The molecular and clinicopathologic characteristics of bilateral breast cancer.
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ABSTRACT:
SUBMITTER: Chen SF
PROVIDER: S-EPMC3763252 | biostudies-other | 2013
REPOSITORIES: biostudies-other
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Project description:PurposeThis study aimed to evaluate the clinicopathological characteristics of pregnancy-associated breast cancer (PABC) in comparison with non-pregnancy associated breast cancer (non-PABC).MethodsA total of 344 eligible patients with PABC were identified in the Korean Breast Cancer Society Registry database. PABC was defined as ductal carcinoma in situ, invasive ductal carcinoma, or invasive lobular carcinoma diagnosed during pregnancy or within 1 year after the birth of a child. Patients with non-PABC were selected from the same database using a 1:2 matching method. The matching variables were operation, age, and initial stage.ResultsPatients with PABC had significantly lower survival rates than patient with non-PABC (10-year survival rate: PABC, 76.4%; non-PABC, 85.1%; p=0.011). PABC patients had higher histologic grade and were more frequently hormone receptor negative than non-PABC patients. Being overweight (body mass index [BMI], ≥23 kg/m2), early menarche (≤13 years), late age at first childbirth (≥30 years), and a family history of breast cancer were more common in the PABC group than in the non-PABC group. Multivariate analysis showed the following factors to be significantly associated with PABC (vs. non-PABC): early menarche (odds ratio [OR], 2.165; 95% confidence interval [CI], 1.566-2.994; p<0.001), late age at first childbirth (OR, 2.446; 95% CI, 1.722-3.473; p<0.001), and being overweight (OR, 1.389; 95% CI, 1.007-1.917; p=0.045).ConclusionEarly menarche, late age at first childbirth, and BMI ≥23 kg/m2 were more associated with PABC than non-PABC.
| S-EPMC5620441 | biostudies-literature
Project description:Gastric cancer (GC), one of the most common human cancers, can be classified into gastric or intestinal phenotype according to mucin expression. TP53 mutation, allelic deletion of the APC gene and nuclear staining of β-catenin are frequently detected in the intestinal phenotype of GC, whereas CDH1 gene mutation, microsatellite instability and DNA hypermethylation of MLH1 are common events in the gastric phenotype of GC. Our Serial Analysis of Gene Expression (SAGE) and Escherichia coli ampicillin secretion trap (CAST) analyses revealed that CDH17, REG4, OLFM4, HOXA10, DSC2, TSPAN8 and TM9SF3 are upregulated in GC and that CLDN18 is downregulated in GC. Expression of CDH17, REG4, HOXA10 and DSC2 and downregulation of CLDN18 are observed in the intestinal phenotype of GC. In contrast, OLFM4 is expressed in the gastric phenotype of GC. Expression of TSPAN8, TM9SF3 and HER2 are not associated with either gastric or intestinal phenotypes. Ectopic CDX2 expression plays a key function in the GC intestinal phenotype. MUC2, CDH17, REG4, DSC2 and ABCB1 are direct targets of CDX2. Importantly, these genes encode transmembrane/secretory proteins, indicating that the microenvironment as well as cancer cells are also different between gastric and intestinal phenotypes of GC.
| S-EPMC4556382 | biostudies-literature
Project description:BackgroundTriple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), represents a subset of breast cancer with different biologic behaviour. We investigated the clinicopathologic characteristics and prognostic indicators of lymph node-negative TN breast cancer.MethodsMedical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Seoul National University Hospital between Jan. 2000 and Jun. 2003. Clinicopathologic variables and clinical outcomes were evaluated.ResultsAmong 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (< 35 y, p = 0.003), and higher histologic and nuclear grade (p < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for bcl-2 expression (p < 0.001), positive for the epidermal growth factor receptor (p = 0.003), and a high level of p53 (p < 0.001) and Ki67 expression (p < 0.00). The relapse rates during the follow-up period (median, 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (p = 0.004). Relapse free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer (4-year RFS rate 85.5% vs. 94.2%, respectively; p = 0.001). On multivariate analysis, young age, close resection margin, and triple-negativity were independent predictors of shorter RFS.ConclusionTN breast cancer had higher relapse rate and more aggressive clinicopathologic characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into the risk factor analysis for node-negative breast cancer.
| S-EPMC2577689 | biostudies-literature
Project description:Genomewide DNA methylation array profiling of 37 BCOR altered tumors and 37 non-BCOR altered tumors to study the rare tumor entity of EP300::BCOR fusion in central nervous system. The raw methylation idat files and processed beta values were provided here.
2022-10-09 | GSE211156 | GEO
Project description:ImportanceGiven conflicting results regarding the prognosis of erb-b2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-low breast cancer, a large-scale, nationally applicable comparison of ERBB2-low vs ERBB2-negative breast cancer is needed.ObjectiveTo investigate whether ERBB2-low breast cancer is a clinically distinct subtype in terms of epidemiological characteristics, prognosis, and response to neoadjuvant chemotherapy.Design/participants/settingThis retrospective cohort study was conducted using the National Cancer Database, including 1 136 016 patients in the US diagnosed with invasive breast cancer from January 1, 2010, to December 31, 2019, who had ERBB2-negative disease and had immunohistochemistry results available. ERBB2-low tumors were classified as having an immunohistochemistry score of 1+, or 2+ with a negative in situ hybridization test. Data were analyzed from November 1, 2021, through November 30, 2022.ExposuresStandard therapy according to routine clinical practice.Main outcomes and measuresThe primary outcomes were overall survival (OS), reported as adjusted hazard ratios (aHRs), and pathologic complete response, reported as adjusted odds ratios (aORs), for ERBB2-negative vs ERBB2-low breast cancer, controlling for age, sex, race and ethnicity, Charlson-Deyo Comorbidity Index score, treatment facility type, tumor grade, tumor histology, hormone receptor status, and cancer stage.ResultsThe study identified 1 136 016 patients (mean [SD] age, 62.4 [13.1] years; 99.1% female; 78.6% non-Hispanic White), of whom 392 246 (34.5%) were diagnosed with ERBB2-negative and 743 770 (65.5%) with ERBB2-low breast cancer. The mean (SD) age of the ERBB2-negative group was 62.1 (13.2) years and 62.5 (13.0) years for the ERBB2-low group. Higher estrogen receptor expression was associated with increased rates of ERBB2-low disease (aOR, 1.15 per 10% increase). Compared with non-Hispanic White patients, of whom 66.1% were diagnosed with ERBB2-low breast cancer, fewer non-Hispanic Black (62.8%) and Hispanic (61.0%) patients had ERBB2-low disease, although in non-Hispanic Black patients this was mediated by differences in rates of triple-negative disease and other confounders. A slightly lower rate of pathologic complete response was seen in patients with ERBB2-low disease vs patients with ERBB2-negative disease on multivariable analysis (aOR, 0.89; 95% CI, 0.86-0.92; P < .001). ERBB2-low status was also associated with small improvements in OS for stage III (aHR, 0.92; 95% CI, 0.89-0.96; P < .001) and stage IV (aHR, 0.91; 95% CI, 0.87-0.96; P < .001) triple-negative breast cancer, although this amounted to only a 2.0% (stage III) and 0.4% (stage IV) increase in 5-year OS.Conclusions and relevanceThis large-scale retrospective cohort analysis found minimal prognostic differences between ERBB2-low and ERBB2-negative breast cancer. These findings suggest that, moving forward, outcomes in ERBB2-low breast cancer will be driven by ERBB2-directed antibody-drug conjugates, rather than intrinsic differences in biological characteristics associated with low-level ERBB2 expression. These findings do not support the classification of ERBB2-low breast cancer as a unique disease entity.
| S-EPMC9951099 | biostudies-literature
Project description:ImportanceAlopecia induced by classic chemotherapy affects up to 65% of patients and is usually reversible. However, there are increasing reports of persistent chemotherapy-induced alopecia (pCIA), especially for patients treated with taxane-containing chemotherapy regimens.ObjectiveTo analyze the clinicopathologic characteristics and response to treatment of patients with pCIA after chemotherapy for breast cancer.Design, setting, and participantsIn this case series, a retrospective evaluation was performed of patients with a diagnosis of pCIA after chemotherapy for breast cancer in 4 specialist hair clinics from November 1, 2011, to February 29, 2020.Main outcomes and measuresClinical, trichoscopic, and histopathologic characteristics and treatment outcomes were analyzed. For patients who presented with diffuse alopecia or diffuse rarefaction of hair over the midfrontal scalp with widening of the central part line and preservation of the frontal hairline, the Sinclair scale (grades 1-5, where 1 indicates normal hair density and 5 indicates the most severe stage of hair loss, with little or no hair in the centroparietal region) was used to assess severity.ResultsOne hundred patients (99 women [99%]; mean age at presentation, 54.0 years [range, 29.0-74.1 years]) were included. Most patients had diffuse nonscarring alopecia (n = 39), female pattern hair loss (n = 55), or male pattern hair loss (n = 6). Six patients developed cicatricial alopecia. Taxane-containing regimens were used for most patients (92 [92%]) and were associated with more severe alopecia than regimens that did not contain taxanes (median Sinclair grade, 4 [IQR, 3-5] vs 2 [IQR, 2-2.5]; P < .001). A total of 76 of 86 patients (88%) had trichoscopic signs indistinguishable from those of androgenetic alopecia. Of 18 patients who had biopsies, 14 had androgenetic alopecia-like features, 2 had cicatricial alopecia, and 2 had features of both. Both topical and oral minoxidil, sometimes combined with antiandrogen therapy, were associated with an improvement in hair density (median Sinclair grade, 4 [IQR, 3-5] before treatment vs 3 [IQR, 2-4] after treatment; P < .001).Conclusions and relevanceThis case series outlines previously unreported features of pCIA in patients with breast cancer, including a trichoscopic description. Cosmetically significant regrowth was achieved for a significant proportion of patients with topical or systemic treatments, suggesting that pCIA may be at least partly reversible.
| S-EPMC8482302 | biostudies-literature
Project description:Colorectal cancers (CRC) with microsatellite instability (MSI) or mismatch repair-deficiency (dMMR), but without detectable MMR germline mutations are termed Lynch-like syndrome (LLS). We assess the clinicopathologic and molecular characteristics of LLS tumors and the proportion in LLS, which remain poorly investigated in China. We enrolled 404 CRC patients with surgery in our institution from 2014 to 2018. LLS tumors were detected by a molecular stratification based on MMR protein expression, MLH1 methylation and MMR gene mutation. LLS tumors were profiled for germline mutations in 425 cancer-relevant genes. Among 42 MMR-deficient tumors, 7 (16.7%) were attributable to MLH1 methylation and 7 (16.7%) to germline mutations, leaving 28 LLS cases (66.6%). LLS tumors were diagnosed at a mean age of 60.7 years, had an almost equivalent ratio among rectum, left colon and right colon, and had high rates of lymph node metastases (50%, 4/28 N2). Most MMR gene mutations (88.2%, 15/17) in LLS tumors were variants of unknown significance (VUS). Two novel frameshift mutations were detected in ATM and ARID1A, which are emerging as candidate responsible genes for LLS. In this study, 28 (66.6%) MMRd tumors were classified as LLS, which were significantly higher than reports of western countries. LLS tumors were more likely to carry lymph node metastases. However, it's hard to differentiated LLS tumors from LS through family history, tumor location, histological type of tumors, immunohistochemistry (IHC) for MMR proteins and MSI analysis.
| S-EPMC7716154 | biostudies-literature
Project description:Breast cancer is a heterogeneous disease, with several intrinsic subtypes differing by hormone receptor (HR) status, molecular profiles, and prognosis. However, the role of DNA methylation in breast cancer development and progression and its relationship with the intrinsic tumor subtypes are not fully understood.A microarray targeting promoters of cancer-related genes was used to evaluate DNA methylation at 935 CpG sites in 517 breast tumors from the Carolina Breast Cancer Study, a population-based study of invasive breast cancer.Consensus clustering using methylation (?) values for the 167 most variant CpG loci defined four clusters differing most distinctly in HR status, intrinsic subtype (luminal versus basal-like), and p53 mutation status. Supervised analyses for HR status, subtype, and p53 status identified 266 differentially methylated CpG loci with considerable overlap. Genes relatively hypermethylated in HR+, luminal A, or p53 wild-type breast cancers included FABP3, FGF2, FZD9, GAS7, HDAC9, HOXA11, MME, PAX6, POMC, PTGS2, RASSF1, RBP1, and SCGB3A1, whereas those more highly methylated in HR-, basal-like, or p53 mutant tumors included BCR, C4B, DAB2IP, MEST, RARA, SEPT5, TFF1, THY1, and SERPINA5. Clustering also defined a hypermethylated luminal-enriched tumor cluster 3 that gene ontology analysis revealed to be enriched for homeobox and other developmental genes (ASCL2, DLK1, EYA4, GAS7, HOXA5, HOXA9, HOXB13, IHH, IPF1, ISL1, PAX6, TBX1, SOX1, and SOX17). Although basal-enriched cluster 2 showed worse short-term survival, the luminal-enriched cluster 3 showed worse long-term survival but was not independently prognostic in multivariate Cox proportional hazard analysis, likely due to the mostly early stage cases in this dataset.This study demonstrates that epigenetic patterns are strongly associated with HR status, subtype, and p53 mutation status and may show heterogeneity within tumor subclass. Among HR+ breast tumors, a subset exhibiting a gene signature characterized by hypermethylation of developmental genes and poorer clinicopathologic features may have prognostic value and requires further study. Genes differentially methylated between clinically important tumor subsets have roles in differentiation, development, and tumor growth and may be critical to establishing and maintaining tumor phenotypes and clinical outcomes.
| S-EPMC4303129 | biostudies-literature
Project description:Bilateral breast cancer (BBC) may present as synchronous (SBC) or metachronous breast cancer (MBC). Optimal surgical management of BBC patients is not well-defined. In this study, we report on histopathology, treatment, and outcomes in BBC patients.Upon Institutional Review Board approval, we identified BBC patients diagnosed and treated for invasive breast cancer between 1999 and 2007. Retrospective chart review for demographics, histopathology, treatment, and outcomes was performed, and factors associated with BCS choice were collected. Contraindication to BCS was defined as any of the following one-breast findings: multicentric disease, tumor considered too large for BCS, and a patient without a nominal breast size for acceptable cosmetic results. McNemar's test for matched pairs (binary variables) or the paired t test (continuous variables) were used to examine if a pathologic characteristic differed within a cancer pair. Kaplan-Meier methods estimated overall survival (OS).A total of 203 BBC patients (119 SBC, 84 MBC) comprised our study group. Histopathologic characteristics of the first and second cancers diagnosed in both the SBC and MBC patients were very similar in histologic type and molecular profiles. Overall, 57% of MBC patients underwent breast-conserving surgery (BCS) at initial diagnosis versus 34% of patients with SBC. BCS contraindications were similar in both groups: 16 (34%) MBC patients and 28 (36%) SBC patients. Kaplan-Meier OS estimates at 5 and 10 years were 86 and 78% for MBC, and 87 and 77% for SBC patients, respectively.OS was excellent for both the MBC and SBC groups. Contraindications to BCS did not differ between groups. However, patients with SBC were less likely to undergo BCS compared with patients with MBC at the time of initial diagnosis.
| S-EPMC4636081 | biostudies-literature
Project description:BackgroundEvidence suggests that patients with synchronous bilateral breast cancer (SBBC), diagnosed within 4 months, have an inferior prognosis compared to unilateral breast cancer (UBC) patients. Using data from nationwide Danish clinical databases, this cohort study investigated whether the inferior prognosis could be explained by SBBC patients having a more aggressive disease, or whether the prognosis could be explained by the fact that they have two simultaneous cancers.MethodsPatients were diagnosed from 1999-2015. The main outcome was excess mortality, subtracting background population mortality from observed mortality. Differences between SBBC and UBC patients were evaluated by rate ratios (RR) and estimated by Poisson regression.ResultsIn total, 1214 SBBC and 59 177 UBC patients were included. SBBC patients had a significantly higher excess mortality than UBC patients after adjustment for age and period (RR = 1.73; 95% CI:1.44-2.08; p < 0.01) and after adjusting for characteristics of the worst tumour as traditionally done (RR = 1.31; 95% CI:1.08-1.57; p = 0.01). However, adjusting for characteristics of both tumours, using a more advanced competing risks model, no difference was observed (RR = 1.01; 95% CI:0.83-1.22; p = 0.93).ConclusionsOur study does not support that the inferior prognosis in SBBC patients is due to having more aggressive tumours per se, but rather the combined effect of having two simultaneous cancers.
| S-EPMC6461871 | biostudies-literature