Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Breast Cancer Research, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2021-12)
    Abstract: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP 〈  0.15). Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45] , P = 1.4E−08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26] , P = 1.6E−07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03] , P = 5.6E−08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20] , P = 1.7E−08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.
    Type of Medium: Online Resource
    ISSN: 1465-542X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041618-0
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Breast Cancer Research, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2021-12)
    Abstract: The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer risk prediction models are commonly used in clinical practice and have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative prospective validation of these models after incorporating the recently developed 313-variant PRS. Methods Calibration and discrimination of 5-year absolute risk was assessed in a nested case-control sample of 1337 women of European ancestry (619 incident breast cancer cases) aged 23–75 years from the Generations Study. Results The extended BOADICEA model with reproductive/lifestyle factors and PRS was well calibrated across risk deciles; expected-to-observed ratio ( E / O ) at the highest risk decile :0.97 (95 % CI 0.51 − 1.86) for women younger than 50 years and 1.09 (0.66 − 1.80) for women 50 years or older. Adding reproductive/lifestyle factors and PRS to the BOADICEA model improved discrimination modestly in younger women (area under the curve (AUC) 69.7 % vs. 69.1%) and substantially in older women (AUC 64.6 % vs. 56.8%). The Tyrer-Cuzick model with PRS showed evidence of overestimation at the highest risk decile: E / O  = 1.54(0.81 − 2.92) for younger and 1.73 (1.03 − 2.90) for older women. Conclusion The extended BOADICEA model identified women in a European-ancestry population at elevated breast cancer risk more accurately than the Tyrer-Cuzick model with PRS. With the increasing availability of PRS, these analyses can inform choice of risk models incorporating PRS for risk stratified breast cancer prevention among women of European ancestry.
    Type of Medium: Online Resource
    ISSN: 1465-542X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041618-0
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 30, No. 1 ( 2021-01-01), p. 71-79
    Abstract: Evidence suggests etiologic heterogeneity among breast cancer subtypes. Previous studies with six-marker IHC classification of intrinsic subtypes included small numbers of black women. Methods: Using centralized laboratory results for estrogen receptor (ER), progesterone receptor, HER2, proliferation marker, Ki-67, EGFR, and cytokeratin (CK)5/6, we estimated case-only and case–control ORs for established breast cancer risk factors among cases (n = 2,354) and controls (n = 2,932) in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. ORs were estimated by ER status and intrinsic subtype using adjusted logistic regression. Results: Case-only analyses by ER status showed etiologic heterogeneity by age at menarche, parity (vs. nulliparity), and age at first birth. In case–control analyses for intrinsic subtype, increased body mass index and waist-to-hip ratio (WHR) were associated with increased risk of luminal A subtype, whereas older age at menarche and parity, regardless of breastfeeding, were associated with reduced risk. For basal-like cancers, parity without breastfeeding and increasing WHR were associated with increased risk, whereas breastfeeding and age ≥25 years at first birth were associated with reduced risk among parous women. Basal-like and ER−/HER2+ subtypes had earlier age-at-incidence distribution relative to luminal subtypes. Conclusions: Breast cancer subtypes showed distinct etiologic profiles in the AMBER consortium, a study of more than 5,000 black women with centrally assessed tumor biospecimens. Impact: Among black women, high WHR and parity without breastfeeding are emerging as important intervention points to reduce the incidence of basal-like breast cancer.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 32, No. 12_Supplement ( 2023-12-01), p. B070-B070
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 32, No. 12_Supplement ( 2023-12-01), p. B070-B070
    Abstract: Background: Breast cancer subtyping has largely been based on immunohistochemical markers of estrogen receptor status. However, RNA-based intrinsic subtypes, including luminal (hormone receptor-positive) and non-luminal (hormone receptor-negative) have been shown to be etiologically relevant, with studies also suggesting other tumor markers (e.g., TP53 status) to be important contributors to etiologic heterogeneity. Compared to luminal tumors, non-luminal tumors are more likely to be TP53 mutant than wildtype-like. TP53 mutant breast cancers are associated with more aggressive tumor features and these mutations are more common among cases of African descent. However, few RNA-based subtyping studies have described etiologic heterogeneity in indigenous African populations. Therefore, we evaluated associations between established breast cancer risk factors and risk of PAM50 intrinsic subtypes and tumor subtypes defined by RNA-based TP53 functional status in the population-based Ghana Breast Health Study (GBHS). Methods: We analyzed data from 600 invasive breast cancer cases and 2,528 controls in the GBHS. RNA was extracted from formalin-fixed paraffin-embedded tumor samples and run on the nCounter® Breast Cancer 360™ Panel. Samples were then classified for intrinsic subtype (N=285 luminal, N=315 non-luminal) using a research version of the PAM50 assay and for TP53 functional status (N=333 wildtype-like, N=300 mutant-like) using a validated RNA signature. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for risk factors using polytomous logistic regression models adjusted for potential confounders. Results: About 1 in 4 tumors classified as ER-positive by immunohistochemistry were non-luminal by RNA expression. Similarly, about 1 in 5 ER-negative tumors were reclassified as luminal. Etiologic heterogeneity was observed by luminal subtype for certain reproductive factors. Higher parity (≥3 vs. & lt;3 births) was associated with lower risk of luminal tumors (OR [95% CI] = 0.68 [0.49, 0.92] ), but not with non-luminal tumors (0.95 [0.69, 1.30]). Likewise, later age at first birth (≥26 vs. & lt;19 years) was more strongly associated with risk of luminal than non-luminal tumors (2.16 [1.37, 3.40] and 1.30 [0.84, 2.00] , respectively). Consistent with previous findings, TP53 status was also an important etiologic factor and risk factor patterns mirrored those for luminal/non-luminal subtypes. Finally, we evaluated cross-classification of these two etiologic markers to identify risk factors that represent the dual action of both an estrogenic and a DNA-repair pathway. Age at first birth seems to suggest dual action. Conclusions: This study used high-quality RNA expression data to show that intrinsic subtype and TP53 status are useful breast tumor markers for describing etiologic heterogeneity, with cross-classification leading to improved understanding of the etiologic underpinnings of certain risk factors. This work has important implications for the use of gene-expression-based subtyping for breast cancer classification in this population. Citation Format: Amber N. Hurson, Ebonee N. Butler, Alina M. Hamilton, Bernard Petershie, Thomas U. Ahearn, Melissa A. Troester, Jonine Figueroa, Nicolas Titiloye, Montserrat Garcia-Closas, Mustapha Abubakar. Characterizing breast cancer etiologic subtypes in the Ghana Breast Health Study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B070.
    Type of Medium: Online Resource
    ISSN: 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-07-03)
    Abstract: Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2553671-0
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 876-876
    Abstract: Purpose: TP53 and estrogen receptor (ER) both play essential roles in breast cancer development and progression, with recent research revealing crosstalk between TP53 and ER signaling pathways. While many studies have demonstrated heterogeneity of risk factor associations across ER subtypes, TP53 status has been inconsistently linked to breast cancer risk factors. This may be due to few studies evaluating TP53 effects in the context of ER. Additionally, studies have generally classified TP53 status using immunohistochemistry (IHC) staining or DNA sequencing, which are prone to misclassification of TP53 pathway function. RNA-based methods of measuring TP53 pathway activity may reduce misclassification and clarify etiologic associations. Methods: This case-only analysis included 4,466 incident breast cancer cases from the Carolina Breast Cancer Study (1993-2013). Using RNA expression previously quantified using NanoString assays on FFPE tumor samples, tumors were classified for TP53 functional status (mutant-like or wildtype-like) using a validated 52-gene RNA signature. We used a two-stage polytomous logistic regression model to evaluate sources of risk factor heterogeneity due to RNA-based TP53 or ER, adjusting for each other and for PR, HER2, and grade, while accounting for missing tumor marker data. Risk factor heterogeneity was also evaluated for IHC-based TP53 and ER. For each risk factor, joint effects of TP53 and ER were evaluated by allowing for an interaction between the two markers. Results: When classifying TP53 status using the RNA signature, the effects of several hormone-related factors (oral contraceptive use, menopausal status, age at menopause, and pre- and post-menopausal BMI) were heterogeneous across TP53 subtypes, while heterogeneity of reproductive factors (age at first birth and parity) and smoking status was observed across ER subtypes. The effect of number of births was heterogenous across both TP53 and ER-based subtype definitions. Additionally, we observed an interaction between RNA-based TP53 and ER status with family history of breast cancer in a first-degree relative (p=0.05). When classifying TP53 status using IHC, the TP53 effects were not recapitulated but there was minimal change in the ER effects. We observed an interaction between IHC-based TP53 and ER status with age at menarche (p=0.02), smoking status (p=0.05), and alcohol use (p=0.06). Conclusions: This study demonstrates that TP53 and ER are valuable for defining etiologic subtypes of breast cancer, although IHC measures may not have as much value as RNA. Analyses of the joint effects of TP53 and ER with breast cancer risk factors revealed intriguing findings that could lead to new hypotheses. However, larger studies incorporating multiple correlated tumor characteristics will be required to confirm our findings to conclusively define etiologically relevant subtypes of breast cancer. Citation Format: Amber N. Hurson, Mustapha Abubakar, Kathleen Conway-Dorsey, Katherine Hoadley, Michael I. Love, Andrew F. Olshan, Montserrat Garcia-Closas, Melissa A. Troester. TP53 pathway function, estrogen receptor status, and breast cancer risk factors in the Carolina Breast Cancer Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 876.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 3670-3670
    Abstract: Background: Studies have reported differences in associations between breast cancer risk factors and subtypes defined by hormone receptor status, particularly estrogen receptor (ER) positive versus ER negative tumors. Most studies have been conducted in women of European descent, and an expanding body of literature in other populations suggests differences by race/ethnicity. Clarifying whether associations between risk factors and disease subtypes are consistent across racial/ethnic populations has important implications for understanding disease etiology and for improving risk prediction models. To address this question, we conducted a qualitative literature review to investigate the consistency in associations between multiple breast cancer risk factors and risk of tumor subtypes in women of African, Asian, Hispanic, and European descent. Methods: We searched PubMed for publications between January 1, 1990 and June 8, 2021 that reported associations between breast cancer risk factors and risk of subtypes of the disease. We evaluated 19 risk factors, including reproductive, anthropometric, lifestyle, and diet factors, as well as medical history and use of menopausal hormone therapy (MHT). Subtypes were defined as ER positive or negative (specifically triple negative when available). We prioritized review studies (i.e., meta-analyses, systematic reviews, and pooled analyses) and included individual studies with populations not included in the reviews. The number of publications per risk factor ranged from 3 for calcium intake to 28 for parity, with up to 7 reviews per risk factor. Most publications reported estimates for women of European descent, followed by Asian, African, and Hispanic. Evidence of subtype heterogeneity was determined by expert review. Results: There was strong evidence of association between reproductive factors and MHT with risk of ER positive but not ER negative disease. Parity, younger age at first birth and older age at menarche were associated with lower risk of ER positive disease, while MHT use was associated with higher risk of ER positive disease. For these risk factors, we did not find evidence that risk associations or etiologic heterogeneity varied by race/ethnicity. For the other risk factors, there was limited or no evidence of heterogeneity in risk associations by subtype, which was consistent across racial/ethnic groups. Few publications, however, specifically studied women of non-European ancestry. Conclusion: For most breast cancer risk factors, evidence is insufficient to evaluate differences in ER-specific risk associations by race/ethnicity. More studies are needed to evaluate subtype-specific breast cancer risk factors in diverse populations, which will be important for informing the development of multi-ethnic/racial BC risk prediction models that account for subtype heterogeneity. Citation Format: Amber N. Hurson, Thomas U. Ahearn, Renske Keeman, Mustapha Abubakar, Audrey Y. Jung, Pooja Middha Kapoor, Hela Koka, Xiaohong R. Yang, Jenny Chang-Claude, Elena Martínez, Rulla M. Tamimi, Melissa A. Troester, Elisa V. Bandera, Marjanka K. Schmidt, Montserrat Garcia-Closas. Systematic literature review of risk factor associations with breast cancer subtypes in women of African, Asian, Hispanic, and European descents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3670.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: BMJ Global Health, BMJ, Vol. 7, No. 2 ( 2022-02), p. e006975-
    Abstract: It has been nearly 2 years since the first case of COVID-19 was reported. Governments worldwide have introduced numerous non-pharmaceutical interventions (NPIs) to combat this disease. Many of these NPIs were designed in response to initial outbreaks but are unsustainable in the long term. Governments are exploring how to adjust their current NPIs to resume normal activities while effectively protecting their population. As one of the most controversial NPIs, the implementation of travel restrictions varies across regions. Some governments have abandoned their previous travel restrictions because of the induced costs to society and on the economy. Other areas, including Hong Kong (Special Administrative Region of China) and Singapore, continue employing these NPIs as a long-term disease prevention tactic. However, the multidimensional impacts of travel restrictions require careful consideration of how to apply restrictions more appropriately. We have proposed an adapted framework to examine Hong Kong and Singapore’s travel restrictions. We aimed to study these two regions’ experiences in balancing disease control efforts with easing the burden on lives and livelihoods. Based on the experiences of Hong Kong and Singapore, we have outlined six policy recommendations to serve as the cornerstone for future research and policy practices.
    Type of Medium: Online Resource
    ISSN: 2059-7908
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2851843-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: npj Breast Cancer, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2022-06-14)
    Abstract: TP53 and estrogen receptor (ER) are essential in breast cancer development and progression, but TP53 status (by DNA sequencing or protein expression) has been inconsistently associated with survival. We evaluated whether RNA-based TP53 classifiers are related to survival. Participants included 3213 women in the Carolina Breast Cancer Study (CBCS) with invasive breast cancer (stages I–III). Tumors were classified for TP53 status (mutant-like/wildtype-like) using an RNA signature. We used Cox proportional hazards models to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific survival (BCSS) among ER- and TP53-defined subtypes. RNA-based results were compared to DNA- and IHC-based TP53 classification, as well as Basal-like versus non-Basal-like subtype. Findings from the diverse (50% Black), population-based CBCS were compared to those from the largely white METABRIC study. RNA-based TP53 mutant-like was associated with BCSS among both ER-negatives and ER-positives (HR (95% CI) = 5.38 (1.84–15.78) and 4.66 (1.79–12.15), respectively). Associations were attenuated when using DNA- or IHC-based TP53 classification. In METABRIC, few ER-negative tumors were TP53-wildtype-like, but TP53 status was a strong predictor of BCSS among ER-positives. In both populations, the effect of TP53 mutant-like status was similar to that for Basal-like subtype. RNA-based measures of TP53 status are strongly associated with BCSS and may have value among ER-negative cancers where few prognostic markers have been robustly validated. Given the role of TP53 in chemotherapeutic response, RNA-based TP53 as a prognostic biomarker could address an unmet need in breast cancer.
    Type of Medium: Online Resource
    ISSN: 2374-4677
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2843288-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2023
    In:  Breast Cancer Research and Treatment Vol. 199, No. 1 ( 2023-05), p. 147-154
    In: Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 199, No. 1 ( 2023-05), p. 147-154
    Abstract: The PAM50 assay is used routinely in clinical practice to determine breast cancer prognosis and management; however, research assessing how technical variation and intratumoral heterogeneity contribute to misclassification and reproducibility of these tests is limited. Methods We evaluated the impact of intratumoral heterogeneity on the reproducibility of results for the PAM50 assay by testing RNA extracted from formalin-fixed paraffin embedded breast cancer blocks sampled at distinct spatial locations. Samples were classified according to intrinsic subtype (Luminal A, Luminal B, HER2-enriched, Basal-like, or Normal-like) and risk of recurrence with proliferation score (ROR-P, high, medium, or low). Intratumoral heterogeneity and technical reproducibility (replicate assays on the same RNA) were assessed as percent categorical agreement between paired intratumoral and replicate samples. Euclidean distances between samples, calculated across the PAM50 genes and the ROR-P score, were compared for concordant vs. discordant samples. Results Technical replicates ( N  = 144) achieved 93% agreement for ROR-P group and 90% agreement on PAM50 subtype. For spatially distinct biological replicates ( N  = 40 intratumoral replicates), agreement was lower (81% for ROR-P and 76% for PAM50 subtype). The Euclidean distances between discordant technical replicates were bimodal, with discordant samples showing higher Euclidian distance and biologic heterogeneity. Conclusion The PAM50 assay achieved very high technical reproducibility for breast cancer subtyping and ROR-P, but intratumoral heterogeneity is revealed by the assay in a small proportion of cases.
    Type of Medium: Online Resource
    ISSN: 0167-6806 , 1573-7217
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2004077-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages