Dataset Information

Breast Subtypes and Prognosis of Breast Cancer Patients With Initial Bone Metastasis: A Population-Based Study.

ABSTRACT:

Background

Metastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases.

Methods

From 2010 to 2015, 6,860 breast cancer patients diagnosed with initial bone metastasis were analyzed from Surveillance, Epidemiology, and End Results (SEER) database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk groups differentiated by nomogram.

Results

Hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) positive patients showed the best outcome compared to other subtypes. Patients of younger age (<60 years old), white race, lower grade, lower T stage (<=T2), not combining visceral metastasis tended to have better outcome. About 37% (2,249) patients received surgery of primary tumor. Patients of all subtypes could benefit from surgery. Patients of bone-only metastases (BOM), bone and liver metastases, bone and lung metastases also showed superior survival time if surgery was performed. However, patients of bone and brain metastasis could not benefit from surgery (p = 0.05). The C-index of nomogram was 0.66. Cutoff values of nomogram point were identified as 87 and 157 points, which divided all patients into low-, intermediate- and high-risk groups. Patients of all groups showed better overall survival when receiving surgery.

Conclusion

Our study has provided population-based prognostic analysis in patients with initial bone metastatic breast cancer and constructed a predicting nomogram with good accuracy. The finding of potential benefit of surgery to overall survival will cast some lights on the treatment tactics of this group of patients.

SUBMITTER: Liu D

PROVIDER: S-EPMC7739957 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Breast Subtypes and Prognosis of Breast Cancer Patients With Initial Bone Metastasis: A Population-Based Study.

Liu Deyue D Wu Jiayi J Lin Caijin C Andriani Lisa L Ding Shuning S Shen Kunwei K Zhu Li L

Frontiers in oncology 20201202

<h4>Background</h4>Metastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases.<h4>Methods</h4>From 2010 to 2015, 6,860 breast cancer patients diagnosed with initial bone metastasis were analyzed from Surveillance, Epidemiology, and End Results (SEER) database. Univa ...[more]

PMID: 33344236

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Project description:Background Bone is the most common metastatic site of patients with advanced breast cancer and the survival time is their primary concern; however, we lack accurate predictive models in clinical practice. In addition to this, primary surgery for breast cancer patients with bone metastases is still controversial. Method The data used for analysis in this study were obtained from the SEER database (2010–2019). We made a COX regression analysis to identify prognostic factors of patients with bone metastatic breast cancer (BMBC). Through cross-validation, we constructed an XGBoost model to predicting survival in patients with BMBC. We also investigated the prognosis of patients treated with neoadjuvant chemotherapy plus surgical and chemotherapy alone using propensity score matching and K–M survival analysis. Results Our validation results showed that the model has high sensitivity, specificity, and correctness, and it is the most accurate one to predict the survival of patients with BMBC (1-year AUC = 0.818, 3-year AUC = 0.798, and 5-year survival AUC = 0.791). The sensitivity of the 1-year model was higher (0.79), while the specificity of the 5-year model was higher (0.86). Interestingly, we found that if the time from diagnosis to therapy was ≥1 month, patients with BMBC had even better survival than those who started treatment immediately (HR = 0.920, 95%CI 0.869–0.974, P < 0.01). The BMBC patients with an income of more than USD$70,000 had better OS (HR = 0.814, 95%CI 0.745–0.890, P < 0.001) and BCSS (HR = 0.808 95%CI 0.735–0.889, P < 0.001) than who with income of < USD$50,000. We also found that compared with chemotherapy alone, neoadjuvant chemotherapy plus surgical treatment significantly improved OS and BCSS in all molecular subtypes of patients with BMBC, while only the patients with bone metastases only, bone and liver metastases, bone and lung metastases could benefit from neoadjuvant chemotherapy plus surgical treatment. Conclusion We constructed an AI model to provide a quantitative method to predict the survival of patients with BMBC, and our validation results indicate that this model should be highly reproducible in a similar patient population. We also identified potential prognostic factors for patients with BMBC and suggested that primary surgery followed by neoadjuvant chemotherapy might increase survival in a selected subgroup of patients.

Project description:INTRODUCTION:Population-based data on the incidence and prognosis of bone metastases at diagnosis of breast cancer are currently limited. Hence, we conducted this study to analyze the incidence proportions and prognostic factors of patients with breast cancer and bone metastases at the time of cancer diagnosis. MATERIALS AND METHODS:Patients with primary invasive breast cancer and bone metastases at initial diagnosis between 2010 and 2014 were identified using the Surveillance, Epidemiology, and End Results (SEER) dataset and Fudan University Shanghai Cancer Center (FUSCC) cohort. Multivariable logistic regression was performed to identify predictors of the presence of bone metastases at diagnosis. Univariate and multivariate analyses were performed to determine the effects of each variable on survival. RESULTS:Of 229, 195 patients from SEER database included in the analysis, 8295 patients had bone metastases at initial diagnosis, reflecting 3.6% of the entire study population, and 65.1% of the subset with metastatic disease to any distant site. Patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative represented the highest incidence proportions among patients with metastatic disease (73.9%). Among entire cohort, multivariable logistic regression identified eight factors as predictors of the presence of bone metastases at diagnosis. Median OS for the patients with bone metastases in SEER and FUSCC cohorts was 30.0 and 68.2 months, respectively. Patients with HR-positive HER2-positive subtype had the longest median OS, and patients with triple-negative subtype showed the shortest median OS. Multivariable Cox model in SEER cohort confirmed age, histology, grade, tumor subtype, extraosseous metastatic sites, history of primary surgery, insurance status, marital status, and income as independent prognostic factors for both OS and BCSS. CONCLUSIONS:The findings of this study provide population-based estimates of the incidence and prognosis for patients with bone metastases at initial diagnosis of breast cancer.

Project description:IntroductionPrevious studies in mouse models and pilot epidemiology studies have demonstrated that inherited polymorphisms are associated with inherited risk of tumor progression and poor outcome in human breast cancer. To extend these studies and gain better understanding of the function of inherited polymorphism in breast cancer progression, a validation prognosis study was performed in a large independent breast cancer patient population.MethodsThe study population consisted of 1863 Dutch patients with operable primary breast cancer from Rotterdam, The Netherlands. Genomic DNA was genotyped for the missense Pro436Leu RRP1B single nucleotide polymorphism (SNP) rs9306160 and the intronic SIPA1 SNP rs2448490 by SNP-specific PCR.ResultsA significant association of variants in RRP1B with metastasis-free survival was observed (P = 0.012), validating the role of RRP1B with inherited metastatic susceptibility. Stratification of patients revealed that association with patients' survival was found to be specifically restricted to estrogen receptor positive, lymph node-negative (ER+/LN-) patients (P = 0.011). The specific association with metastasis-free survival only in ER+/LN- patients was replicated for SIPA1, a second metastasis susceptibility gene known to physically interact with RRP1B (P = 0.006). Combining the genotypes of these two genes resulted in the significant ability to discriminate patients with poor metastasis-free survival (HR: 0.40, 95% CI: 0.24 to 0.68, P = 0.001).ConclusionsThese results validate SIPA1 and RRP1B as metastasis susceptibility genes and suggest that genotyping assays may be a useful supplement to other clinical and molecular indicators of prognosis. The results also suggest that lymphatic and hematogeneous metastases are genetically distinct that may involve different mechanisms. If true, these results suggest that metastatic disease, like primary breast cancer, may be multiple diseases and that stratification of late stage patients may therefore be required to fully understand breast cancer progression and metastasis.

Project description:BACKGROUND:Bone is a preferential site for prostate cancer (PCa) metastasis. However, sites of synchronous distant metastases in PCa patients with bone metastases at initial diagnosis and their impacts on prognosis are still unclear, limiting our ability to better stratify and treat the patients. In this study, we examined the sites of synchronous extra-skeletal metastases in de novo PCa patients with bone metastases and their associated prognoses. METHODS:In total, 16,643 de novo PCa patients with bone metastases from the SEER database were included. After stratification of metastatic sites (bone, lung, liver, and brain) and treatment modalities, overall survival (OS) and independent predictors of OS, were analyzed. RESULTS:Lung was the most frequent site of synchronous metastases, followed by liver, while brain metastases were relatively uncommon. Patients with bone-only metastases showed the longest mean survival time (35.87 months, p?<?0.001), followed by patients with bone and lung metastases (30.74 months, p?<?0.001). Patients with bone and liver metastases had the shortest mean survival time (17.39 months, p?<?0.001). Age?>?70 years, unmarried status, high tumor grade, prostate-specific antigen (PSA)?>?50 ng/ml, and Gleason score???8 were associated with poor OS (all p?<?0.01). Asian or Pacific Islander ethnic background was associated with a favorable OS (all p?<?0.01). Chemotherapy improved OS in patients without brain metastases (all p?<?0.05). For patients with bone-only metastases, radical prostatectomy (RP) (HR, 0.339; 95% CI 0.231-0.495; p?<?0.001), brachytherapy (BT) (HR, 0.567; 95% CI 0.388-0.829; p?=?0.003), and chemotherapy (HR, 0.850; 95% CI 0.781-0.924; p?<?0.001) were associated with prolonged OS. CONCLUSIONS:Age, race, tumor grade, PSA, Gleason score, sites of synchronous extra-skeletal metastases, as well as treatment modalities affected OS in newly diagnosed PCa patients with bone metastases. Synchronous liver metastases were associated with poor OS. Chemotherapy improved OS in patients without brain metastases. RP and BT improved OS in patients with bone-only metastases. Further investigation is warranted to validate these findings.

Project description:BackgroundBreast cancer is one of the most common cancer in women and a proportion of patients experiences brain metastases with poor prognosis. The study aimed to construct a novel predictive clinical model to evaluate the overall survival (OS) of patients with postoperative brain metastasis of breast cancer (BCBM) and validate its effectiveness.MethodsFrom 2010 to 2020, a total of 310 female patients with BCBM were diagnosed in The Affiliated Cancer Hospital of Xinjiang Medical University, and they were randomly assigned to the training cohort and the validation cohort. Data of another 173 BCBM patients were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database as an external validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) Cox regression model was used to determine the fundamental clinical predictive indicators and the nomogram was constructed to predict OS. The model capability was assessed using receiver operating characteristic, C-index, and calibration curves. Kaplan-Meier survival analysis was performed to evaluate clinical effectiveness of the risk stratification system in the model. The accuracy and prediction capability of the model were verified using the validation and SEER cohorts.ResultsLASSO Cox regression analysis revealed that lymph node metastasis, molecular subtype, tumor size, chemotherapy, radiotherapy, and lung metastasis were statistically significantly correlated with BCBM. The C-indexes of the survival nomogram in the training, validation, and SEER cohorts were 0.714, 0.710, and 0.670, respectively, which showed good prediction capability. The calibration curves demonstrated that the nomogram had great forecast precision, and a dynamic diagram was drawn to increase the maneuverability of the results. The Risk Stratification System showed that the OS of low-risk patients was considerably better than that of high-risk patients ( P < 0.001).ConclusionThe nomogram prediction model constructed in this study has a good predictive value, which can effectively evaluate the survival rate of patients with postoperative BCBM.

Dataset Information

Breast Subtypes and Prognosis of Breast Cancer Patients With Initial Bone Metastasis: A Population-Based Study.

Background

Methods

Results

Conclusion

Publications

Breast Subtypes and Prognosis of Breast Cancer Patients With Initial Bone Metastasis: A Population-Based Study.

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