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.
