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Clinicopathological and Treatment-Associated Prognostic Factors in Patients with Breast Cancer Leptomeningeal Metastases in Relation to Tumor Biology.

ABSTRACT: BACKGROUND:Breast cancer (BC) is one of the solid tumors most commonly associated with leptomeningeal disease (LMD). LMD carries a devastating prognosis; however, disease presentation and prognostic factors are uncertain. SUBJECTS, MATERIALS, AND METHODS:In order to describe patient characteristics, treatment patterns, and factors associated with survival in a contemporary multicentric cohort, 153 consecutive BC patients diagnosed with LMD at two European institutions (2002-2017) were included. Time to LMD and overall survival (OS) after LMD diagnosis were evaluated using the Kaplan-Meier method and Cox proportional hazards models. RESULTS:Median age at LMD diagnosis was 58 years (25-84). Tumor phenotype distribution was as follows: hormone receptor (HR) positive (HR+)/human epidermal growth receptor 2 (HER2) negative 51.0%, triple-negative 15.0%, HR+/HER2 positive (HER2+) 13.1% and HR negative/HER2+ 7.2%. Most patients received active anticancer treatments (radiation therapy [RT] n = 42, systemic therapy n = 110, intrathecal treatment n = 103).Median OS was 3.9 months (95% confidence interval [CI] 2.4-5.5). Eastern Cooperative Oncology Group performance status (ECOG PS) >2, high white blood cells count, low glucose, and high protein in cerebrospinal fluid (CSF) were poor prognostic factors. Having received RT or systemic treatment was associated with better prognosis. In multivariate analysis, ECOG PS (hazard ratio 2.22, 95% CI 1.25-3.94), CSF glucose levels (hazard ratio 1.74, 95% CI 1.05-2.88), and having received systemic treatment (hazard ratio 0.17, 95% CI 0.09-0.32) were confirmed as independent prognostic factors. In HER2+ BC patients, having received systemic HER2-targeted therapy was the only factor maintaining independent prognostication (hazard ratio 0.12, 95% CI 0.02-0.67) in multivariate analysis. CONCLUSION:Despite being limited by their retrospective nature, these results highlight the need for clinical trials in BC LMD, stratified on tumor biology. IMPLICATIONS FOR PRACTICE:Leptomeningeal disease (LMD) is a devastating complication of breast cancer (BC), and its optimal therapy is still not defined. Here, patient characteristics, treatment patterns, and prognostic factors from a contemporary cohort of 153 BC-related LMD patients are reported. In multivariate analysis, Eastern Cooperative Oncology Group performance status, cerebrospinal fluid glucose levels, and having received systemic treatment were confirmed as independent prognostic factors in the overall population, whereas in human epidermal growth receptor 2 (HER2) positive BC patients, having received systemic HER2-targeted therapy was the only factor maintaining independent prognostication in multivariate analysis. These results highlight the need to consider stratification on tumor biology in the treatment of BC LMD.

SUBMITTER: Griguolo G

PROVIDER: S-EPMC6291333 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Clinicopathological and Treatment-Associated Prognostic Factors in Patients with Breast Cancer Leptomeningeal Metastases in Relation to Tumor Biology.

Griguolo Gaia G Pouderoux Stephane S Dieci Maria Vittoria MV Jacot William W Bourgier Céline C Miglietta Federica F Firmin Nelly N Conte Pierfranco P Viala Marie M Guarneri Valentina V Darlix Amélie A

The oncologist 20180817 11

<h4>Background</h4>Breast cancer (BC) is one of the solid tumors most commonly associated with leptomeningeal disease (LMD). LMD carries a devastating prognosis; however, disease presentation and prognostic factors are uncertain.<h4>Subjects, materials, and methods</h4>In order to describe patient characteristics, treatment patterns, and factors associated with survival in a contemporary multicentric cohort, 153 consecutive BC patients diagnosed with LMD at two European institutions (2002-2017) ...[more]

PMID: 30120164

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Project description:BackgroundSecondary tumors of the ovary (STOs) account for 10-25% of all ovarian malignancies, including metastases from primary gynecological tumors. Colorectal cancer (CRC) has been recognized as one of the most common causes of STOs in Western countries. Despite it being well-known that CRC originating from the right versus left side of the colon/rectum differ substantially, there is a paucity of information regarding the effect of the primary tumor sidedness on the clinicopathological characteristics of STOs.MethodsThis retrospective, observational chart review study included patients with histologically confirmed STOs of CRC origin diagnosed between January 2000 and December 2019. The clinicopathological characteristics of STOs originating from left-sided and right-sided CRC were compared. Univariable and multivariable analyses employing elastic net Cox proportional hazard models were used to evaluate potential prognostic factors. Further, the role of imaging methods in STOs diagnostics was evaluated.ResultsFifty-one patients with STOs of colorectal origin were identified. The primary tumor originated in the right and left colon/rectum in 39% and 61% of the cases, respectively. STOs originating from right-sided primary tumors were more frequently bilateral, associated with peritoneal carcinomatosis, had the ovarian surface affected by the tumor, and contained a mucinous component. The independent prognostic factors for overall survival in the whole cohort included: the presence of macroscopic residual disease after cytoreductive surgery, menopausal status, the application of systemic therapy, and the application of targeted therapy. In 54% of cases, the imaging methods failed to determine the laterality of the STOs correctly as compared to pathological reports and/or intraoperative findings.ConclusionSTOs originating from left-sided and right-sided CRC show distinct clinicopathological characteristics. Moreover, different metastatic pathways might be employed according to the primary tumor sidedness. Considering the discrepancies between radiological assessment and histopathological findings regarding the laterality of STOs, bilateral adnexectomy should be advised whenever feasible.

Project description:BackgroundLiver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM).MethodsData on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients.ResultsYoung age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88-3.66; P < 0.001) and HR-/HER2+ (HR = 3.43; 95% CI = 2.28-5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001).ConclusionsBreast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.

Dataset Information

Clinicopathological and Treatment-Associated Prognostic Factors in Patients with Breast Cancer Leptomeningeal Metastases in Relation to Tumor Biology.

Publications

Clinicopathological and Treatment-Associated Prognostic Factors in Patients with Breast Cancer Leptomeningeal Metastases in Relation to Tumor Biology.

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