A multicenter study of the clinicopathological characteristics and a risk prediction model of early-stage breast cancer with hormone receptor-positive/human epidermal growth factor receptor 2-low expression.

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.

Breast Cancer Awareness and Association with Frequency of Screening Among Women - China, 2020.

What is already known about this topic?: Breast cancer awareness plays a crucial role in promoting screening attendance, enabling early detection, and improving survival rates associated with breast cancer. Nevertheless, a persistent issue is the low public awareness of breast cancer warning signs and risk factors. What is added by this report?: Breast cancer awareness rate was 10.2%, with particularly low rates among never-screened and inadequately screened women. Factors associated with low awareness levels included low income, agricultural occupation, limited educational attainment, smoking, and the absence of professional recommendations. What are the implications for public health practice?: Consideration should be given to effective health education and delivery strategies aimed at women who have never been screened or have received inadequate screening.

Neoadjuvant therapy for early human epidermal growth factor receptor 2 positive breast cancer in China: A multicenter real-world study (CSBrS-015).

BACKGROUND: Pertuzumab has been approved for application in China by the National Medical Products Administration, and both national and international guidelines make recommendations for the use of neoadjuvant treatment with trastuzumab or trastuzumab + pertuzumab plus chemotherapy regimens for patients with indications. The goal of this study was to investigate the short-term clinical efficacy of the neoadjuvant therapies trastuzumab and trastuzumab+pertuzumab for patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer in China. METHODS: A real-world study was conducted using the clinicopathological data of patients with early HER2-positive breast cancer who were admitted to the member hospitals of the Chinese Society of Breast Surgery, Chinese Surgical Society of Chinese Medical Association between March 2019 and December 2020. This study analyzed the efficacy and tolerance of trastuzumab+chemotherapy and trastuzumab+pertuzumab+chemotherapy in patients with early HER2-positive breast cancer. The Response Evaluation Criteria in Solid Tumors 1.1 was adopted to evaluate clinical efficacy. The pathological efficacy was evaluated using the MillerPayne grade. The Common Terminology Criteria for Adverse Events (version 5.0) was adopted to evaluate adverse events (AEs). The propensity scores were subjected to propensity score matching using the R language (1:1 matching with a maximum allowable difference of 0.05 between the two groups). Efficacy was compared using the chi-square test, and correlation analysis was performed using linear regression. RESULTS: A total of 1032 patients with early HER2-positive breast cancer met the enrollment criteria and were included in this study. Among these patients, 472 received neoadjuvant trastuzumab+chemotherapy (the trastuzumab group), and 560 received neoadjuvant trastuzumab+pertuzumab+chemotherapy (the trastuzumab+pertuzumab group). The overall pathologic complete response (pCR) rate was 47.2% (487/1032), while the pCR rates of the trastuzumab and trastuzumab+pertuzumab groups were 34.5% (163/472) and 57.9% (324/560), respectively, and the difference was significant (P < 0.001). The incidence of grade 4 AEs was 24/321 (7.5%) in the trastuzumab+pertuzumab group, and there were no cases in which the left ventricular ejection fraction decreased by more than 10%. CONCLUSIONS: Patients in the trastuzumab+pertuzumab group had a higher pCR rate than those in the trastuzumab group, and the toxic side effects were tolerable.

Correlation between Androgen Receptor Expression in Luminal B (HER-2 Negative) Breast Cancer and Disease Outcomes.

(1) Background: Hormone receptor positive breast cancer is a subtype of breast cancer with relatively good prognosis, but luminal B (HER−2 negative) breast cancer has a higher risk of recurrence and metastasis. Patients with endocrine therapy resistance and chemotherapy insensitivity have poor prognosis. Androgen receptor (AR) is widely expressed in breast cancer, but there is no clear conclusion about its function and correlation with prognosis in luminal B breast cancer. Further research is needed to reveal the role of AR in luminal B (HER−2 negative) breast cancer. (2) Methods: Retrospectively analyzed patients with early−stage luminal B breast cancer. The correlation between AR and its associated indexes with long−term survival was determined. (3) Results: A total of 985 patients were included with 143 treated by neoadjuvant therapy. Of these, 83.5% of the patients had AR expression ≥65%. High AR expression was associated with good disease−free survival (DFS) and overall survival (OS). In the neoadjuvant population, AR/estrogen receptor (ER) > 1.06 and residual tumor Ki67 > 23% had significantly worse DFS. (4) Conclusion: Low AR (<65%) expression is associated with poor prognosis in luminal B (HER−2 negative) breast cancer patients. High AR/ER and residual tumor Ki67 were associated with poor DFS in neoadjuvant group with a cutoff value of AR/ER > 1.06 and residual tumor Ki67 > 23%.

Multicenter study of the clinicopathological features and recurrence risk prediction model of early-stage breast cancer with low-positive human epidermal growth factor receptor 2 expression in China (Chinese Society of Breast Surgery 021).

BACKGROUND: : Breast cancer with low-positive human epidermal growth factor receptor 2 (HER2) expression has triggered further refinement of evaluation criteria for HER2 expression. We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors. METHODS: : Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association, from January 2015 to December 2016 were collected. The prognostic factors of these patients were analyzed. RESULTS: : Twenty-nine hospitals provided valid cases. From 2015 to 2016, a total of 25,096 cases of early-stage breast cancer were treated, 7642 (30.5%) of which had low-positive HER2 expression and were included in the study. After ineligible cases were excluded, 6486 patients were included in the study. The median follow-up time was 57 months (4-76 months). The disease-free survival rate was 92.1% at 5 years, and the overall survival rate was 97.4% at 5 years. At the follow-up, 506 (7.8%) cases of metastasis and 167 (2.6%) deaths were noted. Multivariate Cox regression analysis showed that tumor stage, lymphvascular invasion, and the Ki67 index were related to recurrence and metastasis (P < 0.05). The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815 (95% confidence interval: 0.750-0.880). CONCLUSIONS: : Early-stage breast cancer patients with low-positive HER2 expression account for 30.5% of all patients. Tumor stage, lymphvascular invasion, and the Ki67 index are factors affecting prognosis. The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years. TRIAL REGISTRATION: : ChiCTR.org.cn, ChiCTR2100046766.

Androgen Receptor: A New Marker to Predict Pathological Complete Response in HER2-Positive Breast Cancer Patients Treated with Trastuzumab Plus Pertuzumab Neoadjuvant Therapy.

(1) Background: Neoadjuvant therapy is the main therapeutic strategy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, and the combination of trastuzumab and pertuzumab (HP) has become a routine treatment. How to predict and screen patients who are less likely to respond to neoadjuvant therapy is the focus of research. The androgen receptor (AR) is a biomarker that is widely expressed in all breast cancer subtypes and is probably related to treatment response and prognosis. In this study, we investigated the relationship between AR expression and treatment response in HER2-positive breast cancer patients treated with HP neoadjuvant therapy. (2) Methods: We evaluated early breast cancer patients treated with HP neoadjuvant therapy from Jan. 2019 to Oct. 2020 at Peking University First Hospital Breast Cancer Center. The inclusion criteria were as follows: early HER2-positive breast cancer patients diagnosed by core needle biopsy who underwent both HP neoadjuvant therapy and surgery. We compared the clinical and pathological features between pathological complete response (pCR) and non-pCR patients. (3) Results: We included 44 patients. A total of 90.9% of patients received neoadjuvant therapy of taxanes, carboplatin, trastuzumab and pertuzumab (TCHP), and the total pCR rate was 50%. pCR was negatively related to estrogen receptor (ER) positivity (OR 0.075 [95% confidence interval (CI) 0.008-0.678], p = 0.021) and positively related to high expression levels of AR (OR 33.145 [95% CI 2.803-391.900], p = 0.005). We drew a receiver operating characteristic (ROC) curve to assess the predictive value of AR expression for pCR, and the area under the curve was 0.737 (95% CI 0.585-0.889, p = 0.007). The optimal cutoff of AR for predicting pCR was 85%. (4) Conclusion: AR is a potential marker for the prediction of pCR in HER2-positive breast cancer patients treated with HP neoadjuvant therapy.

Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case-Control Study in Chinese Females.

BACKGROUND: Leptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk. METHODS: In the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant-associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database. RESULTS: There were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101 (GA vs. GG; adjusted OR = 0.719, 95% CI = 0.578-0.894, p = 0.003) and rs4655555 (TT vs. AA; adjusted OR = 0.574, 95% CI = 0.377-0.873, p = 0.009) significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI ≤ 24 kg/m2 or WHR ≥ 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data. CONCLUSION: Our study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer.

Circulating microRNAs as indicators in the prediction of neoadjuvant chemotherapy response in luminal B breast cancer.

PURPOSE: Circulating microRNAs (miRNAs) have been indicated as predictive biomarker for the response to neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer (BC); however, to date the conclusions have been controversial. The biological characteristics of BC were affected by molecular subtypes. Hence, we aimed to investigate the predictive effect of miRNAs on NAC response in luminal B BC patients. METHODS: Thirty-seven luminal B BC patient under NAC were prospectively enrolled in this study. Based on their clinical, pathological, and comprehensive response, the patients were defined as responder or non-responders, respectively. Circulating miRNAs were isolated from blood samples before and at the middle of NAC, and candidate miRNAs (miR-34a-5p, miR-125b-5p, miR-210, miR-222, miR-375, miR-718, miR-4516, and let-7g) were analyzed by quantitative real-time polymerase chain reaction (PCR). In addition, the association between miRNAs and disease-free survival (DFS) was examined. RESULTS: miR-718, miR-4516, miR-210, and miR-125b-5p were found to be specific miRNAs associated with chemo-sensitivity of luminal B HER2 negative patients (n = 24). In the luminal B HER2 positive cohort (n = 13), dynamics of miR-222 and let-7g correlated with pathological response. Treatment-induced increase in miR-34a-5p in the responders except who reached pathologic complete response (pCR) was consistently identified across all luminal B patients and its two subgroups. Finally, after adjustments for Neo-Bioscore, patients with increased levels of miR-125b-5p during NAC had a worse DFS than those with decreased levels (HR = 5.86, 95% CI = 1.39-24.62, p = 0.016). CONCLUSION: Specific circulating miRNAs were identified as predictive markers for NAC response and prognosis in luminal B BC. The underlying mechanism needs further studies.

Case report: Secondary sclerosing cholangitis induced by lapatinib and vinorelbine in a metastasis breast cancer patient.

Secondary sclerosing cholangitis (SSC) is a rare cholestatic liver disease that may have a severe clinical course. A 61-year-old woman with a history of metastasis breast cancer was admitted to our hospital for the second cycle of chemotherapy with lapatinib and vinorelbine. The patient had no reports of elevated liver function tests (LFTs) in the previous multiple chemotherapies or history of liver disease. However, the admission laboratory results showed severe cholestatic liver injury with the possibility of SSC by magnetic resonance cholangiopancreatography. Although chemotherapy was discontinued and patient was treated with hepatoprotective drugs, the LFTs did not improve and liver biopsy indicated mild injury of intrahepatic bile duct epithelium and hepatocyte. We added ursodeoxycholic acid and prednisolone to protect the liver, and laboratory data showed a response. To prevent the progression, lapatinib and vinorelbine were reintroduced and transient increases in alanine aminotransferase and γ-glutamyl transpeptidase were observed. With no evidence of viral or autoimmune liver disease, SSC induced by lapatinib and vinorelbine was diagnosed. This is the first case report of tyrosine kinase inhibitors and vinorelbine induced SSC and clinicians should be aware of the possibility of it. More case reports about this adverse drug reaction are needed to delineate optimal management.

Assessment of CPS + EG, Neo-Bioscore and Modified Neo-Bioscore in Breast Cancer Patients Treated With Preoperative Systemic Therapy: A Multicenter Cohort Study.

This study was to assess the prognosis stratification of the clinical-pathologic staging system incorporating estrogen receptor (ER)-negative disease, the nuclear grade 3 tumor pathology (CPS + EG), Neo-Bioscore, and a modified Neo-Bioscore system in breast cancer patients after preoperative systemic therapy (PST). A retrospective multicenter cohort study was conducted from 12 participating hospitals' databases from 2006 to 2015. Five-year disease free survival (DFS), disease specific survival (DSS), and overall survival (OS) were calculated using Kaplan-Meier Method. Area under the curve (AUC) of the three staging systems was compared. Wald test and maximum likelihood estimates in Cox proportional hazards model were used for multivariate analysis. A total of 1,077 patients were enrolled. The CPS + EG, Neo-Bioscore, and modified Neo-Bioscore could all stratify the DFS, DSS, and OS (all P < 0.001). While in the same stratum of Neo-Bioscore scores 2 and 3, the HER2-positive patients without trastuzumab therapy had much poorer DSS (P = 0.013 and P values < 0.01, respectively) as compared to HER2-positive patients with trastuzumab therapy and HER2-negative patients. Only the modified Neo-Bioscore had a significantly higher stratification of 5-year DSS than PS (AUC 0.79 vs. 0.65, P = 0.03). So, the modified Neo-Bioscore could circumvent the limitation of CPS + EG or Neo-Bioscore. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03437837.

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

Retrospective analysis of sentinel lymph node biopsy using methylene blue dye for early breast cancer.

BACKGROUND: Methylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses. METHODS: We retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves. RESULTS: Between January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ2 = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ2 = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ2 = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224-0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006). CONCLUSION: Our single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.

Prognostic value of residual cancer burden and Miller-Payne system after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: To verify the feasibility of using the residual cancer burden (RCB) index to stratify prognosis of patients after neoadjuvant chemotherapy (NAC) and to compare RCB with the Miller-Payne system. METHODS: We retrospectively analyzed clinicopathological data of patients receiving treatment between January 1, 2010 and December 31, 2018. Kaplan-Meier curves were used to compare the survival outcomes and estimate disease-free survival (DFS) and disease-specific survival (DSS). Harrell's concordance index (C-index) was used to evaluate the predictive accuracy of RCB and Miller-Payne system. RESULTS: A total of 423 female patients with complete data were included in the analysis, with a median follow-up time of 58.5 months (range, 7-126 months); 84 patients experienced recurrence, and 48 experienced breast cancer related death. RCB index and the Miller-Payne system were associated with prognosis in the whole cohort. Patients who achieved RCB-I had similar survival outcomes as those with pathological complete response (pCR, RCB-0). In whole cohort, for the RCB index and the Miller-Payne system, respectively, C-indexes for DFS were 0.73 and 0.64, for DSS were 0.74 and 0.64. The average RCB score was different among three subtypes (F=9.335, P<0.001). CONCLUSIONS: The RCB index and the Miller-Payne system can stratify survival outcome of patients after NAC, and RCB had a superior prediction accuracy, especially for triple-negative breast cancer (TNBC). New cut-off value should be sought in order to improve prediction accuracy.

Relationship Between Lifestyle Habits and Health-Related Quality of Life of Recently Diagnosed Breast Cancer Patients: A Comparison Between Younger and Older Women in China.

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being (p = 0.003), functional well-being (p = 0.006), breast cancer subscale (p = 0.038), and FACT-B Total scores (p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer.

Exosomal miR-1246 and miR-155 as predictive and prognostic biomarkers for trastuzumab-based therapy resistance in HER2-positive breast cancer.

PURPOSE: This study aimed to investigate the predictive and prognostic roles of circulating exosomal miRNAs in breast cancer treated with trastuzumab-based chemotherapy. METHODS: Circulating exosomal miRNAs from trastuzumab-resistant (n = 4) and -sensitive (n = 4) patients were profiled using miRNA microarray. The predictive and prognostic roles of filtered miRNAs were validated in 107 early-stage and 68 metastatic patients treated with trastuzumab-based chemotherapy through receiver-operating characteristic (ROC) curve analysis, logistic regression and Cox proportional hazards regression analysis, and Kaplan-Meier survival analysis. RESULTS: MiRNA microarray analysis revealed miR-1246 and miR-155 were the most up-regulated miRs in trastuzumab-resistant HER2-positive breast cancer patients, which were further validated in trastuzumab-resistant patient samples (n = 32) compared with trastuzumab sensitive ones (n = 36). MiR-1246 showed a ROC curve area of 0.750 with 78.1% sensitivity and 75% specificity in discriminating resistant from sensitive patients (p < 0.001), while miR-155 showed a ROC curve area of 0.877 with 68.8% sensitivity and 97.2% specificity (p < 0.001). Predictive factors and multivariate analysis showed that high levels of miR-1246 and miR-155 strongly predicted poor event-free survival (EFS) for early-stage patients, and poor progression-free survival (PFS) for metastatic patients. However, both miRNAs were revealed not to be associated with overall survival (OS). In addition, Kaplan-Meier survival analysis demonstrated that early-stage and metastatic patients with high expression of miR-1246 and miR-155 had poorer EFS or PFS, respectively, than those with decreased expression of both miRs. CONCLUSIONS: This study demonstrated the valuable roles of circulating exosomal miR-1246 and miR-155 in distinguishing trastuzumab resistant from sensitive patients.

Erratum: Addendum: Metabolic Syndrome, and Particularly the Hypertriglyceridemic-Waist Phenotype, Increases Breast Cancer Risk, and Adiponectin Is a Potential Mechanism: A Case-Control Study in Chinese Women.

[This corrects the article DOI: 10.3389/fendo.2019.00905.].

Prognostic value of tumor-infiltrating lymphocyte subtypes in residual tumors of patients with triple-negative breast cancer after neoadjuvant chemotherapy.

BACKGROUND: After neoadjuvant chemotherapy (NAC), non-pathological complete response of breast cancer patients can benefit from tailored adjuvant chemotherapy. However, it is difficult to select patients with poorer prognosis for additional adjuvant chemotherapy to maximize the benefits. Our study aimed to explore whether the subtypes of tumor-infiltrating lymphocytes (TILs) in residual tumors (RT) is related to the prognosis of triple-negative breast cancer (TNBC) after NAC. METHODS: Data from patients with primary TNBC consecutively diagnosed at the Breast Disease Center of Peking University First Hospital from 2008 to 2014 were retrieved, and the cases with RT in the breast after NAC were enrolled. TILs subtypes in RT were observed by double-staining immunohistochemistry, and counted with the median TILs value per square millimeter as the cut-off to define high versus low TILs density in each subtype. The relationships between the TIL density of each subgroup and the clinicopathological characteristics of the RT after NAC patients were analyzed by Fisher exact test. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank statistics. RESULTS: A total of 37 eligible patients were included in this study, and the median follow-up period was 50 months (range 17-106 months). There was no significant correlation between the infiltrate density of CD4, CD8, CD20, and CD68 lymphocytes and clinic-pathological characteristics. Significantly better prognosis was observed in patients with high CD4-TILs (DFS: P = 0.005, OS: P = 0.021) and high CD8-TILs (DFS: P = 0.018) and low CD20-TILs (OS: P = 0.042). Further analysis showed that patients with CD4/CD20 ratio greater than 1 (DFS: P = 0.001, OS: P = 0.002) or CD8/CD20 ratio greater than 1 (DFS: P = 0.009, OS: P = 0.022) had a better prognosis. CONCLUSIONS: Subtypes of TILs in RT is a potential predictive biomarker of survival in TNBC patients after NAC.

Clinicopathologic analysis of 722 breast cancer patients who met the inclusion criteria of the TAILORx trial.

BACKGROUND: The results of the Trial Assigning IndividuaLized Options for Treatment (TAILORx) suggested that approximately 70% of T1-2N0M0, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients can avoid chemotherapy and receive only adjuvant endocrine therapy. We conducted a retrospective analysis of the clinicopathologic features and prognostic factors of patients with breast cancer who met the inclusion criteria of the TAILORx trial. METHODS: According to the enrollment criteria of the TAILORx trial, a retrospective analysis was performed on patients with breast cancer who were treated from January 2008 to December 2015 at Peking University First Hospital. The clinicopathologic characteristics of all patients were analyzed, and prognoses were calculated using the Kaplan-Meier method and a Cox proportionate hazards model. RESULTS: A total of 2430 patients with early stage breast cancer who were admitted at our hospital had complete clinicopathologic data and follow-up information. Of these patients, 722 met the inclusion criteria and were enrolled in the present study, accounting for 29.7% of all patients. Among them, 417 (57.8%) patients received only adjuvant endocrine therapy (the non-chemo group), and 305 (42.2%) patients received adjuvant chemotherapy followed by adjuvant endocrine therapy (the chemo group). No statistically significant difference was observed in overall survival (OS) between the two groups (non-chemo vs. chemo: 5-year OS: 97.9% vs. 97.9%, χ = 1.00, P = 0.995; hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.46-2.21). A significant difference was observed in disease-free survival (DFS) between the two groups (non-chemo vs. chemo: 5-year DFS: 97.9% vs. 94.7%, χ = 8.65, P = 0.003; HR = 3.05, 95% CI: 1.40-6.67). The choice of adjuvant therapy was associated with clinicopathologic factors, such as the age at diagnosis, T stage, histologic grade, the Ki67 index, the presence of intravascular tumor thrombus (P < 0.001), pathologic type, and menstrual status (P = 0.014). CONCLUSIONS: In the absence of internationally recognized multigene testing methods, for patients with early hormone receptor-positive, HER2-negative breast cancer, clinicians can develop a treatment plan based on clinicopathologic features only, which can effectively screen some patients who do not need adjuvant chemotherapy. However, nearly half of patients still receive adjuvant chemotherapy, and whether these patients can be exempted from chemotherapy warrants further exploration.