Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in gBRCA1/2 Mutations and High-Risk Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer.

PURPOSE: The OlympiA randomized phase III trial compared 1 year of olaparib (OL) or placebo (PL) as adjuvant therapy in patients with germline BRCA1/2, high-risk human epidermal growth factor receptor 2-negative early breast cancer after completing (neo)adjuvant chemotherapy ([N]ACT), surgery, and radiotherapy. The patient-reported outcome primary hypothesis was that OL-treated patients may experience greater fatigue during treatment. METHODS: Data were collected before random assignment, and at 6, 12, 18, and 24 months. The primary end point was fatigue, measured with the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary end points, assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 item, included nausea and vomiting (NV), diarrhea, and multiple functional domains. Scores were compared between treatment groups using mixed model for repeated measures. Two-sided P values <.05 were statistically significant for the primary end point. All secondary end points were descriptive. RESULTS: One thousand five hundred and thirty-eight patients (NACT: 746, ACT: 792) contributed to the analysis. Fatigue severity was statistically significantly greater for OL versus PL, but not clinically meaningfully different by prespecified criteria (≥3 points) at 6 months (diff OL v PL: NACT: -1.3 [95% CI, -2.4 to -0.2]; P = .022; ACT: -1.3 [95% CI, -2.3 to -0.2]; P = .017) and 12 months (NACT: -1.6 [95% CI, -2.8 to -0.3]; P = .017; ACT: -1.3 [95% CI, -2.4 to -0.2]; P = .025). There were no significant differences in fatigue severity between treatment groups at 18 and 24 months. NV severity was worse in patients treated with OL compared with PL at 6 months (NACT: 6.0 [95% CI, 4.1 to 8.0]; ACT: 5.3 [95% CI, 3.4 to 7.2]) and 12 months (NACT: 6.4 [95% CI, 4.4 to 8.3]; ACT: 4.5 [95% CI, 2.8 to 6.1]). During treatment, there were some clinically meaningful differences between groups for other symptoms but not for function subscales or global health status. CONCLUSION: Treatment-emergent symptoms from OL were limited, generally resolving after treatment ended. OL- and PL-treated patients had similar functional scores, slowly improving during the 24 months after (N)ACT and there was no clinically meaningful persistence of fatigue severity in OL-treated patients.

An iron metabolism and immune related gene signature for the prediction of clinical outcome and molecular characteristics of triple-negative breast cancer.

BACKGROUND: An imbalance of intracellular iron metabolism can lead to the occurrence of ferroptosis. Ferroptosis can be a factor in the remodeling of the immune microenvironment and can affect the efficacy of cancer immunotherapy. How to combine ferroptosis-promoting modalities with immunotherapy to suppress triple-negative breast cancer (TNBC) has become an issue of great interest in cancer therapy. However, potential biomarkers related to iron metabolism and immune regulation in TNBC remain poorly understand. METHODS: We constructed an optimal prognostic TNBC-IMRGs (iron metabolism and immune-related genes) signature using least absolute shrinkage and selection operator (LASSO) cox regression. Survival analysis and ROC curves were analyzed to identify the predictive value in a training cohort and external validation cohorts. The correlations of gene signature with ferroptosis regulators and immune infiltration are also discussed. Finally, we combined the gene signature with the clinical model to construct a combined model, which was further evaluated using a calibration curve and decision curve analysis (DCA). RESULTS: Compared with the high-risk group, TNBC patients with low-risk scores had a remarkably better prognosis in both the training set and external validation sets. Both the IMRGs signature and combined model had a high predictive capacity, 1/3/5- year AUC: 0.866, 0.869, 0.754, and 1/3/5-yaer AUC: 0.942, 0.934, 0.846, respectively. The calibration curve and DCA also indicate a good predictive performance of the combined model. Gene set enrichment analysis (GSEA) suggests that the high-risk group is mainly enriched in metabolic processes, while the low-risk group is mostly clustered in immune related pathways. Multiple algorithms and single sample GSEA further show that the low-risk score is associated with a high tumor immune infiltration level. Differences in expression of ferroptosis regulators are also observed among different risk groups. CONCLUSIONS: The IMRGs signature based on a combination of iron metabolism and immune factors may contribute to evaluating prognosis, understanding molecular characteristics and selecting treatment options in TNBC.

Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer.

Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist's experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928-0.989; P < 0.0001). Next, we conducted a study of archival FNAs of ipsilateral palpable LNs (malignant, N = 72, benign, N = 53 by cytology) collected in the outpatient setting prior to neoadjuvant chemotherapy (NAC). Using the ROC-threshold determined in the prospective study, compared to cytology, BCDA achieved a sensitivity of 94.4% and a specificity of 92.5% with a ROC-AUC = 0.977 (95% CI: 0.953-1.000; P < 0.0001). Our study shows that the automated assay detects cancer in suspicious lymph nodes with a high level of accuracy within 5 h. This cancer detection assay, scalable for analysis to scores of LN FNAs, could assist in determining eligibility of patients to different treatment regimens.

Multiple cancer susceptible genes sequencing in BRCA-negative breast cancer with high hereditary risk.

BACKGROUND: Hereditary factors contributed to breast cancer susceptibility. Low BRCA mutation prevalence was demonstrated in previous BRCA mutation screening in Chinese breast cancer patients. Multiple-gene sequencing may assist in discovering detrimental germline mutation in. BRCA: negative breast cancers. METHODS: A total of 384 Chinese subjects with any two of high-risk factors were recruited and screened by next-generation sequencing (NGS) for 30 cancer susceptible genes. Variants with a truncating, initiation codon or splice donor/acceptor effect, or with pathogenicity demonstrated in published literature were classified into pathogenic/likely-pathogenic mutations. RESULTS: In total, we acquired 39 (10.2%) patients with pathogenic/likely-pathogenic germline mutations, including one carrying two distinct mutations. Major mutant non-BRCA genes were MUTYH (n=11, 2.9%), PTCH1 (n=7, 1.8%), RET (n=6, 1.6%) and PALB2 (n=5, 1.3%). Other mutant genes included TP53 (n=3, 0.8%), RAD51D (n=2, 0.5%), CHEK2 (n=1, 0.3%), BRIP1 (n=1, 0.3%), CDH1 (n=1, 0.3%), MRE11 (n=1, 0.3%), RAD50 (n=1, 0.3%) and PALLD (n=1, 0.3%). A splicing germline mutation, MUTYH c.934-2A>G, was a hotspot (9/384, 2.3%) in Chinese breast cancer. CONCLUSIONS: Among BRCA-negative breast cancer patients with high hereditary risk in China, 10.2% carried mutations in cancer associated susceptibility genes. MUTYH and PTCH1 had relatively high mutation rates (2.9% and 1.8%). Multigene testing contributes to understand genetic background of BRCA-negative breast cancer patients with high hereditary risk.

The Survival Outcomes of T1aN0M0 Triple-Negative Breast Cancer With Adjuvant Chemotherapy.

Purpose: Triple-negative breast cancer (TNBC) is a subtype with distinct heterogeneity, high invasiveness, and poorer prognosis. There is a controversy about adjuvant chemotherapy (ACT) at the T1aN0M0 stage. This study was carried out to assess the survival benefit of ACT for these patients. Methods: We identified 1,099 patients with T1aN0M0 TNBC who were diagnosed between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariable analyses were conducted to determine factors related to survival. One-to-one (1:1) propensity score matching (PSM) was applied to construct a matched sample consisting of pairs of ACT and non-ACT subjects. Breast cancer-specific survival (BCSS) and overall survival (OS) of the two groups were evaluated by Kaplan-Meier plots and Cox proportional hazard regression models. Stratified analysis according to different variables was also performed. Results: No obvious differences in demographic or clinical characteristics were found between patients who had ACT and those without ACT therapy in terms of race, marital status, laterality, or radiation therapy. A higher proportion of patients who were older, had a higher histological grade tumor, and who received breast-conserving surgery had adjuvant chemotherapy. The ACT group did not exhibit better survival in BCSS or OS before PSM. After PSM, the ACT and non-ACT groups consisted of 255 patients, respectively, and Kaplan-Meier curves and multivariate analysis both indicate that adjuvant chemotherapy was not associated with better survival in terms of BCSS or OS. Furthermore, we did not observe any survival advantage in any subgroup irrespective of age, race, marital status, histological grade, surgery type, or radiotherapy status. Conclusions: The study results indicate that there is no strong association between ACT and better survival in T1aN0M0 TNBC. It implies that the chemotherapy decision should be made cautiously and further research into therapeutic strategies are needed in T1aN0M0 TNBC patients.

Different Clinicopathological Characteristics and Prognostic Factors for Occult and Non-occult Breast Cancer: Analysis of the SEER Database.

Purpose: The aim of our study was to evaluate the different clinicopathological characteristics and prognostic factors for occult and non-occult breast cancer. Methods: 572 OBC cases and 117,217 non-OBC patients between 2004 and 2015 was selected from Surveillance, Epidemiology, and End Results (SEER) database. We analyzed the clinicopathological characteristics and survival outcomes between OBC and non-OBC patients. Furthermore, the propensity score matching method was utilized to reduce the influences of baseline differences in demographic and clinical characteristics on outcome differences. Univariable and multivariable analyses were used to evaluate the prognostic factors of OBC patients. Results: Compared with non-OBC patients, OBC patients in this study presented a higher proportion of older age, American Joint Committee on Cancer (AJCC) N3 stage, estrogen receptor (ER)-negative status, progesterone receptor (PR)-negative status, and human epidermal growth factor receptor-2 (HER-2)-positive status, and underwent more chemotherapy. Multivariate analysis revealed a better survival in overall patients with OBC patients according to breast cancer-specific survival (BCSS) and overall survival (OS). Propensity score analysis also achieved a similar result for OBC patients. Stratified analyses by nodal status and molecular subtypes indicated that these survival advantage were mainly presented in patients with AJCC N2/N3 stage or hormone receptor (HR)-positive tumors. In addition, nodal status, HER-2 status, and radiation status were demonstrated to be three independent prognostic factors for OBC patients. Conclusion: Patients with OBC retained exclusive clinical characteristics and were shown to have a better outcome compared with non-OBC patients, especially for those with N2/N3 stage or HR-positive tumors.

Effect of Adjuvant Paclitaxel and Carboplatin on Survival in Women With Triple-Negative Breast Cancer: A Phase 3 Randomized Clinical Trial.

Importance: The value of platinum-based adjuvant chemotherapy in patients with triple-negative breast cancer (TNBC) remains controversial, as does whether BRCA1 and BRCA2 (BRCA1/2) germline variants are associated with platinum treatment sensitivity. Objective: To compare 6 cycles of paclitaxel plus carboplatin (PCb) with a standard-dose regimen of 3 cycles of cyclophosphamide, epirubicin, and fluorouracil followed by 3 cycles of docetaxel (CEF-T). Design, Setting, and Participants: This phase 3 randomized clinical trial was conducted at 9 cancer centers and hospitals in China. Between July 1, 2011, and April 30, 2016, women aged 18 to 70 years with operable TNBC after definitive surgery (having pathologically confirmed regional node-positive disease or node-negative disease with tumor diameter >10 mm) were screened and enrolled. Exclusion criteria included having metastatic or locally advanced disease, having non-TNBC, or receiving preoperative anticancer therapy. Data were analyzed from December 1, 2019, to January 31, 2020, from the intent-to-treat population as prespecified in the protocol. Interventions: Participants were randomized to receive PCb (paclitaxel 80 mg/m2 and carboplatin [area under the curve = 2] on days 1, 8, and 15 every 28 days for 6 cycles) or CEF-T (cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2, and fluorouracil 500 mg/m2 every 3 weeks for 3 cycles followed by docetaxel 100 mg/m2 every 3 weeks for 3 cycles). Main Outcomes and Measures: The primary end point was disease-free survival (DFS). Secondary end points included overall survival, distant DFS, relapse-free survival, DFS in patients with germline variants in BRCA1/2 or homologous recombination repair (HRR)-related genes, and toxicity. Results: A total of 647 patients (mean [SD] age, 51 [44-57] years) with operable TNBC were randomized to receive CEF-T (n = 322) or PCb (n = 325). At a median follow-up of 62 months, DFS time was longer in those assigned to PCb compared with CEF-T (5-year DFS, 86.5% vs 80.3%, hazard ratio [HR] = 0.65; 95% CI, 0.44-0.96; P = .03). Similar outcomes were observed for distant DFS and relapse-free survival. There was no statistically significant difference in overall survival between the groups (HR = 0.71; 95% CI, 0.42-1.22, P = .22). In the exploratory and hypothesis-generating subgroup analyses of PCb vs CEF-T, the HR for DFS was 0.44 (95% CI, 0.15-1.31; P = .14) in patients with the BRCA1/2 variant and 0.39 (95% CI, 0.15-0.99; P = .04) in those with the HRR variant. Safety data were consistent with the known safety profiles of relevant drugs. Conclusions and Relevance: These findings suggest that a paclitaxel-plus-carboplatin regimen is an effective alternative adjuvant chemotherapy choice for patients with operable TNBC. In the era of molecular classification, subsets of TNBC sensitive to PCb should be further investigated. Trial Registration: ClinicalTrials.gov Identifier: NCT01216111.

The Expression, Clinicopathologic Characteristics, and Prognostic Value of Androgen Receptor in Breast Cancer: A Bioinformatics Analysis Using Public Databases.

The role of androgen receptor (AR) in breast cancer has been unveiled in succession for the past few years. In this study, we conducted a comprehensive analysis based on four online public databases of data from many previous studies. We found that the expression of AR is significantly related to age, histological grade, and subtype but not to lymph node status. The low expression level of AR is strongly associated with poor recurrence-free survival, especially with poor distance metastasis-free survival in luminal A patients, but inverse in HER2 (human epidermal growth factor receptor-2) enriched patients. AR might be a biomarker of chemosensitivity in the basal subtype. Besides, the expression of melanophilin (MLPH) is distinctly in accordance with that of AR. AR could play diverse roles in different subtypes of breast cancer.

Association of Axillary Lymph Node Evaluation With Survival in Women Aged 70 Years or Older With Breast Cancer.

BACKGROUND: Survival in elderly patients undergoing sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) has not been specifically analyzed. This study aimed to explore the association between different types of axillary lymph node (ALN) evaluations and survival of elderly breast cancer patients. METHODS: A retrospective cohort study was conducted of invasive ductal breast cancer patients 70 years and older in the Surveillance, Epidemiology, and End Results database (2004-2016). Analyses were performed to compare the characteristics and survival outcomes of patients who received surgical lymph node dissection and those who did not. Breast cancer specific survival (BCSS) and overall survival were compared by using Cox proportional hazards regression analysis and propensity score matching (PSM) methods to account for selection bias from covariate imbalance. RESULTS: Of the 75,950 patients analyzed, patients without ALN evaluation had a significantly worse prognosis, while there was no significant difference for BCSS between using a sentinel lymph node biopsy (SLNB) and an axillary lymph node dissection (ALND) after adjustment for known covariates [adjusted hazard ratio (HR) = 0.991, 95% confidence interval (CI) = 0.925-1.062, p = 0.800]. In the stratification analyses after PSM, the ALND did not show a significant BCSS advantage compared with SLNB in any subgroups except for the pN1 stage or above. Furthermore, after PSM of the pN1 stage patients, SLNB was associated with a significantly worse BCSS in hormone receptor negative (HR-) patients (HR = 1.536, 95%CI = 1.213-1.946, p < 0.001), but not in the hormone receptor positive (HR+) group (HR = 1.150, 95%CI = 0.986-1.340, p = 0.075). CONCLUSION: In our study, ALND does not yield superior survival compared with SLNB for elderly patients with pN1 stage HR+ breast cancer. Although our findings are limited by the bias associated with retrospective study design, we believe that in the absence of results from randomized clinical trials, our findings should be considered when recommending the omission of ALND for elderly breast cancer patients.

Validation of the Prognostic Significance of the Prognostic Stage Group According to the Eighth Edition of American Cancer Joint Committee on Cancer Staging System in Triple-Negative Breast Cancer: An Analysis From Surveillance, Epidemiology, and End Results 18 Database.

BACKGROUND: The eighth edition of the American Cancer Joint Committee on Cancer (AJCC) staging system for breast cancer put forward the prognostic stage groups for the first time based on the traditional anatomic tumor-node-metastasis staging system. Our study intends to validate the predictive significance of the eighth edition staging system in triple-negative breast cancer (TNBC) patients. MATERIALS AND METHODS: We collected and accessed 26,589 eligible cases of TNBC from the Surveillance, Epidemiology, and End Results database (2010-2015) and reclassified the patient cohort according to the eighth edition of the AJCC staging system into anatomic and prognostic stages. RESULTS: The results showed that more than half of the patients upstaged in the prognostic stage when compared with the anatomic stage. By comparing with the anatomic stage, the prognostic stage had a higher likelihood ratio and linear trend χ2 values. The prognostic stage group also had higher Akaike information criterion and Bayesian information criterion values than the anatomic stage group. CONCLUSIONS: The prognostic staging system in TNBC patients performs more optimistic prognostic stratification and predictability than the anatomic staging system. Moreover, the latest AJCC staging system has a milestone importance to the history of breast cancer staging system.

Effect of postmastectomy radiotherapy on triple-negative breast cancer with T1-2 and 1-3 positive axillary lymph nodes: a population-based study using the SEER 18 database.

There is consensus on the routine use of postmastectomy radiotherapy (PMRT) in patients with four or more positive axillary lymph nodes. However, the benefits of PMRT in patients with T1-2 and 1-3 involved lymph nodes still remain controversial. Data from the Surveillance, Epidemiology, and End Results Program (SEER) of the United States between 2010 and 2012 were used to analyze the outcomes of 675 triple-negative breast cancer (TNBC) patients with T1-2 and 1-3 lymph nodes involved. Those patients were subdivided into radiotherapy (RT) (312) and no-RT groups (363). After a median follow-up time of 37 months, Kaplan-Meier analysis showed that PMRT significantly improved overall survival (OS) but not breast cancer-specific survival (BCSS) in the total cohort of 675 patients (P=0.033 and P=0.063). And it was demonstrated that PMRT were independently associated with increased OS according to univariate and multivariate analyses. However, no significant differences in BCSS or OS were observed between the groups stratified by the number of positive lymph nodes. In conclusion, PMRT significantly improved OS for TNBC patients with T1-2 and 1-3 lymph nodes involved. Additional prospective studies are needed to provide a stronger evidence base for choosing patients for PMRT.

Serum miR-4530 sensitizes breast cancer to neoadjuvant chemotherapy by suppressing RUNX2.

PURPOSE: Neoadjuvant chemotherapy (NAC) plays a pivotal role in the treatment of locally advanced breast cancer (LABC); however, breast cancer is a heterogeneous disease, individual responses to chemotherapy are highly variable. Therefore, the purpose of the current research is to identify biomarkers that can predict the chemotherapeutic response. PATIENTS AND METHODS: We recruited 78 patients with primary breast cancer who underwent taxane- and anthracycline-based NAC; these patients were divided into sensitive and resistant groups according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The microRNA microarray was conducted to explore differentially expressed miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) further validated the relationship between miR-4530 and chemosensitivity in breast cancer patients. RESULTS: No significant differences were observed between the two groups regarding the clinicopathological characteristics. miR-4530 showed the most potential involving breast cancer chemosensitivity. Mechanically, RUNX2 was identified one of the direct targets of miR-4530 and responsible for breast cancer chemosensitivity. CONCLUSION: Our results revealed that elevated serum miR-4530 levels may sensitize breast cancer to taxane- and anthracycline-based NAC by suppressing RUNX2; therefore, this miRNA has the potential to be a new biomarker for predicting breast cancer chemosensitivity.

The spectrum of BRCA mutations and characteristics of BRCA-associated breast cancers in China: Screening of 2,991 patients and 1,043 controls by next-generation sequencing.

To characterize the prevalence of BRCA mutations and characteristics of BRCA carriers in China and to update the clinical recommendations for BRCA testing, we conducted a wide screen for BRCA mutations using next-generation sequencing (NGS). A total of 4,034 Chinese subjects were screened for germline BRCA1/2 mutations, including 2,991 breast cancer patients and 1,043 healthy individuals from the community enrolled as controls. We developed an NGS-based approach to perform BRCA1/2 screening. BRCA mutations were identified in 9.1% (232/2,560) of cases with at least one risk factor, in 3.5% (15/431) of sporadic patients and in 0.38% (4/1,043) of healthy controls. The mutation frequency ranged from 8.9 to 15.2% in cohorts with a single risk factor to 16.6-100% in groups with multiple risk factors. We identified 70 novel BRCA mutations. A high frequency of BRCA1 c.5470_5477del was detected, accounting for 13.9% (16/115) of the BRCA1 mutations detected in our study. Clinical characteristics such as family history, invasive carcinoma, negative human epidermal growth factor receptor 2 (HER2), high Ki67 index, lymph node status, and high tumour grade were closely related to BRCA mutations. BRCA2 carriers had poorer disease-free survival among HER2- or hormone receptor-positive patients (hazard ratio = 1.892; 95% confidence interval: 1.132-3.161; p = 0.013). This study shows that BRCA mutation carriers could be frequently identified among breast cancer patients with multiple risk factors. Importantly, we established an NGS-based pipeline for BRCA1/2 testing in clinical practice and strongly suggest that breast cancer patients of premier- and moderate-grade risks receive BRCA1/2 mutations testing in China.

Similar outcomes between adenoid cystic carcinoma of the breast and invasive ductal carcinoma: a population-based study from the SEER 18 database.

Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients.

The different outcomes between breast-conserving surgery and mastectomy in triple-negative breast cancer: a population-based study from the SEER 18 database.

Breast-conserving surgery (BCS) including radiotherapy (RT) has been demonstrated to provide at least equivalent prognosis to mastectomy in early-stage breast cancer. However, studies on triple-negative breast cancer (TNBC) patients are relatively scarce. The current population-based study aimed to investigate the distinct outcomes between BCS+RT and mastectomy in patients with TNBC. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled 11,514 female TNBC cases diagnosed during the years 2010-2013. Those patients were subdivided into BCS+RT (5,469) and mastectomy groups (6,045), and we conducted a survival comparison between the two groups. The endpoints were breast cancer-specific survival (BCSS) and overall survival (OS). In the overall cohort, patients with BCS+RT exhibited distinctly better breast cancer-specific survival (BCSS) (log-rank, p < 0.001) and overall survival (OS) (log-rank, p < 0.001) than did mastectomy patients. When stratifying the TNBC patients according to age, histology grade, TNM stage, tumor size, and lymph node (LN) status, most patients in the BCS+RT group presented with better survival than did the patients in the mastectomy group, except for the grade I (log-rank, p = 0.830, both BCSS and OS) and stage I (log-rank, BCSS, p = 0.127; OS, p = 0.093) patients. In addition, after adjusting for confounding variables by multivariable Cox proportional hazard analysis, BCS+RT still tended to present with higher BCSS and OS. In conclusion, from our study on SEER data, BCS+RT displayed elevated BCSS and OS in TNBC patients compared to mastectomy, at least equally. Our study provided further evidence for surgeons that BCS with RT is available for TNBC patients.

High expression of microRNA-454 is associated with poor prognosis in triple-negative breast cancer.

MicroRNA-454 (miR-454) has been reported to play an oncogenic or tumor suppressor role in most cancers. However, the clinical relevance of miR-454 in breast cancer remains unclear. We examined the expression of miR-454 in a tissue microarray containing 534 breast cancer specimens from female patients at Fudan University Shanghai Cancer Center using in situ hybridization (ISH). Of these, 250 patients formed the training set and the other 284 were the validation set. The relationship between miR-454 and clinical outcome was analyzed by the Kaplan-Meier method. High expression of miR-454 indicated worse disease-free survival (DFS) in both cohorts (P = 0.006 for training set; P = 0.010 for validation set). Furthermore, in the triple-negative breast cancer (TNBC) subtype, miR-454 was positively correlated with worse clinical outcome (P = 0.013 for training set, P = 0.014 for validation set). In addition, patients in the low miR-454 expression cohort had better response to anthracycline compared to non-anthracycline chemotherapy (P = 0.056), but this difference was not observed in the high miR-454 expression cohort. Our findings indicated that miR-454 is a potential predictor of prognosis and chemotherapy response in TNBC.

Effect of nodal status on clinical outcomes of triple-negative breast cancer: a population-based study using the SEER 18 database.

Triple-negative breast cancer (TNBC) is an aggressive malignancy with a poor prognosis. Data from the Surveillance, Epidemiology and End Results database (2010-2012) were used to identify 10,771 patients with TNBC, and we assessed the effects of lymph node (LN) status on breast cancer-specific survival (BCSS) and overall survival (OS). In our study, a Kaplan-Meier plot showed that LN-negative patients (N0) had better survival outcomes than LN-positive patients and that patients with ≥10 positive LNs (N3) exhibited the worst survival outcomes regardless of tumor size. A pairwise comparison showed no difference in survival outcomes among each group stratified by tumor size. Further, for LN-positive patients with a tumor size ≤2 cm (T1) or >5 cm (T3), there were similar outcomes between patients with one to three LNs (N1) and those with four to nine LNs (N2), whereas N1 patients experienced significantly better survival outcomes than N3 patients (P<0.001). Therefore, ten metastatic lymph nodes was the cut-off value for poor prognosis. Nevertheless, for patients with a tumor size of 2-5 cm (T2), the extent of LN involvement contributed prognostic value to OS but not BCSS. In summary, we found that nodal status and tumor size exhibited distinct interaction patterns for predicting the outcomes of TNBC. These results provide deeper insight into the prognostic value of nodal status in TNBC.

Difference in characteristics and outcomes between medullary breast carcinoma and invasive ductal carcinoma: a population based study from SEER 18 database.

Medullary breast carcinoma (MBC) is a unique histological subtype of breast cancer. Our study was designed to identify difference in characteristics and outcomes between MBC and invasive ductal carcinoma (IDC), and further confirm the prognostic factors of MBC. Utilizing Surveillance, Epidemiology, and End Results (SEER), we identified 84,764 eligible patients, including 309 MBC and 84,455 IDC. Compared with the IDC group, the MBC group was associated with younger age at diagnosis, higher grade, more advanced stage, larger tumor size, and higher proportion of triple-negative breast cancer (TNBC). Kaplan-Meier analysis and univariate Cox proportional hazard regression model showed that patients with IDC had significantly better breast cancer-specific survival (BCSS) compared to MBC, but they had similar overall survival (OS). However, MBC histology was no longer a surrogate for worse BCSS or OS after 1:1 matching by age, American Joint Committee on Cancer (AJCC) stage, grade and breast subtype. In addition, it was exposed that not married status, high grade, large tumor size, positive nodal status, the subtype of TNBC and no receipt of radiation therapy were significantly associated with poor BCSS and OS. In conclusion, MBC demonstrated more aggressive behavior but similar outcomes compared to IDC, which may be determined by prognostic factors such as breast subtype. These results not only confer deeper insight into MBC but contribute to individualized and tailored therapy, and thereby may improve clinical management and outcomes.

A Prospective Evaluation of the Association between a Single Nucleotide Polymorphism rs3775291 in Toll-Like Receptor 3 and Breast Cancer Relapse.

BACKGROUND: Toll-like receptors (TLRs) regulate the balance between the innate and adaptive immune responses. Missense single nucleotide polymorphisms (SNPs) in TLRs might be functional and thus influence the risks of chronic infection and cancer development. Here, we investigated the association of two missense SNPs, rs3775291 (c.1234G>A) in the TLR3 gene and rs4833095 (c.743T>C) in the TLR1 gene, with relapse-free survival (RFS) in a cohort of prospectively observed breast cancer patients. METHODS: In this prospective observational study, rs3775291 in TLR3 and rs4833095 in TLR1 were genotyped in 715 patients with primary breast cancer in a Chinese population. RESULTS: Univariate analysis revealed that the patients with the AA genotype of rs3775291 had a shorter RFS compared with those carrying the G allele in the recessive model (P<0.01), but this finding was not observed with the dominant model (P = 0.31). The results remained significant after adjusting for the clinical parameters in the recessive model (HR = 3.53, 95% confidence interval [CI]: 1.98-6.31, P<0.01). Further survival analysis indicated that this SNP was significant in the luminal-B, triple-negative breast cancer (TNBC), and human epidermal growth factor receptor 2-positive (HER2+) patients using the recessive model but that it was not significant in the luminal-A patients. The SNP rs4833095 showed a non-significant tendency toward an increased RFS rate in the patients with the TT genotype. CONCLUSION: Our results suggest that the SNP rs3775291 in TLR3 may influence patient outcome. Further studies with larger sample sizes should be conducted to validate our findings.

Differences in breast cancer characteristics and outcomes between Caucasian and Chinese women in the US.

Chinese breast cancer patients living in the United States (US) can experience different disease patterns than Caucasians, which might allow for predicting the future epidemiology of breast cancer in China. We aimed to compare the clinicopathologic characteristics and outcomes of Caucasian and Chinese female breast cancer patients residing in the US. The study cohort consisted of 3868 Chinese and 208621 Caucasian women (diagnosed from 1990 to 2009) in the US Surveillance, Epidemiology, and End Results (SEER) database. Compared with the Caucasian patients, the US-residing Chinese patients had a younger age at diagnosis and a higher family income, remained married longer, and more frequently lived in metropolitan areas. Other tumor characteristics were similarly distributed between the two races. Compared with the Caucasians, the Chinese patients had a significantly improved overall survival (OS) but similar breast cancer-specific survival (BCSS). Our analysis suggested that US-residing Chinese patients had significant differences in age, family income, marital status and area of residence, compared with their Caucasian counterparts. No significant disparities were noted in BCSS between the two races, whereas the Chinese patients had a significantly better OS. These findings warrant further investigation and should be considered in the screening and treatment of breast cancer.