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: In patients with pleural, axillary and/or neck lymph node, and other distant soft tissue metastases, there was no significant difference in metastatic patterns among the BCS and a different focus in the postoperative follow-up and monitoring of breast cancer patients with different BCS.
Abstract: // San-Gang Wu 1, * , Jia-Yuan Sun 2, * , Li-Chao Yang 3, * , Li-Ying Tang 4 , Xue Wang 4 , Xue-Ting Chen 4 , Gui-Hua Liu 5 , Huan-Xin Lin 2 , Qin Lin 1 , Zhen-Yu He 2 1 Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China 2 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China 3 Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361005, People’s Republic of China 4 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen 361005, People’s Republic of China 5 School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Qin Lin, email: linqin05@163.com Zhen-Yu He, email: hezhy@sysucc.org.cn Keywords: breast cancer, breast cancer subtype, distant metastasis, patterns Received: December 25, 2015 Accepted: May 20, 2016 Published: June 16, 2016 ABSTRACT To access possible relationships between breast cancer subtypes (BCS) and patterns of distant metastasis in advanced breast cancer. Breast cancer patients with distant metastasis at two academic centers from 2000-2015 were retrospectively reviewed. The breast cancer was classified into four subtypes: hormone receptor (HR) +/ human epidermal growth factor receptor 2 (HER2) − (i.e., estrogen receptor [ER] + and/or progesterone receptor [PR] +, HER2−); HR+/HER2+ (ER+ and/or PR+, HER2+), HR−/HER2+ (ER− and PR−, and HER2+); and HR−/HER2− (ER− and PR−, and HER2−). A total of 679 patients were identified. The distribution of the BCS was 39.9% (271/679), 23.7% (161/679), 16.8% (114/679), and 19.6% (133/679) in HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−, respectively. Patients with HR+/HER2+ and HR−/HER2+ subtypes were prone to abdominal and pelvic metastasis, those with HR+/HER2− and HR+/HER2+ subtypes were prone to bone metastasis, while patients with the HR−/HER2− subtype were prone to lung/mediastinal and brain metastases. In patients with pleural, axillary and/or neck lymph node, and other distant soft tissue metastases, there was no significant difference in metastatic patterns among the BCS. There are different patterns of distant metastasis associated with different BCS. There should be a different focus in the postoperative follow-up and monitoring of breast cancer patients with different BCS.
22 citations
Cites background or result from "Pattern of distant recurrence accor..."
...However, two studies of the Korean population did not find a significant correlation between BCS and bone metastasis [18, 20]....
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...did not find differences in liver metastasis between different subtypes [18], but there were only 18 patients with liver metastases in Park’s study, whereas the number of patients with abdominal and pelvic metastasis in our study was 221, and there were 435 patients with liver metastasis in the study of Kennecke et al....
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TL;DR: The preferential and long-term risk of brain metastasis in the HER2 subtype underlines the importance of alternative anti-HER2 therapies and subtype-specific individualization of systemic treatment and close surveillance are suggested.
Abstract: Although gene expression profiling provides critical information, knowledge remains limited regarding the differential effects of molecular subtype on clinical course. This study evaluated the impact of molecular status on long-term patterns of failure in patients with non-metastatic breast cancer. We analyzed data from 1181 individuals with invasive breast cancer undergoing surgery plus PORT from 2003 to 2011. Molecular subtypes were defined as luminal A (LA), luminal B (LB)-HER2(−), LB-HER2(+), HER2, and triple-negative (TN) based on the 2013 St. Gallen Consensus criteria. Competing risks analysis and baseline hazard rate function plots were used to explore subtype-specific recurrence patterns. The 10-year overall survival rates of LA, LB-HER2(−), LB-HER2(+), HER2, and TN groups were 96, 93, 94, 84, and 85%, respectively (P < 0.001). Distant metastatic events differed significantly according to molecular subtype (P < 0.001). In competing risks regression analysis, initial development of distant metastasis was the highest with TN tumors, followed by HER2, LB-HER2(−), and LB-HER2(+) subtypes (P = 0.005). Regarding preferential sites of distant metastasis, the risk of initial brain metastasis was significantly higher with HER2 tumors, followed by TN tumors (P = 0.001). A low-level but sustained metastatic risk increment was observed in luminal tumors, whereas TN and HER2 subtypes showed a short-term risk surge within 5 years. From the significant impact of molecular profile on distant metastasis, subtype-specific individualization of systemic treatment and close surveillance are suggested. The preferential and long-term risk of brain metastasis in the HER2 subtype underlines the importance of alternative anti-HER2 therapies.
21 citations
Cites background from "Pattern of distant recurrence accor..."
...Although a potential bone-seeking phenotype of luminal tumors has been suggested [21–24], some reports could not verify this tendency [16, 25]....
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TL;DR: Investigation of the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery found organ-specific metastasis may depend on the Molecular subtype of breast cancer.
Abstract: Purpose: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergon
16 citations
TL;DR: The results of the present study suggested that different molecular subtypes of breast cancer have different metastatic behavior, as well as mean OS.
Abstract: Breast cancer is a highly heterogeneous disease at the molecular level and >90% of mortalities are due to metastasis and its associated complications. The present study determined the impact of molecular subtypes on metastatic behavior and overall survival (OS) of patients with metastatic breast cancer. The influence of molecular subtypes on the sites and number of metastases in 166 patients with metastatic breast cancer from a single center were assessed; and the influence of molecular subtypes on the sites and number of metastases and OS in 15,322 metastatic cases among 329,770 patients with primary breast cancer from the Surveillance, Epidemiology and End Results database were assessed. Analysis of both datasets revealed that different molecular subtypes exhibited differences in the prevalence of different metastatic sites and number of metastases. A larger proportion of bone metastasis was observed in the hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)+ subtype than in other subtypes, more lung metastasis was observed in the HR-/HER2+ subtype and more liver metastasis occurred in the HR+/HER2+ and HR-/HER2+ subtypes. Single-site metastasis was more common for the HR+/HER2- subtype than in other subtypes, while 2-3 sites of metastases were more common for the HR+/HER2+ subtype and ≥4 sites of metastases were more frequent in the HR-/HER2+ and HR-/HER2- subtypes. The mean OS of patients with primary breast cancer in the HR+/HER2- subtype group was the longest (78.5 months), while the HR-/HER2- group had the shortest mean OS (69.1 months). The mean OS of the metastatic HR+/HER2+ group was the longest (46.0 months), while the mean OS of the metastatic HR-/HER2- group was the shortest (18.5 months). In conclusion, the results of the present study suggested that different molecular subtypes of breast cancer have different metastatic behavior, as well as mean OS.
15 citations
TL;DR: If the association between two possible relapses for the increased incidence of distant metastases observed in patients with local relapses injuries is not taken into account, the effects of relapses on death and the correlation between local and distant recurrences may be lost.
11 citations
References
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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]....
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...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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