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  • American Society of Clinical Oncology (ASCO)  (17)
  • 1
    Online Resource
    Online Resource
    Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 14 ( 2013-05-10), p. 1748-1757
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 14 ( 2013-05-10), p. 1748-1757
    Abstract: To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M 0 ), metastasis-free survival (MFS), and CSS from metastasis (CSS_M 1 ). Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2012.43.1882
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 14 ( 2022-05-10), p. 1529-1541
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 14 ( 2022-05-10), p. 1529-1541
    Abstract: To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.21.02112
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 10 ( 2023-04-01), p. 1849-1863
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 10 ( 2023-04-01), p. 1849-1863
    Abstract: A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS 313 ) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS 313 with clinicopathologic characteristics of, and survival following, breast cancer. METHODS Women with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS 313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS 313 (continuous, per standard deviation) with overall survival (OS) and breast cancer–specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment. RESULTS The PRS 313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS 313 was associated with lower grade, hormone receptor–positive status, and smaller tumor size. In MINDACT, PRS 313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS 313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent. CONCLUSION An increased PRS 313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS 313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS 313 as increasing PRS 313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.22.01978
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 4
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    Tamoxifen and Risk of Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 25 ( 2013-09-01), p. 3091-3099
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 25 ( 2013-09-01), p. 3091-3099
    Abstract: To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. Methods Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up. Results Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 BRCA2 mutation carriers with 100 CBCs over 4,392 person-years of prospective follow-up. HRs did not differ by estrogen receptor status of the first BC (missing for 56% of cases). Conclusion This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2012.47.8313
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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  • 5
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    Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 20 ( 2017-07-10), p. 2240-2250
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 20 ( 2017-07-10), p. 2240-2250
    Abstract: BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated—for the first time to our knowledge—associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10 −6 ). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10 −9 ). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.69.4935
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 6
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    Effect of Chest X-Rays on the Risk of Breast Cancer Among BRCA1/2 Mutation Carriers in the International BRCA1/2 Carrier Cohort Study: A Report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators’ Group
    American Society of Clinical Oncology (ASCO) ; 2006
    In:  Journal of Clinical Oncology Vol. 24, No. 21 ( 2006-07-20), p. 3361-3366
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 21 ( 2006-07-20), p. 3361-3366
    Abstract: Women who carry germline mutations in the BRCA1 and BRCA2 genes are at greatly increased risk of breast cancer (BC). Numerous studies have shown that moderate to high doses of ionizing radiation are a risk factor for BC. Because of the role of the BRCA proteins in DNA repair, we hypothesized that BRCA carriers might be more sensitive to ionizing radiation than women in the general population. Patients and Methods A retrospective cohort study of 1,601 female BRCA1/2 carriers was performed. Risk of breast cancer from exposure to chest x-rays, as assessed by questionnaire data, was analyzed using a weighted Cox proportional hazards model. Results In this cohort, any reported exposure to chest x-rays was associated with an increased risk of BC (hazard ratio [HR] = 1.54; P = .007). This risk was increased in carrier women aged 40 years and younger (HR = 1.97; P 〈 .001) and in women born after 1949 (HR = 2.56; P 〈 .001), particularly those exposed only before the age of 20 years (HR = 4.64; P 〈 .001). Conclusion In our series of BRCA carriers, we detected a relatively large effect on BC risk with a level of radiation exposure that is at least an order of magnitude lower than in previously studied medical radiation–exposed cohorts. Although part of this increase may be attributable to recall bias, the observed patterns of risk in terms of age at exposure and attained age are consistent with those found in previous studies. If confirmed, the results have important implications for the use of x-ray imaging in young BRCA1/2 carriers.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2005.03.3126
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2006
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  • 7
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    Online Resource
    BRCA1 and BRCA2 Cancer Risks
    American Society of Clinical Oncology (ASCO) ; 2006
    In:  Journal of Clinical Oncology Vol. 24, No. 20 ( 2006-07-10), p. 3312-3313
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 20 ( 2006-07-10), p. 3312-3313
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2006.06.7934
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2006
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  • 8
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    Online Resource
    Risk of breast or ovarian cancer in family members who do not carry the BRCA1 or BRCA2 family mutation: Findings from the EMBRACE study.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 1558-1558
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 1558-1558
    Abstract: 1558 Background: BRCA1/BRCA2 true-negatives are proven non-carriers of the BRCA mutation segregating within their family. Currently, there is no conclusive evidence on the risk of developing breast or ovarian cancer in these individuals, potentially leading to non-uniform clinical practices. The purpose of this study was to estimate breast and ovarian cancer risks for true-negatives from the EMBRACE prospective cohort study. Methods: Risks were calculated separately for incident invasive breast cancer and epithelial ovarian cancer (EOC). We used cohort analysis to estimate incidences, cumulative risks and standardised incidence ratios (SIRs). Results: A total of 1895 unaffected women were eligible for inclusion in the breast cancer analysis and 1736 for the ovarian cancer analysis. There were 23 incident invasive breast cancers and 2 EOCs diagnosed during follow-up. The cumulative risk of invasive breast cancer was 9.4% (95% CI 5.9%-15%) by the age of 85-years, whilst the corresponding risk of EOC was 0.6% (95% CI 0.2%-2.6%). The SIR for breast cancer was 0.93 (95% CI 0.62-1.40) in the overall cohort, 0.85 (95% CI 0.48-1.50) in non-carriers from BRCA1 families and 1.03 (95% CI 0.57-1.87) in non-carriers from BRCA2 families. The SIR for EOC was 0.79 (95% CI 0.20-3.17) in the overall cohort and 1.74 (95% CI 0.44-6.98) in non-carriers from BRCA2 families. Conclusions: This is the largest cohort to date of prospectively ascertained true-negatives from BRCA1/ BRCA2 families. Our results did not provide evidence for elevated risks of invasive breast cancer or EOC in proven non-carriers. Risk-reducing bilateral mastectomy and risk-reducing salpingo-oophorectomy may not be appropriate for these individuals. Female relatives of a known BRCA1/BRCA2 mutation carrier should be advised towards genetic testing to avoid unnecessary surgical procedures. However, we were not able to investigate variation in risks by cancer family history. Therefore, we cannot rule out that risks may be slightly higher for close relatives of affected mutation carriers. In such cases, model-based estimates incorporating family history, such as those given by BOADICEA, can be used in the counselling process.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.1558
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 9
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    Risk Factors for the Incidence of Breast Cancer: Do They Affect Survival From the Disease?
    American Society of Clinical Oncology (ASCO) ; 2008
    In:  Journal of Clinical Oncology Vol. 26, No. 20 ( 2008-07-10), p. 3310-3316
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 20 ( 2008-07-10), p. 3310-3316
    Abstract: Risk factors that influence the incidence of breast cancer may also affect survival after diagnosis. Methods Data from 4,560 women with invasive breast cancer who had taken part in the population-based Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) breast cancer study were used to investigate the influence on survival of variables related to pregnancy, menarche and menopause, prior use of exogenous hormones, height, weight, body mass index (BMI), smoking history, and alcohol intake. Results In univariate analyses, there was no association between prognosis and age at menarche and menopause, menopausal status at diagnosis, smoking history, or prior use of the oral contraceptive pill. Women whose most recent pregnancy was more than 30 years ago had a 35% reduced risk of dying (95% CI, 8% to 54%) compared with women who had a full-term pregnancy in the past 15 years, and the use of hormone replacement therapy for more than 4 years was associated with a similar risk reduction. BMI was associated with a 3% (95% CI, 1% to 4%) increase in mortality per unit increase. Improved prognosis was seen with increasing current alcohol consumption, with a 2% (95% CI, 1% to 3%) reduction in the risk of death per unit of alcohol consumed per week. Conclusion The apparent benefit of alcohol intake has not been described before, and our data need to be interpreted with some caution. However, our finding that an increase in BMI is associated with a poorer prognosis supports previously published data and suggests that advice on weight loss should be given to all obese patients with breast cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2006.10.3168
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2008
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  • 10
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    Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 7 ( 2020-03-01), p. 674-685
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 7 ( 2020-03-01), p. 674-685
    Abstract: To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10 −76 ), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10 −3 ), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10 −3 ), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10 −2 ). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age ( P for trend = 2.0 × 10 −3 ). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies ( P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.19.01907
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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