BACKGROUND Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis.AIM To evaluate the outcomes of young hormone receptor(HR)-positive patients with breast cancer treated with neo...BACKGROUND Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis.AIM To evaluate the outcomes of young hormone receptor(HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy(NAC),and the oncologic efficacy of gonadotropin-releasing hormone(GnRH)agonists.METHODS This retrospective study involved a prospectively enrolled cohort.We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017.Among patients with HR-positive and human epidermal grow factor 2(HER2)-negative breast cancer,we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years.RESULTS Among 431 patients with NAC and HR-positive/HER2-negative breast cancer,78 were 35 years old or younger,and 353 patients were older than 35 years.The median follow-up was 71.0 months.There was no statistically significant difference in disease free survival(DFS,P=0.565)and overall survival(P=0.820)between the patients equal to or younger than 35 years and the patients older than 35 years.The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group(52.4%vs 11.2%,P<0.001).Interestingly,for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years,patients treated with the GnRH agonist had better DFS(P=0.037).CONCLUSION Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.展开更多
Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi...Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS)in 755 HRpositive breast cancer patients(273,265,and 217 in the training,internal,and external validation sets,respectively).This model,presented as a nomogram,included four parameters:the 10-mi RNA RS found in our previous study,progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)status,and volume transfer constant(K).Favorable calibration and discrimination of 10-mi RNA RS-based model with areas under the curve(AUC)of 0.865,0.811,and 0.804 were shown in the training,internal,and external validation sets,respectively.Patients who have higher nomogram score(>92.2)with NAC treatment would have longer DFS(hazard ratio=0.57;95%CI:0.39–0.83;P=0.004).In summary,our data showed the 10-mi RNA RS-based model could precisely identify more patients who can attain p CR to NAC,which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HRpositive breast cancer.展开更多
Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deace...Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deacetylase(HDAC) inhibitor with multiple functions in tumor growth inhibition and microenvironment modulation via epigenetic reprogramming.The purpose of this study was to evaluate the safety,pharmacokinetics(PK),and preliminary efficacy of chidamide in combination with exemestane in HR+ ABC patients.Methods: Eligible patients were postmenopausal women with HR+ ABC recurrent or progressed to at least one endocrine therapy.Blood samples were obtained in the run-in period and the first day of combination treatment for PK analysis.In combination treatment,patients were given exemestane 25mg daily and chidamide 30mg twice a week(BIW) until progression of disease or intolerable toxicities.A treatment cycle was defined as 4 weeks.Safety,PK parameters,and preliminary efficacy were evaluated.Results: A total of 20 patients were enrolled between July and December,2015.The median number of treatments cycle was 5.2(20.8 weeks) with 2 patients still on treatment at the data cut-off date of October,2017.The treatment-related adverse events(AE) ≥ grade 3 in more than 2 patients were neutropenia(35%),thrombocytopenia(30%),and leucopenia(20%).The plasma exposure of exemestane was consistent in the presence or absence of chidamide.A slight increase in chidamide exposure was noted in the presence of exemestane,probably due to the inter-and intra-patient variations.The best response in 16 evaluable patients was assessed by Response Evaluation Criteria in Solid Tumors(RECIST),including 4 patients with partial response,10 patients with stable disease.The median progression-free survival(PFS) was 7.6 months.Conclusions: The combination of chidamide with exemestane was generally well tolerated with promising preliminary efficacy in HR+ ABC patients.The overall results from this study encourage further pivotal trial in this patient population.展开更多
Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthrac...Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.展开更多
The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a highe...The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.展开更多
AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 ...AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.展开更多
This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese female breast cancer patients. The expression of estrogen receptor（ER）, proges...This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese female breast cancer patients. The expression of estrogen receptor（ER）, progesterone receptor（PR） and Ki67 among 525 neoadjuvant chemotherapy cases was studied by immunohistochemistry.Differences between specimens made through preoperative core needle biopsy and excised tissue biopsy were observed. The positive rates of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy were 65.3% and 63.2%, 51.0% and 42.6%, 65.6% and 43.4%, respectively. The expression of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy had no statistically significant difference. However, after neoadjuvant chemotherapy, the discordance rates of ER, PR and Ki67 were 15.2%（79/521）, 26.9%（140/520） and 44.8%（225/502）, respectively. The ER, PR and Ki67 status changed from positive to negative in 7.5%（39/521）, 13.3%（69/520） and 21.1%（106/502） of the patients, whereas ER, PR and Ki67 status changed from negative to positive in 7.7%（40/521）, 13.6%（71/520）and 23.7%（119/502） of the patients, respectively. These results showed that the status of some biomarkers changes after neoadjuvant chemotherapy and biomarker status needs to be reexamined to optimize adjuvant systemic therapy and better prognosis assessment.展开更多
Objective: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 Chi...Objective: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.Methods: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.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced 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.Eventfree 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.Conclusions: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.展开更多
Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast c...Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated.The results of the Women’s Health Initiative’s randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy,with an elevated risk of breast cancer.The evidence currently available from randomized trials and observational studies is based on data from different populations,drug formulations,and routes of administration.Even though the risks of MHT and breast cancer have received a great deal of attention,information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed.Furthermore,the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied.Therefore,this review aimed to describe the biological effects of estrogen,progesterone,and their metabolites on the proliferation of breast cancer cells,based on relevant basic research and clinical trials,to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.展开更多
Clinical, pathological features and steroid hormone receptors (SR) including receptors of estrogen (ER), progesterone (PR) and androgen (AR) were observed in 58 cases of breast carcinoma, and related to patient 5- yea...Clinical, pathological features and steroid hormone receptors (SR) including receptors of estrogen (ER), progesterone (PR) and androgen (AR) were observed in 58 cases of breast carcinoma, and related to patient 5- year survival rate through stratification and multivariatc analysis. The results showed that histologic tumor type and grading, lymphnode status, ER value and patient age took more important role in patient survival, and SR, especially, conferred survival advantage in advanced cases with tumor size larger than 2 cm, node involved, or TNM Stage Ⅱ-Ⅲ.展开更多
Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and...Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen treatments.The need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis.展开更多
Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) is the most common biologic subtype of breast cancer. Although adjuvant therapy has demonstrated a survival benefi...Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) is the most common biologic subtype of breast cancer. Although adjuvant therapy has demonstrated a survival benefit in clinical trials, its use is poorly understood in the real-world among elderly breast cancer patients since age is a barrier to receiving adjuvant therapy. An examination of treatment patterns and outcomes associated with receipt of adjuvant/neoadjuvant therapy among elderly HR + HER2-breast cancer patients was undertaken. Methods: There were 18,470 HR + HER2-breast cancer patients from the linked SEER-Medicare database. Patients were diagnosed with stage I-III disease between 1/1/2007-12/31/2011, ≥66 years, enrolled in Medicare Parts A, B and D, and underwent breast cancer surgery after diagnosis. Time-varying Cox proportional hazards regression assessed overall survival. Results: There were 13,670 (74%) patients treated with adjuvant/neoadjuvant therapy and 4800 (26%) untreated. Compared to treated patients, untreated patients were older, had earlier stage, lower grade, smaller tumors, poorer performance, higher comorbidity score, and less use of a 21-gene recurrence score (RS) assay (p < 0.0001). In the survival model, increasing age, stage, tumor size, tumor grade, comorbidity score and poor performance were significantly associated with higher mortality risks, while use of an RS assay was associated with lower risks. The Cox model showed a 48% higher risk of death in untreated compared to treated patients. In a subset of 8967 patients with stage I disease, tumor size < 2.0 cm and grade 1/2;untreated patients had a 22% higher risk of death compared to treated patients. Conclusions: Older patients with favorable clinical characteristics (earlier stage, smaller tumor, lower grade) are less likely to be treated and have a higher risk of death compared to adjuvant/neoadjuvant treated patients. An unmet need among older breast cancer patients persists.展开更多
To explore breast cancer etiology, literature was searched using Medline. We explored the (1) plausibility of smoking in breast carcinogenesis; (2) physiological properties, susceptibility windows, and exposure timing...To explore breast cancer etiology, literature was searched using Medline. We explored the (1) plausibility of smoking in breast carcinogenesis; (2) physiological properties, susceptibility windows, and exposure timing of breast cells; (3) role of exogenous hormones in breast carcinogenesis; (4) biological mechanism of synergistic interactions between smoking and exogenous hormones in breast carcinogenesis; and (5) evidence from epidemiologic studies and the fitted secular trend between smoking rate, exogenous hormone use, and breast cancer incidence in past decades. We deduced that exogenous hormone use per se is not a significant cause and its association with breast cancer is distorted by chronic exposure to environmental carcinogens, especially smoking. We hypothesize that smoking is one of the causes of breast cancer and that this causality is strengthened by synergistic interaction between smoking and exogenous hormone use. Physicians should be cautious of prescribing exogenous hormones for those with chronic exposure to environmental carcinogens to prevent breast cancer.展开更多
Recent clinical trials with histone deacetylase inhibitors (HDACi) have shown increased progression free survival by re-sensitizing resistant estrogen receptor positive (ER+) breast cancer cells to hormone suppressive...Recent clinical trials with histone deacetylase inhibitors (HDACi) have shown increased progression free survival by re-sensitizing resistant estrogen receptor positive (ER+) breast cancer cells to hormone suppressive therapies (HT). However, these trials lacked a sensitive, specific assay to identify and monitor HDACi/HT sensitive or resistant tumors. We tested detection of ER expression and histone acetylation of chromatin at the growth regulation by estrogen in breast cancer 1 (GREB1) gene, an estrogen-responsive gene involved in ER expression, in circulating tumor cell (CTC) as potential candidate assays for HDACi/HT sensitivity. ER+ and ER- CTC were detected and isolated from breast cancer patient peripheral blood by high speed fluorescence activated cell sorting (FACS) for use in mRNA analysis and anti-acetylated histone-mediated Chromatin Immunoprecipitation (ChIP). cDNA from mRNA and DNA extracted from the ChIP isolates were quantified by real-time PCR for GREB1. CTC isolates from patients who had an ER+ breast cancer primary contained both ER+ and ER- cells. More ER+ than ER- CTC was found in HT sensitive patients compared to HT resistant patients (p = 0.0559). GREB1 was found in acetylated histone chromatin from both ER+ and ER- CTC. The number of ER+ and ER- CTC found in peripheral blood appears to parallel patient outcomes as to their sensitivity to HT. Acetylated histone analysis can detect chromatin containing GREB1 in CTC, suggesting it may be useful as a more specific measure of HDACi effects on breast tumor cells. A larger, longitudinal data set following patients through HT/HDACi trials is needed to confirm these observations and their development for clinical use.展开更多
Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging outcomes.This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemest...Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging outcomes.This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR+ABC that relapsed/progressed after≥1 endocrine therapy.Patients were randomized(2:1)to oral exemestane 25 mg/day plus entinostat(n=235)or placebo(n=119)5 mg/week in 28-day cycles.The primary endpoint was the independent radiographic committee(IRC)-assessed progression-free survival(PFS).The median age was 52(range,28—75)years and 222(62.7%)patients were postmenopausal.CDK4/6 inhibitors and fulvestrant were previously used in 23(6.5%)and 92(26.0%)patients,respectively.The baseline characteristics were comparable between the entinostat and placebo groups.The median PFS was 6.32(95%CI,5.30—9.11)and 3.72(95%CI,1.91—5.49)months in the entinostat and placebo groups(HR,0.76;95%CI,0.58—0.98;P=0.046),respectively.Grade≥3 adverse events(AEs)occurred in 154(65.5%)patients in the entinostat group versus 23(19.3%)in the placebo group,and the most common grade≥3 treatment-related AEs were neutropenia[103(43.8%)],thrombocytopenia[20(8.5%)],and leucopenia[15(6.4%)].Entinostat plus exemestane significantly improved PFS compared with exemestane,with generally manageable toxicities in HR+ABC(ClinicalTrials.gov#NCT03538171).展开更多
Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast canc...Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer(HR+/HER2-MBC),while chemotherapy(CT)is commonly used in clinical practice.The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2-MBC.Methods:Patients diagnosed with HR+/HER2-MBC between January 1st,1996 and September 30th,2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database.The initial and maintenance first-line treatment,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Among the 1877 included patients,1215(64.7%)received CT and 662(35.3%)received ET as initial first-line treatment.There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population(PFS:12.0 vs.11.0 months,P=0.22;OS:54.0 vs.49.0 months,P=0.09)and propensity score matched population.For patients without disease progression after at least 3 months of initial therapy,maintenance ET following initial CT(CT-ET cohort,n=449)and continuous schedule of ET(ET cohort,n=527)had longer PFS than continuous schedule of CT(CT cohort,n=406)in the total population(CT-ET cohort vs.CT cohort:17.0 vs.8.5 months;P<0.01;ET cohort vs.CT cohort:14.0 vs.8.5 months;P<0.01)and propensity score matched population.OS in the three cohorts yielded the same results as PFS.Conclusions:ET was associated with similar clinical outcome to CT as initial first-line treatment.For patients without disease progression after initial CT,switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.展开更多
Background:In light of the significant clinical benefits of antibody-drug conjugates in clinical trials,the human epidermal growth factor receptor 2(HER2)-low category in breast cancers has gained increasing attention...Background:In light of the significant clinical benefits of antibody-drug conjugates in clinical trials,the human epidermal growth factor receptor 2(HER2)-low category in breast cancers has gained increasing attention.Therefore,we studied the clinicopathological characteristics of Chinese patients with hormone receptor(HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model.Methods:Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery(CSBrS)from Jan 2015 to Dec 2016 were enrolled.Their clinicopathological data and prognostic information were collected,and machine learning methods were used to analyze the prognostic factors.Results:In total,25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016,and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected.Among them,5629 patients(86.79%)were HR-positive.The median follow-up time was 57 months(4,76 months);the 5-year disease-free survival(DFS)rate was 92.7%,and the 5-year overall survival(OS)rate was 97.7%.In total,412 cases(7.31%)of metastasis were observed,and 124(2.20%)patients died.Multivariate Cox regression analysis revealed that T stage,N stage,lymphovascular thrombosis,Ki-67 index,and prognostic stage were associated with recurrence and metastasis(P<0.05).A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%,specificity of 71.7%,positive predictive value of 74.1%,and negative predictive value of 79.2%.Conclusion:Most of patients with HER2-low early-stage breast cancer were HR-positive,and patients had favorable outcome;tumor N stage,lymphovascular thrombosis,Ki-67 index,and tumor prognostic stage were prognostic factors.The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events.Registritation:ChiCTR.org.cn,ChiCTR2100046766.展开更多
Objective: The aim of this study was to determine body composition, gynecological, and obstetric data, sex hormones, and prolactin serum levels in pre- (PREW) and postmenopausal women (PMW) with breast cancer (BC) and...Objective: The aim of this study was to determine body composition, gynecological, and obstetric data, sex hormones, and prolactin serum levels in pre- (PREW) and postmenopausal women (PMW) with breast cancer (BC) and compare them with a control group (CG) of healthy women. Methodology: BC patients without treatment or use of hormone replacement therapy, or hormonal birth control, and without data of metastasis were included. CG was matched for age, BMI, and menstrual cycle status. FSH, LH, E<sup>2</sup>, progesterone, testosterone, and prolactin (PRL) were measured using radioimmunoassay kits. Comparisons between BC and CG were made with “t” tests, and with the Mann-Whitney U-test;χ<sup>2</sup> test was used to compare the qualitative variables between the groups. Results: Seventy-two patients with BC, and 74 CG women were evaluated. Both groups presented overweight data, BMI (kg/mt<sup>2</sup>) = 27.21 ± 5.51 vs. 28.40 ± 4.66, p = ns, for BC patients and CG, respectively. In PREW, the age at menarche was later in BC patients compared to the CG (13.3 ± 1.36 years vs. 12.41 ± 1.27 years, p = 0.005). The PMW with BC presented a higher age at menarche and menopause compared to the women of the CG (13.51 ± 1.48 vs. 12.91 ± 1.41, p = 0.09, and 49.03 ± 2.86 vs. 45.5 ± 8.78, p = 0.03, respectively). PRL levels were significantly higher in PMW with BC, in comparison with the CG;median and minimum and maximum values (min-max) were: 14.7 ng/mL (3.6 - 52.7) vs. 5.9 ng/mL (1.9 - 33.3), p = 0.005). A higher percentage of PMW with BC (26.0% vs. 7.1%, χ<sup>2</sup> = 5.57, p = 0.01) presented hyperprolactinemia (PRL serum levels > 20 ng/mL), compared to the GC. Conclusions: The higher levels of PRL in PMW with BC compared with CG, suggest a proliferative effect of this hormone in the affected breast tissue. This study demonstrates the need to use biological markers such as PRL to determine the risk of BC in PMW.展开更多
Background: Continued exposure to sex hormones such as estrogen is a critical risk for subsequent breast cancer. Thus the present study aimed to assess the levels of knowledge towards hormonal related breast cancer ri...Background: Continued exposure to sex hormones such as estrogen is a critical risk for subsequent breast cancer. Thus the present study aimed to assess the levels of knowledge towards hormonal related breast cancer risk factors in Qurayyat, Northern Saudi Arabia. Methodology: This descriptive study included 737 Saudi volunteers living in the city of Qurayyat, Northern Saudi Arabia. For females, only those agreeing to participate in the breast self-examination workshop were included, and non-respondents were included in the questionnaire. Results: For the question apropos “Inheritance as a risk factor for BC,” 405/607 (66.7%) females signposted certainly “Yes,” as well as, 70/130 (54%) males signposted certainly “Yes.” The odds ratio (OR) and 95% confidence interval (95% CI) were not statistically significant, but the level of knowledge was relatively higher among females OR (95% CI) = 1.4321 (0.9597 to 2.1370), P = 0.0786. “Are early puberty and late menopause risk factors for breast cancer?” No statistical significant differences were eminent between males and females, OR (95% CI) = 0.8878 (0.5932 to 1.3287), P = 0.5629. Conclusion: Saudi women are enthusiastically willing to raise their knowledge and awareness of breast cancer prevention and control. Although women have greater knowledge about breast cancer risk factors compared to men, still some gaps need to be filled.展开更多
BACKGROUND There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P4502D6(CYP2D6)polymorphisms.AIM To evaluate how knowledge of CYP2D6 genotyp...BACKGROUND There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P4502D6(CYP2D6)polymorphisms.AIM To evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical outcomes.METHODS Eighty-two women were recruited.Seventy-eight completed CYP2D6 genotyping and were categorized into poor,intermediate(IM)and extensive or ultra metabolizer phenotypes.Women with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred agent.RESULTS More than 70%of the women had an IM phenotype,32%an extensive or ultra metabolizer phenotype,and 0%had a poor metabolizer phenotype.Regardless of genotype,more women opted for aromatase inhibitors.Overall,80%of women completed 5 years of hormonal therapy.Five women developed recurrence,3 contralateral breast cancer,5 died,and 1 was diagnosed with a second primary cancer.Five-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype,though not statistically significant[P=0.743,hazard ratio(HR):1.441,95%confidence interval(CI):0.191 to 10.17 and P=0.798,HR:1.327,95%CI:0.172 to 9.915,respectively].Women receiving aromatase inhibitors also appeared to have a better,but also nonsignificant,5-year recurrence-free and overall survival(P=0.253,HR:0.368,95%CI:0.031 to 0.258 and P=0.292,HR:0.252,95%CI:0.005 to 4.951,respectively).CONCLUSION The IM phenotype was highly prevalent but was not associated with clinical outcome.展开更多
文摘BACKGROUND Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis.AIM To evaluate the outcomes of young hormone receptor(HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy(NAC),and the oncologic efficacy of gonadotropin-releasing hormone(GnRH)agonists.METHODS This retrospective study involved a prospectively enrolled cohort.We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017.Among patients with HR-positive and human epidermal grow factor 2(HER2)-negative breast cancer,we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years.RESULTS Among 431 patients with NAC and HR-positive/HER2-negative breast cancer,78 were 35 years old or younger,and 353 patients were older than 35 years.The median follow-up was 71.0 months.There was no statistically significant difference in disease free survival(DFS,P=0.565)and overall survival(P=0.820)between the patients equal to or younger than 35 years and the patients older than 35 years.The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group(52.4%vs 11.2%,P<0.001).Interestingly,for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years,patients treated with the GnRH agonist had better DFS(P=0.037).CONCLUSION Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.
基金the National Natural Science Foundation of China(92159303,81621004,81720108029,81930081,91940305,81672594,81772836,81872139,82072907,and 82003311)Guangdong Science and Technology Department(2020B1212060018 and 2020B1212030004)+8 种基金Clinical Innovation Research Program of Bioland Laboratory(2018GZR0201004)Bureau of Science and Technology of Guangzhou(20212200003)Program for Guangdong Introducing Innovative and Enterpreneurial Teams(2019BT02Y198)the Project of The Beijing Xisike Clinical Oncology Research Foundation(YRoche2019/2-0078)the Technology Development Program of Guangdong province(2021A0505030082)the Project of The Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation(2020B1212060018)Sun Yat-Sen Memorial Hospital Cultivation Project for Clinical Research(SYS-C-201805 and SYS-Q-202004)Guangzhou Science and Technology Program(202102010272)Medical Science and Technology Research Fund of Guangdong Province(A2020391)。
文摘Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS)in 755 HRpositive breast cancer patients(273,265,and 217 in the training,internal,and external validation sets,respectively).This model,presented as a nomogram,included four parameters:the 10-mi RNA RS found in our previous study,progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)status,and volume transfer constant(K).Favorable calibration and discrimination of 10-mi RNA RS-based model with areas under the curve(AUC)of 0.865,0.811,and 0.804 were shown in the training,internal,and external validation sets,respectively.Patients who have higher nomogram score(>92.2)with NAC treatment would have longer DFS(hazard ratio=0.57;95%CI:0.39–0.83;P=0.004).In summary,our data showed the 10-mi RNA RS-based model could precisely identify more patients who can attain p CR to NAC,which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HRpositive breast cancer.
基金partly supported by grants from the Chinese National Major Project for New Drug Innovation(No.2015ZX09101005)the Shenzhen municipal science and technology project(No.JCYJ20120618162903087 and No.JSGG20140515161400837)
文摘Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deacetylase(HDAC) inhibitor with multiple functions in tumor growth inhibition and microenvironment modulation via epigenetic reprogramming.The purpose of this study was to evaluate the safety,pharmacokinetics(PK),and preliminary efficacy of chidamide in combination with exemestane in HR+ ABC patients.Methods: Eligible patients were postmenopausal women with HR+ ABC recurrent or progressed to at least one endocrine therapy.Blood samples were obtained in the run-in period and the first day of combination treatment for PK analysis.In combination treatment,patients were given exemestane 25mg daily and chidamide 30mg twice a week(BIW) until progression of disease or intolerable toxicities.A treatment cycle was defined as 4 weeks.Safety,PK parameters,and preliminary efficacy were evaluated.Results: A total of 20 patients were enrolled between July and December,2015.The median number of treatments cycle was 5.2(20.8 weeks) with 2 patients still on treatment at the data cut-off date of October,2017.The treatment-related adverse events(AE) ≥ grade 3 in more than 2 patients were neutropenia(35%),thrombocytopenia(30%),and leucopenia(20%).The plasma exposure of exemestane was consistent in the presence or absence of chidamide.A slight increase in chidamide exposure was noted in the presence of exemestane,probably due to the inter-and intra-patient variations.The best response in 16 evaluable patients was assessed by Response Evaluation Criteria in Solid Tumors(RECIST),including 4 patients with partial response,10 patients with stable disease.The median progression-free survival(PFS) was 7.6 months.Conclusions: The combination of chidamide with exemestane was generally well tolerated with promising preliminary efficacy in HR+ ABC patients.The overall results from this study encourage further pivotal trial in this patient population.
基金This work was sup-ported by National Natural Sclence Foundatlon of China(no.81202108)
文摘Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.
文摘The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.
文摘AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.
基金supported by National Natural Science Foundation of China (NSFC) (81372851)
文摘This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese female breast cancer patients. The expression of estrogen receptor（ER）, progesterone receptor（PR） and Ki67 among 525 neoadjuvant chemotherapy cases was studied by immunohistochemistry.Differences between specimens made through preoperative core needle biopsy and excised tissue biopsy were observed. The positive rates of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy were 65.3% and 63.2%, 51.0% and 42.6%, 65.6% and 43.4%, respectively. The expression of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy had no statistically significant difference. However, after neoadjuvant chemotherapy, the discordance rates of ER, PR and Ki67 were 15.2%（79/521）, 26.9%（140/520） and 44.8%（225/502）, respectively. The ER, PR and Ki67 status changed from positive to negative in 7.5%（39/521）, 13.3%（69/520） and 21.1%（106/502） of the patients, whereas ER, PR and Ki67 status changed from negative to positive in 7.7%（40/521）, 13.6%（71/520）and 23.7%（119/502） of the patients, respectively. These results showed that the status of some biomarkers changes after neoadjuvant chemotherapy and biomarker status needs to be reexamined to optimize adjuvant systemic therapy and better prognosis assessment.
文摘Objective: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.Methods: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.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced 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.Eventfree 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.Conclusions: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.
基金This study was supported by grants from the National Natural Science Foundation of China(Grant Nos.61673024 and 81971348)the Clinical Medicine Plus X-Young Scholar Project,Peking University,and the Fundamental Research Funds for the Central University(Grant No.PKU2018LCXQ001).
文摘Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated.The results of the Women’s Health Initiative’s randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy,with an elevated risk of breast cancer.The evidence currently available from randomized trials and observational studies is based on data from different populations,drug formulations,and routes of administration.Even though the risks of MHT and breast cancer have received a great deal of attention,information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed.Furthermore,the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied.Therefore,this review aimed to describe the biological effects of estrogen,progesterone,and their metabolites on the proliferation of breast cancer cells,based on relevant basic research and clinical trials,to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.
文摘Clinical, pathological features and steroid hormone receptors (SR) including receptors of estrogen (ER), progesterone (PR) and androgen (AR) were observed in 58 cases of breast carcinoma, and related to patient 5- year survival rate through stratification and multivariatc analysis. The results showed that histologic tumor type and grading, lymphnode status, ER value and patient age took more important role in patient survival, and SR, especially, conferred survival advantage in advanced cases with tumor size larger than 2 cm, node involved, or TNM Stage Ⅱ-Ⅲ.
基金Supported by Ricerca Sanitaria LILT 2015Beneficentia Foundation Stiftung,No.BEN2016/16 grants
文摘Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen treatments.The need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis.
文摘Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) is the most common biologic subtype of breast cancer. Although adjuvant therapy has demonstrated a survival benefit in clinical trials, its use is poorly understood in the real-world among elderly breast cancer patients since age is a barrier to receiving adjuvant therapy. An examination of treatment patterns and outcomes associated with receipt of adjuvant/neoadjuvant therapy among elderly HR + HER2-breast cancer patients was undertaken. Methods: There were 18,470 HR + HER2-breast cancer patients from the linked SEER-Medicare database. Patients were diagnosed with stage I-III disease between 1/1/2007-12/31/2011, ≥66 years, enrolled in Medicare Parts A, B and D, and underwent breast cancer surgery after diagnosis. Time-varying Cox proportional hazards regression assessed overall survival. Results: There were 13,670 (74%) patients treated with adjuvant/neoadjuvant therapy and 4800 (26%) untreated. Compared to treated patients, untreated patients were older, had earlier stage, lower grade, smaller tumors, poorer performance, higher comorbidity score, and less use of a 21-gene recurrence score (RS) assay (p < 0.0001). In the survival model, increasing age, stage, tumor size, tumor grade, comorbidity score and poor performance were significantly associated with higher mortality risks, while use of an RS assay was associated with lower risks. The Cox model showed a 48% higher risk of death in untreated compared to treated patients. In a subset of 8967 patients with stage I disease, tumor size < 2.0 cm and grade 1/2;untreated patients had a 22% higher risk of death compared to treated patients. Conclusions: Older patients with favorable clinical characteristics (earlier stage, smaller tumor, lower grade) are less likely to be treated and have a higher risk of death compared to adjuvant/neoadjuvant treated patients. An unmet need among older breast cancer patients persists.
基金supported by the Department of Epidemiology at the Johns Hopkins University Bloomberg School of Public Health
文摘To explore breast cancer etiology, literature was searched using Medline. We explored the (1) plausibility of smoking in breast carcinogenesis; (2) physiological properties, susceptibility windows, and exposure timing of breast cells; (3) role of exogenous hormones in breast carcinogenesis; (4) biological mechanism of synergistic interactions between smoking and exogenous hormones in breast carcinogenesis; and (5) evidence from epidemiologic studies and the fitted secular trend between smoking rate, exogenous hormone use, and breast cancer incidence in past decades. We deduced that exogenous hormone use per se is not a significant cause and its association with breast cancer is distorted by chronic exposure to environmental carcinogens, especially smoking. We hypothesize that smoking is one of the causes of breast cancer and that this causality is strengthened by synergistic interaction between smoking and exogenous hormone use. Physicians should be cautious of prescribing exogenous hormones for those with chronic exposure to environmental carcinogens to prevent breast cancer.
文摘Recent clinical trials with histone deacetylase inhibitors (HDACi) have shown increased progression free survival by re-sensitizing resistant estrogen receptor positive (ER+) breast cancer cells to hormone suppressive therapies (HT). However, these trials lacked a sensitive, specific assay to identify and monitor HDACi/HT sensitive or resistant tumors. We tested detection of ER expression and histone acetylation of chromatin at the growth regulation by estrogen in breast cancer 1 (GREB1) gene, an estrogen-responsive gene involved in ER expression, in circulating tumor cell (CTC) as potential candidate assays for HDACi/HT sensitivity. ER+ and ER- CTC were detected and isolated from breast cancer patient peripheral blood by high speed fluorescence activated cell sorting (FACS) for use in mRNA analysis and anti-acetylated histone-mediated Chromatin Immunoprecipitation (ChIP). cDNA from mRNA and DNA extracted from the ChIP isolates were quantified by real-time PCR for GREB1. CTC isolates from patients who had an ER+ breast cancer primary contained both ER+ and ER- cells. More ER+ than ER- CTC was found in HT sensitive patients compared to HT resistant patients (p = 0.0559). GREB1 was found in acetylated histone chromatin from both ER+ and ER- CTC. The number of ER+ and ER- CTC found in peripheral blood appears to parallel patient outcomes as to their sensitivity to HT. Acetylated histone analysis can detect chromatin containing GREB1 in CTC, suggesting it may be useful as a more specific measure of HDACi effects on breast tumor cells. A larger, longitudinal data set following patients through HT/HDACi trials is needed to confirm these observations and their development for clinical use.
基金sponsored by EOC Pharmaceutical CO,and CAMS Innovation Fund for Medical Sciences(CIFMS,2021I2M-1-014,China)Taizhou EOC Pharma Co.,Ltd.for supporting,developing and sponsoring this trial。
文摘Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging outcomes.This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR+ABC that relapsed/progressed after≥1 endocrine therapy.Patients were randomized(2:1)to oral exemestane 25 mg/day plus entinostat(n=235)or placebo(n=119)5 mg/week in 28-day cycles.The primary endpoint was the independent radiographic committee(IRC)-assessed progression-free survival(PFS).The median age was 52(range,28—75)years and 222(62.7%)patients were postmenopausal.CDK4/6 inhibitors and fulvestrant were previously used in 23(6.5%)and 92(26.0%)patients,respectively.The baseline characteristics were comparable between the entinostat and placebo groups.The median PFS was 6.32(95%CI,5.30—9.11)and 3.72(95%CI,1.91—5.49)months in the entinostat and placebo groups(HR,0.76;95%CI,0.58—0.98;P=0.046),respectively.Grade≥3 adverse events(AEs)occurred in 154(65.5%)patients in the entinostat group versus 23(19.3%)in the placebo group,and the most common grade≥3 treatment-related AEs were neutropenia[103(43.8%)],thrombocytopenia[20(8.5%)],and leucopenia[15(6.4%)].Entinostat plus exemestane significantly improved PFS compared with exemestane,with generally manageable toxicities in HR+ABC(ClinicalTrials.gov#NCT03538171).
基金supported by research and development project of medical data and artificial intelligence in Chinese PLA General Hospital(Grant No.2019MBD-056)
文摘Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer(HR+/HER2-MBC),while chemotherapy(CT)is commonly used in clinical practice.The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2-MBC.Methods:Patients diagnosed with HR+/HER2-MBC between January 1st,1996 and September 30th,2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database.The initial and maintenance first-line treatment,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Among the 1877 included patients,1215(64.7%)received CT and 662(35.3%)received ET as initial first-line treatment.There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population(PFS:12.0 vs.11.0 months,P=0.22;OS:54.0 vs.49.0 months,P=0.09)and propensity score matched population.For patients without disease progression after at least 3 months of initial therapy,maintenance ET following initial CT(CT-ET cohort,n=449)and continuous schedule of ET(ET cohort,n=527)had longer PFS than continuous schedule of CT(CT cohort,n=406)in the total population(CT-ET cohort vs.CT cohort:17.0 vs.8.5 months;P<0.01;ET cohort vs.CT cohort:14.0 vs.8.5 months;P<0.01)and propensity score matched population.OS in the three cohorts yielded the same results as PFS.Conclusions:ET was associated with similar clinical outcome to CT as initial first-line treatment.For patients without disease progression after initial CT,switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.
基金supported by grants from the Youth Cultivation Fund of Beijing Medical Ward Foundation(No.20180502)Beijing Medical Ward Foundation(Nos.YXJL-2016-0040-0065,YXJL-2020-0941-0736)Chinese junior breast surgeon research award fund(No.2020-CHPASLP-01)
文摘Background:In light of the significant clinical benefits of antibody-drug conjugates in clinical trials,the human epidermal growth factor receptor 2(HER2)-low category in breast cancers has gained increasing attention.Therefore,we studied the clinicopathological characteristics of Chinese patients with hormone receptor(HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model.Methods:Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery(CSBrS)from Jan 2015 to Dec 2016 were enrolled.Their clinicopathological data and prognostic information were collected,and machine learning methods were used to analyze the prognostic factors.Results:In total,25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016,and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected.Among them,5629 patients(86.79%)were HR-positive.The median follow-up time was 57 months(4,76 months);the 5-year disease-free survival(DFS)rate was 92.7%,and the 5-year overall survival(OS)rate was 97.7%.In total,412 cases(7.31%)of metastasis were observed,and 124(2.20%)patients died.Multivariate Cox regression analysis revealed that T stage,N stage,lymphovascular thrombosis,Ki-67 index,and prognostic stage were associated with recurrence and metastasis(P<0.05).A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%,specificity of 71.7%,positive predictive value of 74.1%,and negative predictive value of 79.2%.Conclusion:Most of patients with HER2-low early-stage breast cancer were HR-positive,and patients had favorable outcome;tumor N stage,lymphovascular thrombosis,Ki-67 index,and tumor prognostic stage were prognostic factors.The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events.Registritation:ChiCTR.org.cn,ChiCTR2100046766.
文摘Objective: The aim of this study was to determine body composition, gynecological, and obstetric data, sex hormones, and prolactin serum levels in pre- (PREW) and postmenopausal women (PMW) with breast cancer (BC) and compare them with a control group (CG) of healthy women. Methodology: BC patients without treatment or use of hormone replacement therapy, or hormonal birth control, and without data of metastasis were included. CG was matched for age, BMI, and menstrual cycle status. FSH, LH, E<sup>2</sup>, progesterone, testosterone, and prolactin (PRL) were measured using radioimmunoassay kits. Comparisons between BC and CG were made with “t” tests, and with the Mann-Whitney U-test;χ<sup>2</sup> test was used to compare the qualitative variables between the groups. Results: Seventy-two patients with BC, and 74 CG women were evaluated. Both groups presented overweight data, BMI (kg/mt<sup>2</sup>) = 27.21 ± 5.51 vs. 28.40 ± 4.66, p = ns, for BC patients and CG, respectively. In PREW, the age at menarche was later in BC patients compared to the CG (13.3 ± 1.36 years vs. 12.41 ± 1.27 years, p = 0.005). The PMW with BC presented a higher age at menarche and menopause compared to the women of the CG (13.51 ± 1.48 vs. 12.91 ± 1.41, p = 0.09, and 49.03 ± 2.86 vs. 45.5 ± 8.78, p = 0.03, respectively). PRL levels were significantly higher in PMW with BC, in comparison with the CG;median and minimum and maximum values (min-max) were: 14.7 ng/mL (3.6 - 52.7) vs. 5.9 ng/mL (1.9 - 33.3), p = 0.005). A higher percentage of PMW with BC (26.0% vs. 7.1%, χ<sup>2</sup> = 5.57, p = 0.01) presented hyperprolactinemia (PRL serum levels > 20 ng/mL), compared to the GC. Conclusions: The higher levels of PRL in PMW with BC compared with CG, suggest a proliferative effect of this hormone in the affected breast tissue. This study demonstrates the need to use biological markers such as PRL to determine the risk of BC in PMW.
文摘Background: Continued exposure to sex hormones such as estrogen is a critical risk for subsequent breast cancer. Thus the present study aimed to assess the levels of knowledge towards hormonal related breast cancer risk factors in Qurayyat, Northern Saudi Arabia. Methodology: This descriptive study included 737 Saudi volunteers living in the city of Qurayyat, Northern Saudi Arabia. For females, only those agreeing to participate in the breast self-examination workshop were included, and non-respondents were included in the questionnaire. Results: For the question apropos “Inheritance as a risk factor for BC,” 405/607 (66.7%) females signposted certainly “Yes,” as well as, 70/130 (54%) males signposted certainly “Yes.” The odds ratio (OR) and 95% confidence interval (95% CI) were not statistically significant, but the level of knowledge was relatively higher among females OR (95% CI) = 1.4321 (0.9597 to 2.1370), P = 0.0786. “Are early puberty and late menopause risk factors for breast cancer?” No statistical significant differences were eminent between males and females, OR (95% CI) = 0.8878 (0.5932 to 1.3287), P = 0.5629. Conclusion: Saudi women are enthusiastically willing to raise their knowledge and awareness of breast cancer prevention and control. Although women have greater knowledge about breast cancer risk factors compared to men, still some gaps need to be filled.
基金Supported by the NHG-KTPH Small Innovative Grants(SIG),No.SIG/11009 and No.SIG/15025.
文摘BACKGROUND There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P4502D6(CYP2D6)polymorphisms.AIM To evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical outcomes.METHODS Eighty-two women were recruited.Seventy-eight completed CYP2D6 genotyping and were categorized into poor,intermediate(IM)and extensive or ultra metabolizer phenotypes.Women with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred agent.RESULTS More than 70%of the women had an IM phenotype,32%an extensive or ultra metabolizer phenotype,and 0%had a poor metabolizer phenotype.Regardless of genotype,more women opted for aromatase inhibitors.Overall,80%of women completed 5 years of hormonal therapy.Five women developed recurrence,3 contralateral breast cancer,5 died,and 1 was diagnosed with a second primary cancer.Five-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype,though not statistically significant[P=0.743,hazard ratio(HR):1.441,95%confidence interval(CI):0.191 to 10.17 and P=0.798,HR:1.327,95%CI:0.172 to 9.915,respectively].Women receiving aromatase inhibitors also appeared to have a better,but also nonsignificant,5-year recurrence-free and overall survival(P=0.253,HR:0.368,95%CI:0.031 to 0.258 and P=0.292,HR:0.252,95%CI:0.005 to 4.951,respectively).CONCLUSION The IM phenotype was highly prevalent but was not associated with clinical outcome.
