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Background: Altered body composition has been attributed to major health problems globally, particularly in patients with cancer. To date, there have not been sufficient indices for body compositions in predicting the survival of locally advanced breast cancer (LABC). Purpose: To assess the association between body composition and overall survival (OS) as well as disease-free survival (DFS) in patients with LABC. Material and Methods: A retrospective study was conducted of patients with LABC diagnosed between 2010 and 2018. Body composition parameters, including skeletal muscle and adiposity parameters, were measured using computed tomography at the L3 vertebra using in-house software developed by MATLAB and freeware Python 3.6.13. The association between body composition and OS and DFS were analyzed using a log-rank test and multivariate Cox-proportional hazard regression. Results: Of 199 patients, 72 (36%) died during the follow-up period (range = 3.8–150.7 months). Median survival was 101 months. Low visceral-to-subcutaneous ratio ≤0.3 (adjusted hazard ratio [aHR] = 2.57, 95% confidence interval [CI] = 1.51−4.37; aHR = 2.46, 95% CI = 1.33−4.56), and high composite fat (aHR = 3.26, 95% CI = 1.69−6.29; aHR = 2.19, 95% CI = 1.11−4.3) were associated with lower OS and DFS. Positive lymph nodes ≥3, progesterone receptor negative, and total radiation dose >5000 cGy significantly decreased both OS and DFS. A history of previous treatment before body composition assessment and surgery had a protective effect on OS and DFS. No association of sarcopenia, body mass index, and adiposity areas with survival outcomes was observed. Conclusion: Low visceral-to-subcutaneous ratio and high composite fat were independent prognostic factors for OS and DFS in patients with LABC. However, other body composition parameters showed no effect on survival. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine whether breast cancer patients at stage T2N0 with tumor size ≥4 cm and <4 cm. Method: Patients with T2N0 stage breast cancer diagnosed between 2010 and 2019 were analyzed in 2 groups as <4 cm (T2a) and ≥4 cm (T2b) in the study using the SEER 17 Research Plus database. The patients' clinicopathological characteristics and oncological outcomes were included. Group comparisons of prognostic factors, overall survival (OS), and cancer-specific survival (CSS) were made. Results: In this study, which involved 70971 patients, the T2a group had higher 5-year OS rate (87.2 ±.2 vs 80.8 ±.5%) and 5-year CSS rate (93.7 ±.1% vs 89.4 ±.4%) than the T2b group (P <.001). Univariate analysis revealed that the overall risk of death was 1.5 times higher in T2b than T2a (HR: 1.533 [95% CI: 1.450-1.622], P <.001), whereas multivariate analysis demonstrated the risk was 1.4 times higher (HR: 1.384 [95% CI: 1.307-1.466], P <.001). The risk of cancer-specific death was 1.7 times higher in univariate analysis (HR: 1.691 [95% CI: 1.561-1.832], P <.001) and 1.4 times higher in multivariate analysis (HR: 1.420 [95% CI: 1.309-1.541], P <.001). Conclusion: Overall survival and BCSS rates in stage T2b breast cancer patients are significantly lower than in T2a patients. Tumor size ≥4 cm in breast cancer is a negative predictor of prognosis. [ABSTRACT FROM AUTHOR]

Objective: Despite the relatively high cure rates in early-stage breast cancer, advanced and metastatic breast cancer cases are associated with more inauspicious patient outcomes. Fortunately, with the advent of cyclin-dependent kinase (CDK)4/6 inhibitors (e.g. palbociclib, ribociclib, and abemaciclib) with endocrine therapy, survival in advanced and metastatic breast cancer has appreciably improved. In the current review, we discuss these distinctions and the concomitant implications associated with the individual CDK4/6 inhibitors. Data sources: We conducted an extensive PubMed search comprising several review articles on the topic of advanced or metastatic breast cancer treatment, with specific terms that included CDK4/6 inhibitors, treatment, and breast cancer. Data summary: Palbociclib, ribociclib, and abemaciclib have exhibited superior progression-free survival differences compared to endocrine therapy alone. However, there are differences among the various CDK4/6 inhibitors with regard to overall survival, tolerability and quality of life. Conclusions: Ribociclib may be indicated for pre/perimenopausal patients, whereas abemaciclib is potentially recommended to address endocrine-resistant or visceral disease. Alternatively, palbociclib is associated with lower discontinuation rates than abemaciclib and unlike ribociclib, QTc prolongation is not observed with palbociclib. [ABSTRACT FROM AUTHOR]

Background: In retrospective studies investigating the difference in survival by gender, there are conflicting results. It was aimed to compare overall survival (OS) and breast cancer-specific survival (BCSS) in male and female breast cancer subtypes according to the prognostic staging system. Methods: Overall survival rates and BCSS rates of patients diagnosed with breast cancer between 2010 and 2019 compared by gender for all cohorts, stages, and molecular subtypes using the SEER Database. The stage has been rearranged according to the eighth edition of the AJCC. Results: 364 039 patients were included in the study..7% (n = 2503) of all breast cancers were male breast cancer. Overall survival (male: 5-year OS 73.9%, female = 5-year OS 86%) and BCSS rates (male: 5-year BCSS 78.9%, female = 5-year BCSS 94.7%) were significantly higher in females than in males for all cohorts. OS (male: 5-year OS 66.2% vs female: 5-year OS 88.3%), and BCSS (male: 5-year BCSS 88.4% vs female: 5-year 93.6%) rates were higher in hormone receptor (HR)-positive/Her2-negative female patients. Overall survival rate is higher in females in stage I (male: 5-year OS 81.5%, female: 5-year OS 92.8%), and BCSS rate is higher in stage I (male: 5-year BCSS 94.8%, female: 5-year BCSS 97.5%). Males have 2 times (HR = 2.023) higher overall mortality risk than females, but the risk of dying from breast cancer is only 1.6 times (HR = 1.596) higher. Conclusions: Breast cancer-specific mortality is significantly higher in male breast cancers, especially in the early stage, and HR-positive subtype than females. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer (BC) is one of the commonest cancers among women worldwide. Differences regarding tumor biology, presentation, genetics, and molecular subtypes may contribute to the relatively poorer prognosis among younger women. Limited information exists regarding pathologic characteristics and long-term outcomes among this group. Methods: This retrospective cohort study included 695 BC patients diagnosed over a 10-year period and investigated the clinicopathological characteristics and long-term disease outcomes among patients diagnosed at age less than or equal to 40 years compared with older ones. Cox regression analysis was performed, and Kaplan-Meier curves were generated to assess overall survival (OS). Results: Compared with the younger patients (⩽40 years) estrogen receptor (ER) and progesterone receptor (PR) expression was mainly positive in older patients (>40 years) (76.2% vs 61.3% and 64.2% vs 49.6%, respectively). The most common molecular subtype in both age groups was luminal B (44.1% in older and 40.3% in younger). A clinical complete remission after neoadjuvant therapy was observed more frequently in older patients (76.7%; N = 442) in comparison with the younger patients (66.4%; N = 79) (P =.018). Recurrence and disease progression were significantly more likely to occur among younger patients accounting for 12.6% and 29.4% of the cases, compared with 6.3% and 18.2% in older patients (P =.016 and P =.006, respectively). The overall mortality was 132 (19%) of 695, with 88% cancer-related deaths. Estrogen receptor and PR expression (P ⩽.001 and P =.003, respectively), molecular subtype (P =.002), tumor grade (P =.002), and N stage (P =.038) were the variables that were found to be significantly influenced by age. The OS was not statistically different among 2 age groups, but younger patients with luminal A molecular subtype showed significantly poor outcome (P =.019). Conclusion: Overall survival in women diagnosed with BC at age less than or equal to 40 years is not significantly worse than older patients. However, among patients with luminal A subtype, younger women had relatively poor survival. Further research is needed to understand this age-based disparity in outcomes. [ABSTRACT FROM AUTHOR]

Background: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. Methods: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. Results: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P =.246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P =.357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P =.157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P =.013). Conclusions: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients. [ABSTRACT FROM AUTHOR]

Aims: To assess the impact of the molecular subtype (MS) on the total number of CK19 mRNA copies in all positive SLN (TTL) threshold, to predict non-SLN affectation, and to compare 5 years progression-free survival (PFS) according to the risk of recurrence (ROR) group by PAM50. Methods: Cohort with infiltrating breast cancer with intra-operative metastatic SLN detected by one-step nucleic acid amplification (OSNA) assay who underwent subsequent ALND. Logistic regression was used to assess a possible interaction between TTL and MS(Triple Negative, Her-2-Enriched, Luminal A, or Luminal B), or hormone receptors (HR: positive or negative) by immunohistochemistry (IMH). Cox regression was used to compare PFS and OS in the 3 ROR groups (high, medium, or low). Results: TTL was predictive of non-SLN affectation in both univariate (OR [95% CI]: 1.72 [1.43, 2.05], P <.001) and multivariate (1.55 [95% CI: 1.04, 2.32], P =.030) models, but MS-IMH or HR-IMH, and their interactions with TTL were not (best multivariate model: HR + main effect OR 1.16 [95% CI: 0.18, 7.64], P =.874; interaction OR: 1.04 [0.7, 1.55], P =.835; univariate model: HR + main effect OR: 1.44 [95% CI: 0.85, 2.44], P =.180). PFS was lower in the high-risk ROR group (81.1%) than in the low-risk group (93.9%) (HR: 3.68 [95 CI: 1.70, 7.94], P <.001). Conclusions: our results do not provide evidence to support the utilization of subtype-specific thresholds for TTL values to make therapeutic decisions on the axilla. The ROR group was predictive of 5 years-PFS. [ABSTRACT FROM AUTHOR]

Background: The use of antibody–drug conjugates for the treatment of advanced-stage human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer (BC) has shown prominent curative effects, which has led to increased academic interest. However, the role of HER2-low expression in the prognosis of BC remains controversial. Methods: We conducted a systematic search of the PubMed, Embase, and Cochrane library databases and several oncology conferences until 20 September 2022. We used fixed- and random-effects models to calculate odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and pathological complete response (pCR) rates. Results: Overall, 26 studies encompassing 677,248 patients were included in the meta-analysis. Patients with HER2-low BC showed significantly better OS than those with HER2-zero BC in the overall population (HR = 0.90; 95% CI: 0.85–0.97) and hormone receptor-positive population (HR = 0.98; 95% CI: 0.96–0.99), whereas no significant difference was observed in the OS of the hormone receptor-negative population (p > 0.05). In addition, there was no significant difference in the DFS of the overall and hormone receptor-negative population (p > 0.05), but better DFS than those with HER2-zero BC in the hormone receptor-negative population (HR = 0.96; 95% CI: 0.94–0.99). There was also no significant difference in the PFS of the overall population, hormone receptor-positive, and hormone receptor-negative population (p > 0.05). Patients with HER2-low BC had a lower pCR rate after neoadjuvant treatment than those with HER2-zero BC. Conclusions: Compared to patients with HER2-zero BC, those with HER2-low BC had better OS in the overall population and hormone receptor-positive population, DFS in hormone receptor-positive population and lower pCR in the overall population. The biological differences between HER2-low and HER2-zero BCs, particularly in hormone receptor-positive patients, and the relationship between HER2-low expression status and prognosis need to be explored further. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nicotinamide N-methyltransferase (NNMT) and Dickkopf-1 (DKK1) play an important role in the development of breast cancer, and the purpose of this study was designed to examine the clinical and prognostic significance of NNMT and DKK1 in breast cancer. METHODS: The GEPIA2 database was used to evaluate the expression and survival of NNMT mRNA and DKK1 mRNA of breast cancer. Then an immunohistochemical study was carried out on 374 cases of breast tissue to identify the protein expression and significance of NNMT and DKK1. Next, the prognostic significance of DKK1 in breast cancer was explored by COX and Kaplan-Meier models. RESULTS: Protein NNMT expression was correlated with lymph node metastasis and histological grade (P < .05) while protein DKK1 expression was related to tumor size, pT stage, histological grade, and Ki-67 (P < .05). Protein DKK1 was related to disease-specific survival (DSS), and low DKK1 expression indicated a poor prognosis of breast cancer patients (P < .05). Combined expression of protein NNMT and protein DKK1 predicted different prognosis of DSS (P < .05). CONCLUSIONS: Nicotinamide N-methyltransferase and DKK1 were linked to breast cancer malignancy and invasion. Breast cancer patients with low DKK1 expression had a worse prognosis. Oncotypes of NNMT and DKK1 expression predicted patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Whether sentinel lymph node biopsy should be performed in patients ≥70 years old with early-stage invasive breast cancer is controversial. We examined the effect of sentinel lymph node biopsy on the treatment and outcomes in this population. Materials and Methods: In this retrospective study, patients aged ≥70 years who were treated for invasive breast cancer with sentinel lymph node biopsy followed by mastectomy or lumpectomy between 2010 and 2019 were identified from our database. Patients were compared according to sentinel lymph node status. Outcomes were analyzed using the Kaplan–Meier method and Cox multivariate analysis. Results: Of the 376 patients enrolled in this study, 311 (82.7%) were sentinel lymph node-negative and 65 (17.3%) were sentinel lymph node-positive. The median follow-up duration for all patients was 70 months. Systemic treatment and radiation were similar between sentinel lymph node-negative and -positive groups. Disease-free survival, distant disease-free survival, breast cancer-specific survival, overall survival were not significantly different between groups (88.2% vs 87.6%, 96.7% vs 94.8%, 96.2% vs 93.6%, and 93.5% vs 90.0%, respectively). Sentinel lymph node status, tumor size, chemotherapy, endocrine therapy, and adjuvant radiation were included in Cox multivariate analysis. None of the variables were found to significantly affect disease-free survival, distant disease-free survival, breast cancer-specific survival, and overall survival. Conclusions: Our analysis indicated that sentinel lymph node status may not affect systemic treatment decisions or survival in patients aged ≥70 years with breast cancer. [ABSTRACT FROM AUTHOR]

Background and Objects: Malignant phyllodes tumor of the breast (MPTB) is a rare tumor for which surgery or surgery combined with radiotherapy (RT) is the primary treatment method. However, recently, the therapeutic effect of RT on MPTB has been controversial. We aimed to explore the role of RT, chemotherapy (CT), and surgical modalities in patients with MPTB. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to select patients with MPTB who met the criteria between 2010 and 2018. Kaplan–Meier curves and Cox proportional risk regression models were used to analyze the effects of RT on MPTB patients. Based on this, we compared the effects of breast-conserving surgery (BSC) and mastectomy on the postoperative survival of MPTB. Results: A total of 298 patients with MPTB were included in this study. RT was received by 22.1% (n = 66) of the patients while 77.9% (n = 232) did not receive RT. CT was received by 4.7% (n = 14) patients while 95.3% (n = 284) did not receive CT. According to Kaplan–Meier curves, RT and CT combined resulted in a decrease in breast cancer-specific survival (BCSS) and overall survival (OS) compared to patients who did not receive RT. Mastectomy improved the OS and BCSS of the patients more than BCS). The findings of univariate and multivariate Cox regression analyses suggested that "distant metastasis", "tumor grade" and "number of positive lymph node biopsies" affected OS of breast cancer, while "distant metastasis", "tumor grade", "surgery combined with radiotherapy/surgery", and "radiotherapy/chemotherapy or not", had a significant effect on BCSS. Conclusion: RT and CT did not significantly improve the long-term survival of MPTB patients. Mastectomy improved OS and BCSS of the patient more than BCS. RT in an early stage improved early prognosis moderately in MPTB patients with tumor diameter less than 50 mm. [ABSTRACT FROM AUTHOR]

Published trials of alpelisib + fulvestrant demonstrate efficacy and high rates of adverse effects as a first-line treatment option for metastatic breast cancer and as an option after cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i). The purpose of this analysis is to determine the real-world efficacy and safety of this regimen in heavily pretreated patients. This is a retrospective cohort analysis evaluating patients receiving alpelisib + fulvestrant for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer who previously received ≤ 2 lines of therapy in the metastatic setting and those who previously received ≥ 3 lines of therapy in the metastatic setting. Adverse effects, specifically hyperglycemia, rash, and diarrhea, were reported for the entire population. Thirty-three patients were included in this analysis. Progression-free survival (PFS), overall survival, time to change in therapy, and time to discontinuation were similar in the two groups. Forty-nine percent of patients discontinued alpelisib + fulvestrant due to progression of disease, and 27% of patients discontinued treatment due to adverse effects. Hyperglycemia, rash, and diarrhea occurred at high rates: 66.7%, 45.5%, and 72.7%, respectively. All three of these adverse effects required hospitalizations and pharmacological treatment. This analysis demonstrates that the outcomes of alpelisib + fulvestrant were worse in the real-world salvage setting in HR+, HER2- metastatic breast cancer as compared to the front-line setting. The real-world tolerability of this regimen is still of great concern. [ABSTRACT FROM AUTHOR]

The prognostic significance of hypoxia markers, hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), and carbonic anhydrase IX (CAIX), was investigated in estrogen receptor (ER)-positive breast cancer patients. Immunohistochemistry determined the expression of makers in two independent ductal ER-positive cohorts (Training set, n =373 and Validation set, n =285) and was related to clinicopathological parameters and disease-free survival (DFS). In the training cohort, nuclear HIF-1α (1) was independently associated with poorer DFS in luminal A tumors [hazard ratio (HR) = 0.53 95% confidence interval (CI): 0.30–0.94, p =0.030]. In the validation cohort, both HIF-1α (1) and CAIX were independently associated with decreased DFS in the entire cohort (HR = 1.85 95% CI: 1.10–3.11, p =0.019; HR = 1.74 95% CI: 1.08–2.82, p =0.023), in luminal A disease (HR = 1.98 95% CI: 1.02–3.83, p =0.042), and in luminal B disease (HR = 2.75 95% CI: 1.66–4.55, p <0.001), respectively. Taken together, elevated cytoplasmic HIF-1α (1) expression was an independent prognostic factor in luminal A disease, whereas CAIX was an independent prognostic factor in luminal B disease. Further work in large tissue cohorts is required. [ABSTRACT FROM AUTHOR]

Introduction: The MONALEESA-7 trial compared ribociclib plus endocrine therapy (ET) with placebo as first-line treatment of advanced luminal/HER2-negative breast cancer (ABC) in premenopausal and perimenopausal women (age <50 years) and showed significant benefits to progression-free survival and overall survival. This study aimed to compare the cost-effectiveness of ribociclib + ET versus ET alone in patients with ABC from the perspective of the Brazilian public national health system. Methods: We calculated the incremental cost-effectiveness ratio (ICER) using a Markov model with progression-free survival, post-progression survival, and death states. We expressed ICER as incremental costs per progression-free life-year (PFLY) and quality-adjusted life-year (QALY) gained in a 10-year time horizon. We used parametric survival distributions fit to MONALEESA-7 data to generate survival distributions for progression-free and post-progression survival. The largest British preference study in breast cancer served as the basis to estimate health-state utilities. We estimated direct costs (ABC treatment, follow-up, monitoring, and adverse events) using Brazilian-specific values from public sources. An expert consensus panel determined the resource patterns required. We applied annual discounts of 5% to costs and QALYs. Results: Ribociclib + ET resulted in an incremental gain of 1.03 PFLYs and 0.80 QALYs at a cost of $37,319.31. The ICER of ribociclib + ET versus ET was $36,379.41 per PFLY gained and $46,590.79 per QALY gained. In deterministic sensitivity analysis, results were primarily affected by the annual discount rate, followed by the cost of ribociclib. In probabilistic sensitivity analysis, simulations agreed with the base-case. Conclusion: Ribociclib increased PFLYs and QALYs in patients with HR+/HER2− ABC when added to ET. Because Brazil does not have a formally defined cost-effectiveness threshold, other domains need to be considered for incorporation decisions, such as disease burden and humanistic impact on this young, economically active population. These findings may be useful in discussions for incorporation of ribociclib into the Brazilian public health system. [ABSTRACT FROM AUTHOR]

Worldwide breast cancer ranks first in mortality and incidence rates in women over 20 years old. Rather than one disease, breast cancer is a heterogeneous group of diseases that express distinct molecular profiles. Neoadjuvant chemotherapy is an important therapeutic strategy for breast cancer patients independently of their molecular subtype, with the drawback of resistance development. In addition, chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. Although great efforts have been made to find diagnostic and prognostic biomarkers for breast cancer and for response to targeted and immune therapy for this pathology, little has been explored regarding biomarkers of response to anthracyclines and taxanes based neoadjuvant chemotherapy. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to identify differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who were candidates for neoadjuvant chemotherapy were enrolled in this study. After treatment and according to their pathological response, they were assigned as sensitive or resistant. To evaluate DEGs, Gene Ontology, Kyoto Encyclopedia Gene and Genome (KEGG), and protein–protein interactions, RNA-seq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found, and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine–cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study and the ductal carcinoma dataset of The Cancer Genome Atlas (TCGA) database. Nine DEGs correlated with overall survival, of which the subexpression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN, KRT15, HLA-A, and the overexpression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival. [ABSTRACT FROM AUTHOR]

Ultrahigh-dimensional gene features are often collected in modern cancer studies in which the number of gene features p is extremely larger than sample size n. While gene expression patterns have been shown to be related to patients' survival in microarray-based gene expression studies, one has to deal with the challenges of ultrahigh-dimensional genetic predictors for survival predicting and genetic understanding of the disease in precision medicine. The problem becomes more complicated when two types of survival endpoints, distant metastasis-free survival and overall survival, are of interest in the study and outcome data can be subject to semi-competing risks due to the fact that distant metastasis-free survival is possibly censored by overall survival but not vice versa. Our focus in this paper is to extract important features, which have great impacts on both distant metastasis-free survival and overall survival jointly, from massive gene expression data in the semi-competing risks setting. We propose a model-free screening method based on the ranking of the correlation between gene features and the joint survival function of two endpoints. The method accounts for the relationship between two endpoints in a simply defined utility measure that is easy to understand and calculate. We show its favorable theoretical properties such as the sure screening and ranking consistency, and evaluate its finite sample performance through extensive simulation studies. Finally, an application to classifying breast cancer data clearly demonstrates the utility of the proposed method in practice. [ABSTRACT FROM AUTHOR]

Background: Completion of surgical resection and adjuvant/neoadjuvant treatments (chemotherapy, radiation, and endocrine therapy) is necessary to achieve optimal outcomes in invasive breast cancer. The objective of this study was to determine the characteristics of patients refusing treatment and to analyze the impact of refusal on survival.Study Design: A retrospective cohort study of invasive breast cancer cases diagnosed 2004-2016 was performed utilizing the National Cancer Database.Results: Of 2 058 568 cases comprising the study cohort, .6% refused recommended surgery, 14.1% refused chemotherapy, 5.5% refused radiation, and 6.3% refused endocrine therapy. Patients refusing therapy were older and more likely uninsured; they did not live farther from the treating hospital. Racial disparities were also associated with refusal. Surgery refusal had the highest hazard ratio for mortality (2.7; 95% CI: 2.5-3.0, P < .001) compared to chemotherapy (1.3; 95% CI: 1.3-1.4, P < .001), radiation (1.8; 95% CI: 1.7-1.9, P < .001), and endocrine therapy (1.5; 95% CI: 1.4-1.6, P < .001) independent of race, insurance, receptor status, and stage.Conclusion: This study demonstrates significant associations with refusal of breast cancer treatment and quantifies the impact on mortality, which may help to identify at-risk groups for whom interventions could prevent increases in mortality associated with declining treatment. [ABSTRACT FROM AUTHOR]

Background: Cancer Program Practice Profile Reports (CP3R) metrics were released by the Commission on Cancer to provide standards for high-quality care. One metric is the recommendation of combination chemotherapy or chemo-immunotherapy (CIT) within 120 days of diagnosis for women under 70 with AJCC T1cN0M0 or Stage IB-III HER2+ or hormone receptor negative breast cancer ([Multi-agent chemotherapy] MAC). Our study assesses national concordance rates for MAC and CIT.Methods: The National Cancer Database was queried from 2004-2014.Results: 122,045 patients met criteria, of whom treatment for 101,800 (83.4%) patients was concordant with MAC and CIT. Treatment concordance increased from 75.7% in 2004 to 89.5% in 2014. For HER2+ patients, use of CIT treatment downtrended with progression of pathological stage, from 70.1% (stage I) to 58.1% (stage III). Mean overall survival of patients whose treatment was concordant with MAC and CIT was longer than that of patients who were non-concordant (146.6 vs 143.8 months, P <.01). On Cox regression, there was a survival benefit for concordant patients who were treated at academic hospitals (HR .89, 95% CI 0.802-.976) and had private insurance (HR .76, 95% CI 0.65-.89).Conclusion: Compliance with MAC and CIT has improved over the past decade and is associated with a significant improvement in overall survival. [ABSTRACT FROM AUTHOR]

Background: High cathepsin D has been associated with poor prognosis in breast cancer; however, the results of many studies are controversial. Here, we assessed the association between high cathepsin D levels and worse breast cancer prognosis by conducting a meta-analysis. Methods: A comprehensive search strategy was used to search relevant literature in PUBMED and EMBASE by September 2018. The meta-analysis was performed in Review Manager 5.3 using hazard ratios (HRs) with 95% confidence intervals (CIs). Results: A total of 15,355 breast cancer patients from 26 eligible studies were included in this meta-analysis. Significant associations between elevated high cathepsin D and poor overall survival (OS) (HR = 1.61, 95% CI: 1.35–1.92, p < 0.0001) and disease-free survival (DFS) (HR = 1.52, 95% CI: 1.31–2.18, p < 0.001) were observed. In the subgroup analysis for DFS, high cathepsin D was significantly associated with poor prognosis in node-positive patients (HR = 1.38, 95% CI: 1.25–1.71, p < 0.00001), node-negative patients (HR = 1.78, 95% CI: 1.39–2.27, p < 0.0001), early stage patients (HR = 1.73, 95% CI: 1.34–2.23, p < 0.0001), and treated with chemotherapy patients (HR = 1.60, 95% CI: 1.21–2.12, p < 0.001). Interestingly, patients treated with tamoxifen had a low risk of relapse when their cathepsin D levels were high (HR = 0.71, 95% CI: 0.52–0.98, p = 0.04) and a high risk of relapse when their cathepsin D levels were low (HR = 1.50, 95% CI: 1.22–1.85, p = 0.0001). Conclusions: Our meta-analysis suggests that high expression levels of cathepsin D are associated with a poor prognosis in breast cancer. Based on our subgroup analysis, we believe that cathepsin D can act as a marker for poor breast cancer prognosis and also as a therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]

Studies have shown that vitamin D could have a role in breast cancer survival; however, the evidence of the relationship between patients’ vitamin D levels and their survival has been inconsistent. This meta-analysis explores possible dose-response relationships between vitamin D levels and overall survival by allowing for differences in vitamin D levels among populations of the various studies. Studies relating vitamin D (25-OH-D [25-hydroxyvitamin D]) levels in breast cancer patients with their survival were identified by searching PubMed and Embase. A pooled HR (hazard ratio) comparing the highest with the lowest category of circulating 25-OH-D levels were synthesized using the Mantel-Haenszel method under a fixed-effects model. A two-stage fixed-effects dose-response model including both linear (a log-linear dose-response regression) and nonlinear (a restricted cubic spline regression) models were used to further explore possible dose-response relationships. Six studies with a total number of 5984 patients were identified. A pooled HR comparing the highest with the lowest category of circulating 25-OH-D levels under a fixed-effects model was 0.67 (95% confidence interval = 0.56-0.79, P < .001). Utilizing a dose-response meta-analysis, the pooled HR for overall survival in breast cancer patients was 0.994 (per 1 nmol/L), Pfor linear trend < .001. At or above a 23.3 nmol/L threshold, for a 10 nmol/L, 20 nmol/L, or 25 nmol/L increment in circulating 25-OH-D levels, the risk of breast cancer overall mortality decreased by 6%, 12%, and 14%, respectively. There was no significant nonlinearity in the relationship between overall survival and circulating 25-OH-D levels. Our findings suggest that there is a highly significant linear dose-response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer. However, better designed prospective cohort studies and clinical trials are needed to further confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Eribulin mesylate is a non-taxane microtubule inhibitor which can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of eribulin monotherapy in heavily pretreated patients with MBC. Methods: In this study, a total of 45 eligible patients with MBC who received eribulin in HCG Cancer Speciality Center from November 2014 to March 2016 were prospectively analyzed. Breslow (generalized Wilcoxon) survival analysis was carried out for progression-free survival and for overall survival. Patients were excluded if they had not taken treatment for 3 cycles and defaulted/expired during the treatment. Results: In this study, median age of patients was 52 years. A total of 27 (60%) patients had estrogen receptor and progesterone receptor (PR) positive primary tumors, whereas HER2 was overexpressed or amplified in 7 (15.6%); a triple negative subtype was recorded in 13 patients (28.9%). Regarding toxicity, 30 patients (66.67%) tolerated treatment well and 3 patients (6.67%) got anemia, 6 patients (13.3%) experienced neutropenia, and 7 (15.62%) patients had neurological toxicity. About 14 (31.1%) patients showed PR, 12 (26.7%) patients had stable disease (SD), whereas 19 (42.25%) patients showed progression disease (PD). Response evaluation at 6 cycles was possible in 18 patients and revealed that 4 (22.5%) patients showed PR, 10 (55.5%) patients had SD, whereas 4 (22.2%) patients had PD. Progression-free survival of the overall study population was 3.95 months. Conclusions: Eribulin mesylate is efficacious and tolerable chemotherapy as second- and third-line treatment options for MBC. [ABSTRACT FROM AUTHOR]