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: Evaluated patients who were treated definitively and had developed organ-specific metastasis and local recurrence according to biological subtype demonstrated an association between molecular subtype and pattern of recurrence.
Abstract: Background: Despite the advances in breast cancer treatment, it has a higher rate of mortality. The response of treatment varies significantly; this could be due to the various subtypes that determine the course of the disease. In this study, we evaluated patients who were treated definitively and had developed organ-specific metastasis and local recurrence according to biological subtype. Materials and Methods: Out of 856 patients who were diagnosed to have carcinoma breast from the year January 2015 to January 2020, 468 patients were treated definitively, out of which 55 patients developed recurrent or metastatic disease after completion of treatment. Results: The most frequent subgroup for relapse was triple-negative breast cancer (TNBC) 23 (41.8%). Twenty-two (40%) had multiple metastases at the time of first distant recurrence. The most common site of distant recurrence was bone 28 patients (50.9%) with maximum incidence in Luminal B subgroup (23.6%), followed by liver metastasis 23 patients (41.81%) with the highest incidence seen among TNBC (18%), followed by lung 19 (34.5%) patients with maximum incidence in TNBC (16.3%) followed by brain 5 (9%) patients. Locoregional recurrence was observed in 13 patients, out of which 8 (61.5%) patients had TNBC molecular subgroup. Conclusion: Our results demonstrate an association between molecular subtype and pattern of recurrence.
TL;DR: A rare case of spine metastasis diagnosed 12 years (144 months) in a breast cancer survivor is reported and it is reported that patients with primary breast cancer are surviving longer.
Abstract: Breast cancer is the most commonly diagnosed malignancy and is the second leading cause of cancerrelated death in the western world. Spine metastasis commonly occurs in breast cancer, accounting for approximately two-thirds of the osseous metastases discovered. The incidence of spine metastasis from breast cancer is increasing because patients with primary breast cancer are surviving longer. Median time to spine metastasis is about 42 months with the longest reported interval of 97 months. We report a rare case of spine metastasis diagnosed 12 years (144 months) in a breast cancer survivor.
Cites background from "Pattern of distant recurrence accor..."
...The frequency of breast cancer metastasis to different sites is affected by the histological subtypes of breast cancer, example, the risks of spine metastasis from breast cancer is seen more in luminal-A (ER or PR expression positivity and low Her-2 neu expression) and luminal-Her-2 neu (ER or PR positive and HER2 positive) histological subtypes.(6,7) Indeed, ER, PgR and Her-2 neu were all negative (triple negative) in this case, which are not considered to be high risk indicators for developing spine metastasis....
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TL;DR: In this paper , the neutrophil-to-lymphocyte ratio (NLR) and platelet-tolymphocytes ratio (PLR) values of women operated for breast cancer were associated with their clinicopathological features.
Abstract: AIM: In this study, we aimed to examine whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values of women operated for breast cancer were associated with their clinicopathological features.
MATERIAL AND METHOD: The data of 463 females who were operated for breast cancer in our center between Januray 2015 and December 2020 were analyzed retrospectively. Age, menopausal status, hematological values, histopathological features of tumors, presence of hormone receptors, surgical and biopsy techniques were evaluated in detail. NLR and PLR values were calculated using the results of routinely performed hemogram test before the operation, and their relationships with all parameters were analyzed.
RESULTS: The ages of the cases ranged from 23 to 88 years, with a mean of 53.57 ± 12.66. Postmenopausal women constituted 62.42% of the cases. A negative correlation was found between age and PLR, but neither PLR nor NLR were found to be associated with menopause status. It was found that high NLR value was associated with high N stage, high TNM stage, high number of metastatic lymph nodes and presence of extracapsular invasion (p
Journal Article•
TL;DR: This study detected the characterization of IHC subgroups in patients treated for breast cancer at a reference center for cancer treatment in northeastern Mexico.
Abstract: Background : Breast cancer is a heterogeneous illness, with subtypes of varying etiology. Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2/neu (Human Epidermal Growth Factor Receptor 2) expressions have been identified as predicting factors. Objective : To demonstrate the possible association of the five immunohistochemical (IHC) expression profiles with clinical and histopathological variables of breast cancer in northeastern Mexico. Methodology : In 522 women with breast carcinoma, five IHC profiles were defined [Luminal A, Luminal B, Mixed, HER2/neu and Triple-negative (TN)]. An analysis was done to determine if there were differences between them in relation to the clinical and histopathological variables. Results : The distribution of the histological subtypes was: luminal A (32.97%), TN (27.53%), HER2/neu (19.02%), mixed (13.41%) and luminal B (7.07%). The average age at diagnosis was 53.07 ± 12.08 years, in 90.5% of the patients the size of the tumor was ≥ 2.0 cm, and 40.94% had lymph node involvement. Luminal A subtype had the highest percentage in the postmenopausal state (63.7%, p =0.071). Illness recurred in 21.01% of the patients (n=116), principally with the TN subtype (28.3%, p =0.012). Conclusions : This study detected the characterization of IHC subgroups in patients treated for breast cancer at a reference center for cancer treatment in northeastern Mexico.
Cites result from "Pattern of distant recurrence accor..."
...A high frequency of tumors 2 cm, lymphatic node involvement and metastasis was observed in the luminal A subtype, followed by TN; this data also agrees with previous studies, such as Park and collaborators’ publication [42], however, it should be noted that a study done in Spain by Piñero-Madrona reports a higher frequency of lymph node involvement in the luminal B subtype, explained by the possible presence of a different immunophenotype in the breast tumors of their population [43]....
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...Menopausic state had a higher association with subtype luminal A tumors, in more than 60% of the cases, agreeing with the information reported by Park and collaborators in a study done with women from Korea [42]....
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TL;DR: Wang et al. as discussed by the authors explored the relationship between hormone receptor (HR), human epidermal growth factor receptor 2 (HER2) status, and bone involvement in the first distant metastases (DM) of Chinese breast cancer patients who lacked the HER2 targeted therapy.
Abstract: Abstract Background This retrospective study explored the relationship between hormone receptor (HR), human epidermal growth factor receptor 2 (HER2) status, and bone involvement in the first distant metastases (DM) of Chinese breast cancer (BC) patients who lacked the HER2 targeted therapy. Such therapy was rarely received due to its lag approval or high cost in China compared with the developed countries. Methods All eligible women with primary unilateral stage I – III BC and first DM diagnosed in 2008—2018 at one cancer center were identified for enrollment. Based on chart records, a full or no/partial compliance status of endocrine therapy (ET) was assigned for HR-positive patients. Multivariate logistic regression was used to estimate the adjusted odd ratio (aOR), its 95%CI and p value. Results Four hundred eighteen patients had an average age of 50.7 years and median disease-free survival of 27.1 months at DM. Bone, lung, liver and brain metastasis rates in patients were 55.7%, 34.7%, 33.0% and 8.1%, respectively. Compared to HR-negative patients, HR-positive patients with the full and non/partial compliance of ET were significantly associated with higher risk of bone involvement with an aOR of 2.329 (1.316 – 1.741, p = 0.004 ) and 2.317 (1.330 – 4.036, p = 0.003 ), respectively. No difference of such risk was found between the two groups of ET compliance ( p = 0.984 ) nor between HER2-negative and HER2-positive patients (aOR 0.827, p = 0.431 ). Stratified analyses further indicated that HR-positive was associated with bone involvement only in HER2-negative BC patients ( p = 0.006—0.015 ). Conclusions HR-positive tumors are significantly associated with bone involvement in HER2-negative metastatic BC patients. ET does not appear to impact this association. HER2 status per se is not associated with such risk.
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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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