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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 [ 712 ]. Since molecular subtypes of breast cancer have been identified [ 4 ], many studies have explored the clinical value of the molecular subtypes of breast cancer [ 589 ].
Pattern of distant recurrence according to the molecular subtypes in korean women with breast cancer
ER and PR status were reviewed by medical records. The c-erbB2 to chromosome 17 centromere ratio was measured in at least 60 nuclei from the tumor cells, and an average score was taken. This was not concordant with the studies that demonstrated TNBC- or ER-negative tumors are related with early relapse [ 71417 ].
Three hundred thirteen women with primary breast cancer who underwent surgery at Seoul St. Mary's Hospital between and were enrolled in the study. Ann Oncol. Therefore, the discordance between DRFS and OS might derive from the difference of the sites of the distant recurrence of the four subtypes.
A Cox proportional hazard model was used for evaluating risk factors for distant recurrence-free survival and overall survival. The site of the first distant recurrence was categorized as follows: bone, extra-bone metastasis lung, pleural or peritoneal metastasis, liver, and other site metastasis excluding brain metastasis, bone metastasis with synchronous extra-bone metastasis, brain metastasis, and brain metastasis with synchronous bone or extra-bone metastasis.
A retrospective study analyzed a large dataset and demonstrated a distinct pattern of metastatic behavior of the molecular subtypes using a validated six-marker immunohistochemical panel applied to tissue microarrays, even though the clinicopathological features of the molecular subtypes that might influence the pattern of distant recurrence differed among the molecular subtypes [ 7 ]. Bone was the most common site of distant recurrence. Cancer Metastasis Rev.
Spitale A, Mazzola P, Soldini D, Mazzucchelli L, Bordoni A: Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland. Hormone receptor status was determined using an enzyme immunoassay and reported in the medical record between and The receptor status had been determined using a commercial enzyme immunoassay according to the instructions of the manufacturer Abbott Laboratories, Chicago, IL, USA.
The IHC method was briefly described as follows; Five-micrometer sections of paraffin-embedded tissue arrays were deparaffinized, rehydrated in a graded series of alcohol solutions and microwave-treated for 10 min in a pH 6.
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Norton L, Massague J: Is cancer a disease of self-seeding?. Distant recurrence-free survival was not different among the subtypes, yet OS showed ificant differences. The predictive and prognostic factors including tumor size, nodal status, lymphovascular invasion, estrogen receptor ER or progesterone receptor PRand human epithelial receptor 2 HER2 has been investigated widely concerning molecular subtypes [ 6 ]. Regarding the study population of the current study, the ethnicity is also considered to interpret Fremont discordance from studies which were mainly from Western countries [ 714 ].
Clinicopathological features including tumor size; nodal status; operation type; expression of ER, PR, and HER2; lymphovascular invasion; status of systemic therapy including endocrine or chemotherapy; radiation therapy; site and date of up to the first three recurrences; and survival data were reviewed using the medical database of Seoul St.
Mary's Hospital. Thus, the aim of the study was to investigate whether these subtypes were related dating an organ-specific metastasis. Statistical analyses were performed with SPSS Mary's Hospital, the Catholic University of Korea. 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.
Breast Cancer Res Treat. Overall survival according to the onset of distant recurrence. The endogenous peroxidase activity was blocked korean 0. Nat Med. t S: The distribution of secondary growths in cancer of the breast. When multivariate analysis for DRFS was performed Table 4tumor size, lymph node status, subtypes, and the site of the women recurrence were not associated with DRFS.
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However, interpretation of this discordance needs to be done cautiously, because the definition of early relapse and study de of the studies are so heterogenous that directly comparison with each study cannot be made. 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 ificant difference in survival among the molecular subtypes of breast cancer [ 45 ].
All tests were two sided. A major strength of the study is that the well-balanced clinicopathological features in this cohort allowed more clear demonstration of the metastatic pattern according to molecular subtypes.
studies have reported a ificant 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 [ 1417 ]. However, data are limited concerning differences in distant recurrence sites between the breast cancer subtypes [ 7 ].
The limitations of the study are the small of the cases, its retrospective de, and the fact that systemic therapy guidelines during the era of this cohort are not representative of current practice guidelines. Distant recurrence-free survival A and overall survival B according to molecular subtypes. More than two copies of c-erbB2 for each chromosome 17 were considered to be a positive for c-erbB2 gene amplification. The complex interaction between the primary cancer and metastatic sites includes tumor intravasation, circulation, extravasation, proliferation, and angiogenesis, and the microenvironment of the target tissue, so called "seed and soil" theory, may be associated with organ-specific metastasis in cancer patients [ 23 ].
In conclusion, this study demonstrates that the pattern of distant metastasis is different among the molecular subtypes as defined by ER, PR, and HER2 status, and may contribute to an understanding of molecular subtype that will allow for tailored therapy for metastatic breast cancer. 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 [ 712 ].
In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was ificantly different among the subtypes. In addition, a full review of the medical records permitted a check of the detailed documented metastatic sites and date of up to the first three distant recurrences, providing a more apparent pattern of cumulative frequency of distant metastasis sites as well as onset of distant metastasis. Distant recurrence was diagnosed by clinical evaluations including imaging studies or biopsy.
J Clin Oncol. Organ-specific metastasis may depend on the molecular subtype of breast cancer. Their medical data were retrospectively analyzed. Distant recurrence of breast cancer in poor survival outcome and the site of the distant recurrence is also important to predict the clinical outcome [ 1 ].
The patients with HER2 overexpression, luminal-HER2 and HER2-enriched subtypes, with late distant recurrence were associated with poorer survival than luminal-A and TNBC; these findings may be associated with lack of trastzumab therapy because this therapy was approved and covered by the government and national insurance system in Korea in the mids.
In addition, a study reported gene expression profile differences in breast cancer between African American and non-African American women supporting that genetic heterogeneity in the tumor microenvironment from different ethnicity may for the difference in the site of distant metastasis [ 20 ]. There might be an ethnic factor related to metastatic patterns of breast cancer, and further investigations are needed. In addition, race may influence the discordance because disparities in breast cancer prognostic factors by race may exist [ 18 ].
The pattern of distant recurrence in TNBC has been well-investigated because of its distinct pattern [ 21 — 24 ]. Multiple distant metastasis as the first distant recurrence was occurred in 11 patients: Eight patients with bone and extra-bone metastasis excluding brain metastasis and four patients with brain with other metastasis were presented.
Distant recurrence-free survival DRFS was defined as the time from operation to the first distant recurrence, and the cases of death without distant recurrence was censored at the time of the death. In the current study, early distant recurrence was not related to the molecular subtypes. The current study demonstrated that different patterns of distant recurrence among the subtypes with well-balanced clinicopathologic features remained in terms of the first distant recurrence site, frequency of brain metastasis, overall survival, and onset of distant recurrence.
Extra-bone metastasis had been shown in 25 patients, and brain metastasis was four patients. Cumulative frequency of bone including bone marrowlung, pleural or peritoneal, liver, brain, and other sites of metastasis including soft tissue, pericardium, ovary, periampullary area, and other organs not elsewhere documented during follow-up was analyzed regarding to the molecular subtypes. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer.
Distant recurrence was defined as a recurrence of breast cancer developing beyond the ipsilateral or contralateral breast, chest wall, or regional lymph node including ipsilateral axillary, supraclavicular, or internal mammary lymph node. A Taiwanese study mentioned that TNBC in Taiwan may have different prognostic factors and features compared with Western countries, possibly due to genetic heterogeneity [ 19 ]. Clinicopathological characteristics are shown in Table 1.
The incidence of first distant recurrence site was ificantly different among the subtypes.
No ificant difference in DRFS was present among the subtypes. B OS according to the subtypes in patients with early distant recurrence distant recurrence within 24 months after surgery. Overall survival OS was defined as the time from operation to death from any cause. Mean age of the patients was Median follow-up time was 93 months range months.
Pearson's chi-square test or Fisher's exact test were used for measuring statistical differences in categorical variables, and all statistical tests were two-sided. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered. While bone metastasis was the most common type of the distant recurrence in luminal-A and luminal-HER2 types Brain metastasis alone developed in Cumulative frequency data of distant metastasis site during follow-up are shown in Table 3. In the absence of trastuzumab therapy for HER2-positive breast cancer patients, other visceral metastases may develop and earlier failure in other visceral organ may cause death before the development of brain metastasis.
Kaplan-Meier method was accessed for survival analysis, and the generalized Wilcoxon test was used for estimating the difference of survival among subtypes. Distant recurrence occurred in 70 patients.