Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer
TL;DR: Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered, and organ-specific metastasis may depend on the Molecular subtype of breast cancer.
Abstract: Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR), and human epithelial receptor-2 (HER2) were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC) according to ER, PR, and HER2 status. Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.
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TL;DR: The pathological subtypes of breast cancer are clearly different in metastatic behavior with regard to the sites of distant metastasis, emphasizing that this knowledge may help to determine the appropriate strategy for follow-up and guide personalized medicine.
Abstract: // Qi Wu 1, * , Juanjuan Li 1, * , Shan Zhu 1 , Juan Wu 2 , Chuang Chen 1 , Qian Liu 1 , Wen Wei 1 , Yimin Zhang 1 , Shengrong Sun 1 1 Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China 2 Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China * These authors contributed equally to this work Correspondence to: Shengrong Sun, email: sun137@sina.com Yimin Zhang, email: dryiminzhang@163.com Keywords: breast cancer subtypes, distant metastases, SEER Received: November 01, 2016 Accepted: February 20, 2017 Published: March 02, 2017 ABSTRACT Background and Aims: This study aimed to access possible relationships between breast cancer subtypes and sites of distant metastasis in breast cancer. Results: A total of 243,896 patients, including 226,451 cases in control groups were identified. Bone metastasis was found in 8848 cases, compared with 1,000 brain metastasis cases, 3434 liver metastasis cases and 4167 lung metastasis cases. Patients with all subtypes were most prone to bone metastases, the incidence of bone metastasis in HR+/HER2+ subtype was up to 5.1 %. Further, HR−/HER2+ subtype patients had a higher probability of brain (OR = 1.978) metastasis compared to HR+/HER2− subtype patients. In addition, liver metastasis was more frequently observed in the HER2 positive subtypes compared with HER2 negative subtypes. Patients with TN primarily presented lung metastasis, but it made no difference in the probability of lung metastases of all subtypes. Materials and Methods: Using the 2010–2013 Surveillance, Epidemiology, and End Results Program(SEER) data, a retrospective, population-based cohort study to investigate tumor subtypes-specific differences in the sites of distant metastasis. Metastatic patterns information was provided for bone, brain, liver and lung. The breast cancer was classified into four subtypes: hormone receptor (HR) +/ human epidermal growth factor receptor 2 (HER2) −, HR+/HER2+, HR−/HER2+ and triple negative (TN). Conclusions: The pathological subtypes of breast cancer are clearly different in metastatic behavior with regard to the sites of distant metastasis, emphasizing that this knowledge may help to determine the appropriate strategy for follow-up and guide personalized medicine.
221 citations
TL;DR: Stage IV breast cancer patients have different clinicopathological characteristics and survival outcomes according to different metastatic sites, and patients with bone metastasis have the best prognosis, and brain metastasis is the most aggressive subgroup.
Abstract: The features and survival of stage IV breast cancer patients with different metastatic sites are poorly understood. This study aims to examine the clinicopathological features and survival of stage IV breast cancer patients according to different metastatic sites. Using the Surveillance, Epidemiology, and End Results database, we restricted our study population to stage IV breast cancer patients diagnosed between 2010 to 2015. The clinicopathological features were examined by chi-square tests. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients with different metastatic sites by the Kaplan-Meier method with log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors. A total of 18,322 patients were identified for survival analysis. Bone-only metastasis accounted for 39.80% of patients, followed by multiple metastasis (33.07%), lung metastasis (10.94%), liver metastasis (7.34%), other metastasis (7.34%), and brain metastasis (1.51%). The Kaplan-Meier plots showed that patients with bone metastasis had the best survival, while patients with brain metastasis had the worst survival in both BCSS and OS (p < 0.001, for both). Multivariable analyses showed that age, race, marital status, grade, tumor subtype, tumor size, surgery of primary cancer, and a history of radiotherapy or chemotherapy were independent prognostic factors. Stage IV breast cancer patients have different clinicopathological characteristics and survival outcomes according to different metastatic sites. Patients with bone metastasis have the best prognosis, and brain metastasis is the most aggressive subgroup.
190 citations
Cites result from "Pattern of distant recurrence accor..."
...However, there are some other studies reported that liver metastasis was not associated with breast cancer subtype [16]....
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TL;DR: It is important for radiologists to understand the nuances of these breast cancer subtypes to predict metastatic behaviours and guide possible imaging surveillance.
Abstract: There is accumulating evidence that molecular phenotyping of breast cancer determines the timing, pattern, and outcome of metastatic disease. The most clinically relevant subtypes are hormonal-positive [oestrogen and progesterone receptor (ER/PR) positive], HER2 expressing, and triple-negative breast cancers (TNBCs). ER/PR-positive breast cancers demonstrate the best prognosis; however, metastases, in particular osseous disease, may develop much later. HER2-expressing breast cancers, although aggressive, have improved outcomes due to the advent of HER2-targeted therapies, with increased risk of central nervous system (CNS) relapses later. Finally, TNBCs present in younger women, BRCA1 mutations carriers, and carry the worst overall prognosis, with high incidence of CNS metastases, especially during the first 5 years of diagnosis. It is important for radiologists to understand the nuances of these breast cancer subtypes to predict metastatic behaviours and guide possible imaging surveillance.
56 citations
TL;DR: It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+ /HER2+ and HR-/her2+ subgroup, and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS.
Abstract: Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P 0.05).
56 citations
TL;DR: Of the four subtypes, the LA subtype tends to have the best prognosis, fairly high survival, and low recurrent or metastases rates, and a statistically significant association between survival and molecular subtypes in an univariate analysis is demonstrated.
Abstract: Background and purpose No longer considered a single disease entity, breast cancer is being classified into several distinct molecular subtypes based on gene expression profiling. These subtypes appear to carry prognostic implications and have the potential to be incorporated into treatment decisions. In this study, we evaluated patterns of local recurrence (LR), distant metastasis (DM), and association of survival with molecular subtype in breast cancer patients in the post-adjuvant radiotherapy setting. Material and methods The medical records of 1,088 consecutive, non-metastatic breast cancer patients treated at a single institution between 2004 and 2012 were reviewed. Estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2) enrichment were evaluated by immunohistochemistry. Patients were categorized into one of four subtypes: luminal-A (LA; ER/PR+, HER2-, Grade 1-2), luminal-B (LB; ER/PR+, HER2-, Grade > 2), HER2 over-expression (HER2; ER/PR-, HER2+), and triple negative (TN; ER/PR-, HER2-). Results: The median follow-up time was 6.9 years. During the follow-up, 16% (174/1,088) of patients failed initial treatment and developed either LR (48) or DM (126). The prevalence of LR was the highest in TN (12%) and the lowest in LA (2%). Breast or chest wall relapse was the most frequent site (≈80%) of recurrence in LA, LB, and HER2 subtypes, whereas the regional lymph nodes and chest wall were the common sites of relapse in the TN group (50.0%). DM rates were 6.4% in LA, 12.1% in LB, 19.2% in HER2, and 27.4% in TN subgroups. Five-year survival rates were 84%, 83%, 84%, and 77% in the LA, LB, HER2 and TN subgroups, respectively. There was a statistically significant association between survival and molecular subtypes in an univariate analysis. In the adjusted multivariate analysis, the following variables were independent prognostic factors for survival: T stage, N stage, and molecular subtype. Conclusions Of the four subtypes, the LA subtype tends to have the best prognosis, fairly high survival, and low recurrent or metastases rates. The TN and HER2 subtypes of breast cancer were associated with significantly poorer overall survival and prone to earlier recurrence and metastases. Our results demonstrate a significant association between molecular subtype and survival. The risk of death and relapse/metastases increases fewfold in TN compared to LA. Future prospective studies are warranted and could ultimately lead to the tailoring of adjuvant radiotherapy treatment fields based on both molecular subtype and the more conventional clinicopathologic characteristics.
54 citations
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TL;DR: Variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals were characterized using complementary DNA microarrays representing 8,102 human genes, providing a distinctive molecular portrait of each tumour.
Abstract: Human breast tumours are diverse in their natural history and in their responsiveness to treatments. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identified for which variation in messenger RNA levels could be related to specific features of physiological variation. The tumours could be classified into subtypes distinguished by pervasive differences in their gene expression patterns.
14,768 citations
"Pattern of distant recurrence accor..." refers background in this paper
...Since molecular subtypes of breast cancer have been identified [4], many studies have explored the clinical value of the molecular subtypes of breast cancer [5,8,9]....
[...]
...The advances in the understanding of molecular subtypes analyzed by hierarchical clustering using an intrinsic gene list have identified molecular subtypes of breast cancer, and it has been noted that there is a significant difference in survival among the molecular subtypes of breast cancer [4,5]....
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TL;DR: Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.
Abstract: The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome. A total of 85 cDNA microarray experiments representing 78 cancers, three fibroadenomas, and four normal breast tissues were analyzed by hierarchical clustering. As reported previously, the cancers could be classified into a basal epithelial-like group, an ERBB2-overexpressing group and a normal breast-like group based on variations in gene expression. A novel finding was that the previously characterized luminal epithelial/estrogen receptor-positive group could be divided into at least two subgroups, each with a distinctive expression profile. These subtypes proved to be reasonably robust by clustering using two different gene sets: first, a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and, second, a gene set that highly correlated with patient outcome. Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.
10,791 citations
"Pattern of distant recurrence accor..." refers background in this paper
...Since molecular subtypes of breast cancer have been identified [4], many studies have explored the clinical value of the molecular subtypes of breast cancer [5,8,9]....
[...]
...The advances in the understanding of molecular subtypes analyzed by hierarchical clustering using an intrinsic gene list have identified molecular subtypes of breast cancer, and it has been noted that there is a significant difference in survival among the molecular subtypes of breast cancer [4,5]....
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Journal Article•
4,173 citations
3,105 citations
TL;DR: Breast cancer subtypes are associated with distinct patterns of metastatic spread with notable differences in survival after relapse, and luminal/HER2 and HER2-enriched tumors were associated with a significantly higher rate of brain, liver, and lung metastases.
Abstract: Purpose Prognostic and predictive factors are well established in early-stage breast cancer, but less is known about which metastatic sites will be affected. Methods Patients with early-stage breast cancer diagnosed between 1986 and 1992 with archival tissue were included. Subtypes were defined as luminal A, luminal B, luminal/human epidermal growth factor receptor 2 (HER2), HER2 enriched, basal-like, and triple negative (TN) nonbasal. Distant sites were classified as brain, liver, lung, bone, distant nodal, pleural/peritoneal, and other. Cumulative incidence curves were estimated for each site according to competing risks methods. Association between the site of relapse and subtype was assessed in multivariate models using logistic regression. Results Median follow-up time among 3,726 eligible patients was 14.8 years. Median durations of survival with distant metastasis were 2.2 (luminal A), 1.6 (luminal B), 1.3 (luminal/HER2), 0.7 (HER2 enriched), and 0.5 years (basal-like; P < .001). Bone was the most ...
1,768 citations
"Pattern of distant recurrence accor..." refers background or methods or result in this paper
...Regarding the study population of the current study, the ethnicity is also considered to interpret the discordance from previous studies which were mainly from Western countries [7,14]....
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...Brain metastasis is common in TNBC; previous studies have reported an incidence of brain metastasis of 6%10% [7,12,23,24], similar to our results....
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...However, most studies have focused on clinicopathological features, different risks of recurrence, and response to systemic therapies according to the molecular subtypes [9-11], and only a few studies have described different distant metastatic patterns according to molecular subtypes [7,12]....
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...Generally, patients with bone metastasis show better survival than those with visceral metastasis [13], and bone metastasis is more common in luminal types than the other subtypes [7,12]....
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...However, data are limited concerning differences in distant recurrence sites between the breast cancer subtypes [7]....
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