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1.
Am J Obstet Gynecol ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33493488

RESUMO

BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. OBJECTIVE: This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. RESULTS: Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with <5 years: 5-9 years [hazard ratio, 0.67; 95% confidence interval, 0.40-1.12]; >10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; Ptrend=.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 <15 years since last use [hazard ratio, 0.24; 95% confidence interval, 0.14-0.43]; BRCA1 >15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18-0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size. CONCLUSION: For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.

2.
Public Health Genomics ; 23(3-4): 100-109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32640451

RESUMO

Swedish national breast cancer guidelines recommend that all women diagnosed with breast cancer (BC) at the age of 35 years or younger should be referred to their regional oncogenetic clinic for genetic counseling and testing, regardless of family history of cancer. The main objective of this study was to evaluate whether place of residence at BC diagnosis and treating hospital were associated with the fact that not all BC patients diagnosed at ≤35 years in the southern part of Sweden have attended genetic counseling and testing. Between 2000 and 2013, 279 women in the South Swedish Health Care Region were diagnosed with BC at ≤35 years. Information regarding place of residence at BC diagnosis, treating hospital, time of registration and first meeting at the Oncogenetic Clinic in Lund, and genetic testing was collected. With a follow-up period until August 2018, 64% were registered at the clinic (60% underwent genetic testing) and 36% were not. BC patients from 2 counties and from rural settings with a population of <10,000 inhabitants were significantly less likely to be registered at the clinic. Our results suggest that place of residence at BC diagnosis and treating hospital were associated with the probability of referral for genetic counseling and testing for women diagnosed with BC at ≤35 years in the South Swedish Health Care Region. We propose, as a generalizable finding, that further educational and outreach activities within the health care system and the community may be needed to ensure that all women diagnosed with early-onset BC receive proper genetic counseling.

3.
Nat Commun ; 11(1): 312, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949161

RESUMO

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.


Assuntos
Neoplasias da Mama/genética , Variação Genética , Estudo de Associação Genômica Ampla , Células Germinativas , Apoptose , Relógios Circadianos , Biologia Computacional , Feminino , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Redes Reguladoras de Genes , Genótipo , Humanos , Prognóstico , Receptores Estrogênicos/genética , Transdução de Sinais
4.
Cancer Causes Control ; 29(2): 243-251, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29299723

RESUMO

The purpose was to elucidate the interplay between current smoking, anthropometric measurements, and endogenous hormone levels in women ≤ 40 years. Questionnaires on lifestyle and reproductive factors were completed by 269 healthy women from high-risk breast cancer families between 1996 and 2006 in Sweden. Blood samples for analyses of plasma testosterone, estradiol, androstenedione, sex hormone-binding globulin, and body measurements were obtained 5-10 days before predicted onset of the next menstrual period. Women without smoking status, who were currently breastfeeding, or using hormonal contraception other than combined oral contraceptives (OCs) were excluded (n = 27). Current smokers (n = 57) had larger waist circumference (adjp = 0.004) and waist-to-hip ratio (WHR) (adjp = 0.007) than non-smokers (n = 185). In non-OC users, adjusted mean androstenedione levels were higher in current smokers compared with non-smokers (10.3 vs. 8.6 nmol/L; adjp = 0.0002). While in current OC users estradiol levels were higher in smokers compared with non-smokers (22.5 vs. 17.4 pg/mL; adjp = 0.012). In multivariable models, WHR was associated with both current smoking (adjp ≤ 0.016) and higher levels of androstenedione (adjp = 0.05) or bioavailable testosterone (adjp = 0.001). Among non-OC users, a more androgenic profile was observed in current smokers compared with non-smokers, but not in current OC users. Irrespective of OC use, current smoking was associated with increased waist circumference.


Assuntos
Neoplasias da Mama/epidemiologia , Fumar/epidemiologia , Circunferência da Cintura , Adulto , Androgênios/sangue , Estradiol/sangue , Feminino , Humanos , Globulina de Ligação a Hormônio Sexual/metabolismo , Fumantes , Suécia , Testosterona/sangue , Relação Cintura-Quadril , Adulto Jovem
5.
Acta Oncol ; 57(5): 595-603, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29164969

RESUMO

BACKGROUND: The main objectives of this study were to evaluate the concordance between self-reported and registry-reported information regarding family history of breast cancer (BC), ovarian cancer (OvC) and other types of cancer in first-degree relatives of patients with early onset BC, and to determine the frequency of mutation carriers and non-mutation carriers. The secondary objective was to describe tumor characteristics for each mutation group. MATERIAL AND METHODS: Between 1993 and 2013, 231 women who were ≤35 years old when diagnosed with BC were registered at the Oncogenetic Clinic at Skåne University Hospital in Lund, Sweden. Self-reported and registry-reported information regarding first-degree family history of cancer was collected together with information regarding tumor characteristics. RESULTS: Almost perfect agreement was observed between self-reported and registry-reported information regarding first-degree family history of BC (κ = 0.92) and OvC (κ = 0.86). Lesser agreement was observed between reports regarding family history of other types of cancer (κ = 0.51). Mutation screening revealed pathogenic germline mutations in 30.4%; 18.8% in BRCA1, 7.1% in BRCA2 and 4.5% in other genes. Compared with other mutation groups, BRCA1 mutation carriers were more likely to be diagnosed with high-grade, ER-, PR- and triple-negative tumors. CONCLUSIONS: Our results demonstrate that physicians and genetic counselors can rely on self-reported information regarding BC and OvC in first-degree relatives. However, self-reported information regarding other types of cancer is not communicated as effectively, and there should be more focus on retrieving the correct information regarding family history of all tumor types. Furthermore, we observed that even though all BC patients fulfilled the criteria for genetic counseling and testing, a large number of patients diagnosed at ≤35 years of age did not receive genetic counseling at the Oncogenetic Clinic. This finding merits further elucidation.


Assuntos
Neoplasias da Mama/genética , Anamnese , Sistema de Registros , Autorrelato , Adulto , Idade de Início , Neoplasias da Mama/patologia , Feminino , Heterozigoto , Humanos , Neoplasias/genética , Neoplasias Ovarianas/genética , Suécia
6.
Genes Chromosomes Cancer ; 54(1): 39-50, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25251729

RESUMO

Three studies have reported that BRCA1/2 mutations of paternal origin confer an earlier age at breast cancer diagnosis compared with maternal origin. The primary aim of this study was to investigate the impact of parental origin of BRCA1/2 mutations on age at breast and ovarian cancer diagnosis. This study included 577 female BRCA1/2 mutation carriers. All BRCA1/2 mutation carriers belonged to families registered between 1993 and 2011 at the Oncogenetic Clinic at Skånes University Hospital, Lund, Sweden. Cox proportional hazard ratios were used to analyze time to breast or ovarian cancer diagnosis. A novel finding was that carriers of BRCA1 mutations of paternal origin were 4 years older at age of ovarian cancer (P = 0.009) compared with those carrying a BRCA1 mutation of maternal origin. BRCA1 carriers with mutations of paternal origin were 4 years younger at breast cancer diagnosis (P = 0.017) compared with those carrying a BRCA1 mutation of maternal origin, which is in agreement with three previous studies. Both findings were adjusted for of year of inclusion, birth date, and oral contraceptive pill use. No associations between parental origin of BRCA2 mutations and time to breast or ovarian cancer diagnosis were found. An attempt to handle a potential selection bias regarding use of oral contraceptives was made using multiple imputations by chained equations. The observed age difference may allow a greater understanding of mechanisms associated with the differences in cancer penetrance in BRCA1/2 mutation carriers, some of which may depend on paternal origin.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Impressão Genômica , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Suécia
7.
Springerplus ; 2: 357, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24010029

RESUMO

INTRODUCTION: Breast cancer (BC) is one of the leading causes of death among women worldwide. Immunostimulatory treatment has increasingly been used as adjuvant therapy in the last few years, in patients with melanoma and other cancer forms, often with an induction of autoimmunity as a consequence of a successful treatment. We aimed at investigating if coexisting autoimmune diseases (AD) or hypersensitivities (HS) similarly to the side effects of immunostimulatory treatment resulted in a better overall survival, compared to patients without these disorders. MATERIAL AND METHODS: The patient material used was a consecutive clinical material consisting of 1705 patients diagnosed with BC between 1980 and 2010 in Sweden. The patients were stratified according to coexisting AD, HS or lack of both. Overall survival was calculated using Kaplan-Meier and the Cox proportional hazard model. RESULTS: Our main finding was that BC patients with estrogen receptor (ER) negative tumors together with preexisting AD or HS had a statistically significant better overall survival (HR=0.53; 95% CI= 0.30-0.96) compared to patients without. Premenopausal BC patients with a coexistence of AD or HS had a better overall survival, but this was not statistically significant. DISCUSSION: For patients with premenopausal or ER-negative BC, coexistence with AD or HS was associated with a better overall survival. Although these findings require validation, and the mechanisms responsible need to be found, they hint to possible new treatment strategies for BC, especially for those with ER-negative tumors and potentially for premenopausal patients.

8.
Breast Cancer Res Treat ; 131(1): 177-86, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21830013

RESUMO

Angiogenesis is one of the hallmarks of breast cancer. The status of angiogenesis is important in therapy choice. Spider telangiectasias (telangiectasias) may reflect an increased ability to form vessels. Our first aim was to identify patient and tumor characteristics associated with the occurrence of telangiectasias at the time of breast cancer diagnosis. The second aim was to study the overall survival in relation to the occurrence of telangiectasias at the time of breast cancer diagnosis. A standardized questionnaire was used to interview 1682 consecutive breast cancer patients about risk factors between 1980 and 2009. Occurrence of telangiectasias at the time of breast cancer diagnosis on the upper thorax, head, and/or neck was recorded by one physician. In the cohort, 93 women (5.5%) had telangiectasias. Occurrence of telangiectasias was positively associated with weight, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.00-1.05) per kg, ever-use of oral contraceptives OR 2.67(CI 1.55-4.63) and hormone replacement therapy OR 2.68(CI 1.63-4.39), and negatively associated with parity OR 0.45(CI 0.25-0.79). Telangiectasias were not present in patients with comedo breast cancer. Patients with occurrences of telangiectasias diagnosed before the age of 50 had a statistically non-significant worse overall survival, whereas the patients with occurrences of telangiectasias diagnosed at age 50 or after had a statistically significant better overall survival (P interaction = 0.016). The relationship between the occurrence of telangiectasias and the overall survival in the older patient-group was independent of ever-use of HRT. Hormonal risk factors for breast cancer were associated with the occurrence of spider telangiectasias. The occurrence of telangiectasias may reflect the angiogenic status of the tumor. We hypothesize that telangiectasias could be used as selection criteria for anti-angiogenic therapy in younger breast cancer patients. Therefore, patients with comedo breast cancers maybe a group that may benefit less from anti-angiogenic therapy.


Assuntos
Neoplasias da Mama/patologia , Telangiectasia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Feminino , Terapia de Reposição Hormonal , Humanos , Pessoa de Meia-Idade , Neovascularização Patológica , Prognóstico , Fatores de Risco , Adulto Jovem
9.
BMC Cancer ; 11: 497, 2011 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-22117567

RESUMO

BACKGROUND: The association between lobular breast cancer and family history is not clear. The aim of the study was to possibly identifying new hereditary patterns predisposing for cancer in the different histopathologic subtypes of breast cancer, with focus on patients with lobular breast cancer and cancer in their first degree relatives. METHODS: In 1676 consecutive breast cancer patients detailed family history of cancer was related to histopathologic subtype of breast cancer. RESULTS: Patients with lobular breast cancer were found to be significantly positively associated with having a father diagnosed with cancer, OR 2.17 (95% confidence interval (CI) 1.37-3.46). The finding persisted after excluding breast cancer in the family. Ductal breast cancer was associated with having a mother diagnosed with cancer. There was a significant association between lobular breast cancer and having a father with prostate cancer, OR 2.4 (CI 1.1-5.3). The occurrence of having a father with prostate cancer for lobular breast cancer patients was higher in the younger patient group, OR 2.9 (CI 1.1-7.8), and was still high but lost statistical significance in the older patient group, OR 1.9 (CI 0.5-7.4). The association between lobular breast cancer and a father remained significant after excluding fathers with prostate cancer, OR 1.94 (CI 1.20-3.14). Other commonly occurring tumor types in the father included sarcoma and leukemia. CONCLUSION: We propose that lobular breast cancer is associated with having a father diagnosed with cancer, most commonly prostate carcinoma. Since the association remained after excluding family history of breast cancer, the association seems independent of classical breast cancer heredity. The association with a father diagnosed with cancer also remained after removing prostate cancer, indicating an independence from prostate cancer as well. The reason for this association is genetically unclear, but could involve sex-specific imprinting.


Assuntos
Neoplasias da Mama/genética , Carcinoma Lobular/genética , Pai , Neoplasias da Próstata/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Carcinoma Lobular/epidemiologia , Carcinoma Lobular/patologia , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fatores Sexuais , Adulto Jovem
10.
Fam Cancer ; 9(4): 525-30, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20549370

RESUMO

While a dominant inheritance of breast cancer (vertical inheritance) is well known, less is known about a possible recessive inheritance (horizontal inheritance). In a clinical series of 1676 breast cancer patient's family history was scored as vertical (grandmother-aunt-mother-sister-daughter) or horizontal (sister-sister) and related to histopathological tumor type, presence of germline mutations, bilaterality, multifocality, screening, parity, hormone replacement therapy (HRT) use and age at diagnosis. Prognosis was estimated by also adding tumor size, lymph node status, distant metastases and hormone receptor status at diagnosis into a Cox proportional hazard model. Excluding mutations carriers, a horizontal family history (5% of all cases) was significantly associated with tubular tumor type [OR = 3.87(1.44-10.41)]. A vertical family history (23% of all cases) was significantly related to tumor multifocality [OR = 2.30(1.51-3.50)], tumor bilaterality [OR = 2.08(1.44-3.00)] and screening detection [OR = 1.50(1.10-2.05)]. No significant difference in survival could be seen between patients with none, horizontal or vertical family history. However, germline mutation carriers (BRCA1/2, TP53 or CDKN2A, present in 0.95% of the cases) had a significantly worse survival. Screening detected cases, HRT ever users and patients with estrogen receptor positive tumors had a significantly better survival adjusting for age at diagnosis, tumor size, lymph node status and presence of distant metastases at diagnosis. Factors associated with a horizontal family history were found, defining a possible phenotype for a recessive inheritance: tubular breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Genes Recessivos , Predisposição Genética para Doença , Mutação/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/terapia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/terapia , Carcinoma Lobular/genética , Carcinoma Lobular/mortalidade , Carcinoma Lobular/terapia , Carcinoma Medular/genética , Carcinoma Medular/mortalidade , Carcinoma Medular/terapia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Análise Mutacional de DNA , DNA de Neoplasias/genética , Feminino , Genótipo , Terapia de Reposição Hormonal , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase , Gravidez , Prognóstico , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética , Adulto Jovem
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