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1.
Artigo em Inglês | MEDLINE | ID: mdl-33423179

RESUMO

PURPOSE: It is not known whether the risk of breast cancer among BRCA1 and BRCA2 mutation carriers after age 60 is high enough to justify intensive screening or prophylactic surgery. Thus, we conducted a prospective analysis of breast cancer risk in BRCA1 and BRCA2 mutation carriers from age 60 until age 80. METHODS: Subjects had no history of cancer and both breasts intact at age 60 (n = 699). Women were followed until a breast cancer diagnosis, prophylactic bilateral mastectomy or death. We calculated the annual cancer rate and cumulative incidence of breast cancer (invasive and in situ) from age 60 to age 80. We assessed the associations between hormone replacement therapy, family history of breast cancer and bilateral oophorectomy and breast cancer risk. RESULTS: Over a mean follow-up of 7.9 years, 61 invasive and 20 in situ breast cancers were diagnosed in the cohort. The mean annual rate of invasive breast cancer was 1.8% for BRCA1 mutation carriers and 1.7% for BRCA2 mutation carriers. The cumulative risk of invasive breast cancer from age 60 to 80 was 20.1% for women with a BRCA1 mutation and was 17.3% for women with a BRCA2 mutation. Hormone replacement therapy, family history and oophorectomy were not associated with breast cancer risk. CONCLUSIONS: Findings from this large prospective study indicate that the risk of developing breast cancer remains high after age 60 in both BRCA1 and BRCA2 mutation carriers. These findings warrant further evaluation of the role of breast cancer screening in older mutation carriers.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33326624

RESUMO

OBJECTIVE: To compare the long-term survival outcomes for women with advanced ovarian cancer treated with chemotherapy either before or after surgery (neoadjuvant chemotherapy vs primary cytoreductive surgery) at a single tertiary cancer center. METHODS: Retrospective cohort study of 326 patients with Stage IIIC or IV high-grade serous ovarian cancer who received neoadjuvant chemotherapy or primary cytoreductive surgery between 2001 and 2011. Clinical treatments were recorded and 10-year survival rates were measured. RESULTS: A total of 183 women (56.1%) underwent primary cytoreductive surgery and 143 women (43.9%) received neoadjuvant chemotherapy. Women who received neoadjuvant chemotherapy were more likely to have no residual disease than those who underwent primary cytoreductive surgery (51.4% vs 41.5%; P = 0.030) but experienced inferior 10-year overall survival (9.1% vs 19.3%; P < 0.001). Among those who had primary cytoreductive surgery, those with no residual disease had superior 10-year overall survival than those who had any evidence of residual disease (36.0% vs 7.2%; P < 0.001). CONCLUSION: Among women with advanced ovarian cancer, those who underwent primary cytoreductive surgery had better survival than those who received neoadjuvant chemotherapy. Neoadjuvant chemotherapy should be reserved for those in whom optimal primary cytoreductive surgery is not feasible.

3.
Nutrients ; 12(11)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126678

RESUMO

Arsenic is a widespread environmental contaminant and recognized carcinogen for the skin, bladder and lungs. In recent years, there has been an increasing number of studies that have investigated the effects of arsenic exposure and cancer risk at other sites, including the breast. However, to date, the association between arsenic exposure and breast cancer risk remains unclear. This article will provide an overview of arsenic metabolism, the clinically important biomarkers commonly used to assess arsenic exposure, and review the epidemiologic studies examining the role of arsenic exposure on breast cancer risk. Given the large burden of disease associated with breast cancer, it is of the upmost importance to identify risk factors and preventative strategies that could reduce cancer incidence. Limiting exposure to endemic environmental toxins, such as arsenic, represents one such strategy. More studies are required to better ascertain this relationship and to develop the public policy necessary to significantly reduce breast cancer incidence.

4.
Gynecol Oncol ; 159(3): 820-826, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33010967

RESUMO

OBJECTIVE: BRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation. METHOD: Thus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures. RESULTS: A history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66-0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57-0.81; P < 0.0001) and did not vary by BRCA gene or age at diagnosis. The combination of breastfeeding and oral contraceptive use was strongly protective (0.47; 95%CI 0.37-0.58; P < 0.0001). CONCLUSIONS: These findings support a protective effect of breastfeeding for at least seven months among women with a BRCA1 or BRCA2 mutation, that is independent of oral contraceptive use.

5.
Fam Cancer ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32964297

RESUMO

Women at risk of developing ovarian cancer because of a BRCA1 or BRCA2 pathogenic variant are candidates for prophylactic bilateral salpingo-oophorectomy (BSO). While BSO surgeries are routinely performed, to our knowledge there are no studies that have examined patient-reported experiences following laparoscopic BSO performed in an ambulatory care setting. The objective of this study was to examine whether women undergoing prophylactic laparoscopic BSO felt they were adequately informed about post-operative outcomes. A telephone interview was conducted among 46 women undergoing laparoscopic BSO to collect detailed information regarding surgical outcomes, complications, symptoms, and time to return to daily activities. The average age at surgery was 45.0 years (range 34-66) and 67% of women underwent BSO prior to age 50. The mean reported hospital stay was 7.2 h (range 4-12 h) and at time of discharge, 78% of the women felt well enough to go home. None of the women required a readmission to hospital. Forty-three percent (n = 20) of the women did not feel well informed about what to expect post-operatively. Most of the patient-reported outcomes (including pain, vaginal bleeding, and nausea/vomiting) were expected and patient-reported menopausal symptoms were more common among women who were premenopausal at surgery. In terms of returning to regular activities, premenopausal women (n = 36) resumed sexual activity on average at 43 days (range 2-365), which is later than postmenopausal women (n = 15) at 19 days (range 7-30). On average, women returned to full-time work in 16 days (range 1-56 days). Despite patients receiving pre-surgery counselling, our findings suggest that there is a need to provide supplemental, reinforcing patient materials in preparing patients for what to expect after surgery.

6.
Menopause ; 27(12): 1396-1402, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32796289

RESUMO

OBJECTIVE: Bilateral salpingo-oophorectomy (oophorectomy) is recommended to women with a germline BRCA1 or BRCA2 mutation before natural menopause to prevent ovarian and fallopian tube cancer. The adverse effects of early surgical menopause are well established. Although many of the side effects can be ameliorated by the use of hormone therapy (HT); use of HT in this group of predominantly young patients remains suboptimal. The goal of this study was to identify the frequency of HT use, as well as predictors of HT uptake in BRCA mutation carriers who underwent preventive oophorectomy before natural menopause. METHODS: Eligible participants were identified from a longitudinal study of BRCA mutation carriers. We included premenopausal women with no personal history of cancer who underwent oophorectomy before age 50 and who had a minimum of 2 years of follow-up. Detailed information on HT use and other important variables was collected by a research questionnaire every 2 years. Descriptive statistics were used to evaluate the use of HT in various subgroups. RESULTS: A total of 793 women with a BRCA1 or BRCA2 mutation were included in this analysis. The mean age at oophorectomy was 42 years (range 28-49). Sixty-one percent of the women reported using HT after oophorectomy. Factors associated with HT use included young age at surgery, a high level of education and preventive mastectomy. CONCLUSIONS: The uptake of HT after oophorectomy in women with a BRCA1 or BRCA2 mutation varies by age, education, and surgical history. Clinician and patient awareness may lead to better utilization of HT in women who undergo oophorectomy at an early age to help mitigate the adverse effects associated with surgical menopause.

7.
Int J Gynecol Cancer ; 30(6): 825-830, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32354794

RESUMO

INTRODUCTION: Preventive bilateral salpingo-oophorectomy is the most effective means of reducing the risk of ovarian cancer among women with an inherited BRCA1 or BRCA2 mutation. Some women are diagnosed with an invasive cancer (ovarian or fallopian tube) at the time of preventive surgery, referred to as an 'occult' cancer. The survival experience of these women is not known. METHODS: We estimated the 10-year survival for 52 BRCA mutation carriers diagnosed with an occult ovarian or fallopian tube cancer at the time of preventive bilateral salpingo-oophorectomy. RESULTS: The mean age at diagnosis was 51.6 (range 33-69) years. All were serous cancers (although 14 were missing information on histologic subtype). Of the 20 cases with information available on stage at diagnosis, 10 were stage I, 1 was stage II, and 9 were stage III (n=32 missing). After a mean of 6.8 years, 12 women died (23%). The 10-year all-cause survival was 74%. CONCLUSION: Although based on only 52 cases, these findings suggest a more favorable prognosis for BRCA mutation carriers diagnosed with an occult rather than incident disease.

8.
Cancer Epidemiol Biomarkers Prev ; 29(6): 1264-1270, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32277005

RESUMO

BACKGROUND: Emerging evidence supports a role of the receptor activator of NF-κB (RANK) pathway in normal mammary gland development and breast carcinogenesis. Osteoprotegerin (OPG) is the endogenous decoy receptor for RANK-ligand (RANKL), which inhibits RANK-signaling. Whether OPG may be a biomarker of breast cancer risk remains unclear. METHODS: We evaluated the association between plasma OPG and breast cancer risk in a case (n = 297)-control (n = 297) study nested within the Nurses' Health Study II. Cases were women who were cancer-free and premenopausal at blood collection who developed invasive breast cancer. OPG was quantified using an ELISA. Conditional logistic regression was used to estimate multivariable odds ratios (OR) and 95% confidence intervals (CI) for the association between OPG levels and breast cancer risk, adjusting for potential confounders. Unconditional logistic regression, additionally adjusting for matching factors, was used for stratified analyses. RESULTS: Overall, there was no substantial evidence for an association between plasma OPG levels and breast cancer risk, although the point estimate for the highest (vs. lowest) quartile was below 1 (OR = 0.78; 95% CI, 0.46-1.33; P trend = 0.30). There was no evidence of heterogeneity by various reproductive, hormonal, or tumor characteristics, including hormone receptor status and grade (all P heterogeneity ≥ 0.17). CONCLUSIONS: Findings from this prospective study do not provide substantial evidence for an association between circulating OPG and breast cancer risk among premenopausal women; however, we were underpowered in stratified analyses. IMPACT: Results do not provide strong evidence for OPG as a potential biomarker of breast cancer risk among premenopausal women.

9.
Int J Cancer ; 147(5): 1354-1373, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32022258

RESUMO

Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress-related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population-based case-control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER-/PR- breast cancer risk (all ptrend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR>18 vs. 0 mg/day = 0.68, 95% CI: 0.51-0.91), and dietary heme iron was associated with an increased risk, particularly the ER-/PR- subtype (ORhighest vs. lowest quintile = 1.69, 95% CI: 1.16-2.47; ptrend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (pinteraction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.

10.
Int J Cancer ; 147(5): 1245-1251, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32037528

RESUMO

Ovarian cancer is the most fatal gynecologic malignancy (50% 5-year survival) due to a typically advanced stage at diagnosis and a high rate of recurrence. Chemoprevention options are limited, and few interventions have been shown to reduce cancer risk or mortality. Emerging data support the model that fallopian tubes are the site of origin for a proportion of high-grade serous cancers. This implies that a subset of cancers may be prevented by removing the fallopian tubes while leaving the ovaries intact. Accordingly, there has been shift in clinical practice for average risk women; some now recommend removal of both the fallopian tubes only instead of tubal ligation for sterilization or at the time of benign gynecologic surgery. This has been termed opportunistic salpingectomy and represents a means of decreasing the burden of ovarian cancer by preventing cancers that arise in the fallopian tubes. There have been no detailed, prospective reports that have estimated ovarian cancer risk reduction with opportunistic salpingectomy, neither among women at baseline population risk nor among women at a high risk of developing the disease. The situation is complicated for women with a BRCA mutation-bilateral salpingo-oophorectomy is a proven means of risk reduction and salpingectomy alone is not the standard of care. Based on the existing data, salpingectomy alone should only be reserved for women with a lifetime risk of ovarian cancer of less than 5%.

11.
Int J Cancer ; 146(10): 2721-2727, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31348523

RESUMO

Arsenic is recognized as a potent carcinogen at high concentrations, but the relationship between environmental arsenic and breast cancer risk has not well been studied. Most research has focused on the effect of arsenic in populations with high endemic exposure, and not in populations with arsenic levels within normal limits. We sought to determine if blood arsenic levels predict the risk of breast and other cancers risk among women in northern Poland. The cohort consisted of 1,702 healthy women, aged 40 and above, identified between 2010 and 2017. Blood arsenic level was determined by inductively coupled plasma mass spectrometry. After an average of 4.5 years of follow-up (range 0.7-7.3 years), there were 110 incident cases of cancer diagnosed in the cohort, including 68 cases of breast cancer. Women in the highest quartile of arsenic had a highly significant 13-fold increased risk of developing breast cancer, compared to women in the lowest quartile (hazard ratio [HR] = 13.2; 95% confidence interval [CI] 4.02-43.0). Results were similar for arsenic and all incident cancers (HR quartile 4 vs. quartile 1 = 13.3; 95% CI 4.78-37.0). If confirmed, our study suggests that the blood arsenic level may be a useful predictive marker of cancer risk in women.


Assuntos
Arsênico/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Adulto , Idoso , Exposição Ambiental/efeitos adversos , Feminino , Predisposição Genética para Doença/genética , Humanos , Incidência , Pessoa de Meia-Idade , Polônia , Fatores de Risco
12.
Menopause ; 27(2): 156-161, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31644510

RESUMO

OBJECTIVE: BRCA mutation carriers are advised to undergo bilateral salpingo-oophorectomy to prevent ovarian cancer. The abrupt hormonal withdrawal associated with early surgical menopause has been shown to increase the risk of depression and anxiety among women in the general population. The impact in women with a BRCA1 or BRCA2 mutation is not known. METHODS: We undertook a matched prospective study of BRCA mutation carriers to evaluate the impact of oophorectomy on self-reported initiation of antidepressant use. We identified women with no personal history of cancer or depression and prospectively evaluated the frequency of self-reported medication use after surgery. Each exposed participant (oophorectomy) was randomly matched to a control participant (no oophorectomy) according to year of birth (within 3 years), BRCA mutation type (BRCA1 or BRCA2), and country of residence (Canada, United States, Poland). A total of 506 matched sets were included. We estimated the odds ratio (OR) and 95% confidence intervals (CIs) of antidepressant use (ever/never) following preventive oophorectomy in the entire study population and stratified by age at oophorectomy and by use of hormone therapy. RESULTS: Oophorectomy was not associated with more frequent antidepressant use among BRCA mutation carriers (OR = 0.46; 95% CI 0.22-0.96). We observed reductions in the odds of antidepressant medication use among women who underwent oophorectomy before the age of 50 years (OR = 0.33; 95% CI 0.14-0.78) and among those who initiated hormone therapy use after oophorectomy (OR = 0.35; 95% CI 0.14-0.90). Findings were similar when the analysis was based on self-reported depression (rather than antidepressant use). CONCLUSIONS: Although based on a small number of women, these findings suggest that oophorectomy does not increase psychological distress among women at an elevated risk of ovarian cancer.


Assuntos
Antidepressivos/uso terapêutico , Depressão/epidemiologia , Predisposição Genética para Doença/psicologia , Procedimentos Cirúrgicos Profiláticos/psicologia , Salpingo-Ooforectomia/psicologia , Adulto , Proteína BRCA1/genética , Proteína BRCA2/genética , Canadá/epidemiologia , Depressão/tratamento farmacológico , Depressão/etiologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Pessoa de Meia-Idade , Mutação , Razão de Chances , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Polônia/epidemiologia , Estudos Prospectivos , Estados Unidos/epidemiologia
13.
Lancet ; 394(10204): 1116-1118, 2019 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-31474333
14.
Gynecol Oncol ; 155(2): 270-274, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31500890

RESUMO

OBJECTIVE: To compare the survival experience of women with a BRCA1 mutation who enrolled in an ovarian cancer screening program with that of women who opted for preventive oophorectomy. METHODS: We followed 1964 women with a BRCA1 mutation and two ovaries intact in a prospective study. No women had ovarian cancer or had a bilateral oophorectomy prior to study initiation. There were 1814 women in the cohort who had at least one screening ultrasound. They were followed from the date of first ultrasound until the date of preventive oophorectomy, death or last follow-up. There were 659 women in the cohort who had preventive oophorectomy. They were followed from the date of preventive oophorectomy until death or last follow-up. RESULTS: Among the 1196 women who had one or more ultrasound examinations and no oophorectomy, there were 73 incident cancers detected and 27 deaths from ovarian/fallopian cancer. The ten year cumulative risk of death was 2.0%. Among the 659 women who had a preventive oophorectomy there were 12 incident cancers (9 detected at oophorectomy and 3 in the follow up period) and two deaths from ovarian cancer. The ten year cumulative risk of death was 0.5%. The hazard ratio for oophorectomy versus ultrasound was 0.23 (95% CI: 0.05 to 0.97; p = 0.05). CONCLUSION: The survival of women diagnosed with ovarian cancer enrolled in an ultrasound screening program is relatively poor and screening is not a viable alternative to preventive oophorectomy.


Assuntos
Neoplasias Ovarianas/mortalidade , Ovariectomia/mortalidade , Adulto , Idoso , Detecção Precoce de Câncer , Feminino , Genes BRCA1/fisiologia , Heterozigoto , Humanos , Programas de Rastreamento/mortalidade , Pessoa de Meia-Idade , Mutação/genética , Neoplasias Ovarianas/prevenção & controle , Polônia/epidemiologia , Estudos Prospectivos , Ultrassonografia , Adulto Jovem
15.
JAMA Netw Open ; 2(8): e198420, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31390031

RESUMO

Importance: Preventive surgery is strongly recommended for individuals with a BRCA mutation at a young age to prevent ovarian cancer and improve overall survival. The overall effect of early surgical menopause on various health outcomes, including bone health, has not been clearly elucidated. Objective: To evaluate the association of prophylactic bilateral salpingo-oophorectomy with bone mineral density (BMD) loss among individuals with a BRCA mutation. Design, Setting, and Participants: This retrospective cohort study of participants with a BRCA mutation who underwent oophorectomy through the University Health Network, Toronto, Ontario, Canada, recruited participants from January 2000 to May 2013. Eligibility criteria included having a BRCA mutation, at least 1 ovary intact prior to surgery, and no history of any cancer other than breast cancer. Bone mineral density was measured using dual-energy x-ray absorptiometry before and after surgery. Data analysis began in December 2018 and finished in January 2019. Main Outcomes and Measures: The annual change in BMD from baseline to follow-up was calculated for the following 3 anatomical locations: (1) lumbar spine, (2) femoral neck, and (3) total hip. Results: A total of 95 women had both a baseline and postsurgery BMD measurement with a mean (SD) follow-up period of 22.0 (12.7) months. The mean (SD) age at oophorectomy was 48.0 (7.4) years. Among women who were premenopausal at time of surgery (50 [53%]), there was a decrease in BMD from baseline to follow-up across the lumbar spine (annual change, -3.45%; 95% CI, -4.61% to -2.29%), femoral neck (annual change, -2.85%; 95% CI, -3.79% to -1.91%), and total hip (annual change, -2.24%; 95% CI, -3.11% to -1.38%). Self-reported hormone therapy use was associated with significantly less bone loss at the lumbar spine (-2.00% vs -4.69%; P = .02) and total hip (-1.38% vs -3.21; P = .04) compared with no hormone therapy use. Among postmenopausal women at time of surgery (45 [47%]), there was also a significant decrease in BMD across the lumbar spine (annual change, -0.82%; 95% CI, -1.42% to -0.23%) and femoral neck (annual change, -0.68%; 95% CI, -1.33% to -0.04%) but not total hip (annual change, -0.18%; 95% CI, -0.82% to 0.46%). Conclusions and Relevance: This study found that oophorectomy was associated with postoperative bone loss, especially among women who were premenopausal at the time of surgery. Targeted management strategies should include routine BMD assessment and hormone therapy use to improve management of bone health in this population.


Assuntos
Densidade Óssea/fisiologia , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Genes BRCA1 , Osteoporose/etiologia , Osteoporose/prevenção & controle , Procedimentos Cirúrgicos Profiláticos/efeitos adversos , Salpingo-Ooforectomia/efeitos adversos , Adulto , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Ontário , Estudos Retrospectivos
16.
BMC Cancer ; 19(1): 631, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242899

RESUMO

BACKGROUND: Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation. METHODS: We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates. RESULTS: Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm2 vs. 53.1cm2; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant. CONCLUSIONS: In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.


Assuntos
Peso Corporal , Densidade da Mama/genética , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Saúde da Família , Mamografia , Adulto , Idoso , Estudos Transversais , Ex-Fumantes/estatística & dados numéricos , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Estilo de Vida , Modelos Lineares , Pessoa de Meia-Idade , Paridade , Pós-Menopausa , Pré-Menopausa , Saúde Reprodutiva , Fatores de Risco , Fumantes/estatística & dados numéricos
17.
Int J Epidemiol ; 48(3): 822-830, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211375

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer. METHODS: Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls). RESULTS: An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85-0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65-0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations. CONCLUSION: Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.


Assuntos
Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma Mucinoso/epidemiologia , Carcinoma Endometrioide/epidemiologia , Neoplasias Ovarianas/epidemiologia , Síndrome do Ovário Policístico/epidemiologia , Feminino , Humanos , Análise da Randomização Mendeliana , Neoplasias Císticas, Mucinosas e Serosas/epidemiologia , Síndrome do Ovário Policístico/genética
18.
Oncotarget ; 10(25): 2475-2483, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-31069010

RESUMO

Background: Aberrant progesterone/receptor activator of nuclear factor κß (RANK) signaling has been implicated in BRCA1 breast cancer development. Furthermore, lower circulating RANKL has been reported among women with a BRCA mutation compared to non-carriers; however, there have been no reports of plasma RANKL levels and subsequent breast cancer risk. We prospectively evaluated the relationship between plasma RANKL and breast cancer risk among women with a BRCA1 or BRCA2 mutation. Methods: An enzyme-linked immunosorbent assay was used to quantify plasma RANKL levels in 184 BRCA mutation carriers. Women were stratified into high vs. low RANKL based on the median levels of the cohort (5.24 pg/ml). Kaplan-Meier survival analysis was used to estimate the cumulative incidence of breast cancer by baseline plasma RANKL and cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for the association between plasma RANKL and risk. Results: Over a mean follow-up of 6.3 years (0.02-19.24), 15 incident breast cancers were identified. The eight-year cumulative incidence was 10% in the low RANKL group and 12% in the high RANKL group (P-log-rank = 0.85). There was no significant association between plasma RANKL levels and breast cancer risk (multivariate HR high vs. low = 1.06; 95%CI 0.34-3.28; P-trend = 0.86). Conclusions: These findings suggest that circulating RANKL levels are not associated with breast cancer among BRCA mutation carriers. Pending validation in a larger sample, these findings suggest that RANKL is likely not a biomarker of breast cancer risk among BRCA mutation carriers.

19.
Breast Cancer Res Treat ; 175(2): 443-449, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30756284

RESUMO

PURPOSE: Following a diagnosis of breast cancer, BRCA mutation carriers face an increased risk of developing a second (contralateral) cancer in the unaffected breast. It is important to identify predictors of contralateral cancer in order to make informed decisions about bilateral mastectomy. The impact of bilateral salpingo-oophorectomy (i.e., oophorectomy) on the risk of developing contralateral breast cancer is unclear. Thus, we conducted a prospective study of the relationship between oophorectomy and the risk of contralateral breast cancer in 1781 BRCA1 and 503 BRCA2 mutation carriers with breast cancer. METHODS: Women were followed from the date of diagnosis of their first breast cancer until the date of diagnosis of a contralateral breast cancer, bilateral mastectomy, date of death, or date of last follow-up. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of contralateral breast cancer associated with oophorectomy. Oophorectomy was included as a time-dependent covariate. We performed a left-censored analysis for those women who reported a primary breast cancer prior to study entry (i.e., from completion of baseline questionnaire). RESULTS: After an average of 9.8 years of follow-up, there were 179 (7.8%) contralateral breast cancers diagnosed. Oophorectomy was not associated with the risk of developing a second breast cancer (HR 0.92; 95% CI 0.68-1.25). The relationship did not vary by BRCA mutation type or by age at diagnosis of the first breast cancer. There was some evidence for a decreased risk of contralateral breast cancer among women with an ER-positive primary breast cancer, but this was based on a small number of events (n = 240). CONCLUSION: Overall, our findings suggest that oophorectomy has little impact on the risk of contralateral breast cancer.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Ovário/cirurgia , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Mastectomia , Pessoa de Meia-Idade , Mutação , Ovariectomia , Ovário/patologia , Modelos de Riscos Proporcionais , Fatores de Risco
20.
Breast Cancer Res Treat ; 174(3): 769-774, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30612273

RESUMO

PURPOSE: Women with an inherited germline BRCA1 mutation have a high lifetime risk of developing breast cancer. We have previously shown that, among BRCA mutation carriers, incidence rates of breast cancer vary by country of residence. METHODS: In the current study, we prospectively calculated the cumulative and annual incidence rates of incident breast cancer, contralateral breast cancer and ipsilateral breast cancer recurrence among BRCA1 mutation carriers in Poland. Study subjects comprised a cohort of 1776 Polish women with a BRCA1 mutation who had no prior diagnosis of breast or ovarian cancer at the time of enrollment, the women were followed with a biennial follow-up by questionnaire. Women were followed for an average of 6.1 years (range 0.0-18.2) and 191 new breast cancer cases were diagnosed. RESULTS: The cumulative incidence of breast cancer to age 70 was 52%. The annual risk of breast cancer was estimated at 1.78%; the maximum annual risk was observed between the ages of 30 and 65. Among the 941 women with a prior diagnosis of breast cancer, 106 women developed a contralateral breast cancer. The 20-year cumulative incidence of contralateral breast cancer was 31% and the annual rate of contralateral breast cancer was 1.96%. There were 11 recurrences among the 215 women with breast cancer (ipsilateral breast cancers). The cumulative incidence at 20 years was 17% and the annual rate of an ipsilateral recurrence was 1.03%. CONCLUSION: Our findings confirm the high annual rates of early-onset incident, contralateral and recurrent breast cancer among Polish BRCA1 mutation carriers. These risk estimates are important in the context of the clinical management of unaffected women as well as in the treatment of newly diagnosed primary breast cancers and can also be used as the basis for the planning of prevention trials.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/epidemiologia , Grupo com Ancestrais do Continente Europeu/genética , Mutação , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idade de Início , Idoso , Neoplasias da Mama/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Incidência , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Polônia
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