Efficacy and safety of eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with anthracycline/taxanes.

BACKGROUND: This prospective real-world study aimed to assess the efficacy and safety of eribulin in the clinical practice against advanced breast cancer (ABC) in China. PATIENTS AND METHODS: In this study, eligible patients with inoperable locally advanced or metastatic breast cancer who had experienced prior neo-/adjuvant or failed the palliative treatment with anthracycline/taxanes were included. Eribulin (1.4 mg/m2) was infused intravenously on Day 1 and Day 8 every 3 weeks until disease progression or intolerable toxicity occurred. The progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety of the treatment were assessed. RESULTS: One hundred and thirty-four patients were enrolled. The median PFS (mPFS) was 4.3 months (95% CI: 0.3-15.4). The ORR and DCR was 32.1% and 79.1%, respectively. The mPFS of patients who received eribulin as first- or second-line treatment was significantly better than those who received eribulin as ≥3-line treatment (6.9 months [95% CI: 3.2-8.8] vs. 4.0 months [95% CI: 3.4-4.6], p = 0.006). The mPFS of patients with triple-negative, HER2-positive, and HER2(-)/HR(+) was 3.4 (95% CI: 2.7-4.1), 6.2 (95% CI: 2.3-10.1) and 5.0 months (95% CI: 4.1-5.9), respectively. HER2(+) patients had significantly longer PFS than TNBC patients (p = 0.022). Patients received combination therapy had a significantly longer mPFS than those who received eribulin monotherapy (5.0 months [95% CI 3.6-6.3] vs. 4.0 months [95% CI: 3.3-4.7] [p = 0.016]). Multivariate analysis revealed that MBC patients with a molecular typing of non-TNBC receiving eribulin as ≤2-line therapy and combination therapy had a low risk of disease progression. Neutropenia (33.58%), leukopenia (11.94%), and thrombocytopenia (4.48%) were the most common treatment-related adverse events. CONCLUSION: Eribulin demonstrated effective clinical activity and a favorable tolerability profile in Chinese patients with ABC in the real-world. The efficacy and safety profile were consistent with those reported in previous randomized phase 3 trials.

Cost-Effectiveness Analysis of Adjuvant Endocrine Therapy With Ovarian Suppression in Premenopausal Patients With Hormone Receptor-Positive Early Breast Cancer in China.

PURPOSE: Endocrine therapy combined with ovarian function suppression (OFS) is recommended in intermediate- or high-risk patients among premenopausal women with hormone receptor-positive early breast cancer. However, in China, the cost-effectiveness of this strategy compared with endocrine therapy alone is unclear. This study aimed to evaluate the long-term cost-effectiveness of tamoxifen (TAM), TAM+OFS, and exemestane plus OFS (EXE+OFS). METHODS: On the basis of prognostic data from the Suppression of Ovarian Function Trial (SOFT), cost data from the Hospital Information System of the West China Hospital of Sichuan University, and health utility values from the published literature, a Markov model was established. The incremental cost-effectiveness ratio (ICER) was used to compare the treatment strategies. RESULTS: In a 25-year simulation of adjuvant therapy in Chinese women with early breast cancer, the total costs of TAM, TAM+OFS, and EXE+OFS were $7821, $9318, and $9445, respectively. The quality-adjusted life-years (QALYs) were 11.615, 11.896, and 11.734 years, respectively. Compared with TAM, the ICERs of TAM+OFS and EXE+OFS were $5,327.4021/QALY and $13,647.0588/QALY, respectively. The ICERs of TAM+OFS and EXE+OFS were below the threshold of $32,517/QALY. The reliability and stability of the simulation results were verified using Monte Carlo simulation and sensitivity analysis. CONCLUSION: In the context of limited resources in China, TAM+OFS and EXE+OFS are cost-effective options compared with TAM.

Real-world efficacy and safety of pyrotinib in patients with HER2-positive metastatic breast cancer: A prospective real-world study.

Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC). Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records. Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies. Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.

CDK4/6 inhibitors for primary endocrine resistant HR-positive/HER2-negative metastatic breast cancer: a case report.

Background: We report a case of hormone receptor (HR) positive, human epidermal growth factor receptor-2 (HER2) negative breast cancer with multiple liver metastases who achieved good clinical benefit across cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine therapy. Prior to this, the patient underwent neoadjuvant therapy and surgery as well as adjuvant endocrine therapy. We present and discuss three important treatment decision nodes associated with it. Case Description: A 60-year-old woman was diagnosed with invasive ductal carcinoma of the left breast (cT4bN2M0, stage IIIB, Luminal B HER2-negative type) at the West China Hospital of Sichuan University in 2020, and received neoadjuvant chemotherapy and modified radical mastectomy of the left breast from 2020 to 2021. Postoperative radiotherapy was performed in the left chest wall and left upper and lower clavicular region. Adjuvant therapy is anastrozole endocrine therapy. Multiple liver metastases developed in 2022. The pathological molecular typing of liver metastases was confirmed to be consistent with the primary lesion. In the context of primary endocrine resistance, the first-line treatment of choice was fulvestrant in combination with a targeted CDK4/6 inhibitor (abemaciclib). This combination regimen made the liver metastases visibly shrunk, leading to partial response (PR) and has achieved a progression-free survival of 12 months. And there were no serious drug-related adverse events during first-line treatment. Conclusions: CDK4/6 inhibitor is a promising antineoplastic agent for HR positive, HER2 negative breast cancer patients. With the development of research, the application scope of CDK4/6 inhibitors is gradually expanding, and the precision treatment of breast cancer requires more rational drug selection and combination.

Impact of financial support on the prognosis of HER2-positive breast cancer from 2002 to 2020: a prospective cohort from western China.

Background: Trastuzumab has significantly improved the outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer over 20 years, and remains a cornerstone of treatment for this subtype today. Higher mortality was reported in underinsured breast cancer, but the mechanism remains unclear. Financial support for trastuzumab has transitioned from no support, to the Breast Cancer Assistant Program (BCAP), and finally, health insurance. Exploring the association between survival outcomes and different financial supports is necessary to further improve the outcomes of HER2-positive breast cancer in resource-limited regions. Methods: A prospective cohort of primary early unilateral HER2-positive breast cancer patients registered between January 2002 and December 2020 was used. Patients were divided into the following 3 groups, based on when they were diagnosed with breast cancer: (I) before 2011 (no financial support); (II) 2011-2017 (BCAP support); and (III) 2018 onwards (health insurance support). Overall survival and invasive disease-free survival (iDFS) were the primary outcomes. The follow-up was performed according the standard procedure. Cox proportional hazards regression was used to explore the association between financial support and prognosis with adjustment of demographic and clinicopathological characteristics, and treatments. Results: A total of 2,972 patients were finally identified. During the median follow-up period of 3.9 years, there were 153 breast cancer-related deaths. When fully adjusted potential covariates, patients supported by the BCAP had a 37% [hazard ratio (HR): 0.63, 95% CI: 0.41-0.96] decreased risk of overall mortality and that of patients covered by health insurance had a 64% decreased of overall mortality (HR: 0.36, 95% CI: 0.17-0.74) when compared with those who did not receive any financial support. Lower overall mortality was observed in patients covered by a higher reimbursement rate (HR: 0.68, 95% CI: 0.49-0.94) or the urban scheme (HR: 0.61, 95% CI: 0.43-0.86) than those covered by a lower reimbursement rate or the rural scheme. The same trends were also observed for iDFS and breast cancer-specific survival. Conclusions: Our findings revealed the independent role of financial support in improving the survival outcomes of the HER2-positive breast cancer in resource-limited regions and the underneath mechanism.

Neoadjuvant pyrotinib plus trastuzumab and nab-paclitaxel for HER2-positive early or locally advanced breast cancer: an exploratory phase II trial.

BACKGROUND: The anti-tumor activity and acceptable tolerability of pyrotinib plus chemotherapy have been demonstrated in phase III trials in human epidermal growth factor receptor 2-positive metastatic breast cancer (BC). In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel in women with human epidermal growth factor receptor 2-positive early or locally advanced BC. METHODS: In this single-arm exploratory phase II trial, patients with untreated human epidermal growth factor receptor 2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily, trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg once a week, and albumin-bound paclitaxel 125 mg/m2 once a week for four 21-day cycles before surgery. The primary endpoint of the study was total pathological complete response (pCR) rate, defined as no microscopic invasive tumor remnants in the breast and axillary lymph nodes. The secondary endpoints were investigator-assessed objective response rate (ORR) and adverse event profiles. RESULTS: Between May 17, 2019 and November 26, 2019, a total of 21 patients were enrolled. The total pCR rate was 57.1% (12/21), whereas 23.8% (5/21) and 19.0% (4/21) of patients had minimal and moderate residual disease (RD), respectively. The ORR reached 100% (21/21) at the end of the neoadjuvant therapy. Grade ≥3 treatment-related adverse events were observed in 42.9% (9/21) of patients, including decreased neutrophil count [7 (33.3%)], diarrhoea [6 (28.6%)], decreased white blood cell count [5 (23.8%)], and vomiting [2 (9.5%)]. Adverse event-related dose reduction and interruption of pyrotinib occurred in 6 (28.6%) and 11 (52.4%) patients, respectively. CONCLUSIONS: In women with human epidermal growth factor receptor 2-positive early or locally advanced BC, neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel effectively promoted total pCR rate with an acceptable safety profile (ClinicalTrials.gov, NCT04152057).

A Retrospective Analysis of the Effect of Irinotecan-Based Regimens in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes.

BACKGROUND: At present, patients with metastatic breast cancer (MBC) have few treatment options after receiving anthracyclines and taxanes. Studies have shown that irinotecan has modest systemic activity in some patients previously treated with anthracyclines and taxanes. This study aimed to evaluate the efficacy of irinotecan-based chemotherapy for breast cancer patients in a metastatic setting. METHODS: We retrospectively collected the clinical information and survival data of 51 patients with MBC who received irinotecan at West China Hospital of Sichuan University. The primary endpoints were the progression free survival (PFS) and overall survival (OS), and the secondary endpoint was the objective response rate (ORR). To minimize potential confounding factors, we matched 51 patients who received third-line chemotherapy without irinotecan through propensity score matching (PSM) based on age, hormone receptor (HR), and human epidermal growth factor receptor 2 (HER2), compared their OS and PFS rates to those treated with irinotecan. RESULTS: From July 2012 to October 2020, 51 patients were treated with an irinotecan-containing regimen. The median number of previous treatment lines was 4, and a median of two previous chemotherapy cycles (ranging from 1-14 cycles) were given in a salvage line setting. The ORR was 15.7%, and the disease control rate (DCR) was 37.3%. For the irinotecan group, the median PFS was 3.2 months (95% CI 2.7-3.7), while the median OS was 33.1 months (95% CI 27.9-38.3). Univariate analysis results suggested that irinotecan could improve PFS in patients with visceral metastasis (P=0.031), which was 0.7 months longer than patients without visceral metastasis (3.5 months vs. 2.8 months). Compared to the patients who received third-line non-irinotecan chemotherapy, the irinotecan group showed a longer trend of PFS without statistical significance (3.2 months vs 2.1 months, P = 0.052). Similarly, the OS of the irinotecan group was longer than the third-line survival without irinotecan, but it was not statistically significant (33.1 months vs 18.0 months, P = 0.072). CONCLUSIONS: For MBC patients who were previously treated with anthracyclines and/or taxanes, an irinotecan-containing regimen achieved moderate objective response and showed a trend of survival benefit, which deserves further study.

The Effect of Postmastectomy Radiotherapy on Breast Cancer Patients After Neoadjuvant Chemotherapy by Molecular Subtype.

BACKGROUND: The effect of postmastectomy radiotherapy (PMRT) on patient outcomes after neoadjuvant chemotherapy (NAC) remains controversial. We aimed to establish a model to identify the subsets benefiting from PMRT and to examine the effect of PMRT according to molecular subtype. PATIENTS AND METHODS: We retrospectively analyzed 1118 cT1-4cN0-3M0 breast cancer patients treated with NAC and mastectomy. A nomogram predicting locoregional recurrence (LRR) was established based on 418 unirradiated patients, and X-tile analysis was performed to divide the patients into two risk groups. The effect of PMRT on LRR, distant recurrence (DR), and breast cancer mortality (BCM) was estimated for patients with different molecular subtypes in two risk groups. RESULTS: A nomogram predicting LRR was developed using six factors: histologic classification, lymphovascular invasion, ypT stage, ypN stage, estrogen receptor status, and Ki-67 expression. Our study found that PMRT correlated with lower 5-year LRR, DR, and BCM rates for the high-risk group; however, no significant improvement in these endpoints was observed in the low-risk group. Among patients with high risk, subgroup analysis showed that LRR control was improved after PMRT for the human epidermal growth factor receptor 2 (HER2)-negative/hormone receptor (HR)-positive (HER2-/HR+), HER2-positive (HER2+)/HR+, and HER2-/HR-negative (HR-) subtypes, with hazard ratios of 0.113 (95% confidence [CI] 0.034-0.379; p < 0.001), 0.159 (95% CI 0.038-0.671; p = 0.017), and 0.243 (95% CI 0.088-0.676; p = 0.007), respectively, but not for the HER2+/HR- subtype (p = 0.468). CONCLUSIONS: We built a nomogram showing favorable risk quantification and patient stratification. Patients in the high-risk group benefited from PMRT, but patients in the low-risk group did not. PMRT may show different benefits for each molecular subtype.

Weekly taxane-anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer: a randomized controlled trial.

BACKGROUND: Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-based chemotherapy on breast cancer. However, few studies have assessed the efficacy of weekly taxane-anthracycline regimens on locally advanced breast cancer. This study was to compare the efficacy and safety of a weekly taxane-anthracycline regimen with those of tri-weekly anthracycline-based regimen in patients with locally advanced breast cancer. METHODS: Patients with locally advanced breast cancer were randomized to receive 4-6 cycles of neoadjuvant chemotherapy with tri-weekly 5-fluorouracil-epirubicin-cyclophosphamide (FEC) regimen or weekly paclitaxel-epirubicin (PE) regimen. The primary endpoint was the pathologic complete response (pCR) rate. Other endpoints included the clinical tumor response, breast-conserving surgery rate, and adverse events. RESULTS: Between March 2010 and September 2013, 293 patients were randomized to the FEC (n = 151) and PE (n = 142) arms. The overall clinical response rate was significantly higher in the PE arm than in the FEC arm (76.06% vs. 59.95%, P = 0.001). Consistently, the post-chemotherapy pathologic T and N stages were significantly lower in the PE arm than in the FEC arm (P < 0.001). However, the pCR rate was similar in the two arms (10.61% vs. 12.31%, P = 0.665). Overall, 36 (27.27%) patients in the FEC arm and 6 (35.28%) in the PE arm were qualified for breast-conserving surgery. Most adverse events were comparable in both arms, with more severe neutropenia in the PE arm than in the FEC arm (11.97% vs. 5.96%, P = 0.031). CONCLUSIONS: In patients with locally advanced breast cancer, weekly PE was not superior to FEC in terms of pCR. However, weekly PE has a higher response rate and superior down-staging effects. On this account, the PE regimen may be considered an alternative option for locally advanced breast cancer. Long-term follow-up data are needed to confirm the efficacy of this regimen on locally advanced breast cancer. Trial registration Chinese clinical trial registry, ChiCTR-TRC-10001043, September 21, 2014.

Application status of tamoxifen in endocrine therapy for early breast cancer.

The aim of the present study was to investigate the application status of tamoxifen as an adjuvant treatment for early-stage breast cancer. Data for patients with early breast cancer were collected from an information management system for breast cancer in a single hospital between 1989 and 2012. The inclusion criteria included no distant metastasis during diagnosis with breast cancer, and a diagnosis of estrogen and/or progesterone receptor-positive breast cancer, or an unclear hormonal receptor status with tamoxifen used as the preferred drug. A total of 2,738 patients were selected, with 99.4% female and 0.6% male patients. Within females, 75.7% were premenopausal when diagnosed with early breast cancer, 24.3% were postmenopausal, and the median age of menopause was 47 years. The percentage of tamoxifen preference in adjuvant therapy was 97.3% prior to 2000, which decreased to 60.4% in 2011. Tamoxifen preference among premenopausal patients reduced from 97.3% prior to 2000 to 89.5% in 2011, while in postmenopausal patients tamoxifen preference declined from 97.4% prior to 2000 to 22.7% in 2011. One-year duration of tamoxifen treatment accounted for 79.4% of cases, while five-year duration accounted for 24.7%. The rate of one-year disease-free survival (DFS) was 98.5% and of five-year DFS was 89.1%. Patients with early breast cancer had a one-year overall survival (OS) rate of 99.2% and a five-year OS rate of 95.6%. The gradually decreased usage and shortened duration of tamixofen treatment, as well as reduced DFS and OS rates were observed in a 'real world' clinical setting. Improved treatment compliance in patients is recommended.

Trends and present treatment patterns of early breast cancer in Southwest China.

To analyze the changing patterns of treatment and to explore the current treatment approaches for breast cancer in Southwest China, we conducted a population-based retrospective cohort study of early breast cancer cases. The data of patients who registered in the information management system for breast cancer in Huaxi Hospital, Sichuan University from 1989 to 2012 were extracted. Nearly all patients underwent surgery, among whom radical mastectomy was the predominant option. Chemotherapy (88.7%) was the most predominant adjuvant therapy approach. The percentage of patients receiving radiation therapy displayed fluctuant increase, which was 37.1 % in 2001 and reached up to 67.6% in 2011. Besides, the endocrinetherapy became more and more popular in the hormone-receptor positive patients and the percentage of endocrinetherapy was increased from 54.1 at 2001 to 85.6% at 2011. However, more than 10% of hormone-receptor positive patients still did not receive endocrinetherapy annually. The hormone-receptor positive patients who received endocrinetherapy had better 5-year disease free survival (DFS) and overall survival (OS) compared to those without endocrinetherapy (5-y DFS: 88.4% vs. 75.1 %, P < 0.001; 5-y OS: 95.7% vs. 88.4%, P < 0.001). N stage appeared to have greater impact on the 5-year DFS and OS than molecular subtyping. The treatment for breast cancer in China has been significantly improved but more attentions should be paid to radiotherapy and endocrine therapy. In addition, the value of N stage in the prognosis of breast cancer should not be ignored when the molecular typing draws more and more attentions.

Vascular endothelial growth factor (VEGF) gene polymorphisms and breast cancer risk in a Chinese population.

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumours. Associations between three VEGF gene polymorphisms (-634 G/C, +936 C/T, and +1612 G/A) and breast cancer risk have been extensively studied, but the currently available results are inconclusive. Our aim was to investigate associations between three VEGF gene polymorphisms and breast cancer risk in Chinese Han patients. We performed a hospital-based case-control study including 680 female incident breast cancer patients and 680 female age-matched healthy control subjects. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the three VEGF gene polymorphisms. We observed that women carriers of +936 TT genotypes [odds ratio (OR) =0.46, 95% confidence interval (CI) = 0.28, 0.76; P=0.002] or 936 T-allele (OR=0.81, 95% CI= 0.68, 0.98; P=0.03) had a protective effect concerning the disease. Our study suggested that the +1612G/A polymorphism was unlikely to be associated with breast cancer risk. The -634CC genotype was significantly associated with high tumor aggressiveness [large tumor size (OR=2.63, 95% CI=1.15, 6.02; P=0.02) and high histologic grade (OR=1.47, 95% CI= 1.06, 2.03; P=0.02)]. The genotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. Our study revealed that the VEGF -634 G/C and +936 C/T gene polymorphisms may be associated with breast cancer in Chinese Han patients.