Adjuvant tamoxifen switched to exemestane treatment in postmenopausal women with estrogen receptor-positive early breast cancer:A pragmatic,multicenter,and prospective clinical trial in China

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.

Clinical significance of the negative lymph node count after the axillary dissection of breast cancer patients

Objective： The purpose of this study was to evaluate the impact of the negative lymph node （LN） count on the survival of the breast cancer patients in early stage after the axillary dissection. Methods： The breast cancer patients with T1-2N0-1M0 stage between January 2001 and December 2005 in Jiangsu Cancer Hospital, who underwent the axillary LNs dissection, were enrolled in this study. We analyzed the data of these patients including information of follow-up and postop- erative pathological results. All patients were divided into two groups according to the axillary LN status and each group was divided into four subgroups according to the negative LN count. Cox regression analysis was performed to screen the patho- logical factor including the negative LN count on the survival and to compare the different negative LN count on the survival. Results： COX proportional hazard regression model showed that the survival of the breast cancer was significantly associ- ated with the negative LN count. In T1 2N0 group, when the negative LN count was 3 or less, 4 to 5, 6 to 9 and 10 or more, the median survival time was （82.6 ±4.1） months, （101.5 ± 1.3） months, （104.7 ±1.0） months, and （110.5 ±0.9） months respectively （P 〈 0.05）. In T1-2N0 group, when the negative LN count was 6 or less, 7 to 8, 9 to 10 and 11 or more, the median survival time was （95.4 ± 1.9） months, （101.8 ± 1.1） months, （104.9 ± 1.0） months, and （106.5 ± 0.9） months respectively （P 〈 0.05）. Conclusion： The negative LN count can reflect the adequacy of the axillary dissection. Increasing negative LN count is independently associated with improved survival in pT1-2N0M0 or pT1-2N0M0 staging breast cancer patients. The negative LN count should be considered for incorporation into staging for breast cancer with the axillary LN dissection.

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

N6-methyladenosine(m6A),and its reader protein YTHDF1,play a pivotal role in human tumorigenesis by affecting nearly everystage of RNA metabolism.Autophagy activation is one of the ways by which cancer cells survive hypoxia.However,the possibleinvolvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma(HCO).In this study,specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing,knockout,and-knockdownHCC cells,HCC organoids,and HCC patient-derived xenograft(PDX)murine models.YTHDF1 expression and hypoxia inducedautophagy were significantly correlated in vitro;signifhcant overexpression of YTHDF1 in HCC tissues was associated with poorprognosis,Multivariate cox regression analysis identihed YTHDF1 expression as an independent prognostic factor in patients withHCC.Multiple HC models conhrmed that YTHDF1 deficiency inhibited HCC autophagy,growth,and metastasis.Luciferase reporterassays and chromatin immunoprecipitation demonstrated that HlIF-1a regulated YTHDF1 transcription by directly binding to itspromoter region under hypoxia.The results of methylated RNA immunoprecipitation sequencing,proteomics,and polysomeprofling indicated that YTHDF1 contibuted to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modifhed ATG2A and ATG14 mRNA,thus facilitating autophagy and autophagy-related malignancy of HCC.Taken together,HlE-1d-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent manner.Our fndings suggest thatYTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.

CACA Guidelines for Holistic Integrative Management of Breast Cancer

Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caused by breast cancer.In terms of absolute numbers of cases and deaths,China ranks frst in the world.The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China.Methods:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and consensus.Results:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer patients.Conclusion:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

HJURP indicates poor prognosis of female breast cancer by promoting cell proliferation and migration

Female breast cancer(BCa)has overtaken lung cancer as the most diagnosed cancer worldwide.1 The overall survival for BCa patients without metastasis for five years is over 80%.2 However,relapse and metastasis remain the primary challenge for BCa.In various carcinomas,Holliday junction recognition protein(HJURP)has shown up-regulated patterns and belongs to the CENP-A pre-nucleosomal complex.3-°HJURP's expression pattern,roles,and prognosis remain largely unknown in BCa.