Decision making for breast cancer prevention among women at elevated risk

Padamsee, Tasleem J.; Wills, Celia E.; Yee, Lisa D.; Paskett, Electra D.

doi:10.1186/s13058-017-0826-5

Cited by 76 publications

(83 citation statements)

References 185 publications

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“…However, there is increasing evidence that decision-making in breast cancer risk reduction is much more complex [22,18]. Such findings are strengthened by the DMP-1 study, which shows that discussions on risks and benefits are not driving women’s decision-making.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent review, Padamsee et al [22] highlighted the limited knowledge we have on breast cancer risk reduction decision-making from the perspective of women who are at increased risk of developing the disease but have no known gene mutation. The DMP-1 study is the largest to date of US women counseled on SERM use as part of their regular care, which investigated women’s decision-making about SERM use for breast cancer prevention prospectively after counseling on SERM use.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

NRG Oncology/National Surgical Adjuvant Breast and Bowel Project Decision-Making Project-1 Results: Decision Making in Breast Cancer Risk Reduction

Holmberg

Bandos

Fagerlin

et al. 2017

Cancer Prevention Research

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Selective estrogen receptor modulators (SERMs) reduce breast cancer risk. Adoption of SERMs as prevention medication remains low. This is the first study to quantify social, cultural, and psychological factors driving decision-making regarding SERM use in women counseled on breast cancer prevention options. A survey study was conducted with women counseled by a healthcare provider (HCP) about SERMs. A statistical comparison of responses was performed between those who decided to use and those who decided not to use SERMs. Independent factors associated with the decision were determined using logistic regression. Of 1023 participants, 726 made a decision: 324 (44.6%) decided to take a SERM and 402 (55.4%) decided not to. The most important factor for deciding on SERM use was the HCP recommendation. Other characteristics associated with the decision included: attitudes and perceptions regarding medication intake, breast cancer worry, trust in HCP, family members with blood clots, and others’ experiences with SERMs. The odds of SERM intake when HCP-recommended were higher for participants with a positive attitude towards taking medications than for those with a negative attitude (interaction p-value=0.01). This study highlights the importance of social and cultural aspects for SERM decision-making, most importantly personal beliefs and experiences. HCPs' recommendations play a statistically significant role in decision-making and are more likely to be followed if in line with patients’ attitudes. Results indicate the need of developing interventions for HCPs that not only focus on the presentation of medical information but, equally as important, on addressing patients’ beliefs and experiences.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

NRG Oncology/National Surgical Adjuvant Breast and Bowel Project Decision-Making Project-1 Results: Decision Making in Breast Cancer Risk Reduction

Holmberg

Bandos

Fagerlin

et al. 2017

Cancer Prevention Research

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“…These pose a challenge for clinical genetics testing, since VUS‐carrier families are usually considered as having a negative result, when risk assessment is solely based on family history . Consequently, identification of pathogenic variants will contribute to breast cancer prevention, therapy, and surveillance as well as to a better knowledge of the breast cancer genetics .…”

Section: Introductionmentioning

confidence: 99%

Mis‐splicing in breast cancer: identification of pathogenic BRCA2 variants by systematic minigene assays

Fraile-Bethencourt

Valenzuela-Palomo

Díez-Gómez

et al. 2019

The Journal of Pathology

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Splicing disruption is a common mechanism of gene inactivation associated with germline variants of susceptibility genes. To study the role of BRCA2 mis-splicing in hereditary breast/ovarian cancer (HBOC), we performed a comprehensive analysis of variants from BRCA2 exons 2-9, as well as the initial characterization of the regulatory mechanisms of such exons. A pSAD-based minigene with exons 2-9 was constructed and validated in MCF-7 cells, producing the expected transcript (1016-nt/V1-BRCA2_exons_2-9-V2). DNA variants from mutational databases were analyzed by NNSplice and Human Splicing Finder softwares. To refine ESE-variant prediction, we mapped the regulatory regions through a functional strategy whereby 26 exonic microdeletions were introduced into the minigene and tested in MCF-7 cells. Thus, we identified nine spliceogenic ESE-rich intervals where ESE-variants may be located. Combining bioinformatics and microdeletion assays, 83 variants were selected and genetically engineered in the minigene. Fifty-three changes impaired splicing: 28 variants disrupted the canonical sites, four created new ones, 10 abrogated enhancers, eight created silencers and three caused a double-effect. Notably, nine spliceogenic-ESE variants were located within ESE-containing intervals. Capillary electrophoresis and sequencing revealed more than 23 aberrant transcripts, where exon skipping was the most common event. Interestingly, variant c.67G>A triggered the usage of a noncanonical GC-donor 4-nt upstream. Thirty-six variants that induced severe anomalies (>60% aberrant transcripts) were analyzed according to the ACMG guidelines. Thus, 28 variants were classified as pathogenic, five as likely pathogenic and three as variants of uncertain significance. Interestingly, 13 VUS were reclassified as pathogenic or likely pathogenic variants. In conclusion, a large fraction of BRCA2 variants (∼64%) provoked splicing anomalies lending further support to the high prevalence of this disease-mechanism. The low accuracy of ESE-prediction algorithms may be circumvented by functional ESE-mapping that represents an optimal strategy to identify spliceogenic ESE-variants. Finally, systematic functional assays by minigenes depict a valuable tool for the initial characterization of splicing anomalies and the clinical interpretation of variants.

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“…Kanker payudara merupakan salah satu penyakit yang menyebabkan kematian, dan banyak diderita oleh kaum wanita. Pengobatan kanker yang selama ini digunakan melalui kemoterapi mempunyai efek yang merugikan bagi kesehatan pasien (Padamsee et al, 2017). Saat ini, pencegahan dan pengobatan kanker difokuskan pada pemanfaatan bahan alam yang mengandung senyawa metabolit sekunder yang mempunyai aktivitas biologis (Cragg et al, 2011).…”

Section: Pendahuluanunclassified

FLAVONOID DARI KULIT BATANG AKWAY (Drymis beccariana, Gibbs) DAN AKTIVITAS SITOTOKSIK TERHADAP SEL KANKER PAYUDARA T47D

Herlina

Parubak

2019

j.penelit.has.kehutan

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Flavonoid compounds obtained from natural products could reduce the risk of cancer. Akway plants (Drimys beccariana, Gibbs) are endemic plants in the Papuan highlands, especially in Manokwari. D. beccariana has been widely used in traditional medicine in West Papua. This study aims to determine the cytotoxic activity of flavonoid from D. beccariana bark against T47D breast cancer cells. Pure compound form isolation was characterized using UV and IR spectrophotometers, and tested cytotoxic activity against T47D breast cancer cell using the Sulforodamine B. method. The D. beccariana stem bark (2.5 kg) was extracted with methanol solvent which was then partitioned with n-hexane and ethyl acetate solvents. Ethyl acetate fraction was separated and purified by column chromatography method to yield pure compound (7.1 mg). The UV-Vis spectrum of pure compound showed two bands at λmax 287 (I) and 205 nm (II), as well as the addition of AlCl 3 shifting reagents with the addition of 7 and 5nm wavelengths, specific to the-OH and C=O groups in flavonoid compound. The infrared spectrum of pure compound (KBr) showed the presence of-OH stretch (3422 cm-1), C=O (1659 cm-1), C= C aryl (1463 cm-1), and CO (1060 cm-1) which is typical for flavonoid. The pure flavonoid compound obtained from the of D. beccariana bark showed cytotoxic activity against T47D breast cancer cells with IC50 values of 3.2 µg/mL. D. beccariana is a promising source of breast anticancer agents.

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Decision making for breast cancer prevention among women at elevated risk

Cited by 76 publications

References 185 publications

NRG Oncology/National Surgical Adjuvant Breast and Bowel Project Decision-Making Project-1 Results: Decision Making in Breast Cancer Risk Reduction

NRG Oncology/National Surgical Adjuvant Breast and Bowel Project Decision-Making Project-1 Results: Decision Making in Breast Cancer Risk Reduction

Mis‐splicing in breast cancer: identification of pathogenic BRCA2 variants by systematic minigene assays

FLAVONOID DARI KULIT BATANG AKWAY (Drymis beccariana, Gibbs) DAN AKTIVITAS SITOTOKSIK TERHADAP SEL KANKER PAYUDARA T47D

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