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.
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
References
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TL;DR: In this article, the authors investigated the rate of pCR according to molecular subtypes defined by immunohistochemical staining and analyzed the pCR rate and treatment outcome according to these subtypes.
Abstract: Objective: Pathologic complete response (pCR) is the most predictive factor for patients with neoadjuvant chemotherapy and we investigated the rate of pCR according to molecular subtypes defined by immunohistochemical staining. Methods: Our subjects comprised 257 breast cancer patients who received 3 cycles of anthracycline/taxane-based neoadjuvant chemotherapy. The patients were classified into 4 subtypes: luminal A, luminal B, HER2 and triple negative. We analyzed the pCR rate and treatment outcome according to these subtypes. Results: Of a total of 257 patients, the pCR rate of luminal A, luminal B, HER2 and triple negative was 3.9, 5.0, 10.5 and 21.1%, respectively (p = 0.001). The 5-year disease-free survival of the pCR group (88.4%) was higher than that of the non-pCR group (65.6%), but it was not significant (p = 0.228). Among patients who have residual disease, the 5-year disease-free survival of luminal A, luminal B, HER2 and triple negative was 64.0, 65.7, 75.2 and 66.5%, respectively (p = 0.243). Triple negative and HER2 subtypes are more sensitive to neoadjuvant chemotherapy. Conclusion: To increase the pCR rate, type-specific approaches according to subtypes, such as an addition of trastuzumab, increasing the number of cycles or a novel regimen, should be considered.
59 citations
TL;DR: Adjuvant aromatase inhibitors (AIs), instead of or after tamoxifen, are effective in decreasing recurrence in postmenopausal women with estrogen receptor (ER)‐positive breast cancer.
Abstract: BACKGROUND
Adjuvant aromatase inhibitors (AIs), instead of or after tamoxifen, are effective in decreasing recurrence in postmenopausal women with estrogen receptor (ER)-positive breast cancer. An understanding of which patients are at risk of early recurrence while they are receiving tamoxifen may improve clinical decision making.
METHODS
The patients who were included in this study were women aged ≥50 years with early-stage, ER-positive breast cancer diagnosed between 1986 and 1999 and had been treated with tamoxifen. Characteristics of the patients with early recurrences (within 2.5 years of diagnosis), late recurrences (between 2.5 years and 5 years) and no recurrence within 5 years were compared. Logistic regression analyses were conducted to identify which groups were at risk of early recurrence.
RESULTS
Among 3844 women, 304 women (7.9%) developed disease recurrence within 2.5 years. Higher than average rates of recurrence within 2.5 years were observed in cohorts with lymph node (N)-positive tumors (11.5%), grade 3 histology (14.3%), or low-positive ER levels, ie, 10–49 fmol/mg or 10%–20% staining (14.9%). In multivariate analyses, only pathologically N-positive tumors (1–3 vs 0 positive lymph nodes: odds ratio [OR], 1.6; 4–9 vs 0 positive lymph nodes: OR, 2.23 [P = .03]) and low-positive ER status (OR, 2.04; P = .01) were associated with recurrence within 2.5 years compared with recurrence between 2.5 years and 5 years. Other clinical and pathologic variables were not predictive of early recurrence.
CONCLUSIONS
Subgroups of women with early ER-positive breast cancer may be identified who are at increased risk of recurrence within 2.5 years of diagnosis despite tamoxifen. It remains to be proven whether upfront AI therapy results in an advantage to these women. Cancer 2008. © 2008 American Cancer Society.
43 citations
"Pattern of distant recurrence accor..." refers background 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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...demonstrated TNBC- or ER-negative tumors are related with early relapse [7,14,17]....
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...Previous studies have reported a significant difference in the onset of recurrence according to hormone receptor status and hormonal therapy [14-17]; usually low-ER positive or ER negative tumors are associated with early recurrence [14,17]....
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Journal Article•
TL;DR: Molecular differences between previously known as well as newly defined subtypes of breast cancer have been shown to correlate very well with clinical features and survival, or even better than traditional histopathological parameters.
Abstract: Purpose In the last years, the incidence of breast cancer has been increasing; characteristic patterns of gene expression have emerged, reflecting molecular differences between previously known as well as newly defined subtypes of breast cancer. This study aimed to classify the molecular subtypes of breast cancers based on the expression profile of immunohistochemical markers and to evaluate their association with clinicopathological features. Material and methods A total of 173 cases of breast carcinoma were examined retrospectively using immunostains for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2). Because the triple-negative phenotype, when defined by IHC using only these three markers, is not the optimal method for defining basal-like breast cancer, we need to use an additional marker--CK 5/6. Results The luminal type was the most common subtype in breast cancer (71.6%), which was followed by the basal subtype (21.9%). HER2 subtype were 2.8% from the total of cases, being associated with the highest rate of high-graded cases. Basal type is presented largely in premenopausal women and displayed aggressive features, such as large tumor size and poorly differentiated cancers. Luminal A included the highest percentage of patients older than 60 years, the highest proportion of stage I-II tumors and well/moderately differentiated lesions. HER2-type was more frequent in premenopausal women and showed a high percentage of positive lymph nodes. Conclusions These molecular differences have been shown to correlate very well with clinical features and survival, or even better than traditional histopathological parameters. The discovery of certain molecular characteristics of breast cancers has helped us to understand better the pathophysiology of disease and to develop more direct therapeutic strategies.
36 citations
"Pattern of distant recurrence accor..." refers background in this paper
...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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TL;DR: This study shows that HER2-overexpressing breast cancer displays characteristic patterns of relapse and metastatic spread depending on ER status.
Abstract: The primary aim of this study was to compare the relapse patterns of estrogen receptor (ER)-positive and ER-negative patients with HER2-overexpressing breast cancer. A secondary aim was to distinguish the preferential primary site of metastases in HER2-overexpressing breast cancer. Out of 886 patients treated for metastatic breast cancer (MBC) between January 1995 and December 2006, 269 patients with HER2-positive tumors were identified. Of these, 198 patients with relapsed breast cancer following surgery were included in this study. Rates and patterns of relapse and metastatic spread in HER2+/ER+ and HER2+/ER− patients were analyzed. This analysis was evaluated by the validation patients’ cohort of our institute prospectively. Median relapse-free survival was longer in the HER2+/ER+ group than in the HER2+/ER− group (32.0 vs. 19.5 months, p = 0.0012). The peak of recurrence occurred at 12 months after surgery in the HER2+/ER− patients. The peak of relapse was later and the level was lower in the HER2+/ER+ patients (66 and 78 months following surgery) than in the HER2+/ER− patients (33 and 39 months following surgery, respectively). This result was reproduced by the validation cohort with great similarity. Young age [hazard ratio (HR) 1.59, p = 0.002], TNM stage 3 (HR 1.51, p = 0.005), and ER-negativity (HR 1.68, p < 0.0001) were identified as independent risk factors for relapse. Severe bone metastasis (HR 4.48, p = 0.028) and massive hepatic metastasis (HR 5.24, p = 0.043) were identified as independent risk factors for early relapse. Our study shows that HER2-overexpressing breast cancer displays characteristic patterns of relapse and metastatic spread depending on ER status.
32 citations
"Pattern of distant recurrence accor..." refers background in this paper
...demonstrated TNBC- or ER-negative tumors are related with early relapse [7,14,17]....
[...]
...Previous studies have reported a significant difference in the onset of recurrence according to hormone receptor status and hormonal therapy [14-17]; usually low-ER positive or ER negative tumors are associated with early recurrence [14,17]....
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Journal Article•
TL;DR: Pathological lymph node status 3, stage IIIC, grade 3, oestrogen receptor negativity, and visceral metastases were found to have independent detrimental influence on overall survival following surgery and survival after metastasis.
Abstract: Introduction The present study was undertaken to define the prognostic factors for overall survival subsequent to definitive surgery, and for survival after the development of distant metastasis in breast cancer patients who developed distant metastasis subsequent to definitive surgery. Methods The records of 470 breast cancer patients with T1-3 tumours and distant metastasis following surgery were reviewed. Prognostic factors were compared to the first metastatic sites as solitary skeletal, multiple skeletal, and visceral metastases, and were analysed for overall survival following surgery and survival after metastasis. Survival curves were generated by the Kaplan-Meier method, and multivariate analysis was performed by the Cox proportional hazard model. Results 79 patients (17 percent) had a solitary skeletal metastasis, 105 (22 percent) had multiple skeletal metastases, and 286 (61 percent) had a visceral metastasis. The five-year overall survival was significantly better for patients with a solitary bone metastasis (73 percent) compared to patients who had multiple bone metastases (46 percent), or a visceral metastasis (22 percent) (p-value is less than 0.0001). Pathological lymph node status 3, stage IIIC, grade 3, oestrogen receptor negativity, and visceral metastases were found to have independent detrimental influence on overall survival following surgery and survival after metastasis. A long-term metastasis-free interval affected post-metastatic outcome favourably. Radiotherapy improved overall survival. Conclusion Pathological lymph node status, stage, grade, and oestrogen receptor status predicted survival after surgery as well as after the development of metastasis. Solitary bone metastasis has a more favourable prognosis than multiple bone metastases, and compared to visceral metastasis, skeletal metastasis has a more favourable prognosis.
30 citations
"Pattern of distant recurrence accor..." refers background in this paper
...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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