BRENDA-Score, a Highly Significant, Internally and Externally Validated Prognostic Marker for Metastatic Recurrence: Analysis of 10,449 Primary Breast Cancer Patients

Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project [1]. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell’s c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3); intermediate risk: HR = 5.0, 95%CI.(3.6–6.9); high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival.

Download Full-text

Nomogram for Predicting the Overall Survival and Cancer-Specific Survival of Patients with Occult Breast Cancer: A Population-Based Study

10.21203/rs.3.rs-415600/v1 ◽

2021 ◽

Author(s):

Yang-Yu Huang ◽

Guowei Ma ◽

Shen-Hua Liang ◽

Lei-Lei Wu ◽

Xuan Liu

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Cancer Patients ◽

Subgroup Analysis ◽

External Validation ◽

Breast Cancer Patients ◽

Cancer Specific Survival ◽

Occult Breast Cancer ◽

Training Cohort

Abstract Background: Occult breast cancer is a rare breast tumor, whose prognostic nomogram model has not been established. Thus, we aim to develop and validate a nomogram for evaluating the overall survival (OS) and cancer-specific survival (CSS) of patients with occult breast cancer. Methods: Between 2004 and 2015, 704 eligible occult breast cancer patients were screened from the Surveillance, Epidemiology, and End Results (SEER) database using specific inclusion and exclusion criteria and then included in the surveillance. They were randomly divided into a training cohort (n = 494) and a validation cohort (N = 210). Univariate and multivariate Cox analyses were performed to explore independent prognostic factors and establish two survival-related nomograms. Area under the curve (AUC), consistency index (C index), internal and external validation calibration curve, decision curve analysis (DCA), Kaplan-Meier analysis, and subgroup analysis were used to evaluate the nomogram. Results: A total of seven variables were considered to be independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS): age, chemotherapy, radiotherapy, Progesterone receptor (PR) status, N stage, number of lymph node examinations, and number of positive lymph nodes. In the training cohort, the OS nomogram-predicted AUC for three, five, and ten years were 0.792, 0.775, and 0.783, respectively, while those of the CSS nomogram were 0.807, 0.817, and 0.812, respectively. The calibration chart showed excellent agreement between the actual and the nomogram-predicted survival rates in both the training and validation cohorts. The C-index values of the OS nomogram in the training and validation cohorts were 0.762 and 0.782, respectively, while those of the CSS nomogram were 0.786 and 0.816, respectively. DCA and subgroup analysis proved the usefulness of nomograms. Conclusion: The developed nomogram provided a comprehensive visual model of the risk of each prognostic factor. It can be conveniently used as a personalized prediction tool for the prognosis of occult breast cancer patients.

Download Full-text

NKX6.1 Expression is Associated With The Prognosis in Breast Cancer.

10.21203/rs.3.rs-47888/v1 ◽

2020 ◽

Author(s):

Jie Zhang ◽

Sujie Zhang ◽

Xiaoyan Li ◽

Fan Zhang ◽

Lei Zhao

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Cox Regression ◽

Expression Level ◽

Rank Test ◽

Breast Cancer Patients ◽

Cox Regression Analysis ◽

Log Rank Test ◽

Cancer Tissues

Abstract Background: Breast cancer is the most common cancer among women in the world. NKX6.1 is proved to be involved in several human cancers, but fewer researches have reported the functional roles of NKX6.1 in breast cancer. In this study, we investigated the clinical significance of NKX6.1 expression in breast cancer prognosis.Methods: The expression level of NKX6.1 in breast cancer tissues and paired non-cancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was applied to evaluate the relationship between NKX6.1 expression and clinicopathologic parameters. The overall survival of breast cancer patients were analyzed by Kaplan-Meier method with log rank test. Additionally, cox regression analysis was used for prognosis analysis.Results: NKX6.1 expression level is increased in breast cancer tissues (P<0.001). Moreover, the elevated levels were significantly correlated with tumor size (P=0.002), TNM stage (P=0.018) and lymph node metastasis (P=0.007). In addition, breast cancer patients with high NKX6.1 level had a poorer overall survival than those with low level (log rank test, P=0.001). NKX6.1 was an independent prognostic factor for breast cancer (HR=2.961, 95%CI=1.368-6.411, P=0.006).Conclusions: NKX6.1 is up-regulated in breast cancer, which may be a potential prognostic biomarker for the cancer.

Download Full-text

Chemotherapy for T1 pN0M0 Breast Cancer Patients: A Propensity Score Matching Study Based on SEER Database and External Data

10.21203/rs.3.rs-304571/v1 ◽

2021 ◽

Author(s):

Kaiwen Shen ◽

Longdi Yao ◽

Huihua Cao ◽

Ximing Gu ◽

Jie Wang ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Molecular Subtypes ◽

External Validation ◽

Tumor Grade ◽

Seer Database ◽

Breast Cancer Patients ◽

Grade Ii ◽

Grade Iii

Abstract Background There is no definitive, unified view on chemotherapy for T1 pN0M0 breast cancer. Our study explored the effects of chemotherapy on T1 pN0M0 breast cancer. Methods 75,139 patients diagnosed with T1 pN0M0 breast cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analyses were performed to investigate the effects of chemotherapy on T1a, T1b, and T1c pN0M0 breast cancer, various tumor grades, and four molecular subtypes. Propensity score matching (PSM) was used to eliminate confounding factors and further verify the results between chemotherapy and no chemotherapy. Finally, 545 T1pN0M0 breast cancer patients treated at the Northern Jiangsu People’s Hospital were included for external validation. Univariate and multivariate Cox analyses were used to confirm the role of chemotherapy in T1a, T1b, and T1c pN0M0 breast cancer. Survival curves were plotted using the Kaplan–Meier method for tumor grades and molecular subtypes. Results Chemotherapy demonstrated a statistically significant improvement in T1b and T1c breast cancer, not in T1a breast cancer. With T1b breast cancer, chemotherapy had effects on grade III and molecular subtypes hormone receptor+ [HR+]/human epidermal growth factor receptor 2+ [HER2+], HR-/HER2+, and HR-/HER2-. Chemotherapy was beneficial to overall survival for grade II/III and T1c breast cancer. After PSM, identical results were obtained. We also obtained similar results with external validation, except that chemotherapy made a difference in grade II and T1b breast cancer of external validation. Conclusion Partial T1 pN0M0 breast cancer patients with tumor grade III T1b pN0M0 except HR+/HER2-, those with tumor grade II and III T1c pN0M0 can obtain overall survival benefits from chemotherapy.

Download Full-text

Faculty Opinions recommendation of Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1145093.602227 ◽

2009 ◽

Author(s):

Gilberto Schwartsmann ◽

Fabio Leal

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Overall Survival ◽

Cancer Patients ◽

Primary Breast Cancer ◽

Breast Cancer Patients ◽

Long Term Follow Up ◽

Oral Clodronate

Download Full-text

Faculty Opinions recommendation of Time trends of overall survival among metastatic breast cancer patients in the real-life ESME cohort.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733058465.793562860 ◽

2019 ◽

Author(s):

Sherene Loi

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Time Trends ◽

Real Life ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

The Real

Download Full-text

Clinical impact of PTEN methylation status as a prognostic marker for breast cancer

Journal of Genetic Engineering and Biotechnology ◽

10.1186/s43141-021-00169-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Amal Ramadan ◽

Maha Hashim ◽

Amr Abouzid ◽

Menha Swellam

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Markers ◽

Prognostic Marker ◽

Methylation Status ◽

Clinical Impact ◽

Breast Cancer Patients ◽

Duct Carcinoma ◽

Cancer Group ◽

And Control

Abstract Background Aberrant DNA methylation of phosphatase and tensin homolog (PTEN) gene has been found in many cancers. The object of this study was to evaluate the clinical impact of PTEN methylation as a prognostic marker in breast cancer. The study includes 153 newly diagnosed females, and they were divided according to their clinical diagnosis into breast cancer patients (n = 112) and females with benign breast lesion (n = 41). A group of healthy individuals (n = 25) were recruited as control individuals. Breast cancer patients were categorized into early stage (0–I, n = 48) and late stage (II–III, n = 64), and graded into low grade (I–II, n = 42) and high grade (III, n = 70). Their pathological types were invasive duct carcinoma (IDC) (n = 66) and duct carcinoma in situ (DCI) (n = 46). Tumor markers (CEA and CA15.3) were detected using ELISA. DNA was taken away from the blood, and the PTEN promoter methylation level was evaluated using the EpiTect Methyl II PCR method. Results The findings revealed the superiority of PTEN methylation status as a good discriminator of the cancer group from the other two groups (benign and control) with its highest AUC and increased sensitivity (96.4%) and specificity (100%) over tumor markers (50% and 84% for CEA and 49.1% and 86.4% for CA15.3), respectively. The frequency of PTEN methylation was 96.4% of breast cancer patients and none of the benign and controls showed PTEN methylation and the means of PTEN methylation (87 ± 0.6) were significantly increased in blood samples of breast cancer group as compared to both benign and control groups (25 ± 0.7 and 12.6 ± 0.3), respectively. Methylation levels of PTEN were higher in the blood of patients with ER-positive than in patients with ER-negative cancers (P = 0.007) and in HER2 positive vs. HER2 negative tumors (P = 0.001). The Kaplan-Meier analysis recognizes PTEN methylation status as a significant forecaster of bad progression-free survival (PFS) and overall survival (OS), after 40 months follow-up. Conclusions PETN methylation could be supposed as one of the epigenetic aspects influencing the breast cancer prognosis that might foretell more aggressive actions and worse results in breast cancer patients.

Download Full-text

Multistate model for pharmacometric analyses of overall survival in HER2‐negative breast cancer patients treated with docetaxel

CPT Pharmacometrics & Systems Pharmacology ◽

10.1002/psp4.12693 ◽

2021 ◽

Author(s):

Sreenath M. Krishnan ◽

Lena E. Friberg ◽

René Bruno ◽

Ulrich Beyer ◽

Jin Y. Jin ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Multistate Model

Download Full-text

Lipoplatin Treatment in Lung and Breast Cancer

Chemotherapy Research and Practice ◽

10.1155/2011/125192 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Manuela Fantini ◽

Lorenzo Gianni ◽

Carlotta Santelmo ◽

Fabrizio Drudi ◽

Cinzia Castellani ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Triple Negative ◽

Response Rate ◽

Toxicity Profile ◽

Phase 2 ◽

Breast Cancer Patients ◽

Phase 3 ◽

Cisplatin Analogues

The introduction of cisplatin in cancer treatment represents an important achievement in the oncologic field. Many types of cancers are now treated with this drug, and in testicular cancer patients major results are reached. Since 1965, other compounds were disovered and among them carboplatin and oxaliplatin are the main Cisplatin analogues showing similar clinical efficacy with a safer toxicity profile. Lipoplatin is a new liposomal cisplatin formulation which seems to have these characteristics. Lipoplatin was shown to be effective in NSCLC both in phase 2 and phase 3 trials, with the same response rate of Cisplatin, a comparable overall survival but less toxicity. A new protocol aiming to elucidate the double capacity of Lipoplatin to act as a chemotherapeutic and angiogenetic agent in triple-negative breast cancer patients is upcoming.

Download Full-text

Relationship Between Obesity and Pathologic Response to Neoadjuvant Chemotherapy Among Women With Operable Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.14.4527 ◽

2008 ◽

Vol 26 (25) ◽

pp. 4072-4077 ◽

Cited By ~ 106

Author(s):

Jennifer K. Litton ◽

Ana M. Gonzalez-Angulo ◽

Carla L. Warneke ◽

Aman U. Buzdar ◽

Shu-Wan Kau ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Pathologic Complete Response ◽

Operable Breast Cancer ◽

Obese Patients ◽

Breast Cancer Patients ◽

Significant Difference ◽

Response To Neoadjuvant Chemotherapy

Purpose To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer. Patients and Methods From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI of 25 to < 30 kg/m2), or normal/underweight (BMI < 25 kg/m2). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer–specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided. Results Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years. Conclusion Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.

Download Full-text