Multiple primary tumours in women following breast cancer, 1973-2000.
Ontology highlight
ABSTRACT:
SUBMITTER: Raymond JS
PROVIDER: S-EPMC2361329 | biostudies-other | 2006 Jun
REPOSITORIES: biostudies-other
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Project description:Agents that target the epigenome show activity in breast cancer models. In preclinical studies, the histone deacetylase inhibitor vorinostat induces cell-cycle arrest, apoptosis, and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women with newly diagnosed invasive disease who received vorinostat and those who did not.Tumor specimens were collected from 25 women who received up to 6 doses of oral vorinostat 300 mg twice daily and from 25 untreated controls in a nonrandomized study. Candidate gene expression was analyzed by reverse transcription PCR (RT-PCR) using the Oncotype DX 21-gene assay, and by immunohistochemistry for Ki-67 and cleaved caspase-3. Matched samples from treated women were analyzed for gene methylation by quantitative multiplex methylation-specific PCR (QM-MSP). Wilcoxon nonparametric tests were used to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated controls, and changes in gene methylation between pre- and post-vorinostat samples.Vorinostat was well tolerated and there were no study-related delays in treatment. Compared with untreated controls, there were statistically significant decreases in the expression of proliferation-associated genes Ki-67 (P = 0.003), STK15 (P = 0.005), and Cyclin B1 (P = 0.03) following vorinostat, but not in other genes by the Oncotype DX assay, or in expression of Ki-67 or cleaved caspase-3 by immunohistochemistry. Changes in methylation were not observed.Short-term vorinostat administration is associated with a significant decrease in expression of proliferation-associated genes in untreated breast cancers. This demonstration of biologic activity supports investigation of vorinostat in combination with other agents for the management of breast cancer.
| S-EPMC3718062 | biostudies-literature
Project description:Familial cancer syndromes, which are commonly caused by germline mutations in oncogenes and tumor suppressor genes, are generally considered to be the cause of primary multiple malignant neoplasias (PMMNs). Using targeted genomic sequencing, we screened for eight germline mutations: BRCA1 185delAG, BRCA1 T300G, BRCA1 2080delA, BRCA1 4153delA, BRCA1 5382insC, BRCA2 6174delT, CHEK2 1100delC, and BLM C1642T, which provoke the majority of cases of hereditary breast and ovary cancer syndrome (HBOC), in genomic (blood) DNA from 60 women with PMMNs, including breast (BC) and/or ovarian cancer(s) (OC). Pathogenic allelic forms were discovered in nine samples: in seven instances, it was BRCA1 5382insC, and in the following two, BRCA1 4153delA and BRCA1 T300G. The age of onset in these patients (46.8 years) was younger than in the general Russian population (61.0) for BC but was not for OC: 58.3 and 59.4, correspondingly. There were invasive breast carcinomas of no special type and invasive serous ovarian carcinomas in all cases. Two or more tumors of HBOC-spectrum were only in five out of nine families of mutation carriers. Nevertheless, every mutation carrier has relatives who have developed malignant tumors.
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Project description:The prognosis of malignancies has improved in recent years, subsequent primary cancers (SPCs) have become more frequent. This study investigates the patterns of lung cancer involved multiple primary cancers. We enrolled 206,619 primary lung cancer patients and 2,071,922 patients with other primary malignancies from Surveillance, Epidemiology and End Results (SEER) database. Observed annual risk (OAR) and absolute numbers were used to describe the risk of SPC and observed cases of SPC per 10,000 person-years at risk. Overall, OAR of SPCs following lung cancer was 176.28. At follow-up, 41.26% of SPCs occurred within 12-59 months while the highest OAR appeared after 120 months. The overall OAR of subsequent lung cancer after other malignancies was 27.90. Overall, the highest OAR and the highest absolute numbers of subsequent lung cancers were noticed 60-119 months and over 120 months post-diagnosis, respectively. Ten related cancers were listed. Our findings encourage surveillance for 10 common SPCs in lung cancer survivors during follow-up as well as screening for lung cancer after 10 common malignancies.
| S-EPMC5527071 | biostudies-literature
Project description:Breast cancer in very young women (?35 years; BCVY) presents more aggressive and complex biological features than their older counterparts (BCO). Our aim was to evaluate methylation differences between BCVY and BCO and their DNA epigenetic age. EPIC and 450k Illumina methylation arrays were used in 67 breast cancer tumours, including 32 from BCVY, for methylation study and additionally we analysed their epigenetic age. We identified 2 219 CpG sites differently-methylated in BCVY vs. BCO (FDR?<?0.05; ?-value difference?±?0.1). The signature showed a general hypomethylation profile with a selective small hypermethylation profile located in open-sea regions in BCVY against BCO and normal tissue. Strikingly, BCVY presented a significant increased epigenetic age-acceleration compared with older women. The affected genes were enriched for pathways in neuronal-system pathways, cell communication, and matrix organisation. Validation in an independent sample highlighted consistent higher expression of HOXD9, and PCDH10 genes in BCVY. Regions implicated in the hypermethylation profile were involved in Notch signalling pathways, the immune system or DNA repair. We further validated HDAC5 expression in BCVY. We have identified a DNA methylation signature that is specific to BCVY and have shown that epigenetic age-acceleration is increased in BCVY.
| S-EPMC6800453 | biostudies-literature
Project description:BackgroundAlthough recent findings suggest that de novo stage IV breast cancer is increasing in premenopausal women in the United States, contemporary incidence and survival data are lacking for stage I-III cancer.MethodsWomen aged 20-29 (n = 3826), 30-39 (n = 34 585), and 40-49 (n = 126 552) years who were diagnosed with stage I-III breast cancer from 2000 to 2015 were identified from the Surveillance, Epidemiology, and End Results 18 registries database. Age-adjusted, average annual percentage changes in incidence and 5- and 10-year Kaplan-Meier survival curves were estimated by race and ethnicity, stage, and hormone receptor (HR) status and grade (low to well and moderately differentiated; high to poorly and undifferentiated) for each age decade.ResultsThe average annual percentage change in incidence was positive for each age decade and was highest among women aged 20-29 years. Increased incidence was driven largely by HR+ cancer, particularly HR+ low-grade cancer in women aged 20-29 and 40-49 years. By 2015, incidence of HR+ low- and high-grade cancer each independently exceeded incidence of HR- cancer in each age decade. Survival for HR+ low- and high-grade cancer decreased with decreasing age; survival for HR- cancer was similar across age decades. Among all women aged 20-29 years, 10-year survival for HR+ high-grade cancer was lower than that for HR+ low-grade or HR- cancer. Among women aged 20-29 years with stage I cancer, 10-year survival was lowest for HR+ high-grade cancer.ConclusionsHR+ breast cancer is increasing in incidence among premenopausal women, and HR+ high-grade cancer was associated with reduced survival among women aged 20-29 years. Our findings can help guide further evaluation of preventive, diagnostic, and therapeutic strategies for breast cancer among premenopausal women.
| S-EPMC6668585 | biostudies-literature
Project description:Importance:Given recent advances in screening mammography and adjuvant therapy (treatment), quantifying their separate and combined effects on US breast cancer mortality reductions by molecular subtype could guide future decisions to reduce disease burden. Objective:To evaluate the contributions associated with screening and treatment to breast cancer mortality reductions by molecular subtype based on estrogen-receptor (ER) and human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu). Design, Setting, and Participants:Six Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2012 using national data on plain-film and digital mammography patterns and performance, dissemination and efficacy of ER/ERBB2-specific treatment, and competing mortality. Multiple US birth cohorts were simulated. Exposures:Screening mammography and treatment. Main Outcomes and Measures:The models compared age-adjusted, overall, and ER/ERBB2-specific breast cancer mortality rates from 2000 to 2012 for women aged 30 to 79 years relative to the estimated mortality rate in the absence of screening and treatment (baseline rate); mortality reductions were apportioned to screening and treatment. Results:In 2000, the estimated reduction in overall breast cancer mortality rate was 37% (model range, 27%-42%) relative to the estimated baseline rate in 2000 of 64 deaths (model range, 56-73) per 100?000 women: 44% (model range, 35%-60%) of this reduction was associated with screening and 56% (model range, 40%-65%) with treatment. In 2012, the estimated reduction in overall breast cancer mortality rate was 49% (model range, 39%-58%) relative to the estimated baseline rate in 2012 of 63 deaths (model range, 54-73) per 100?000 women: 37% (model range, 26%-51%) of this reduction was associated with screening and 63% (model range, 49%-74%) with treatment. Of the 63% associated with treatment, 31% (model range, 22%-37%) was associated with chemotherapy, 27% (model range, 18%-36%) with hormone therapy, and 4% (model range, 1%-6%) with trastuzumab. The estimated relative contributions associated with screening vs treatment varied by molecular subtype: for ER+/ERBB2-, 36% (model range, 24%-50%) vs 64% (model range, 50%-76%); for ER+/ERBB2+, 31% (model range, 23%-41%) vs 69% (model range, 59%-77%); for ER-/ERBB2+, 40% (model range, 34%-47%) vs 60% (model range, 53%-66%); and for ER-/ERBB2-, 48% (model range, 38%-57%) vs 52% (model range, 44%-62%). Conclusions and Relevance:In this simulation modeling study that projected trends in breast cancer mortality rates among US women, decreases in overall breast cancer mortality from 2000 to 2012 were associated with advances in screening and in adjuvant therapy, although the associations varied by breast cancer molecular subtype.
| S-EPMC5833658 | biostudies-literature
Project description:Importance:There is little evidence on population-based harms and benefits of screening breast magnetic resonance imaging (MRI) in women with and without a personal history of breast cancer (PHBC). Objective:To evaluate biopsy rates and yield in the 90 days following screening (mammography vs magnetic resonance imaging with or without mammography) among women with and without a PHBC. Design, Setting, and Participants:Observational cohort study of 6 Breast Cancer Surveillance Consortium (BCSC) registries. Population-based sample of 812?164 women undergoing screening, 2003 through 2013. Exposures:A total of 2?048?994 digital mammography and/or breast MRI screening episodes (mammogram alone vs MRI?with or without?screening mammogram within 30 days). Main Outcomes and Measures:Biopsy intensity (surgical?greater than?core?greater than?fine-needle aspiration) and yield (invasive cancer greater than?ductal carcinoma in situ greater than?high-risk benign?greater than?benign) within 90 days of a screening episode. We computed age-adjusted rates of biopsy intensity (per 1000 screening episodes) and biopsy yield (per 1000 screening episodes with biopsies). Outcomes were stratified by PHBC and by BCSC 5-year breast cancer risk among women without PHBC. Results:We included 101?103 and 1?939?455 mammogram screening episodes in women with and without PHBC, respectively; MRI screening episodes included 3763 with PHBC and 4673 without PHBC. Age-adjusted core and surgical biopsy rates (per 1000 episodes) doubled (57.1; 95% CI, 50.3-65.1) following MRI compared with mammography (23.6; 95% CI, 22.4-24.8) in women with PHBC. Differences (per 1000 episodes) were even larger in women without PHBC: 84.7 (95% CI, 75.9-94.9) following MRI and 14.9 (95% CI, 14.7-15.0) following mammography episodes. Ductal carcinoma in situ and invasive biopsy yield (per 1000 episodes) was significantly higher following mammography compared with MRI episodes in women with PHBC (mammography, 404.6; 95% CI, 381.2-428.8; MRI, 267.6; 95% CI, 208.0-337.8) and nonsignificantly higher, but in the same direction, in women without PHBC (mammography, 279.3; 95% CI, 274.2-284.4; MRI, 214.6; 95% CI, 158.7-280.8). High-risk benign lesions were more commonly identified following MRI regardless of PHBC. Higher biopsy rates and lower cancer yield following MRI were not explained by increasing age or higher 5-year breast cancer risk. Conclusions and Relevance:Women with and without PHBC who undergo screening MRI experience higher biopsy rates coupled with significantly lower cancer yield findings following biopsy compared with screening mammography alone. Further work is needed to identify women who will benefit from screening MRI to ensure an acceptable benefit-to-harm ratio.
| S-EPMC5876894 | biostudies-other
Project description:INTRODUCTION:Current evidence suggests that patients who have latissimus dorsi (LD) breast reconstruction following mastectomy for breast cancer can experience long-term shoulder dysfunction. However, as there is no standardised assessment or follow-up period within the literature, findings are conflicting. This research aimed to investigate the impact on daily living of immediate and delayed LD breast reconstruction in women following mastectomy for breast cancer. METHODS:Both qualitative and quantitative methods of enquiry were used. A focus group study explored the musculoskeletal consequences of surgery as perceived by the women (n = 15) and their healthcare professionals (n = 11). A questionnaire survey was administered (n = 159), including a range of outcome measures to quantify both the physical and psychosocial impact of LD breast reconstruction. Dyad interviews were also conducted in order to determine the impact of surgery on function and activities of daily living (ADL) from the woman's perspective and that of her significant other (n = 8). RESULTS:The qualitative studies highlighted a lack of preparedness and unrealistic expectations regarding functional recovery among women and their significant others'. Post-surgery it was apparent that women weighed up reduced shoulder function against survival, demonstrating resilience in their approach to coping with this adaptive way of living. The survey identified low to moderate effect on the outcomes assessed (n = 159), however, node removal significantly impacted certain aspects of quality of life (p<0.05) and disability (p = 0.04). CONCLUSIONS:Breast reconstruction using the LD had an impact on shoulder function and some ADL, which impacted not only on the women but also family and significant others. Despite the functional implications associated with surgery, findings would suggest that shoulder dysfunction is not their main concern. This work identified that women and their significant other require further information to clarify expectation regarding recovery, highlighting the changing priorities of women throughout their journey from diagnosis into long-term recovery.
| S-EPMC6112655 | biostudies-literature
Project description:PurposeThere are numerous biomarkers which may have potential predictive and prognostic significance in breast cancer. This is extremely important in older adults, who may opt for less aggressive therapy. This work outlines the literature on biological assessment outside of standard biomarkers (defined as ER, PgR, HER2, Ki67) in women ≥ 65 years with primary operable invasive breast cancer, to determine which additional biomarkers are relevant to outcome in older women.MethodsMedline and Embase databases were searched. Studies were eligible if included ≥ 50 patients aged ≥ 65 years; stratified results by age; measured a biomarker outside of standard assay and reported patient data.ResultsA total of 12 studies were appraised involving 5000 patients, measuring 28 biomarkers. The studies were extremely varied in methodology and outcome but three themes emerged: 1. Differences in biomarker expression between younger and older women, indicating that breast cancer in older women is generally less aggressive compared to younger women; 2. Relationship of biomarker expression with survival, suggesting biomarkers which may exclusively predict response to primary treatment in older women; 3. Association of biomarker with chemotherapy, suggesting that older patients should not be declined chemotherapy based on age alone.ConclusionThere is evidence to support further investigation of B-cell lymphoma (BCL2), liver kinase (LK)B1, epidermal growth factor receptor (EGFR), cytoplasmic cyclin-E, mucin (MUC)1 and cytokeratins (CKs) as potential predictive or prognostic markers in older women with breast cancer undergoing surgery. Studies exploring these biomarkers in larger cohorts and in women undergoing non-operative therapies are required.
| S-EPMC8354915 | biostudies-literature
Project description:Among colorectal cancer (CRC) survivors, how the prior tumor location affects the risk of subsequent primary colorectal cancer (SPCRC) and the outcome of those suffering from SPCRC remain unknown.CRC cases diagnosed from 1973 to 2012 were screened for SPCRC development using the Surveillance, Epidemiology, and End Results database. The relative risk of SPCRC was estimated using the standardized incidence ratio. Survivals were analyzed using the Kaplan-Meier and Cox regression model.The overall risk of SPCRC increased by 27% in CRC survivors compared to that of the general population. The risk increased in patients with both prior right colon cancer (RCC) and left colon cancer (LCC), and was concentrated in the first 5 years after the prior diagnosis, and among young patients. Among the 6701 SPCRC patients identified, patients with prior RCC were more likely to be elderly, female, and with more low or undifferentiated disease than those with prior LCC or rectal cancer (ReC). The overall survivals differed by both prior tumor location (P?<?0.0001) and age (P?<?0.0001), and the difference by tumor location remained significant when adjusted or stratified by any other potential prognostic factor except age. The cancer specific survivals differed by age (P?<?0.0001) rather than by prior tumor location (P?=?0.455).The overall risk of SPCRC increased among patients with both prior RCC and LCC, but not among those with ReC. The different survival outcomes in CRC survivors suffering from SPCRC were largely explained by the patient age but not by the prior tumor location.
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