Real-world study of palbociclib combined with endocrine therapy for patients with metastatic breast cancer: A comparison of subsequent treatment patterns and HER2 expression analysis.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy (ET) comprise the standard treatment for patients with hormone receptor-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer. The optimal systematic treatment after progression on palbociclib and the role of HER2 expression among these patients remain unclear. METHODS: The authors retrospectively identified 361 patients who received palbociclib combined with ET. Progression-free survival (PFS) and overall survival (OS) were analyzed based on subsequent treatments and HER2 status (PFSsub and OSsub, respectively). PFS1 and OS1 were calculated from palbociclib administration to disease progression/death and death from any cause, respectively. PFSsub and OSsub were calculated from subsequent treatment initiation. RESULTS: The median PFS1 and OS1 were 10.2 and 39.9 months, respectively. The median PFSsub and OSsub of 111 patients (54.7%) who received chemotherapy were 4.9 months and 20.0 months, respectively, whereas those of 89 patients (43.8%) who received endocrine backbone therapy were 5.9 months and 29.3 months, respectively. Among them, 31 patients (15.3%) who received abemaciclib combined with new ET showed better PFSsub and OSsub (12.2 months and not reached, respectively). The median PFS1 was significantly shorter in the HER2-low subgroup than in the HER2-zero subgroup among patients who received second-line or later palbociclib (6.1 vs. 7.8 months; p = .040) but did not differ among patients who received first-line palbociclib. CONCLUSIONS: Various regimens after palbociclib use were received. An improvement was noted in PFS among patients who received endocrine backbone therapy relative to chemotherapy, which may have been secondary to the receipt of chemotherapy by patients with more aggressive disease. HER2 status was not related to the effect of first-line palbociclib, but it may play a role in later lines.

Long-term Outcome Analysis of Pyrotinib in Patients With HER2-Positive Metastatic Breast Cancer and Brain Metastasis: A Real-World Study.

BACKGROUND: Pyrotinib is currently approved for the treatment of HER2-positive advanced breast cancer in China. Data on the overall survival (OS) and efficacy in patients with brain metastasis (BM) remain scarce. This study evaluated the effectiveness of pyrotinib in a real-world setting, especially in patients with BM. METHODS: We reviewed patients with metastatic breast cancer treated with pyrotinib-based therapy between June 2018 and June 2022. Progression-free survival (PFS), OS, objective response rate, and safety were analyzed following the administration of pyrotinib. RESULTS: A total of 239 patients were included. The median PFS in patients who received pyrotinib-based therapy as first-line (15/239), second-line (115/239), or third-or-higher-line (109/239) treatment was 14.00, 9.33, and 8.20 months, respectively, and the median OS was not reached, 29.07 and 22.23 months, respectively. The median PFS in patients who pretreated with trastuzumab (214/239), trastuzumab plus pertuzumab (22/239), lapatinib (68/239), or trastuzumab emtansine (14/239) was 9.33, 6.87, 7.20, and 7.20 months, respectively. In 61 patients with BM, the median PFS was 7.50 months, the median central nervous system (CNS)-PFS was 11.17 months, and the median OS was 21.27 months. Furthermore, 19 patients with concomitant brain radiotherapy tended to achieve a longer OS than 42 patients without radiation (34.17 vs. 20.70 months, P = .112). CONCLUSIONS: Long-term outcomes of pyrotinib-based therapy are promising for patients with HER2-positive metastatic breast cancer in real world and in patients with BM, regardless of the treatment lines and prior anti-HER2 therapies.

Efficacy of apatinib 250 mg combined with chemotherapy in patients with pretreated advanced breast cancer in a real-world setting.

Objectives: This study evaluated the efficacy and safety of apatinib (an oral small-molecule tyrosine kinase inhibitor targeting VEGFR-2) 250 mg combined with chemotherapy in patients with pretreated metastatic breast cancer in a real-world setting. Patients and methods: A database of patients with advanced breast cancer who received apatinib between December 2016 and December 2019 in our institution was reviewed, and patients who received apatinib combined with chemotherapy were included. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR), and treatment-related toxicity were analyzed. Results: In total, 52 evaluated patients with metastatic breast cancer previously exposed to anthracyclines or taxanes who received apatinib 250 mg combined with chemotherapy were enrolled in this study. Median PFS and OS were 4.8 (95% confidence interval [CI] = 3.2-6.4) and 15.4 months (95% CI = 9.2-21.6), respectively. The ORR and DCR were 25% and 86.5%, respectively. Median PFS for the previous line of treatment was 2.1 months (95% CI = 0.65-3.6), which was significantly shorter than that for the apatinib-chemotherapy combination (p < 0.001). No significant difference was identified in the ORR and PFS among the subgroups(subtypes, target lesion, combined regimens and treatment lines). The common toxicities related to apatinib were hypertension, hand-foot syndrome, proteinuria, and fatigue events. Conclusion: Apatinib 250 mg combined with chemotherapy provided favorable efficacy in patients with pretreated metastatic breast cancer regardless of molecular types and treatment lines. The toxicities of the regimen were well tolerated and manageable. This regimen could be a potential treatment option in patients with refractory pretreated metastatic breast cancers.

Effectiveness, safety, and impact on quality of life of eribulin-based therapy in heavily pretreated patients with metastatic breast cancer: A real-world analysis.

INTRODUCTION: Eribulin is currently recommended for the treatment of patients with metastatic breast cancer (MBC) pre-treated with taxanes and anthracyclines. The aim of the present study was to evaluate the effectiveness and safety of eribulin and its impact on health-related quality of life in heavily pre-treated patients with MBC. METHODS: Data from MBC patients who had received eribulin-based therapy at Beijing Cancer Hospital between January 2020 and July 2022 were analyzed retrospectively. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), adverse effects (AEs) and health-related quality of life (HRQoL) were assessed. RESULTS: Data from 118 patients who had received eribulin to treat MBC were included. Median PFS was 4.2 months and median OS had not been reached. The ORR was 13.6% (16/118) and DCR was 75.4% (89/118). The median PFS in patients who received eribulin in second-line (26/118), third-line (29/118), or fourth-line or later (63/118) was 4.5, 4.2, and 3.9 months, respectively. The median OS in patients who received eribulin in third- or later line (n = 92) was 14.1 months. Patients who received eribulin combination therapy had a significantly longer median PFS compared with those who received eribulin monotherapy (4.5 vs. 3.4 months, p = 0.007) and there was a trend towards a longer median OS (not reached vs. 12.1 months). The most common grade 3-4 adverse events were neutropenia (22.9%), leukocytopenia (13.6%) and asthenia/fatigue (8.5%), without significant differences in safety between eribulin monotherapy and combination therapy. Quality of life was similar in patients who received eribulin monotherapy and combination therapy, except for cognitive function and nausea and vomiting symptoms, which were better with combination therapy. CONCLUSIONS: The present study suggests that eribulin-based therapy is an effective treatment option and well tolerated for heavily pre-treated patients with MBC. Eribulin combination therapy might improve PFS and HRQoL compared with eribulin monotherapy.

Pegylated liposomal doxorubicin (Duomeisu®) monotherapy in patients with HER2-negative metastatic breast cancer heavily pretreated with anthracycline and taxanes: a single-arm, phase II study.

PURPOSE: To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) heavily pretreated with anthracycline and taxanes. METHODS: In this single-arm, phase II study, patients with HER2-negative MBC previously treated with anthracycline and taxanes as second- to fifth chemotherapy received PLD (Duomeisu®, generic doxorubicin hydrochloride liposome) 40 mg/m2 every 4 weeks until disease progression, unacceptable toxicity, or completion of six cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety. RESULTS: Of 44 enrolled patients (median age, 53.5 years; range, 34-69), 41 and 36 were evaluable for safety and efficacy, respectively. In total, 59.1% (26/44) of patients had ≥ 3 metastatic sites, 86.4% (38/44) had visceral disease, and 63.6% (28/44) had liver metastases. Median PFS was 3.7 months (95% confidence interval [CI] 3.3-4.1) and median OS was 15.0 months (95% CI 12.1-17.9). ORR, DCR, and CBR were 16.7%, 63.9%, and 36.1%, respectively. The most common adverse events (AEs) were leukopenia (53.7%), fatigue (46.3%), and neutropenia (41.5%), with no grade 4/5 AEs. The most common grade 3 AEs were neutropenia (7.3%) and fatigue (4.9%). Patients experienced palmar-plantar-erythrodysesthesia (24.4%, 2.4% grade 3), stomatitis (19.5%, 7.3% grade 2), and alopecia (7.3%). One patient displayed a left ventricular ejection fraction decline of 11.4% from baseline after five cycles of PLD therapy. CONCLUSION: PLD (Duomeisu®) 40 mg/m2 every 4 weeks was effective and well-tolerated in patients with HER2-negative MBC heavily pretreated with anthracycline and taxanes, revealing a potentially viable treatment option for this population. Trial registration Chinese Clinical Trial Registry: ChiCTR1900022568.

Cell-free DNA comparative analysis of the genomic landscape of first-line hormone receptor-positive metastatic breast cancer from the US and China.

PURPOSE: Meaningful comparison of mutational landscapes across ethnic groups requires the use of standardized platform technology. We have used a harmonized NGS-based liquid biopsy assay to explore the differential genomic landscape of patients with initially hormone receptor-positive (HR+), HER2-negative MBC of first line metastasis or primary Stage IV at diagnosis from the United States (US) and China (CN). METHODS: Plasma circulating tumor DNA (ctDNA) from 27 US patients and 65 CN patients was sequenced using the harmonized CLIA-certified, 152-gene PredicineCare™ liquid biopsy assay. Kaplan-Meier survival analysis was performed to analyze the correlation between genomic alterations and progression-free survival (PFS), and p-values were calculated using the log-rank test. RESULTS: All patients in the CN cohort received chemotherapy and/or hormonal therapy, while 85.2% (23/27) patients in the US cohort received hormonal therapy plus CDK4/6 inhibitors. Mutations were detected in 23 of 27 (85%) US patients and 54 of 65 (83%) CN patients. The prevalence of AKT1 (P = 0.008) and CDH1 (P = 0.021) alterations were both higher in the US vs. CN cohort. In addition, FGFR1 amplification were more frequent in the CN vs. US cohort (P = 0.048). PTEN deletions (P = 0.03) and ESR1 alterations (P = 0.02) were associated with shorter PFS in the CN cohort, neither of these associations were observed in the US cohort. Interestingly, a reduced association between PTEN deletion and PFS was observed in patients receiving CDK4/6 inhibitor treatment. CONCLUSION: The differential prevalence of ctDNA-based alterations such as FGFR1, AKT1, and CDH1 was observed in initially HR+/HER2- MBC patients in the US vs. CN. In addition, the association of PTEN deletions with shorter PFS was found in the CN but not the US cohort. The differential genomic landscapes across the two ethnic groups may reflect biologic differences and clinical implications.

Bilateral breast cancer in China: A 10-year single-center retrospective study (2006-2016).

Bilateral breast cancer (BBC) is an uncommon subset of breast cancer (BC), and it may present as synchronous bilateral breast cancer (sBBC) or metachronous bilateral breast cancer (mBBC). Through this study, we aimed to evaluate the proportion of BBC in BC and compare the clinicopathological characteristics, treatment, and outcomes of sBBC and mBBC at an academic cancer center in China. Patients with BC consecutively treated between 2006 and 2016 were retrospectively reviewed. Patients with BBC were included. In total, 3924 patients with BC were analyzed and 127 patients with BBC (28 sBBC, 99 mBBC) with a median follow-up of 98 months were identified. The proportion of BBC was 3.2% (0.7%, sBBC; 2.5%, mBBC). The median age at the first diagnosis of mBBC was significantly younger than that at the first diagnosis of sBBC (p = 0.027). Patients diagnosed as having sBBC were more likely to have a positive family history (p = 0.047). The first tumors of mBBC were detected at a significantly earlier tumor stage compared with those of sBBC (p = 0.028). The concordance rates of histopathologic type in the first and second tumors were 60.7% and 58.0% in sBBC and mBBC, respectively. sBBC had a significantly poorer disease-free survival than mBBC did (p = 0.001). BBC is a rare disease affecting the Chinese population. sBBC is associated with a greater prevalence of a family history of breast cancer and poorer prognosis, compared with mBBC.

Multicenter phase II study of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis.

OBJECTIVE: Breast cancer (BC) with chest wall metastasis (CWM) usually shows rich neovascularization. This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2 (HER2)-negative advanced BC involving CWM. METHODS: This trial involved four centers in China and was conducted from September 2016 to March 2020. Patients received apatinib 500 mg/d [either alone or with endocrine therapy if hormone receptor-positive (HR+)] until disease progression or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint. RESULTS: We evaluated 26 patients for efficacy. The median PFS (mPFS) and median overall survival (mOS) were 4.9 [range: 2.0-28.5; 95% confidence interval (95% CI): 2.1-8.3] months and 18 (range: 3-55; 95% CI: 12.9-23.1) months, respectively. The objective response rate (ORR) was 42.3% (11/26), and the disease-control rate was 76.9% (20/26). In the subgroup analysis, HR+ patients compared with HR-negative patients had significantly improved mPFS of 7.0 (95% CI: 2.2-11.8) monthsvs. 2.3 (95% CI: 1.2-3.4) months, respectively (P=0.001); and mPFS in patients without or with chest wall radiotherapy was 6.4 (95% CI: 1.6-19.5) monthsvs. 3.0 (95% CI: 1.3-4.6) months, respectively (P=0.041). In the multivariate analysis, HR+ status was the only independent predictive factor for favorable PFS (P=0.014). CONCLUSIONS: Apatinib was highly effective for BC patients with CWM, especially when combined with endocrine therapy. PFS improved significantly in patients with HR+ status who did not receive chest wall radiotherapy. However, adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.

Efficacy of lapatinib combined with capecitabine in patients with HER2-positive metastatic breast cancer in a real-world study.

The aim of the present study was to determine the efficacy and safety of lapatinib-based treatment for patients with human epidermal growth factor receptor-2-positive (HER2+) metastatic breast cancer (MBC). The aim of the present real-world study was to investigate the medical records and follow-up information of 92 patients with HER2+ MBC who received a lapatinib-based regimen at the recurrent/metastatic stage, 78 of whom had been pretreated with trastuzumab. The results demonstrated that the median progression-free survival (PFS) was 5.8 months and the overall survival (OS) was 21.5 months, with an objective response rate (ORR) of 21.7%, disease control rate (DCR) of 87.0% and clinical benefit rate (CBR) of 47.8%. In the patients receiving a lapatinib-based regimen as first-, second- and third/later-line treatment, the median PFS was 10.4, 5.2 and 5.1 months (P=0.048), the median OS was 32.9, 29.1 and 13.0 months (P<0.001), the ORR was 38.9, 23.3 and 13.60%, and the DCR was 100, 83.3 and 84.1%, respectively. In the trastuzumab-resistant (n=71) and trastuzumab-sensitive (n=21) patients, the median PFS was 5.2 and 9.1 months (P=0.032), and the median OS was 21.4 and 44.3 months (P=0.003), respectively. In the patients who received lapatinib plus chemotherapy (n=68), the median PFS with lapatinib plus capecitabine (n=38) was 8.1 months, as compared with the 5.1 months with lapatinib plus other chemotherapy agents (n=30; P=0.005). The median PFS of 14 patients with brain metastases was 8.4 months, with an ORR of 35.7% and a DCR of 85.7%. Multivariate analysis revealed that the line of lapatinib-based treatment and its combination with capecitabine or a different agent were independent prognostic factors for the median PFS in patients with HER2+ MBC. A limited number of adverse events were observed with the combination of lapatinib and capecitabine. Therefore, the findings of the present study suggested that lapatinib-based treatment is effective in patients with HER2+ MBC (even in trastuzumab-pretreated patients), and the combination of lapatinib with capecitabine may be recommended due to its good efficacy, convenience and tolerability.

Long term use of bevacizumab in the treatment of triple negative breast cancer with giant tumor in chest wall: A case report.

RATIONALE: Triple-negative breast cancer (TNBC) is associated with unfavorable prognosis due to lack of targeted agents. Bevacizumab, an anti-angiogenic monoclonal antibody against vascular endothelial growth factor A, has shown clinical effects in patients with TNBC. PATIENT CONCERNS: We reported a 49-year-old woman presenting with a giant breast tumor. DIAGNOSES: Stage IV TNBC with chest wall metastasis. INTERVENTIONS: The patient underwent long-term use of bevacizumab combined with chemotherapy. OUTCOMES: The patient was on follow-up for 46 months, a remarkable improvement of the chest wall cutaneous lesion was observed. LESSONS: Bevacizumab may provide benefits for TNBC patients with chest wall metastasis.

Serum uric acid levels and hyperuricemia in patients with psoriasis: a hospital-based cross-sectional study

Abstract: A hospital-based cross-sectional study was performed, including 117 psoriatic patients and 117 controls matched for age, gender, and body mass index. Psoriatic patients had higher levels of serum uric acid (6.25 ± 1.62 vs 5.71 ± 1.35 mg/dl; P=0.019) and significantly greater prevalence of hyperuricemia (31.6% vs 16.2%; P=0.009) than individuals without psoriasis. Psoriatic patients had significantly higher serum uric acid than controls in subjects without metabolic syndrome. Multivariate logistic regression analysis showed that psoriasis can be a strong predictor of hyperuricemia (odds ratio 2.61; 95% confidence interval 1.34-5.00; P=0.004).

Serum uric acid levels and hyperuricemia in patients with psoriasis: a hospital-based cross-sectional study.

A hospital-based cross-sectional study was performed, including 117 psoriatic patients and 117 controls matched for age, gender, and body mass index. Psoriatic patients had higher levels of serum uric acid (6.25 ± 1.62 vs 5.71 ± 1.35 mg/dl; P=0.019) and significantly greater prevalence of hyperuricemia (31.6% vs 16.2%; P=0.009) than individuals without psoriasis. Psoriatic patients had significantly higher serum uric acid than controls in subjects without metabolic syndrome. Multivariate logistic regression analysis showed that psoriasis can be a strong predictor of hyperuricemia (odds ratio 2.61; 95% confidence interval 1.34-5.00; P=0.004).

Prevalence of metabolic syndrome in Chinese psoriasis patients: A hospital-based cross-sectional study.

AIMS/INTRODUCTION: Psoriasis, a chronic autoimmune skin disorder, is believed to contribute to cardiovascular diseases and metabolic syndrome. Psoriasis's association with the components of metabolic syndrome has been reported previously. However, large-scale cross-sectional studies about psoriasis and metabolic syndrome are rare in China. MATERIALS AND METHODS: We assessed the prevalence of metabolic syndrome in Chinese psoriasis patients and controls. RESULTS: A total of 859 psoriasis patients and 1,718 controls were recruited in an age- and sex-matched cross-sectional study. Metabolic syndrome occurred in 14.3% of the psoriasis patients as opposed to 10.0% of the control participants (P = 0.001). Psoriasis patients had a higher prevalence of overweight/obesity, hyperglycemia and dyslipidemia when compared with controls. Meanwhile, psoriasis patients with metabolic syndrome were older, and had an older age of onset and a longer disease duration when compared with those without metabolic syndrome. CONCLUSIONS: The prevalence of metabolic syndrome is higher in the Chinese psoriatic population, which can favor cardiovascular events. The present study strengthens the value of treating psoriasis patients not only dealing with the skin lesions, and we suggest appropriate screening and relevant health education be carried out in the treatment of psoriasis patients.

Strategies and Progress of Endocrine Therapy for Patients with Metastatic Breast Cancer.

Breast cancer is one of the most prevalent cancers and the leading causes of cancer mortality in women worldwide and in China. For hormone receptor-positive (HR+) breast cancer, accounting for approximately 60-80% of breast cancer, endocrine therapy (ET) is the primary treatment strategy. For patients with HR+ metastatic breast cancer (MBC), there are many endocrine-based treatment options that can improve long-term outcomes and optimize quality of life. With the emergence and availability of new and effective agents, the options for ET have expanded in the last two decades. Although hormone therapy has been a standard of care for many decades, treatment must be individualized based on tumor biology and extent of disease. For example, the patients with impending organ failure may be treated with induction chemotherapy to improve organ function, followed by ET. For the patients who develop metastatic disease while on adjuvant ET, particularly when associated with organ failure, or for those with low expression of hormone receptors or expression of HER2, chemotherapy again may be a preferred initial treatment. ET blocks estrogen-driven tumor growth through different mechanisms; however, HR+ MBC can be intrinsically resistant or may acquire resistance to the treatment. Several targeted agents have been approved to use in combination with ET to improve response and delay development of resistance.

Hybridizing the "Sandwich" and "Chimney" Techniques in the Endovascular Repair of Coarctation of the Aortic Arch and Postcoarctation Ectasia Concomitant with a Left Subclavian Artery Aneurysm.

Coarctation of aorta is a rare congenital malformation and is usually accompanied by other cardiac or vascular lesions. In this case, we describe a 51-year-old patient who presented with coarctation of the aortic arch and postcoarctation ectasia concomitant with a left subclavian artery aneurysm. Endovascular therapy included the deployment of an inverted wedge-shaped covered stent inserted by a long "chimney" stent and another cylinder-covered stent, forming a "sandwich"-like configuration. The symptoms were alleviated after surgery, and no perioperative or stent-graft-related complications were observed at a 2-year follow-up.

Systemic Multiple Aneurysms Caused by Vascular Ehlers-Danlos Syndrome.

Systemic multiple aneurysms are rare and usually associated with collagen tissue disease, such as Ehlers-Danlos syndrome (EDS) or Marfan syndrome. In the present case, we describe a 39-year-old male patient with systemic multiple aneurysms and acute intraperitoneal hemorrhage who was clinically diagnosed with vascular EDS. Coil embolization of the distal segment of the common hepatic artery was performed, which resolved the patient's symptoms. With this case presentation, we aim to increase the awareness of vascular EDS among clinicians and emphasize the extreme fragility of the arteries in patients with vascular EDS.