The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual ...HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.
Stage IV breast cancer is metastatic breast cancer (MBC). Because real-world data are lacking in China, our research attempts to explore the effect of locoregional surgery on the prognosis of ...patients with MBC. A total of 987 patients from 10 hospitals and 2 databases in East China (2004-2018) were included in this study. Overall, 47% of patients underwent locoregional surgery, and 53% did not. Surgeons tended to perform surgery on patients with small tumours (T1/T2), positive hormone receptor (HR) markers, and metastatic sites confined to a single organ and non-visceral sites (bone only/others) (each p < 0.05). Kaplan-Meier survival curves and the log-rank test showed that median survival was longer for patients who had locoregional surgery than for those who did not (45.00 vs. 28.00 months; p < 0.001). Patients who underwent surgery after systemic treatment had better survival than those who underwent surgery immediately (p < 0.001). In most subgroups, overall survival (OS) was significantly longer in the surgery group than in the no-surgery group (each p < 0.05), except for brain metastases and triple negative breast cancer. Therefore, we concluded that locoregional surgery for the primary tumour in MBC patients was associated with a marked reduction in risk of dying except for patients with brain metastases or triple-negative subtype.
Purpose
Bone marrow metastasis (BMM) is uncommon in breast cancer (BC), and early diagnosis is challenging. BMM lacks definitive treatment options and poses a great threat to the survival of ...patients. Herein, we investigated the clinical features, prognosis, and factors affecting the prognosis of BC patients with symptomatic BMM to help improve the understanding of this disease and provide effective diagnostic and treatment strategies.
Methods
Clinical data of 67 patients with BC and BMM were retrospectively analyzed for clinical characteristics, treatment, and prognosis of BMM. Univariate and multivariate analyses were performed to determine factors affecting overall survival following BMM (BMMOS).
Results
Among patients with BMM, 86.6% were diagnosed after bone metastasis (BM), while 13.4% were diagnosed simultaneously with BM. A total of 73.1%, 13.4%, and 13.4% of the patients had hormone receptor‐positive/human epidermal growth factor 2‐negative (HR+/HER2−) tumors, HER2+ tumors, and triple‐negative tumors, respectively. The most common symptoms of BMM were the coexistence of anemia and thrombocytopenia (26.9%), anemia (19.4%), and pancytopenia (17.9%). The median BMMOS was 7.6 months (95% CI, 3.9–11.3). Univariate and multivariate analyses showed that BMMOS was associated with platelet count <75 × 109/L at the time of BMM diagnosis. The BMMOS of patients who underwent endocrine therapy, combined chemotherapy, and mono‐chemotherapy after BMM was 15.7, 9.7, and 8.6 months, respectively, whereas that of untreated patients was 2.9 months, and the difference among the results was statistically significant (χ2 = 20.102, p < 0.0001). Changes in patient hemogram and/or body temperature during treatment were consistent with the overall effect of the disease (p < 0.0001).
Conclusion
BMM should be considered in BC patients with BM, an unexplained reduction in hemogram parameters, especially anemia and thrombocytopenia, and/or fever without chills. Active, effective, individualized treatment strategies can prolong BMMOS.
HR+/HER2− type tumors are more prone to bone marrow metastases (BMM), which occurs after or at the same time as bone metastasis (BM). BMM should be considered in breast cancer patients with BMs, an unexplained reduction in hemogram parameters (especially anemia and thrombocytopenia), and/or fever (without chills). Active, effective, individualized treatment strategies can prolong the BMMOS.
Summary Background Utidelone, a genetically engineered epothilone analogue, has shown promise as a potential treatment for breast cancer in phase 1 and 2 trials. The aim of this phase 3 trial was to ...compare the efficacy and safety of utidelone plus capecitabine versus capecitabine alone in patients with metastatic breast cancer. Methods We did a multicentre, open-label, superiority, phase 3, randomised controlled trial in 26 hospitals in China. Eligible participants were female patients with metastatic breast cancer refractory to anthracycline and taxane chemotherapy regimens. We randomly assigned participants (2:1) using computer based randomisation and block sizes of 6 to a 21-day cycle of either utidelone (30 mg/m2 intravenously once per day on days 1–5) plus capecitabine (1000 mg/m2 orally twice per day on days 1–14), or capecitabine alone (1250 mg/m2 orally twice per day on days 1–14), until disease progression or unacceptable toxicity occurred. Patients, physicians, and assessors were not masked to treatment allocation; however, an independent radiology review committee used to additionally assess response was masked to allocation. The primary endpoint was centrally assessed (by an independent radiology review committee) progression-free survival, and analysed using the Kaplan-Meier product-limit method in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. Follow-up is ongoing. This study is registered at ClinicalTrials.gov , number NCT02253459. Findings Between Aug 8, 2014, and Dec 14, 2015, we enrolled and randomly assigned 270 patients to treatment with utidelone plus capecitabine, and 135 to capecitabine alone. Median follow-up for progression-free survival was 6·77 months (IQR 3·81–10·32) for the utidelone plus capecitabine group and 4·55 months (2·55–9·39) for the capecitabine alone group. Median progression-free survival by central review in the utidelone plus capecitabine group was 8·44 months (95% CI 7·95–9·92) compared with 4·27 months (3·22–5·68) in the capecitabine alone group; hazard ratio 0·46, 95% CI 0·36–0·59; p<0·0001. Peripheral neuropathy was the most common grade 3 adverse event in the utidelone plus capecitabine group (58 22% of 267 patients vs 1 <1% of 130 patients in the capecitabine alone group). Palmar-plantar erythrodysaesthesia was the most prominent grade 3 adverse event in the capacitabine alone group (in 10 8% of 130 patients) and was the next most frequent grade 3 event in the utidelone plus capecitabine group (in 18 7% of 267 patients). 16 serious adverse events were reported in the combination therapy group (diarrhoea was the most common, in three 1% patients) and 14 serious adverse events were reported in the monotherapy group (the most common were diarrhoea, increased blood bilirubin, and anaemia, in two 2% patients for each event). 155 patients died (99 in the combination therapy arm, 56 in the monotherapy arm). All deaths were related to disease progression except for one in each group (attributed to pericardial effusion in the combination therapy group and dyspnoea in the monotherapy group) that were considered possibly or probably treatment-related. Interpretation Despite disease progression with previous chemotherapies, utidelone plus capecitabine was more efficacious compared with capecitabine alone for the outcome of progression-free survival, with mild toxicity except for peripheral sensory neuropathy, which was manageable. The findings from this study support the use of utidelone plus capecitabine as an effective option for patients with metastatic breast cancer. Funding Beijing Biostar Technologies, Beijing, China.
(1) Background: The objective of our study was to provide evidence for choosing the optimal neoadjuvant therapy strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive ...early breast cancer. Three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) were included in the present study; (2) Methods: We retrospectively analyzed patients with HER2-positive breast cancer who were treated with neoadjuvant TCH + Py, TCH or TCHP, followed by surgery. The outcome was the pathological complete response (pCR) rate; (3) Results: In total, 545 patients were enrolled. The pCR rate was 55.6% (35/63) in the TCH + Py cohort, 32.7% (93/284) in the TCH cohort, and 56.6% (112/198) in the TCHP cohort. The multivariate analysis showed that patients who received TCH had less possibility to achieve pCR than those who received TCH + Py (odds ratio (OR) = 0.334, 95% confidence interval (CI): 0.181−0.619, p < 0.001), while patients who received TCHP had comparable possibility to those who received TCH + Py (OR = 1.043, 95%CI: 0.554−1.964, p = 0.896); (4) Conclusions: TCH + Py provides a better pCR rate compared with TCH, and a comparable pCR rate with TCHP among patients with HER2-positive breast cancer in the neoadjuvant setting. The present study supports a novel potential treatment option for these patients. Further studies need to be explored in the future.
This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive (ER+) early breast ...cancer in China.
Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy. The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer, appearance of a second primary or contralateral breast cancer, or death due to any cause. Other endpoints included the proportion of patients experiencing each event, incidence rate per annum, relationships between human epidermal growth factor receptor 2 status and time to event, and relationship between disease history variables and time to event.
Overall, 558 patients were included in the full analysis set: 397 (71.1%) completed the study, 20 experienced an event, and 141 discontinued 47 owing to an adverse event (AE); 37 no longer willing to participate. Median duration of treatment was 29.5 (range, 0.1-57.7) months. Median time to event was not reached. Event-free survival probability at 36 months was 91.4% (95% CI, 87.7%-95.1%). The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years (20/565). Multivariate analysis showed an association between tumor, lymph node, and metastasis stage at initial diagnosis and time to event hazard ratio: 1.532 (95% CI, 1.129-2.080); P=0.006. Most AEs were grade 1 or 2 in severity, with arthralgia (7.7%) being the most common treatment-related AE.
This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+ breast cancer previously treated with adjuvant tamoxifen for 2-3 years. No new safety signals were identified in the Chinese population.
Axillary node status after neoadjuvant chemotherapy (NCT) in early breast cancer patients influences the axillary surgical staging procedure. This study was conducted for the identification of the ...likelihood of patients being node pathological complete response (pCR) post NCT. We aimed to recognize patients most likely to benefit from sentinel lymph node biopsy (SLNB) following NCT and to reduce the risk of missed detection of positive lymph nodes through the construction and validation of a clinical preoperative scoring prediction model.
The existing data (from March 2010 to December 2018) of the Chinese Society of Clinical Oncology Breast Cancer Database (CSCO-BC) was used to evaluate the independent related factors of node pCR after NCT by Binary Logistic Regression analysis. A predictive model was established according to the score of considerable factors to identify ypN0. Model performance was confirmed in a cohort of NCT patients treated between January 2019 and December 2019 in Henan Cancer Hospital, and model discrimination was evaluated via assessing the area under the receiver operating characteristic (ROC) curve (AUC).
Multivariate regression analysis showed that the node stage before chemotherapy, the expression level of Ki-67, biologic subtype, and breast pCR were all independent related factors of ypN0 after chemotherapy. According to the transformation and summation of odds ratio (OR) values of each variable, the scoring system model was constructed with a total score of 1-5. The AUC for the ROC curves was 0.715 and 0.770 for the training and the validation set accordingly.
A model was established and verified for predicting ypN0 after chemotherapy in newly diagnosed cN+ patients and the model had good accuracy and efficacy. The underlined effective model can suggest axillary surgical planning, and reduce the risk of missing positive lymph nodes by SLNB after NCT. It has great value for identifying initial cN+ patients who are more appropriate for SLNB post-chemotherapy.
The aim of the present study was to examine the expression of hepatocyte growth factor (HGF) in breast cancer and its effect on prognosis and sensitivity to chemotherapy. Immunohistochemistry was ...conducted to determine the expression of HGF in 125 breast cancer patients. The correlation between the expression level of HGF and the effect of preoperative chemotherapy or 5-year survival rate was then investigated. The human breast cancer cell line, MCF-7, was transfected with a HGF-small interfering (si)RNA interference sequence. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to confirm the interference efficiency of HGF-siRNA. An MTT assay was used to detect the proliferative activity of MCF-7 cells following silencing of HGF and during co-culture with epirubicin (EPI) at different concentrations. HGF was highly expressed in breast cancer patients and was not associated with patient age, location, size or hormone receptor status of the tumor (P>0.05), however, HGF expression was associated with tumor-node-metastasis (TNM) clinical stage, histological grade, lymph node metastasis and prognosis (P<0.05). The efficiency of chemotherapy in HGF negative patients (90%) was significantly higher (P<0.05) compared with HGF positive patients (68.75%). Following successful downregulation of HGF by HGF-siRNA, the tolerance to EPI decreased in MCF-7 cells. In conclusion, HGF was highly expressed in breast cancer cells and was closely associated with lymph node metastasis, prognosis and sensitivity to chemotherapy. Therefore, HGF may be a potential indicator of the prognosis and effectiveness of chemotherapy for breast cancer.
To investigate the association between metabolic syndrome and breast cancer and to elucidate the potential mechanism underlying this association.
Based on baseline data drawn from 21 hospitals in 11 ...provinces of China, we performed a case-control study among 1,127 women (595 cases and 532 controls), divided into premenopausal, and postmenopausal subgroups. Student's
test, Pearson's χ
test, and logistic regression analyses were performed to ascertain the association between breast cancer and metabolic syndrome, including all of its components. In addition, we attempted to clarify the potential role of adiponectin in this association.
Among the components of metabolic syndrome, abnormal waist circumference was the component that markedly increased breast cancer risk in premenopausal women (OR 1.447, 95% CI 1.043-2.006). Metabolic syndrome with clusters of special risk factors showed an association with breast cancer risk. Among all these components of metabolic syndrome, the hypertriglyceridemic-waist (HW) phenotype significantly increased breast cancer risk (OR 1.56, 95% CI 1.02-2.39), regardless of menopausal status, rendering it a strong predictor of breast cancer. Total adiponectin levels and high-molecular-weight adiponectin were reversely associated with metabolic syndrome. In addition, total adiponectin levels among breast cancer patients were much lower than among controls (6.67 ± 3.05 vs. 8.01 ± 4.18,
= 0.014) only in the HW phenotype subgroup. Furthermore, the HW phenotype was associated with increased risk of estrogen receptor/progesterone receptor-positive (ER+/PR+) and -negative (ER-/PR-) breast cancer, with a 51% (OR 1.51, 95% CI 1.03-2.21) and 69% (OR 1.69, 95% CI 1.05-2.72) increase, respectively. However, there was no significant association between the HW phenotype and the ER+/PR- subtype. These results suggested that low adiponectin levels may be a mechanism that explains the association between the HW phenotype and breast cancer risk.
Metabolic syndrome with special cluster factors is related to breast cancer risk; in particular, the HW phenotype can be regarded as a strong predictor of breast cancer. As an important factor involved in fat metabolism, adiponectin may strongly predict metabolic syndrome, especially the HW phenotype and breast cancer. Further research into this mechanism and epidemiological studies are needed. This study provides new evidence for the role of a healthy lifestyle in preventing breast cancer.
Leptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence ...of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk.
In the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant-associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database.
There were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101 (GA vs. GG; adjusted OR = 0.719, 95% CI = 0.578-0.894, p = 0.003) and rs4655555 (TT vs. AA; adjusted OR = 0.574, 95% CI = 0.377-0.873, p = 0.009) significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI ≤ 24 kg/m
or WHR ≥ 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data.
Our study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer.
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