Grant Number:	5R01CA225697-03 Interpret this number
Primary Investigator:	Kurian, Allison
Organization:	Stanford University
Project Title:	Genetic Testing, Treatment Use, and Mortality After Diagnosis of Breast and Ovarian Cancer: the Georgia-California Genelink Initiative
Fiscal Year:	2020

Project Summary Genetic testing is essential to identify and manage hereditary breast and ovarian cancer syndrome (HBOC), enabling precision prevention and screening and potentially reducing morbidity, mortality, and cost. The most efficient way to find HBOC cases is among women already diagnosed with breast cancer or ovarian cancer, because they are more likely than cancer-free women to have inherited a cancer-predisposing mutation. Once a cancer patient tests positive, then her cancer-free relatives can undergo a cost-effective, definitive test for the identified gene mutation. Testing cancer patients is thus the gateway to population-wide improvements in HBOC care. Yet genetic testing is difficult to integrate into the complex care of a newly diagnosed cancer patient. This is especially true as technology advances, with multiple-gene sequencing panels (MGS) replacing limited tests of only 2 genes (BRCA1 and BRCA2, BRCA1/2). MGS offers more information, but its value is uncertain. This is because the proportion of patients reported to have an uninformative, often anxiety- producing “variant of uncertain significance” (VUS) is 2-5% when only BRCA1/2 are tested, versus >30% with MGS. A major concern is that the increasing volume, complexity and ambiguity of results may worsen gaps in testing use, treatment quality, and health outcomes. To advance precision prevention of HBOC, there is great need to understand deployment of genetic testing and results management. Concerns include potential disparities in test use and results among sociodemographic and clinical subgroups and the impact of results on cancer treatment and mortality. To address these concerns we will examine potential gaps in genetic testing use, test results and treatment (including surgery, radiation and chemotherapy) among newly diagnosed breast and ovarian cancer patients, according to pre-test HBOC risk and sociodemographics. We will study approximately 150,000 breast cancer patients and 12,000 ovarian cancer patients who were diagnosed in 2013-2016 and reported to the statewide Georgia and California SEER registries, and then accrued into a Georgia-California SEER Genetic Testing Linkage Initiative (GeneLINK).Our hypotheses are stated as follows. Compared to breast cancer patients with normal test results, those with VUS only will have more contralateral prophylactic mastectomy. Among breast cancer patients indicated for radiation, pathogenic mutation carriers less often receive it than other patients. Among breast cancer patients who are not indicated for chemotherapy, mutation carriers more often receive it than negative/VUS/untested patients do, suggesting over-treatment. We will examine whether more intensive regimens (e.g., anthracyclines or platinums) are more prevalent in mutation carriers than other chemotherapy recipients, controlling for tumor factors. Among ovarian cancer patients with BRCA1/2 mutations who are indicated for targeted therapy with a PARP inhibitor, those with sociodemographic vulnerability factors less often receive it. Among breast and ovarian cancer patients who received chemotherapy, mortality will be lower in pathogenic mutation carriers than in non-mutation carriers.




A Secondary Analysis of a Preliminary Contingency Management Intervention for Presurgical Cancer Patients: Evaluating Individual Participant Data.
Authors: Sanford B.T. , Toll B.A. , Fucito L.M. , Baker N.L. , Krishnan-Sarin S. , Carpenter M.J. , Bernstein S.L. , Rojewski A.M. .
Source: Nicotine & Tobacco Research : Official Journal Of The Society For Research On Nicotine And Tobacco, 2023-08-19 00:00:00.0; 25(9), p. 1614-1618.
PMID: 37156634
Related Citations

Germline Genetic Testing After Cancer Diagnosis.
Authors: Kurian A.W. , Abrahamse P. , Furgal A. , Ward K.C. , Hamilton A.S. , Hodan R. , Tocco R. , Liu L. , Berek J.S. , Hoang L. , et al. .
Source: Jama, 2023-06-05 00:00:00.0; , .
EPub date: 2023-06-05 00:00:00.0.
PMID: 37276540
Related Citations

Chemotherapy Regimens Received by Women with BRCA1/2 Pathogenic Variants for Early-Stage Breast Cancer Treatment.
Authors: Kurian A.W. , Abrahamse P. , Hamilton A.S. , Caswell-Jin J.L. , Gomez S.L. , Hofer T.J. , Ward K.C. , Katz S.J. .
Source: Jnci Cancer Spectrum, 2022-06-20 00:00:00.0; , .
EPub date: 2022-06-20 00:00:00.0.
PMID: 35723570
Related Citations

Multiple imputation with missing data indicators.
Authors: Beesley L.J. , Bondarenko I. , Elliot M.R. , Kurian A.W. , Katz S.J. , Taylor J.M. .
Source: Statistical Methods In Medical Research, 2021-10-13 00:00:00.0; , p. 9622802211047346.
EPub date: 2021-10-13 00:00:00.0.
PMID: 34643465
Related Citations

Association of Genetic Testing Results with Mortality Among Women with Breast Cancer or Ovarian Cancer.
Authors: Kurian A.W. , Abrahamse P. , Bondarenko I. , Hamilton A.S. , Deapen D. , Gomez S.L. , Morrow M. , Berek J.S. , Hofer T.P. , Katz S.J. , et al. .
Source: Journal Of The National Cancer Institute, 2021-08-09 00:00:00.0; , .
EPub date: 2021-08-09 00:00:00.0.
PMID: 34373918
Related Citations

A Preoperative Contingency Management Intervention for Smoking Abstinence in Cancer Patients: A Preliminary Randomized Controlled Trial.
Authors: Rojewski A.M. , Fucito L.M. , Baker N.L. , Krishnan-Sarin S. , Carpenter M.J. , Bernstein S.L. , Toll B.A. .
Source: Nicotine & Tobacco Research : Official Journal Of The Society For Research On Nicotine And Tobacco, 2021-05-24 00:00:00.0; 23(6), p. 1064-1067.
PMID: 33340400
Related Citations

Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019.
Authors: Kurian A.W. , Ward K.C. , Abrahamse P. , Bondarenko I. , Hamilton A.S. , Deapen D. , Morrow M. , Berek J.S. , Hofer T.P. , Katz S.J. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2021-02-09 00:00:00.0; , p. JCO2002785.
EPub date: 2021-02-09 00:00:00.0.
PMID: 33560870
Related Citations

Predicted Chemotherapy Benefit for Breast Cancer Patients With Germline Pathogenic Variants in Cancer Susceptibility Genes.
Authors: Kurian A.W. , Ward K.C. , Abrahamse P. , Hamilton A.S. , Katz S.J. .
Source: Jnci Cancer Spectrum, 2021 Feb; 5(1), p. pkaa083.
EPub date: 2020-09-18 00:00:00.0.
PMID: 33426465
Related Citations

Association of Family Cancer History With Pathogenic Variants in Specific Breast Cancer Susceptibility Genes.
Authors: Kurian A.W. , Abrahamse P. , Ward K.C. , Hamilton A.S. , Deapen D. , Berek J.S. , Hoang L. , Yussuf A. , Dolinsky J. , Brown K. , et al. .
Source: Jco Precision Oncology, 2021; 5, .
EPub date: 2021-12-22 00:00:00.0.
PMID: 34977446
Related Citations

Emerging Opportunity of Cascade Genetic Testing for Population-Wide Cancer Prevention and Control.
Authors: Kurian A.W. , Katz S.J. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2020-05-01 00:00:00.0; 38(13), p. 1371-1374.
EPub date: 2020-02-25 00:00:00.0.
PMID: 32097078
Related Citations

Association of Germline Genetic Testing Results With Locoregional and Systemic Therapy in Patients With Breast Cancer.
Authors: Kurian A.W. , Ward K.C. , Abrahamse P. , Hamilton A.S. , Deapen D. , Morrow M. , Jagsi R. , Katz S.J. .
Source: Jama Oncology, 2020-02-06 00:00:00.0; , p. e196400.
EPub date: 2020-02-06 00:00:00.0.
PMID: 32027353
Related Citations

Genetic Testing and Results in a Population-Based Cohort of Breast Cancer Patients and Ovarian Cancer Patients.
Authors: Kurian A.W. , Ward K.C. , Howlader N. , Deapen D. , Hamilton A.S. , Mariotto A. , Miller D. , Penberthy L.S. , Katz S.J. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2019-05-20 00:00:00.0; 37(15), p. 1305-1315.
EPub date: 2019-04-09 00:00:00.0.
PMID: 30964716
Related Citations