Abstract P6-09-21: Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis
Authors: Leone BA , Vallejo CT , Romero AO , Machiavelli MR , Perez JE , Leone J , Leone JP 
Published: March 2017

Background: Stage IV breast cancer at initial diagnosis (BCID) can be recognized in approximately 5% of all breast neoplasms. Clinical outcomes of these patients (pts) are highly variable and depend on tumor biology and pt characteristics. The prognostic influence of metastatic pattern (MP) at initial presentation and factors associated with specific organ involvement have been understudied. The primary aim of this study was to analyze the influence of MP compared with other biologic and clinical factors in the survival of pts with stage IV BCID. The secondary aim was to evaluate factors associated with specific sites of metastatic spread.

Methods: We evaluated women with microscopically confirmed stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results (SEER) 18 registries program from 2010 to 2013. Pts with other primary tumor either before or after breast cancer were excluded. MP was categorized as bone only, visceral (lung, liver or brain), bone and visceral and other. Pt characteristics were compared between MP. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with specific sites of metastases.

Results: We included 9143 pts. Median age was 61 years (range 19-102). Median OS for the entire cohort was 28 months (95% CI 27-29 months). At diagnosis, bone only metastases represented 37.5% of pts, visceral 21.9%, bone and visceral 28.8% and other 11.9%. Median OS by MP was: bone only 38 months, visceral 21 months, bone and visceral 19 months and other 33 months (p&lt;0.0001). Bone was the most common site of metastases (66.2%), followed by lung (30.5%), liver (26.2%) and brain (7.4%). Pts with visceral metastases were more often black race, had higher grade, less likely to be lobular histology and more likely to be triple negative (TN) (all p&lt;0.0001). Univariate analysis showed that older age, black race, grade 3/4 tumors, TN pts, bone and visceral MP, higher number of metastatic sites and unmarried pts had worse prognosis (all p&lt;0.0001). In multivariate analysis, older age (HR 1.9; p&lt;0.001), black race (HR 1.17; p=0.002), grade 3/4 tumors (HR 1.6; p&lt;0.001), TN subtype (HR 2.24; p&lt;0.001), bone and visceral MP (HR 2.07, p&lt;0.001) and unmarried pts (HR 1.25; p&lt;0.001) had significantly shorter OS. In adjusted logistic regression, as compared with ER/PR+/HER2- tumors, TN and ER/PR-/HER2+ had higher odds of brain, liver, lung and other metastases (all p&lt;0.05). ER/PR+/HER2+ had higher odds of liver metastases (p&lt;0.001). All three subtypes had lower odds of bone metastases (p&lt;0.001).

Conclusions: To our knowledge, this is the largest study of MP in stage IV BCID. There were substantial differences in prognosis according to MP, bone only was the most common MP and had the best OS, whereas bone and visceral MP had the worst prognosis. We observed significant differences in pt characteristics according to MP. Independent predictors of OS included age at diagnosis, race, marital status, tumor grade, tumor subtype and MP. There was a clear influence of tumor subtype among other factors on specific sites of metastases. Our study identified several prognostic factors that could guide therapy selection in treatment naïve pts.Background: Stage IV breast cancer at initial diagnosis (BCID) can be recognized in approximately 5% of all breast neoplasms. Clinical outcomes of these patients (pts) are highly variable and depend on tumor biology and pt characteristics. The prognostic influence of metastatic pattern (MP) at initial presentation and factors associated with specific organ involvement have been understudied. The primary aim of this study was to analyze the influence of MP compared with other biologic and clinical factors in the survival of pts with stage IV BCID. The secondary aim was to evaluate factors associated with specific sites of metastatic spread.

Methods: We evaluated women with microscopically confirmed stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results (SEER) 18 registries program from 2010 to 2013. Pts with other primary tumor either before or after breast cancer were excluded. MP was categorized as bone only, visceral (lung, liver or brain), bone and visceral and other. Pt characteristics were compared between MP. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with specific sites of metastases.

Results: We included 9143 pts. Median age was 61 years (range 19-102). Median OS for the entire cohort was 28 months (95% CI 27-29 months). At diagnosis, bone only metastases represented 37.5% of pts, visceral 21.9%, bone and visceral 28.8% and other 11.9%. Median OS by MP was: bone only 38 months, visceral 21 months, bone and visceral 19 months and other 33 months (p&lt;0.0001). Bone was the most common site of metastases (66.2%), followed by lung (30.5%), liver (26.2%) and brain (7.4%). Pts with visceral metastases were more often black race, had higher grade, less likely to be lobular histology and more likely to be triple negative (TN) (all p&lt;0.0001). Univariate analysis showed that older age, black race, grade 3/4 tumors, TN pts, bone and visceral MP, higher number of metastatic sites and unmarried pts had worse prognosis (all p&lt;0.0001). In multivariate analysis, older age (HR 1.9; p&lt;0.001), black race (HR 1.17; p=0.002), grade 3/4 tumors (HR 1.6; p&lt;0.001), TN subtype (HR 2.24; p&lt;0.001), bone and visceral MP (HR 2.07, p&lt;0.001) and unmarried pts (HR 1.25; p&lt;0.001) had significantly shorter OS. In adjusted logistic regression, as compared with ER/PR+/HER2- tumors, TN and ER/PR-/HER2+ had higher odds of brain, liver, lung and other metastases (all p&lt;0.05). ER/PR+/HER2+ had higher odds of liver metastases (p&lt;0.001). All three subtypes had lower odds of bone metastases (p&lt;0.001).

Conclusions: To our knowledge, this is the largest study of MP in stage IV BCID. There were substantial differences in prognosis according to MP, bone only was the most common MP and had the best OS, whereas bone and visceral MP had the worst prognosis. We observed significant differences in pt characteristics according to MP. Independent predictors of OS included age at diagnosis, race, marital status, tumor grade, tumor subtype and MP. There was a clear influence of tumor subtype among other factors on specific sites of metastases. Our study identified several prognostic factors that could guide therapy selection in treatment naïve pts.

Citation Format: Leone BA, Vallejo CT, Romero AO, Machiavelli MR, Perez JE, Leone J, Leone JP. Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-21.