Postmenopause
• Prognosis
• Receptor, ErbB-2/metabolism
• Receptors, Estrogen/metabolism
• Receptors, Progesterone/metabolism