Abstract:
Importance:Low-cost sequencing of multiple genes is increasingly available for cancer risk assessment. Little is known about uptake or outcomes of multiple-gene sequencing after breast cancer diagnosis in community practice. Objective:To examine the effect of multiple-gene sequencing on the experience and treatment outcomes for patients with breast cancer. Design, Setting, and Participants:For this population-based retrospective cohort study, patients with breast cancer diagnosed from January 2013 to December 2015 and accrued from SEER registries across Georgia and in Los Angeles, California, were surveyed (n = 5080, response rate = 70%). Responses were merged with SEER data and results of clinical genetic tests, either BRCA1 and BRCA2 (BRCA1/2) sequencing only or including additional other genes (multiple-gene sequencing), provided by 4 laboratories. Main Outcomes and Measures:Type of testing (multiple-gene sequencing vs BRCA1/2-only sequencing), test results (negative, variant of unknown significance, or pathogenic variant), patient experiences with testing (timing of testing, who discussed results), and treatment (strength of patient consideration of, and surgeon recommendation for, prophylactic mastectomy), and prophylactic mastectomy receipt. We defined a patient subgroup with higher pretest risk of carrying a pathogenic variant according to practice guidelines. Results:Among 5026 patients (mean [SD] age, 59.9 [10.7] years), 1316 (26.2%) were linked to genetic results from any laboratory. Multiple-gene sequencing increasingly replaced BRCA1/2-only testing over time: in 2013, the rate of multiple-gene sequencing was 25.6% and BRCA1/2-only testing, 74.4%; in 2015 the rate of multiple-gene sequencing was 66.5% and BRCA1/2-only testing, 33.5%. Multiple-gene sequencing was more often ordered by genetic counselors (multiple-gene sequencing, 25.5% and BRCA1/2-only testing, 15.3%) and delayed until after surgery (multiple-gene sequencing, 32.5% and BRCA1/2-only testing, 19.9%). Multiple-gene sequencing substantially increased rate of detection of any pathogenic variant (multiple-gene sequencing: higher-risk patients, 12%; average-risk patients, 4.2% and BRCA1/2-only testing: higher-risk patients, 7.8%; average-risk patients, 2.2%) and variants of uncertain significance, especially in minorities (multiple-gene sequencing: white patients, 23.7%; black patients, 44.5%; and Asian patients, 50.9% and BRCA1/2-only testing: white patients, 2.2%; black patients, 5.6%; and Asian patients, 0%). Multiple-gene sequencing was not associated with an increase in the rate of prophylactic mastectomy use, which was highest with pathogenic variants in BRCA1/2 (BRCA1/2, 79.0%; other pathogenic variant, 37.6%; variant of uncertain significance, 30.2%; negative, 35.3%). Conclusions and Relevance:Multiple-gene sequencing rapidly replaced BRCA1/2-only testing for patients with breast cancer in the community and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. However, important targets for improvement in the clinical utility of multiple-gene sequencing include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.
journal_name
JAMA Oncoljournal_title
JAMA oncologyauthors
Kurian AW,Ward KC,Hamilton AS,Deapen DM,Abrahamse P,Bondarenko I,Li Y,Hawley ST,Morrow M,Jagsi R,Katz SJdoi
10.1001/jamaoncol.2018.0644subject
Has Abstractpub_date
2018-08-01 00:00:00pages
1066-1072issue
8eissn
2374-2437issn
2374-2445pii
2680748journal_volume
4pub_type
杂志文章相关文献
JAMA Oncology文献大全abstract:Importance:Three years of adjuvant imatinib mesylate therapy is associated with reduced recurrence rates and improved overall survival in patients with high-risk primary gastrointestinal stromal tumor (GIST) compared with patients who receive 1 year of treatment. The impact of a longer duration of therapy is unknown. ...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamaoncol.2018.4060
更新日期:2018-12-01 00:00:00
abstract:Importance:Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor ...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1001/jamaoncol.2020.0249
更新日期:2020-07-01 00:00:00
abstract:Importance:Epidermal growth factor receptor (EGFR) (HER1) signaling depends on ligand binding and dimerization with itself or other HER receptors. We previously showed in a randomized trial that high EGFR ligand expression is predictive of panitumumab benefit in advanced colorectal cancer. Tumor expression of HER3 may ...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1001/jamaoncol.2017.3168
更新日期:2018-04-01 00:00:00
abstract:Importance:Why some triple-negative breast cancers (TNBCs) have high and others have low immune cell infiltration is unknown. Understanding how immune surveillance shapes the cancer genome could help in the selection of patients and the development of more effective immunotherapy strategies. Objective:To examine the a...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2017.2140
更新日期:2017-12-01 00:00:00
abstract:IMPORTANCE:Positive phase 3 cancer clinical trials are widely hailed, while trials with negative results are often interpreted as scientific failures. We hypothesized that these interpretations would be reflected in the scientific literature. OBJECTIVE:To compare the scientific impact of positive vs negative phase 3 c...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2015.6487
更新日期:2016-07-01 00:00:00
abstract:Importance:Administration of anti-programmed cell death protein 1 (anti-PD-1) is now standard therapy in advanced non-small cell lung cancer (NSCLC). However, immune checkpoint inhibitors, including anti-PD-1, have not been assessed in patients with subclinical disease with advanced NSCLC, and no useful clinical biomar...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2018.5860
更新日期:2019-03-01 00:00:00
abstract:Importance:Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. Objective:...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2020.5865
更新日期:2021-01-01 00:00:00
abstract:Importance:RAS wild-type (wt) status is necessary but not sufficient for response to anti-epidermal growth factor receptor (EGFR) agents in advanced colorectal cancer (aCRC). RNA expression of EGFR ligands epiregulin (EREG) and amphiregulin (AREG) may correlate with EGFR-targeted therapy efficacy in aCRC, so may repres...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2015.6065
更新日期:2016-05-01 00:00:00
abstract:Importance:Tumor-treating fields (TTFields) therapy improves both progression-free and overall survival in patients with glioblastoma. There is a need to assess the influence of TTFields on patients' health-related quality of life (HRQoL). Objective:To examine the association of TTFields therapy with progression-free ...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1001/jamaoncol.2017.5082
更新日期:2018-04-01 00:00:00
abstract:Importance:The oligometastatic paradigm postulates that patients with a limited number of metastases can be treated with ablative local therapy to each site of disease with curative intent. Stereotactic ablative radiotherapy (SABR) is a radiation technique that has become widely used in this setting. However, prospecti...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2020.6146
更新日期:2021-01-01 00:00:00
abstract:Importance:Although stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited. Objective:To characterize and compare first-line SRS outcomes (withou...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamaoncol.2020.1271
更新日期:2020-07-01 00:00:00
abstract:Importance:Hyperprogressive disease (HPD) is a new pattern of progression recently described in patients with cancer treated with programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors. The rate and outcome of HPD in advanced non-small cell lung cancer (NSCLC) are unknown. Objectives:To i...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamaoncol.2018.3676
更新日期:2018-11-01 00:00:00
abstract:Purpose:To harmonize the eligibility criteria and radiologic disease assessment definitions in clinical trials of adjuvant therapy for renal cell carcinoma (RCC). Method:On November 28, 2017, US-based experts in RCC clinical trials, including medical oncologists, urologic oncologists, regulators, biostatisticians, rad...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2019.4117
更新日期:2019-11-21 00:00:00
abstract:Importance:The androgen receptor inhibitor enzalutamide prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). In controlled clinical studies, 0.5% (10 of 2051) of patients experienced seizure, but patients with a history of or risk factors for seizure were excluded. Men with mCRPC and s...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamaoncol.2017.3361
更新日期:2018-05-01 00:00:00
abstract:Importance:Breast cancer risk and comorbidities increase with age. Data are lacking on the association of adjuvant chemotherapy with survival in elderly patients with multiple comorbidities and node-positive breast cancer. Objective:To examine the association of chemotherapy with survival in elderly patients with mult...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2020.2388
更新日期:2020-10-01 00:00:00
abstract:Importance:Chemoradiotherapy (CRT), followed by surgery, is the recommended approach for stage II and III rectal cancer. While CRT decreases the risk of local recurrence, it does not improve survival and leads to poorer functional outcomes than surgery alone. Therefore, new approaches to better select patients for CRT ...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2019.0186
更新日期:2019-07-01 00:00:00
abstract:Importance:Remarkable progress has occurred in understanding the pathophysiology and in developing improved personalized therapies in adult acute lymphoblastic leukemia (ALL). Observations:We searched MEDLINE (1990-2018), the American Society of Clinical Oncology, and American Society of Hematology websites (2010-2018...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2018.1915
更新日期:2018-10-01 00:00:00
abstract:Importance:The value of platinum-based adjuvant chemotherapy in patients with triple-negative breast cancer (TNBC) remains controversial, as does whether BRCA1 and BRCA2 (BRCA1/2) germline variants are associated with platinum treatment sensitivity. Objective:To compare 6 cycles of paclitaxel plus carboplatin (PCb) wi...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2020.2965
更新日期:2020-09-01 00:00:00
abstract:Importance:Esophageal adenocarcinoma and its precursor lesion Barrett esophagus have seen a dramatic increase in incidence over the past 4 decades yet marked genetic heterogeneity of this disease has precluded advances in understanding its pathogenesis and improving treatment. Objective:To identify novel disease susce...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2016.2054
更新日期:2016-10-01 00:00:00
abstract:IMPORTANCE:Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and i...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2015.2938
更新日期:2015-11-01 00:00:00
abstract:IMPORTANCE:Objective response rate (ORR) is an increasingly important end point for accelerated development of highly active anticancer therapies, yet its relationship to regulatory approval is not well characterized. OBJECTIVE:To identify circumstances in which a high ORR is associated with regulatory approval, and t...
journal_title:JAMA oncology
pub_type: 杂志文章,meta分析
doi:10.1001/jamaoncol.2015.6315
更新日期:2016-06-01 00:00:00
abstract:IMPORTANCE:A recent randomized radiation dose-escalation trial in unresectable stage III non-small-cell lung cancer (NSCLC) (Radiation Therapy Oncology Group [RTOG] 0617) showed a lower survival rate in the high-dose radiation therapy (RT) arm (74 Gy) than in the low-dose arm (60 Gy) with concurrent chemotherapy. OBJE...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1001/jamaoncol.2015.3969
更新日期:2016-03-01 00:00:00
abstract:Importance:There are long-standing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality, yet data from prospective cohort studies are limited. Objective:To investigate a serum biomarker of vitamin D status, 25-hydroxyvitamin D (25OHD) measured at the time of breast can...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2016.4188
更新日期:2017-03-01 00:00:00
abstract:IMPORTANCE:Time to surgery (TTS) is of concern to patients and clinicians, but controversy surrounds its effect on breast cancer survival. There remains little national data evaluating the association. OBJECTIVE:To investigate the relationship between the time from diagnosis to breast cancer surgery and survival, usin...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2015.4508
更新日期:2016-03-01 00:00:00
abstract:Importance:Unresectable intrahepatic cholangiocarcinoma (IHC) carries a poor prognosis, with a median overall survival (OS) of 11 months. Hepatic arterial infusion (HAI) of high-dose chemotherapy may have potential benefit in these patients. Objective:To evaluate clinical outcomes when HAI chemotherapy is combined wit...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2019.3718
更新日期:2019-10-31 00:00:00
abstract:Importance:Programmed cell death 1 (PD-1) inhibitor-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens. Objective:To compare the incidence of PD-1 inhibitor-related pneumonitis amon...
journal_title:JAMA oncology
pub_type: 杂志文章,meta分析,评审
doi:10.1001/jamaoncol.2016.2453
更新日期:2016-12-01 00:00:00
abstract:Importance:Approximately 50% of the risk for the development of testicular germ cell tumors (TGCTs) is estimated to be heritable, but no mendelian TGCT predisposition genes have yet been identified. It is hypothesized that inherited pathogenic DNA repair gene (DRG) alterations may drive susceptibility to TGCTs. Object...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamaoncol.2018.6477
更新日期:2019-04-01 00:00:00
abstract:Importance:The American Joint Committee on Cancer (AJCC) eighth edition staging manual introduced a new prognostic stage for breast cancer incorporating biologic factors in addition to traditional anatomic factors. Objective:To perform a validation study of the AJCC eighth edition prognostic stage in a single-institut...
journal_title:JAMA oncology
pub_type: 杂志文章
doi:10.1001/jamaoncol.2017.4298
更新日期:2018-02-01 00:00:00
abstract:IMPORTANCE:The anti-PD-1 therapeutic antibody, nivolumab, has demonstrated clinical activity in patients with advanced melanoma. The activity of nivolumab in subgroups of patients with tumors which have wild-type BRAF kinase vs patients with tumors having mutant BRAF has not systematically been explored in a large data...
journal_title:JAMA oncology
pub_type: 杂志文章,meta分析
doi:10.1001/jamaoncol.2015.1184
更新日期:2015-07-01 00:00:00
abstract:Importance:Epithelioid sarcoma (ES) is an exceedingly rare malignant neoplasm with distinctive pathologic, molecular, and clinical features as well as the potential to respond to new targeted drugs. Little is known on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in this diseas...
journal_title:JAMA oncology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamaoncol.2018.0219
更新日期:2018-09-01 00:00:00