[Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer: a prospective cohort study].

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.

[Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer].

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.

[Analysis of the effect of ipsilateral supraclavicular lymph node metastasis on the prognosis of N3 breast cancer].

Objective: The 6th edition American Joint Committee on Cancer (AJCC) staging system for breast cancer classifies ipsilateral supraclavicular lymph node metastasis (ISLM) downing stage from M1 to N3, suggesting more patients might receive radical treatment. The aim of this study was to analyze the effect of ISLM on the prognosis of N3 breast cancer and verify the rationality of modified staging. Methods: A total of 321 breast cancer patients with N3 according to the 6th edition AJCC staging system were retrospectively analyzed. Propensity Score Matching (PSM) was used to pair the different subgroups of N3. The primary end point was disease-free survival (DFS), the secondary end point was overall survival (OS). Kaplan-Meier method was used to calculate the DFS and OS. The differences between two groups were analyzed by the Log-rank test. Results: After PSM pairing twice, 78 patients with none-ISLM and 78 patients with ISLM were enrolled in the first group; 51 patients with none-ISLM was compared patients with isolated ISLM in the second group. The results of the two groups showed that patients with none-ISLM have a prolonged DFS (the first group: 58.9 months vs 32.1 months, P=0.101; the second group: 59.0 months vs 44.0 months, P=0.533), while the OS was opposite (the first group: 87.4 months vs 140.4 months, P=0.289; the second group: 87.4 months vs 137.1 months, P=0.289). Conclusions: The prognosis of breast cancer patients with ISLM is similar to that of patients with none-ISLM in stage N3. It is reasonable to include ISLM in N3 in the 6th edition AJCC staging system. Yet, prospective studies with larger sample size are needed to further confirmation.

[Feasibility and toxicity of EC-T dose-dense adjuvant chemotherapy: A real world study in Chinese early-stage breast cancer patients with high recurrence risk].

Objective: We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk. Methods: 370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed. Results: 370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282). Conclusions: EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m(2) is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

Adjuvant chemotherapy may improve survival of patients with luminal A breast cancer and positive lymph nodes.

The study examined the clinicopathological characteristics and treatment options in patients with luminal A breast cancer. This retrospective cohort included 1580 patients with luminal A breast cancer treated between January 2005 and June 2007. Patients were divided into four subgroups according to lymph node status. Prognostic factors and 5-year overall survival (OS) and disease-free survival (DFS) of patients were analyzed. The median duration of follow-up was 67 months. Multivariate Cox-regression analysis revealed that patients in the LN2 and LN3 subgroups had a higher risk of recurrence and death than patients in the LN0 subgroup (LN2: HR = 2.2 for DFS and HR = 2.1 for OS; LN3: HR = 4.7 for DFS and HR = 4.7 for OS). In the LN2 subgroup, there was a trend towards reduced risk of recurrence and death for patients receiving adjuvant chemotherapy plus endocrine therapy, although this difference did not reach statistical significance. In the LN0 and LN1 subgroups, there was a trend towards an increased risk of death in patients receiving chemotherapy. Although lymph node status remains one of the most important independent prognostic predictors for luminal A breast cancer, in patients with 0-3 positive lymph nodes endocrine therapy can be considered sufficient. However, patients with ≥4 positive lymph nodes, and especially in those with ≥ 10, should receive chemotherapy.

QL1701 (a proposed trastuzumab biosimilar) versus reference trastuzumab plus docetaxel as first-line therapy for HER2-positive metastatic breast cancer: a multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial.

BACKGROUND: QL1701 is a proposed biosimilar to the reference trastuzumab (Herceptin®). This trial compared the efficacy and safety of QL1701 with the reference trastuzumab in first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. MATERIALS AND METHODS: This randomized, double-blinded, parallel-controlled, phase III equivalence trial was conducted in 73 centers in China. Eligible patients with histologically or cytologically diagnosed HER2-positive metastatic breast cancer were randomly assigned (1 : 1) to receive either QL1701 or reference trastuzumab in combination with docetaxel (every 3 weeks) for eight cycles as the first-line treatment. Then, in patients with objective responses or stable disease, the QL1701 or reference trastuzumab with or without docetaxel was maintained for totally up to 12 months if tolerated. The primary endpoint was 24-week objective response rate (ORR) assessed by an independent review committee (IRC). The equivalence margin was 0.80-1.25 with a 90% confidence interval (CI) for the ORR ratio (QL1701 to reference trastuzumab). RESULTS: Between 29 April 2020 and 15 March 2022, 474 patients were randomized, and 473 received either QL1701 (n = 236) or reference trastuzumab (n = 237). The risk ratio for 24-week ORR was 1.07 (90% CI 0.94-1.21). The 90% CI fell within the pre-specified equivalence margin of 0.80-1.25. The 24-week ORR assessed by IRC was 59.7% (95% CI 53.2% to 66.1%) versus 56.1% (95% CI 49.5% to 62.5%) in QL1701 and the reference trastuzumab, respectively. As of 12 April 2023, there were no notable differences in progression-free survival (median: 8.3 versus 8.4 months) and overall survival (1-year rate: 95.1% versus 93.3%) between the two groups. Safety, pharmacokinetic (PK), and immunogenicity profiles were similar between the two groups. CONCLUSION: QL1701 demonstrated equivalent efficacy and similar safety to the reference trastuzumab when combined with docetaxel in the first-line treatment of patients with HER2-positive metastatic breast cancer, with similar PK and immunogenicity profiles.

Docetaxel-cisplatin might be superior to docetaxel-capecitabine in the first-line treatment of metastatic triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) may be more sensitive to platinum. This study was to compare platinum-based regimen with nonplatinum regimen in the first-line treatment of advanced TNBC. PATIENTS AND METHODS: Eligible metastatic TNBC (mTNBC) women without prior treatment for advanced disease were randomized (1 : 1) to receive either docetaxel-cisplatin (TP) or docetaxel -capecitabine (TX) q3w for up to 6 cycles, until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) and the secondary end points included progression-free survival (PFS) and overall survival (OS). In total 53 patients were enrolled. RESULTS: The median follow-up was 24 months. ORR was higher in the TP group than in the TX group (63.0% versus 15.4%, P = 0.001). PFS was more than doubled (10.9 months versus 4.8 months, P < 0.001) and median OS was also greatly improved (32.8 months versus 21.5 months, P = 0.027). Toxic effects were not different except G3/4 vomiting and G2/3 hand-foot syndrome. CONCLUSIONS: This study suggested that cisplatin-based chemotherapy was superior to capecitabine-based regimen in the first-line treatment of mTNBC, as measured by ORR, PFS and OS. Further large-scale study should be warranted. These results are not sufficient to change clinical practice.

A miRNA-based signature predicts development of disease recurrence in HER2 positive breast cancer after adjuvant trastuzumab-based treatment.

Approximately 20% of HER2 positive breast cancer develops disease recurrence after adjuvant trastuzumab treatment. This study aimed to develop a molecular prognostic model that can reliably stratify patients by risk of developing disease recurrence. Using miRNA microarrays, nine miRNAs that differentially expressed between the recurrent and non-recurrent patients were identified. Then, we validated the expression of these miRNAs using qRT-PCR in training set (n = 101), and generated a 2-miRNA (miR-4734 and miR-150-5p) based prognostic signature. The prognostic accuracy of this classifier was further confirmed in an internal testing set (n = 57), and an external independent testing set (n = 53). Besides, by comparing the ROC curves, we found the incorporation of this miRNA based classifier into TNM stage could improve the prognostic performance of TNM system. The results indicated the 2-miRNA based signature was a reliable prognostic biomarker for patients with HER2 positive breast cancer.