Breast Cancer In Chinese Population Research Articles

Abstract PO4-26-08: Prevalence of HER2-low and IHC >0 to < 1+ in breast cancer and its concordance between historical and rescored results: a multi-center, retrospective study in China

Abstract Background: With Trastuzumab deruxtecan (T-DXd) changing the anti-HER2 treatment paradigm, HER2-low (defined as IHC2+/ISH- and IHC1+) breast cancer patients have emerged as a new targetable population. The lower threshold for HER2 expression that can benefit from HER2-directed antibody-drug conjugates (ADCs) is still being investigated, such as HER2 immunohistochemistry (IHC) >0 to < 1+ (defined as IHC 0 with incomplete and faint staining in ≤10% of tumor cells) in the DESTINY-Breast06 trial. Accurate determination of HER2 scores has become a critical topic in clinical discussions, given its clinical relevance to HER2-directed treatment strategies. Hence, we conduct this study (HER2-PATH, NCT05203458) to evaluate the distribution of HER2 status including HER2 IHC >0 to < 1+ in Chinese patients with breast cancer. Concordance between rescored and historical results was also analyzed. Methods: A retrospective study was conducted in breast cancer patients who underwent surgery at 10 sites in China between July 2021 and July 2022. Archived HER2 IHC slides from these patients were subjected to rescoring by a review committee comprising two readers and one adjudicator. The two readers independently evaluated each slide blinded to the historical scores. If their results matched, the recorded outcome was considered final. In cases of disagreement, the adjudicator made the final judgment. All slides were stained using Ventana 4B5 and scored following the ASCO/CAP 2018 guidelines, including the addition of the IHC >0< 1+ as defined in the DESTINY-Breast06 trial. The prevalence of the rescored HER2 status was calculated, and the concordance between the historical and rescored HER2 status was assessed using the Cohen's Kappa coefficient. Results: A total of 2868 patients were included in the analysis. The rescored results categorized 682 (23.8%) patients as HER2 IHC 0, 871 (30.4%) patients as IHC 1+, 800 (27.9%) patients as IHC 2+, and 515 (18.0%) patients as IHC 3+. The rates of HER2-positive, HER2-low, and HER2 IHC 0 (including HER2 null and HER2 IHC >0 to < 1+) were 21.8%, 54.3% and 23.9%, respectively. Notably, the prevalence of HER2-low was numerically higher in the HR-positive subgroup compared to the HR-negative subgroup (60.2% vs 30.6%). Furthermore, the prevalence of HER2 IHC >0 to < 1+ and HER2 null was 10.6% and 13.2% among all patients, respectively. Among the HR-positive subgroup, the prevalence of HER2 IHC >0 to < 1+ was 10.9%, while the rate was 9.1% among the HR-negative subgroup. Overall, there was an 83.1% concordance between the historical and rescored results for HER2 IHC scores. The concordance rate for IHC 1+ was numerically lower (74.5%) compared to IHC 0 (85.2%), IHC 2+ (81.4%), and IHC 3+ (98.6%). However, considering that 12.0% of IHC 1+ patients turned into IHC 2+ with limited impact on HER2-low diagnosis, the concordance rate for HER2-low remained as 91.6%. Conclusion: HER2-low prevalence in Chinese breast cancer patients was found to be consistent with global data, while additional 10.6% of patients were identified as HER2 IHC >0 to < 1+, which is currently being investigated in a randomized controlled trial comparing T-DXd with SoC. To our knowledge, this is the first study to report the prevalence of HER2-low, including HER2 IHC >0 to < 1+, in the Chinese breast cancer population based on rescored results. The concordance of HER2-low between the historical and rescored results was 91.6%, indicating that most cases could be reproducibly classified. Table: Rescored HER2 Expression Level Citation Format: Hong Lv, Junqiu Yue, Qingfu Zhang, Fangping Xu, Jianming Li, Lingfei Kong, Peng Gao, Guanjun Zhang, Haifeng Yang, Xiu Nie, Wen-Tao Yang. Prevalence of HER2-low and IHC >0 to < 1+ in breast cancer and its concordance between historical and rescored results: a multi-center, retrospective study in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-26-08.

Efficacy and safety of Trastuzumab Emtansine in treating human epidermal growth factor receptor 2-positive metastatic breast cancer in Chinese population: a real-world multicenter study.

Trastuzumab emtansine (T-DM1) has been approved worldwide for treating metastatic breast cancer (mBC) in patients who have received first-line therapy, shown disease progression, and are human epidermal growth factor receptor 2 (HER2)-positive. T-DM1 received approval in China to treat early-stage breast cancer (BC) in 2020 and for mBC in 2021. In March 2023, T-DM1 was included in medical insurance coverage, significantly expanding the eligible population. This post-marketing observational study aimed to assess the safety and effectiveness of T-DM1 in real-world clinical practice in China. This study enrolled 31 individuals with HER2-positive early-stage BC and 70 individuals with HER2-positive advanced BC from 8 study centers in Shandong Province, China. The T-DM1 dosage was 3.6 mg/kg injected intravenously every 3 weeks until the disease advanced or the drug toxicity became uncontrollable, whichever occurred earlier. Additionally, efficacy and safety information on T-DM1 were collected. During the 7-month follow-up period, no recurrence or metastases were observed in patients who had early-stage BC. The disease control rate was 31.43% (22/70) in patients with advanced BC. The most common adverse effect of T-DM1 was thrombocytopenia, with an incidence of 69.31% (70/101), and the probability of Grade ≥ 3 thrombocytopenia was 11.88% (12/101). This real-world study demonstrated that T-DM1 had good efficacy and was well tolerated by both HER2-positive early-stage BC and mBC patients.

Artificial intelligence-assisted ultrasound image analysis to discriminate early breast cancer in Chinese population: a retrospective, multicentre, cohort study.

Early diagnosis of breast cancer has always been a difficult clinical challenge. We developed a deep-learning model EDL-BC to discriminate early breast cancer with ultrasound (US) benign findings. This study aimed to investigate how the EDL-BC model could help radiologists improve the detection rate of early breast cancer while reducing misdiagnosis. In this retrospective, multicentre cohort study, we developed an ensemble deep learning model called EDL-BC based on deep convolutional neural networks. The EDL-BC model was trained and internally validated on B-mode and color Doppler US image of 7955 lesions from 6795 patients between January 1, 2015 and December 31, 2021 in the First Affiliated Hospital of Army Medical University (SW), Chongqing, China. The model was assessed by internal and external validations, and outperformed radiologists. The model performance was validated in two independent external validation cohorts included 448 lesions from 391 patients between January 1 to December 31, 2021 in the Tangshan People's Hospital (TS), Chongqing, China, and 245 lesions from 235 patients between January 1 to December 31, 2021 in the Dazu People's Hospital (DZ), Chongqing, China. All lesions in the training and total validation cohort were US benign findings during screening and biopsy-confirmed malignant, benign, and benign with 3-year follow-up records. Six radiologists performed the clinical diagnostic performance of EDL-BC, and six radiologists independently reviewed the retrospective datasets on a web-based rating platform. The area under the receiver operating characteristic curve (AUC) of the internal validation cohort and two independent external validation cohorts for EDL-BC was 0.950 (95% confidence interval [CI]: 0.909-0.969), 0.956 (95% [CI]: 0.939-0.971), and 0.907 (95% [CI]: 0.877-0.938), respectively. The sensitivity values were 94.4% (95% [CI]: 72.7%-99.9%), 100% (95% [CI]: 69.2%-100%), and 80% (95% [CI]: 28.4%-99.5%), respectively, at 0.76. The AUC for accurate diagnosis of EDL-BC (0.945 [95% [CI]: 0.933-0.965]) and radiologists with artificial intelligence (AI) assistance (0.899 [95% [CI]: 0.883-0.913]) was significantly higher than that of the radiologists without AI assistance (0.716 [95% [CI]: 0.693-0.738]; p<0.0001). Furthermore, there were no significant differences between the EDL-BC model and radiologists with AI assistance (p=0.099). EDL-BC can identify subtle but informative elements on US images of breast lesions and can significantly improve radiologists' diagnostic performance for identifying patients with early breast cancer and benefiting the clinical practice. The National Key R&D Program of China.

Germline Mutational Profiles and Clinicopathological Features Of Hereditary Breast Cancer In Chinese Population

Germline Mutational Profiles and Clinicopathological Features Of Hereditary Breast Cancer In Chinese Population

Polymorphisms in lncRNA MIR2052HG and susceptibility to breast cancer in Chinese population.

Background: Published studies based on pharmacokinetics have explored the relationship between the lncRNA MIR2052HG and the prognosis of breast cancer (BC) resistance and recurrence. However, the underlying association of MIR2052HG SNPs with BC development remains unclear.Methods: Combining bioinformatics and databases, SNPs (Single Nucleotide Polymorphisms) in the MIR2052HG gene were screened, and SNPs in the lncRNA MIR2052HG were selected for genotyping among 504 Chinese Han patients and 505 healthy controls, which were frequency-matched for age (±2 years). Logistic regression analysis was used to explore the association between MIR2052HG SNPs and the BC risk. Interactions between the MIR2052HG SNPs and reproductive factors were further evaluated using the multifactor dimensionality reduction (MDR) method. qRT–PCR was performed to detect MIR2052HG expression in individuals with different genotypes of rs34841297. The target miRNA, miR-4456 of MIR2052HG rs34841297 was predicted by websites and confirmed by performing dual luciferase gene reporter assays. CCK-8 and Transwell experiments were designed to explore the effects of miR-4456 on the proliferation, invasion and migration of BC cells.Results: In this study, nine SNPs were screened. After adjusting for age, menarche age, menopausal status, number of pregnancies, history of abortions, breast feeding history and family history of BC, the results of the logistic regression analysis showed the rs34841297 A/- gene polymorphism was positively correlated with the incidence of BC. Compared with the AA genotype, patients with the A-+-- genotype of rs34841297 at age<50 years, and menarche age<14 years, Premenopausal status, history of abortion, no history of breastfeeding and no family history of tumors in first-degree relatives had an increased risk of BC. MDR results revealed that individuals with rs34841297 - (homozygous deletion) of the A allele who were not menopausal and had no history of breastfeeding had a higher risk of BC. qRT–PCR results revealed that homozygous deletion (1.68±1.37) of the rs34841297 A- genotype resulted in higher MIR2052HG expression than the heterozygous deletion genotype (0.95±0.94) and wild AA genotype (0.26±0.12). Binding between MIR2052HG and miR-4456 was occurred when rs34841297 carried the AA genotype. Moreover, preliminary functional studies indicated that the overexpression of miR-4456 increased the proliferation, invasion and migration of BC cells.Conclusion: Our study showed that the MIR2052HG gene polymorphism may be related to BC susceptibility, and the MIR2052HG rs34841297 A/- genotype may probably affect the proliferation, invasion and migration of BC cells by modulating the interactions with of miR-4456.

The association between RAPSN methylation in peripheral blood and breast cancer in the Chinese population.

DNA methylation in peripheral blood is associated with breast cancer (BC) but has mainly been studied in Caucasian populations. We investigated the association between blood-based methylation of receptor-associated protein of the synapse (RAPSN) and BC in Chinese population. The methylation levels of 12 RAPSN CpG sites were quantitatively evaluated by mass spectrometry in two case-control studies with 283 sporadic BC cases and 331 controls totally. The association was analyzed by logistic regression adjusted for covariants. The RAPSN methylation levels in patients with variant clinical characteristics were investigated by non-parametric tests. We found a significant association between BC and altered RAPSN methylation in blood in women at premenopausal and perimenopausal (age < 50 years old), but not in the elder women. This was approved by two independent case-control studies as well as by combining the subjects of the two studies (taken all subjects together, age < 50 years old, per 5% of methylation, odds ratio (OR) range from 1.17 to 1.30 for two CpG sites; OR = 0.75 for one CpG site; all p values < 0.02). This age-related RAPSN methylation was further modified by human epidermal growth factor receptor 2 (HER2) status (age < 50 years old, HER2 negative, per 5% of methylation, OR range from 1.27 to 1.48 for two CpG sites; OR = 0.76 for one CpG site; all p values < 0.02). We elucidated an association between BC and blood-based RAPSN methylation influenced by age and the status of HER2 in Chinese population.

High Expression of Asparagine Synthetase Is Associated with Poor Prognosis of Breast Cancer in Chinese Population.

Aims: This study aimed to determine the expression of asparagine synthetase (ASNS) in breast cancer (BC) tissues and estimate its prognostic value for BC patients. Besides, the roles of ASNS in the proliferation of BC cells were also examined in the study. Methods: Quantitative real-time PCR was conducted to detect the expression of ASNS mRNA in BC tissues and normal controls. The relationship between ASNS expression and clinical characteristics of BC patients was analyzed using χ-square test. MTT assay was performed to explore the effect of ASNS expression on the proliferation of BC cells. Kaplan-Meier curves were plotted to describe the overall survival rate of BC patients. Cox regression analyses were implemented to investigate prognostic factors. Results: ASNS mRNA overexpression was observed in BC tissues (p < 0.05). High expression of ASNS was significantly related to histological grade (p = 0.017), vascular invasion (p = 0.009), and PR status (p = 0.014). The downregulation of ASNS affected the proliferation of BC cells (p < 0.05). Kaplan-Meier survival showed that patients with high ASNS expression lived shorter than those with low expressions (p < 0.001). Finally, Cox regression analyses revealed that ASNS could act as a prognostic marker for BC patients (p < 0.001, HR = 3.293, 95% CI = 1.790-6.058). Conclusion: Taken together, ASNS is a valuable prognostic biomarker for BC patients.

Abstract P2-09-03: Spectrum, prevalence and clinical outcomes of germline mutations in PALB2 genes in 16501 unselected BRCA1/2-negative breast cancer patients: A multi-center analysis

Abstract Background: PALB2 (Partner and Localizer of BRCA2) is a breast cancer predisposition gene, which plays a critical role in homologous recombination via interacting with BRCA1/2 and RAD51 when DNA break. However, the clinical relevance of PALB2 germline mutations in Chinese breast cancer patients remains unknown. We attempted to illustrate the full prevalence and spectrum of PALB2 germline mutations in Chinese breast cancer population, and to investigate the clinical outcomes of PALB2 germline mutations. Patients and methods: A total of 21216 unselected breast cancer patients were enrolled from multiple clinical centers in China. After evaluation of the DNA quality and clinical information, 16501 eligible BRCA1/2-negative breast cancer patients were analyzed. A group of 5890 Chinese women without cancer was enrolled as healthy controls. PALB2 screening was based on next-generation sequencing, by screening complete coding sequence and intron-exon boundaries of PALB2. Clinical information was synchronously collected. Results: The 79 PALB2 deleterious germline mutations included 25 nonsense mutations, 47 frameshift mutations, and 7 splicing mutations. The hotspot region for PALB2 mutations was exon4. A total of 41 novel mutations were identified in PALB2. Among the 16501 BRCA1/2-negative breast cancer patients and 5890 healthy women, PALB2 deleterious mutation carriers account for 0.97% (n=160) and 0.19% (n=11) separately. PALB2 mutations were significantly associated with increased breast cancer risk (OR: 5.23, 95% CI 2.89-9.49; P&amp;lt;0.0001), and especially in women aged 30 or younger (OR: 11.97, 95% CI 3.76-34.39; P&amp;lt;0.0001). PALB2 mutation carriers were significantly more likely to be triple negative breast cancers and have bigger tumors, positive axillary lymph nodes, bilateral breast cancers, family history of breast and/or ovarian cancer and family history of any other cancer, than noncarriers. Conclusions: The PALB2 mutations confer a moderately increased breast cancer risk in women, but relatively highly increased breast cancer risk in those aged 30 or younger. PALB2 mutation status is associated with distinct clinical characteristics in breast cancer. Key words:PALB2, breast cancer, germline mutations, next-generation sequencing Citation Format: Jiaojiao Zhou, Honglian Wang, Fangmeng Fu, Zhanwen Li, Yun Liu, Qingjian Feng, Weizhu Wu, Hongxia Wang, Chuan Wang, Yiding Chen. Spectrum, prevalence and clinical outcomes of germline mutations in PALB2 genes in 16501 unselected BRCA1/2-negative breast cancer patients: A multi-center analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-03.

Mutational analysis of BRCA1 and BRCA2 in northwest Chinese breast cancer patients

Background: BRCA1 and BRCA2 are the most well-known susceptibility genes in breast cancer, indicating high-risk breast cancer families and influencing both treatment options. However, data of BRCA mutation in Chinese breast cancer population was limited. Here we explored the BRCA1/2 mutation status and analyzed their clinicopathological relationships among breast cancer patients with high hereditary risk in northwest China. Methods: Breast cancer patients admitted to Xijing Hospital, between November 2015 and May 2016, with high hereditary risk were recruited. Fresh peripheral venous blood samples were collected for BRCA1/2 gene screening. Risk factors for BRCA1/2 mutations were studied via single-factor analysis and multivariable logistic analysis. Furthermore, we reviewed the literature and discussed the possible mechanism of the mutant genome types. Results: Eighty-two patients were enrolled in the study. Twenty (24.4%) of them were found with BRCA1/2 mutation, including 8 BRCA1 mutation and 13 BRCA2 mutation. BRCA1 and BRCA2 co-mutation was observed in only one case. The mutant genome types included pathogenic variant (4/82), potential pathogenic variant (4/82), beneficial mutations (8/82), and chemotherapy sensitivity-related mutations (5/82). Prognosis-related mutations were enriched in BRCA2 gene, while drug-sensitive related mutations were always observed in BRCA1 gene. Multiple logistic analysis showed that HER2 [odds ratio (OR) 4.58; 95% confidence interval (CI), 1.182–17.74; P=0.028) might be independent factor for BRCA1/2 mutation. Conclusions: The incidence and feature of BRCA1/2 mutation in our center was similar to that in other regions. HER2 expression was independent factor for BRCA1 and BRCA2 mutation. BRCA2 T/-, BRCA2 A/-, BRCA2 G/- and BRCA2 C/-mutation subtypes might be potential harmful mutations for Chinese breast cancer population.

Mutational analysis of BRCA1 and BRCA2 in northwest Chinese breast cancer patients.

BackgroundBRCA1 and BRCA2 are the most well-known susceptibility genes in breast cancer, indicating high-risk breast cancer families and influencing both treatment options. However, data of BRCA mutation in Chinese breast cancer population was limited. Here we explored the BRCA1/2 mutation status and analyzed their clinicopathological relationships among breast cancer patients with high hereditary risk in northwest China.MethodsBreast cancer patients admitted to Xijing Hospital, between November 2015 and May 2016, with high hereditary risk were recruited. Fresh peripheral venous blood samples were collected for BRCA1/2 gene screening. Risk factors for BRCA1/2 mutations were studied via single-factor analysis and multivariable logistic analysis. Furthermore, we reviewed the literature and discussed the possible mechanism of the mutant genome types.ResultsEighty-two patients were enrolled in the study. Twenty (24.4%) of them were found with BRCA1/2 mutation, including 8 BRCA1 mutation and 13 BRCA2 mutation. BRCA1 and BRCA2 co-mutation was observed in only one case. The mutant genome types included pathogenic variant (4/82), potential pathogenic variant (4/82), beneficial mutations (8/82), and chemotherapy sensitivity-related mutations (5/82). Prognosis-related mutations were enriched in BRCA2 gene, while drug-sensitive related mutations were always observed in BRCA1 gene. Multiple logistic analysis showed that HER2 [odds ratio (OR) 4.58; 95% confidence interval (CI), 1.182–17.74; P=0.028) might be independent factor for BRCA1/2 mutation.ConclusionsThe incidence and feature of BRCA1/2 mutation in our center was similar to that in other regions. HER2 expression was independent factor for BRCA1 and BRCA2 mutation. BRCA2 T/-, BRCA2 A/-, BRCA2 G/- and BRCA2 C/-mutation subtypes might be potential harmful mutations for Chinese breast cancer population.

Abstract P4-03-08: Analyzing the clinical actionability of germline CYP2D6 polymorphism in Chinese breast cancer population

Abstract Background:Tamoxifen is effective for endocrine-responsive breast cancer as adjuvant therapy. CYP2D6 enzyme metabolizes tamoxifen to clinically active metabolites, while CYP2D6 polymorphisms may adversely affect tamoxifen efficacy by some retrospective clinical evidence. This study was carried out to estimate genotype frequencies of common variants of CYP2D6 in Chinese population. The relationship between prescription of selective estrogen receptor modulators (SERMs) and CYP2D6 polymorphism was also analyzed. Methods: This was a retrospective research of early-stage patients who underwent surgical treatment at Fudan University Shanghai Cancer Center with ER+ and/or PR+ breast cancer. Genomic DNA was extracted from peripheral blood, which was used for genotyping CYP2D6*10 (C100T) single-nucleotide polymorphisms by polymerase chain reaction-based methods. Results: A total of 312 patients with primary breast cancer were identified. More than 90.0% patients were in premenopausal status. The allele frequence of CYP2D6*10 in the Chinese population was 54.3%. The genotype frequencies of CYP2D6*10 were 20.5%, 50.3%, 29.2%, for wild-type, heterozygous and homozygous type respectively. We also found this SNP had no significant correlation with clinical characteristics. 145 patients were continuing endocrine treatment in first 5 years. 34.5% patients received CYP2D6 polymorphism test before the prescription of SERMs. The results significantly effected the choice of SERMs. Only 6.2% homozygous type patients took tamoxifen, 45.5% heterozygous patients chose tamoxifen, while 75.0% for wild type. 65.5% patients received CYP2D6 polymorphism test during the treatment of tamoxifen. 63.9% homozygous type patients switched to Toremifene, while 18.9% heterozygous patients changed the endocrine treatment. Conclusions: The results showed that the frequence of CYP2D6*10 allele was high and nearly 30% Chinese breast cancer population were intermediate metabolizer for tamoxifen. The cyp2d6 polymorphism would influence prescription of SERM in premenopausal breast cancer patients. Patients with homozygous types should take other endocrine treatment instead of tamoxifen, which need more evidence of prospective clinical trials. Citation Format: Huang L, Cao A. Analyzing the clinical actionability of germline CYP2D6 polymorphism in Chinese breast cancer population [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-03-08.

Association of SENPs single-nucleotide polymorphism and breast cancer in Chinese population

SUMO-specific Cysteine Proteases (SENPs) have involvement in the initiation and progression of human cancers. In the present study, we evaluated the association of SENPs polymorphism with susceptibility as well as clinicopathologic features and patients’ response of breast cancer (BC) in a Chinese population.We genotyped SENP1 (rs61918808), SENP2 (rs6762208), SENP7 (rs61697963) by sequencing in a case–control study including 210 BC patients and 225 healthy volunteers. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assume the association strength.No significant association was found between polymorphism of the 3 SENPs and BC susceptibility. However, SENP1 rs61918808 (C>T) and SENP7 rs61697963 (A>C) was associated with HER-2 expression (P < .05). SENP2 rs6762208(C>A) was correlated with increasing risk of lymph node metastases (P < .05). Among the patients who received neoadjuvant chemotherapy, T allele and TT genotype of SENP1 rs61918808 were less likely to achieve pCR (P < .05).We first reported SENPs variants were not associated with BC risk in Chinese population, but presented specific effect on clinicopathological features of BC. Moreover, SENP1 rs61918808 may be a predictor for the clinical response in local advanced BC patients who received neoadjuvant chemotherapy.

Neutrophil-to-lymphocyte ratio, obesity, and breast cancer risk in Chinese population.

Breast cancer (BC), obesity, and metabolic syndrome (MetS) shared a common mechanism of dysregulated metabolism and inflammatory response in disease initiation. Neutrophil-to-lymphocyte ratio (NLR) is associated with adverse survival of BC patients. The aim of this study is to identify risk effect between NLR and BC in Chinese population with or without obesity and MetS. BC and age-matched breast benign disease (BBD) patients were retrospectively analyzed from Comprehensive Breast Health Center, Shanghai Ruijin Hospital. MetS was defined using AHA/NHLBI criteria. Individuals were classified into very low (0-1.30), low (1.31-1.67), intermediate (1.68-2.20), and high (>2.20) NLR subsets by each NLR quartile. In all, 1540 BC and 1540 BBD patients were included. Univariate and multivariate analysis found that NLR (OR: 1.27, 95% CI: 1.16-1.39, P < .001) and obesity (OR: 1.19, 95% CI: 1.00-1.42, P = .046) but not MetS (P = .060) were significantly associated with increased BC risk. Intermediate or high NLR substantially increased BC risk compared to very low NLR group (OR: 1.57, 95% CI: 1.29-1.92, P < .001; OR: 1.84, 95% CI: 1.50-2.25, P < .001; respectively) in whole population. Subgroup analysis found that the impact of higher NLR on BC risk was more obvious in patients without obesity (intermediate NLR, OR: 1.72, 95% CI: 1.37-2.16, P < .001; high NLR, OR: 1.92, 95% CI: 1.53-2.41, P < .001) or without MetS (intermediate NLR, OR: 1.70, 95% CI: 1.35-2.14, P < .001; high NLR, OR: 1.98, 95% CI: 1.57-2.51, P < .001). Higher preoperative NLR was found in BC patients compared with BBD patients. Intermediate to high NLR level substantially increased BC risk, which was more relevant for those without obesity or MetS.

CYP2D6 polymorphism in Chinese breast cancer population.

e13529Background: This study was carried out to estimate the allele and genotype frequencies of common variants in the CYP2D6 in Chinese population. Methods: We evaluated the CYP2D6 polymorphism of...

Association between serum cytokines and progression of breast cancer in Chinese population.

The aim of this study was to investigate the roles of serum interleukin-6 (IL-6), IL-8, IL-10, squamous cell cancer antigen (SCC-Ag), and cytokeratin 21-1 fragment (CYFRA 21-1) in the metastasis and prognosis of breast cancer.A total of 534 breast cancer patients admitted to our department between January 2011 and December 2014 were enrolled in this study. Besides, 452 matched healthy individuals received physical examination at the same period served as the normal control. Serum IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were determined using an immunoradiometric assay. SCC-Ag level was evaluated using chemiluminescent microparticle immunoassay. CYFRA 21-1 was determined using the chemiluminescence assay.Compared with the control group, a significant increase was noticed in the serum IL-6, IL-8, and IL-10 in breast cancer patients, especially those with severe conditions (P < .01). Serum IL-6, IL-8, and IL-10 showed a significant increase in the patients with severe breast cancer compared with those with mild conditions (P < .05). For the patients with response after radiotherapy, the serum IL-6, IL-8, and IL-10 were significantly decreased compared with the baseline levels (P < .05). The median survival duration for the patients of SCC-Ag negative patients was 25 months, while that for the SCC-Ag positive group was 16 months. Significant difference was noticed in the survival of SCC-Ag negative group compared with that of SCC-Ag positive group (P < .05).Serum IL-6, IL-8, IL-10, SCC-Ag, and CYFRA 21-1 were considered as potential markers in the metastasis and prognosis of breast cancer.

Mutation screening of 10 cancer susceptibility genes in unselected breast cancer patients.

Variants of cancer susceptibility genes other than BRCA1/2 have been proved to be associated with increased risks of breast cancer. This study was performed to investigate the spectrum and prevalence of mutations in 10 cancer susceptibility genes in paired tumor/normal tissues of 292 unselected Chinese breast cancer patients. We performed an analysis of germline and somatic variants in ATM, CDH1, CHEK2, ESR1, GATA3, MAP3K1, MSH2, PALB2, RB1 and STK11 genes by integrating microfluidic PCR-based target enrichment and next-generation sequencing technologies. In total, 3 germline and 25 somatic deleterious mutations were found among 27 patients (9.25%), and 17 of them were novel mutations. Most deleterious mutations were prevalent in luminal A invasive breast cancer (P = .014). We also observed 83 variants of uncertain significance (VUS) in 100 patients (34.25%), 23 of which were predicted to be deleterious by in silico prediction programs (MetaSVM and MetaLR). VUS carriers had higher positive rate of lymph node metastasis than non-carriers (P = .008) and were predominantly present in ER+ tumors (P = .018). Our findings would enhance the understanding of the molecular mechanisms of breast cancer in Chinese population.

Predicting level 2 axillary lymph node metastasis in a Chinese breast cancer population post-neoadjuvant chemotherapy: development and assessment of a new predictive nomogram.

BackgroundWe aimed to develop a new nomogram to predict the probability of level 2 axillary lymph node metastasis (L-2-ALNM) in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC).MethodsData were collected from 709 patients who received neoadjuvant chemotherapy and then underwent axillary lymph node (ALN) dissection between May 2009 and December 2015 at the Liaoning Cancer Hospital. The level 2 axillary lymph node metastasis (L-2-ALNM ) nomogram was created from the logistic regression model. An additional set of 141 consecutive patients treated at the same institution between January 2015 and December 2015 were enrolled as the validation group. The predictive accuracy of the L-2-ALNM nomogram was measured by calculating the area under the receiver operating characteristic curve (AUC).ResultsIn multivariate analysis, age, tumor size, histological grade, skin invasion, and response to neoadjuvant chemotherapy were identified as independent predictors of L-2-ALNM. The new model was accurate and discriminating for both the modeling and validation groups (AUC: 0.819 vs 0.849). The false-negative rates of the L-2-ALNM nomogram were 4.44% and 7.69% for the predicted probability cut-off points of 10% and 20%.ConclusionThe L-2-ALNM nomogram shows reasonable accuracy for making clinical decisions. The omission of level 2 axillary lymph node dissection after neoadjuvant chemotherapy might be possible if the probability of level 2 lymph node involvement was < 10% or < 20% in accordance with the acceptable risk determined by medical staff and patients.

Erratum to: Genetic variants of ESR1 and SGSM3 are associated with the susceptibility of breast cancer in the Chinese population.

The objective of this study was to investigate whether the genetic polymorphism rs12665607 of ESR1, rs10995190 of ZNF365, rs3817198 of LSP1 and rs17001868 of SGSM3/MKL1 are associated with the development of breast cancer (BC) in the Chinese women. The 4 SNPs were genotyped for 453 female BC patients and 750 controls. The differences of genotype and allele distributions between patients and controls were evaluated using the Chi-square test. The comparison of SGSM3 expression in the tumor and the adjacent normal breast tissues was carried out by the Student’s t test. One-way ANOVA test was used to analyze the relationship between genotypes of rs17001868 and the tissue expression of SGSM3. Patients were found to have significantly higher allele T of rs12665607 and allele C of rs17001868 than that of the controls (35.2 % vs. 29.6 %, p = 0.004 for rs12665607; 23.1 % vs. 19.1 %, p = 0.02 for rs17001868). The OR values were 1.29 for rs12665607 and 1.27 for rs17001868, respectively. The mean expression level of SGSM3 was significantly lower in BC tumors than in the adjacent normal tissues (0.0082 ± 0.0038 vs. 0.0134 ± 0.0078; p < 0.001). Patients with genotype CC were found to have a remarkably lower SGSM3 expression in the tumors than those with genotype AA (p = 0.007). ESR1 gene and the SGSM3 gene are associated with the risk of BC in Chinese population. Besides, rs17001868 may be a putative functional variant that can affect the expression of SGSM3 in patients with BC. With the OR ranging from 1.27 to 1.29, variants of these 2 genes can only explain limited variance of BC. Further investigations into the functional role of the susceptible genes would be helpful to clarify the etiology of BC.

Association between genetic variants in p53 binding sites and risks of breast cancer in Chinese population

To investigate the association between breast tissue specified variants in p53 binding sites and the risk of BC in Chinese women. ChIP-seq database on p53 binding sites in MCF-7 cell lines was extracted to identify the possible variants in p53 target genes. A hospital-based case-control study was then performed to investigate the association between variants in p53 binding sites and the risk of BC in a Chinese women population. Three variants were identified from the bioinformatics analysis. A total of 1 274 BC cases and 1 255 frequency-matched cancer-free controls were included in this case-control study. The average age was comparable between the case and the control groups, with the P value as 0.318. Meanwhile, distributions on menopausal status, smoking and alcohol intake between cases and controls were similar with the P values as 0.539, 0.258 and 0.131, respectively. The genotype distribution of rs1295925 was significantly different between the case and the control groups. Individuals that carrying rs1295925-CT and rs1295925-TT genotypes were significantly associated with an increased BC risk when compared with rs1295925-CC genotype after adjustment of age, menopausal status, smoking and alcohol intake (OR=1.32, 95%CI: 1.07-1.62 and OR=1.41, 95%CI: 1.13-1.78, respectively). Positive associations were also observed under the allelic, dominant and additive models. rs1295925 which located in VMP1 gene was associated with increased BC risk in the Chinese women population.

Genetic variants of ESR1 and SGSM3 are associated with the susceptibility of breast cancer in the Chinese population.

The objective of this study was to investigate whether the genetic polymorphism rs12665607 of ESR1, rs10995190 of ZNF365, rs3817198 of LSP1 and rs17001868 of SGSM3/MKL1 are associated with the development of breast cancer (BC) in the Chinese women. The 4 SNPs were genotyped for 453 female BC patients and 750 controls. The differences of genotype and allele distributions between patients and controls were evaluated using the Chi-square test. The comparison of SGSM3 expression in the tumor and the adjacent normal breast tissues was carried out by the Student's t test. One-way ANOVA test was used to analyze the relationship between genotypes of rs17001868 and the tissue expression of SGSM3. Patients were found to have significantly higher allele T of rs12665607 and allele C of rs17001868 than that of the controls (35.2% vs. 29.6%, p=0.004 for rs12665607; 23.1% vs. 19.1%, p=0.02 for rs17001868). The OR values were 1.29 for rs12665607 and 1.27 for rs17001868, respectively. The mean expression level of SGSM3 was significantly lower in BC tumors than in the adjacent normal tissues (0.0082±0.0038 vs. 0.0134±0.0078; p<0.001). Patients with genotype CC were found to have a remarkably lower SGSM3 expression in the tumors than those with genotype AA (p=0.007). ESR1 gene and the SGSM3 gene are associated with the risk of BC in Chinese population. Besides, rs17001868 may be a putative functional variant that can affect the expression of SGSM3 in patients with BC. With the OR ranging from 1.27 to 1.29, variants of these 2 genes can only explain limited variance of BC. Further investigations into the functional role of the susceptible genes would be helpful to clarify the etiology of BC.