| 1. |
- Bai, Lucy, et al.
(författare)
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Body image problems in women with and without breast cancer 6-20 years after bilateral risk-reducing surgery : A prospective follow-up study
- 2019
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Ingår i: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 44, s. 120-127
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To prospectively follow-up and investigate women's perceptions of the cosmetic outcome of their implant-based breast reconstruction, body image, sexuality, anxiety/depressive symptoms, and health-related quality of life (HRQoL) 6-20 years after bilateral risk-reducing mastectomy (RRM), or complementary RRM after breast cancer diagnosis, due to increased risk of hereditary breast cancer.PATIENTS AND METHODS: Women with and without previous breast cancer diagnosis that underwent RRM between March 1997 and September 2010 were invited (n = 200). We compared 146 (73%) sets of long-term questionnaire responses (e.g., EORTC QLQ-BRR26, Body Image Scale, Sexuality Activity Questionnaire, Hospital Anxiety and Depression Scale, and SF-36) with responses one year after surgery. Women with and without previous breast cancer were compared at the long-term assessment point.RESULTS: The HRQoL and anxiety/depressive symptoms remained unchanged compared with one year after surgery, and there were no between-group differences. The negative impact on body image persisted in both groups for most of the items. 'Sexual discomfort' increased significantly for women with previous breast cancer (p = 0.016). Women with previous breast cancer also reported more problems with 'Disease treatment/surgery related symptoms' (p = 0.006) and 'Sexuality' (p = 0.031) in the EORTC QLQ-BRR26 questionnaire.CONCLUSION: Problems with body image appeared to persist long time post-RRM. No differences in HRQoL were found at the long-term follow-up between women with and without previous breast cancer. The results of this investigation might be of use in improving future counselling before risk-reducing surgery for women in the decision-making process.
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| 2. |
- Catucci, Irene, et al.
(författare)
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Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility
- 2018
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600. ; 20:4, s. 452-457
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Tidskriftsartikel (refereegranskat)abstract
- PurposeMonoallelic germ-line mutations in the BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN genes confer high risk of breast cancer. Biallelic mutations in these genes cause Fanconi anemia (FA), characterized by malformations, bone marrow failure, chromosome fragility, and cancer predisposition (BRCA2/FANCD1 and PALB2/FANCN), or an FA-like disease presenting a phenotype similar to FA but without bone marrow failure (BRCA1/FANCS). FANCM monoallelic mutations have been reported as moderate risk factors for breast cancer, but there are no reports of any clinical phenotype observed in carriers of biallelic mutations.MethodsBreast cancer probands were subjected to mutation analysis by sequencing gene panels or testing DNA damage response genes.ResultsFive cases homozygous for FANCM loss-of-function mutations were identified. They show a heterogeneous phenotype including cancer predisposition, toxicity to chemotherapy, early menopause, and possibly chromosome fragility. Phenotype severity might correlate with mutation position in the gene.ConclusionOur data indicate that biallelic FANCM mutations do not cause classical FA, providing proof that FANCM is not a canonical FA gene. Moreover, our observations support previous findings suggesting that FANCM is a breast cancer-predisposing gene. Mutation testing of FANCM might be considered for individuals with the above-described clinical features.Genetics in Medicine advance online publication, 24 August 2017; doi:10.1038/gim.2017.123.
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| 3. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 4. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 5. |
- Isaksson, Karin, et al.
(författare)
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Bilateral risk-reducing mastectomies with implant-based reconstructions followed long term : a consecutive series of 185 patients
- 2019
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 43:9, s. 2262-2270
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bilateral risk-reducing mastectomy (BRRM) is the most effective method to prevent breast cancer in genetically predisposed women and is often performed concomitantly with breast reconstruction. The reconstruction time varies and corrective surgeries are common.METHODS: This study evaluated 185 consecutive cases of BRRM and immediate breast reconstruction with implants with regard to surgical outcome and resource consumption. With an 18-year observation period, it was possible to compare permanent expander implants (PEIs) with permanent fixed volume implants (PIs).RESULTS: A minimum follow-up of 2 years for all participants but one was achieved. Seventy-five percent (n = 138) of the women received PEI and 25% (n = 47) PI. In a multivariate analysis including age, BMI (<25, ≥25), smoking (yes, no), implant type (PEI, PI), incision technique, operation time and specimen weight <350 g, ≥350 g), only BMI ≥25 was associated with an increased risk of an early complication (OR 7.1, 95% CI 2.44-20.4). As expected, there was a significant difference in median reconstruction time between PEI and PI (12.4 vs. 1.0 months, p < 0.001). The cumulative reoperation-free 2-year survival was significantly higher in the PI than in the PEI group (81% vs. 26%, p < 0.001).CONCLUSION: Implant-based reconstruction remains a valid option after BRRM in high-risk women. Whenever possible (low BMI and small breast volume without severe ptosis), permanent fixed volume implants can be safely recommended and are resource saving in comparison with permanent expander implants.
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| 6. |
- Karlsson, Anders, et al.
(författare)
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The accuracy of incremental pre-operative breast MRI findings - Concordance with histopathology in the Swedish randomized multicenter POMB trial
- 2019
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Ingår i: European Journal of Radiology. - : ELSEVIER IRELAND LTD. - 0720-048X .- 1872-7727. ; 114, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Pre-Operative MRI of the Breast (POMB) trial was a randomized, prospective, multicenter trial evaluating the impact of pre-operative breast MRI on treatment regimens and short-term surgical outcomes in women up to 56 years of age with breast cancer. The purpose of this study was to evaluate the performance of pre-operative breast MRI in the POMB trial with respect to incremental MRI findings - over conventional breast imaging methods - and their concordance with histopathology.Patients and methods: Two-hundred and ten patients (n = 210) participating in the POMB trial underwent preoperative breast MRI at two Swedish breast units. Positive predictive values (PPV) for the incremental MRI findings were calculated for three subgroups of patients with: 1. alteration/alterations of treatment plan; 2. no alteration of treatment plan; and, 3. MRI-related conversion from BCS to mastectomy. Area under the receiver operating characteristic curve (AUC) was calculated using in-breast BI-RADS based ratings for the whole MRI group.Results: After exclusions a total number of 99 incremental findings in 78 patients were eligible for statistical analysis resulting in a PPV = 74%: (95% CI 60-84%) in 39 patients with MRI related alterations of initial treatment plans and 27%: (95% CI 14-44%) in 39 patients without. Positive predictive values of incremental findings decisive for specific treatment alteration/s were 83% (95% CI 68-92%) in patients with any alteration of initial treatment plans and 91% (95% CI 70-98%) for patients (n = 20/22) with conversion from breast conserving surgery to mastectomy. The empirical AUC for the incremental findings in the whole MRI group was 85% (95% CI 78-91%).Conclusion: Breast MRI, performed and evaluated together with conventional breast imaging methods can provide relevant information at a high degree of accuracy in the pre-operative setting.
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| 7. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 8. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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