Abstract:
:Genetic risk prediction models such as BRCAPRO are used routinely in genetic counseling for identification of potential BRCA1 and BRCA2 mutation carriers. They require extensive information on the counselee and her family history, and thus are not practical for primary care. To address this gap, we develop and test a two-stage approach to genetic risk assessment by balancing the tradeoff between the amount of information used and accuracy achieved. The first stage is intended for primary care wherein limited information is collected and analyzed using a simplified version of BRCAPRO. If the assessed risk is sufficiently high, more extensive information is collected and the full BRCAPRO is used (stage two: intended for genetic counseling). We consider three first-stage tools: BRCAPROLYTE, BRCAPROLYTE-Plus, and BRCAPROLYTE-Simple. We evaluate the two-stage approach on independent clinical data on probands with family history of breast and ovarian cancers, and BRCA genetic test results. These include population-based data on 1344 probands from Newton-Wellesley Hospital and mostly high-risk family data on 2713 probands from Cancer Genetics Network and MD Anderson Cancer Center. We use discrimination and calibration measures, appropriately modified to evaluate the overall performance of a two-stage approach. We find that the proposed two-stage approach has very limited loss of discrimination and comparable calibration as BRCAPRO. It identifies a similar number of carriers without requiring a full family history evaluation on all probands. We conclude that the two-stage approach allows for practical large-scale genetic risk assessment in primary care.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Biswas S,Atienza P,Chipman J,Blackford AL,Arun B,Hughes K,Parmigiani Gdoi
10.1007/s10549-016-3686-2subject
Has Abstractpub_date
2016-01-01 00:00:00pages
375-83issue
2eissn
0167-6806issn
1573-7217pii
10.1007/s10549-016-3686-2journal_volume
155pub_type
杂志文章abstract:PURPOSE:Compared to breast cancer risk genes such as BRCA2, ATM, PALB2, and NBN, no defined phenotype is currently associated with biallelic pathogenic variants (PVs) in CHEK2. This study compared the prevalence of breast and other cancers in women with monoallelic and biallelic CHEK2 PVs. METHODS:CHEK2 PV carriers we...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05543-3
更新日期:2020-04-01 00:00:00
abstract:PURPOSE:HER2 gene is a member of the epidermal growth factor receptor (EGFR) family. Across different malignancies, aberrations of HER2 gene commonly correspond to gain-of-function alterations leading to increased receptor signaling. METHODS:We have reviewed the literature currently available on HER2 mutations in huma...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-017-4419-x
更新日期:2017-11-01 00:00:00
abstract:OBJECTIVE:To measure the association between dietary fiber intake and eleven hormones and peptides in postmenopausal breast cancer survivors. METHODS:Intake of fiber from food and supplements was measured two to three years after breast cancer diagnosis in 493 postmenopausal women from three western states. Concurrent...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9834-y
更新日期:2008-11-01 00:00:00
abstract::It is common belief among physicians the idea that breast cancer was not diagnosed centuries ago. Nevertheless, there are reports suggesting that old masters and even common people knew this dramatic disease. In the 16th and 17th centuries, famous artists painted things exactly as they saw them. This allows the detect...
journal_title:Breast cancer research and treatment
pub_type: 历史文章,杂志文章
doi:10.1007/s10549-007-9753-y
更新日期:2008-09-01 00:00:00
abstract::Treatment decisions in oncology are based on a balance between the efficacy of therapy and its side effects. Patients with metastases and patients with a limited prognosis are a particular challenge, since communication about the disease situation and the expected therapeutic benefit is difficult not only for patients...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2557-3
更新日期:2013-06-01 00:00:00
abstract::Seventy-two patients underwent dye-guided or dye- and gamma probe-guided sentinel lymphadenectomy (SLND) followed by complete axillary lymph node dissection (ALND). The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) were compared to each other and to the histologi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006268426526
更新日期:1999-09-01 00:00:00
abstract::Number of mitoses and EGF binding were determined in parallel in biopsies of 27 lymph-node positive and of 23 lymph-node negative breast cancer patients. For node-positive patients the parameters for cell growth and EGF binding were quantitatively correlated by the equation y = P3 + P1(1- exp(- P2x]. For node-negative...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01805739
更新日期:1988-09-01 00:00:00
abstract::M1775R and A1789T are two missense variants located within the BRCT domains of BRCA1 gene. The M1775R is a known deleterious variant, while the A1789T is an unclassified variant that has been analyzed and classified as probably deleterious for the first time by our group. In a previous study, we described the expressi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2705-9
更新日期:2013-10-01 00:00:00
abstract:BACKGROUND:Several recent epidemiologic studies examined the association between breast cancer risk and an inherited, single-nucleotide polymorphism in the HER2 gene, codon 655 G to A, which leads to an amino acid substitution of Ile to Val. Results of previous studies have been mixed, with most studies showing no asso...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1024068525763
更新日期:2003-06-01 00:00:00
abstract::Mammosphere culture has been used widely for the enrichment of mammary epithelial stem cells and breast cancer stem cells (CSCs). Epithelial-to-mesenchymal transition (EMT) also induces stem cell features in normal and transformed mammary cells. We examined whether mammosphere culture conditions per se induced EMT in ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1534-y
更新日期:2012-02-01 00:00:00
abstract::Animal models have contributed to our understanding of breast cancer, with publication of results in high-impact journals almost invariably requiring extensive in vivo experimentation. As such, many laboratories hold large collections of surplus animal material, with only a fraction being used in publications relating...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3785-0
更新日期:2016-04-01 00:00:00
abstract:AIMS:To examine the frequency of axillary lymph node (ALN) invasion of operable breast cancers by their combined oestrogen receptor (ER), progesterone receptor (PR) and HER-2 status. METHODS:2227 recently operated cases in one centre were retrieved from the Multidisciplinary Breast Centre database and stratified accor...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-9914-7
更新日期:2009-01-01 00:00:00
abstract:PURPOSE:Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC). PATIENTS AND METHODS:We constructed a Markov model to assess the cost-effectiveness of four diffe...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3978-6
更新日期:2016-11-01 00:00:00
abstract::Progesterone, through its nuclear receptors (PR), regulates the development and growth of breast cancers. PR also serve as markers of hormone dependence and prognosis in patients with this disease, and functional PR are required to mediate the antiproliferative effects of progestin therapies. We find that normal and m...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1005941117247
更新日期:1998-04-01 00:00:00
abstract::The regulation of gene expression by steroid hormones plays an important role in the normal development and function of many organs, as well in the pathogenesis of endocrine-related cancers. Previous experiments have shown that many kallikrein genes are under steroid hormone regulation in breast cancer cell lines. We ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9312-y
更新日期:2007-03-01 00:00:00
abstract::We characterized the structure and the function of insulin receptors isolated from 10 human breast cancer specimens. We observed that the insulin receptor content, as determined by a specific radioimmunoassay, was four fold increased in human breast cancer tissue when compared to normal breast tissues. In both cancer ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00662403
更新日期:1993-01-01 00:00:00
abstract::Women with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. We collected hot flash frequency and severity data over 12 months from 297 women in...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s10549-009-0309-1
更新日期:2009-10-01 00:00:00
abstract::Mutations in breast cancer susceptibility genes, BRCA1 and BRCA2 account for more than 80% of hereditary breast and ovarian cancers. p53 tumor suppressor gene that controls cellular growth and differentiation is also known to be mutated in more than 50% of human cancers including breast cancer. We have carried out a s...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-004-0593-8
更新日期:2004-11-01 00:00:00
abstract::Addition of epirubicin to adjuvant chemotherapy can provide important benefits for patients with early breast cancer, but the optimal dose remains unclear. Further improvements can be achieved with dose-dense regimens, but densification of fluorouracil/epirubicin/cyclophosphamide (FEC) has proved difficult, with FEC(6...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-008-9894-7
更新日期:2008-12-01 00:00:00
abstract::Methylthioadenosine (MTA) phosphorylase activity was measured in 47 biopsies from primary breast cancers (n = 34) and metastatic tumors (n = 13). Most specimens were also evaluated by DNA flow cytometry and determination of estrogen and progesterone receptor contents. Median MTA phosphorylase activity was 317 pmol/mg ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806694
更新日期:1987-01-01 00:00:00
abstract::The mechanism by which transforming growth factor-alpha (TGF-alpha) stimulates breast cancer cell proliferation is largely unknown. Furthermore, its potential role as an autocrine effector of estradiol-17 beta (E2)-stimulated growth of hormone-dependent mammary tumors remains controversial. Transient changes in phosph...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01832359
更新日期:1992-01-01 00:00:00
abstract::The maintenance of hematopoietic progenitor cells as assayed in the mixed colony (CFU-GEMM) assay in human long-term bone marrow cultures was compared between normal allogeneic marrow transplantation donor collections and those from candidates for high-dose therapy and autologous bone marrow transplantation (ABMT). To...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1005732531318
更新日期:1997-06-01 00:00:00
abstract::Epidermal growth factor receptor (EGFr) levels were analyzed in 140 primary breast cancer specimens by immunohistochemical assay (ICA), competitive binding assay (BA), or enzyme immunoassay (EIA). Thirty-nine of 118 specimens (33.1%) were scored as positive by ICA, 30 of 116 (25.9%; cut-off level 10 fmol/mg protein) b...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666582
更新日期:1993-12-01 00:00:00
abstract::The taxanes and anthracyclines have emerged as the most active agents for treating women with advanced breast cancer. As such, investigation of the two drug classes in combination regimens has been eagerly pursued. The rationale for combining docetaxel with an anthracycline includes high clinical activity of each indi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1023/a:1024369220605
更新日期:2003-01-01 00:00:00
abstract::In the present report, we retrospectively analyzed the impact of the timing of surgery during menstrual cycle on disease-free and overall survival of 248 premenopausal patients with stage I/II breast cancer who underwent surgery followed by anthracycline-containing adjuvant chemotherapy. With a median follow-up of 5 y...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1023/a:1006276120841
更新日期:1999-06-01 00:00:00
abstract::Prognostication of breast cancer patients, not operated at diagnosis, poses a clinically difficult problem. To use gene amplification we examined cytological samples and determined c-erb-B2 gene copy number with semi-quantitative PCR. Control experiments showed the same gene-copy number in aliquots that were either ai...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806188
更新日期:1996-01-01 00:00:00
abstract::Tamoxifen has been shown to increase cytoplasmic free Ca2+ levels [Ca2+]i in renal tubular cells and bladder cancer cells, and to after Ca2+ signaling in MCF-7 breast cancer cells. The present study examined the effect of tamoxifen on [Ca2+], in ZR-75-1 human breast cancer cells using fura-2 as an indicator. Tamoxifen...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1013807731642
更新日期:2002-01-01 00:00:00
abstract::Two human cancer cell lines (MA 2 and MA 3) were established from pleural effusions of infiltrating ductal carcinomas of the breast. The lines were maintained in continuous monolayer culture with doubling times of 70 (MA 2) and 78 (MA 3) hr for more than two years and possessed extensively rearranged abnormal karyo-ty...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1005740813216
更新日期:1997-04-01 00:00:00
abstract:PURPOSE:The independent predictive information from progesterone receptor (PgR) positivity for breast cancer treated with tamoxifen has been questioned after an overview by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG). However, the studies in the overview were to a large content performed before mode...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-4007-5
更新日期:2016-11-01 00:00:00
abstract::Inflammatory breast cancer (IBC) is the most aggressive type of advanced breast cancer characterized by rapid proliferation, early metastatic development and poor prognosis. Since there are few preclinical models of IBC, there is a general lack of understanding of the complexity of the disease. Recently, we have devel...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2600-4
更新日期:2013-07-01 00:00:00