To describe breast and ovarian cancer risk reduction strategies in the clinical management of women who test positive for non-BRCA hereditary breast and ovarian cancer (HBOC) pathogenic variants ...compared to those who test positive for pathogenic BRCA variants or have negative germline panel testing.
Examination of imaging and preventive surgeries in women undergoing HBOC genetic testing from 1/1/2015 to 12/31/2018, with follow up to 03/31/2020 in Kaiser Permanente Northern California.
A total of 13,271 tests which included HBOC genes were identified. Rate of bilateral salpingo-oophorectomy after genetic testing were similar for BRCA and the non-BRCA moderate risk ovarian pathogenic variants (PVs) (47.4% vs 54%, p = 0.25). Rates were lower for low risk or unknownrisk non-BRCA PVs (12.8%, p < 0.001, 5.3% (p < 0.001). Rates of surveillance for ovarian cancer with ultrasound and CA 125 in the first year was 63.3% and 64.7% for BRCA PV, 37.5% and 27.1%, for non-BRCA moderate risk PVs and 13.7% and 4.6%, for low-risk PVs. Bilateral mastectomy rates were 19.7% for BRCA PV, 10.1% (p = 0.028) for non-BRCA breast high risk PVs, for moderate risk PVs 7.7% (p < 0.001) and for unknown risk 0.4% (p < 0.001). MRI surveillance rates in the first year similarly were 47.4% for non-BRCA BRCA PV, 43% for breast high risk PV, 39.4% for moderate risk and 4.9% for unknown risk PV.
Surgical and surveillance strategies are underutilized for HBOC PV, however there is concordance of uptake of preventive strategies with specific risk associated with non-BRCA PVs.
To identify racial and health factors associated with referral, assessment and genetic testing patterns for women with ovarian cancer.
Women were identified with a new diagnosis of ovarian cancer in ...a large integrated health care system in Northern California between 8/1/2013 and 12/31/2018. Women were excluded if they had undergone genetic testing prior to the diagnosis of ovarian cancer. Standardized guidelines of the health system at the time of diagnosis were used for genetics referral criteria: from 8/2013 until 4/2015, the guidelines limited referral to ovarian cancer diagnosed under age ≤70 years and non-mucinous histology; from 4/2015-4/2017, ovarian cancer diagnoses of all ages became eligible; and starting in 4/2017, all ovarian cancer histologies were eligible for referral. Demographic variables including race, ethnicity, primary language and personal cancer history were retrieved from the electronic medical record. The primary outcome was referral to genetics for assessment within 12 months of ovarian cancer diagnosis. Secondary outcomes were completion of genetics contact and testing, as well as testing result.
We identified 1,414 women, newly diagnosed with ovarian cancer between 8/1/2013 and 12/31/2018, who were eligible for testing based on the health system criteria. Most of these women, 941 (66.5%) were referred to genetics in the first 12 months after diagnosis with a mean time from diagnosis to referral of 2.3 months. Referral rates varied by race and ethnicity: White 65.9%, Hispanic 69.7%, Black 58.2%, Asian 70.3%. Overall rates of referral to Genetics, seen by a genetic counselor, and tested for genetic mutations were lower for Black women compared to non-Black women although the difference was not significant (p-value = 0.07, 0.06, 0.07, respectively). Over the three time periods of genetics referral criteria, referrals for all races increased, the rate in Blacks increased from 45.8 % to 67.6% from the first period to the last (p-value = 0.09). Overall, 919/941 (65%) were seen by Genetics and 842 (59.5%) completed genetic testing, 796 had a multigene panel test, and the remainder had BRCA or single gene testing, with 161 (20%) with a positive test and 228 with variants of unknown significance. Only 6% (6/98) of Black women had a pathogenic mutation. Display omitted
In a large integrated health system with comprehensive health services, access to medical records for all tests and care, and a uniform cost structure for genetic services, Black women had lower referral and genetic testing rates than women of other races but the difference was not significant. While academic centers have shown significant differences in referral to genetic services of ovarian cancer patients by race, primary language and insurance types, these differences may be mitigated in systems with universal cost structures, integrated referrals and systemwide access for counseling, but more work still needs to be done to reach Black women.
CHEK2 mutations are associated with increased risk of breast, colon, and prostate cancer but not ovarian cancer. Our study investigated if women with CHEK2 mutations underwent risk reducing ...salpingo-oophorectomies (RRSO), despite no known risk of ovarian cancer associated with CHEK2, and if personal or family history of ovarian cancer was related to uptake of salpingo-oophorectomy.
Retrospective cohort study was conducted from 2015-2018 in a large integrated healthcare system. Eligible patients were female, at least 18 years old and identified as CHEK2 mutation carriers. Those with concurrent non-CHEK2 pathogenic gene mutations were excluded. Surgical indications, personal history, family history up to third degree relatives, and mutation type were collected retrospectively. Primary outcome was RRSO rates among women with pathogenic CHEK2 mutation. Secondary outcomes included association of personal and family cancer history in patients with salpingo-oophorectomy.
Of 11,640 men and women who had genetic testing, 150 (1.3%) were identified with pathogenic CHEK2 mutation. 37 patients were excluded because they had more than one gene mutation, and 11 men in the remaining cohort were excluded, resulting in 102 women with a pathogenic CHEK2 mutation in the final cohort. A total of eighteen (18%) patients underwent uni- or bilateral salpingo-oophorectomy (BSO) for any reason, and six (6%) were for risk-reduction. Mean age at time of surgery was 53.0 years for all patients who underwent salpingo-oophorectomy and 54.4 years for those who underwent RRSO. Four (4%) patients total had personal history of ovarian cancer. 24 (24%) patients had family history of ovarian cancer. Four (67%) of the six patients who underwent RRSO had family history of ovarian cancer (p=0.03). Of the two patients without family history: one chose to have BSO for risk-reducing purposes as opposed to follow up for a unilateral benign ovarian cyst after being counseled that there was no increased risk of ovarian cancer and the other chose BSO for hormonal management of breast cancer but also cited risk reduction of ovarian cancer as an indication.
Although, personal history of ovarian cancer is uncommon, family history of ovarian cancer is present in almost one quarter of CHEK2 mutation carriers. Most women with CHEK2 mutations did not have RRSO and the majority of those who chose RRSO had family history of ovarian cancer. This suggests that women and providers correctly assessed risk of ovarian cancer related to CHEK2, with few electing for RRSO because of increased perceived risk.
Patients with mismatch repair (MMR) deficient colorectal cancer (CRC) without detectable germline pathogenic variants (PVs) or likely pathogenic variants (LPVs) in MMR genes are often labeled as ...Lynch-like syndrome (LLS). We sought to evaluate the efficacy of paired tumor and germline testing in risk stratification of patients with LLS in a large, community-based, integrated healthcare setting. Through the universal screening program for Lynch syndrome at Kaiser Permanente Northern California, we identified all patients with MMR deficient colorectal tumors without detectable germline PVs or LPVs between April 2011 and October 2018. These patients were categorized as LLS and were offered paired tumor and germline testing. Risk stratification and patient management were assessed upon completion of all testing. Of the 50 patients with LLS who underwent paired tumor and germline testing, 62% (n = 31) were categorized as sporadic, 6% (n = 3) had Lynch syndrome, and 32% (n = 16) remained inconclusive. Among the sporadic cases, 65% (n = 20) had a PV (n = 18) or LPV (n = 2) in combination with loss of heterozygosity while 35% (n = 11) had two somatic PVs/LPVs involving the same MMR gene. Our findings showed paired tumor and germline testing resolved the etiology in the majority of patients and is a valuable strategy in risk stratification and management of patients with LLS. Further studies are needed to assess the optimal application of paired testing in different practice settings, particularly with evolving technology and decreasing cost of molecular sequencing.
Investigate whether disparities and other factors influence referral to genetic counseling and testing for hereditary breast and ovarian cancer syndrome (HBOC) in a large health care system. ...Examination of clinical, demographic, and socioeconomic factors from electronic health records associated with genetic referral and testing within 12 months after a new cancer diagnosed between August 1, 2013 and December 31, 2018. For patients meeting institutional criteria for HBOC testing, 60.6% were referred for genetic counseling, 88% of whom underwent germline testing; at least one pathogenic variant was found in 15.3%. Referral rates for patients with breast (69%) or ovarian cancer (65.7%) were much higher than for metastatic prostate (11.1%, p < 0.0001) or pancreatic cancer (22.3%, p < 0.0001); referral criteria were implemented more recently for the latter two cancers. Younger age, family history, and chemotherapy were associated with referral. Higher Elixhauser comorbidity score and prior cancer were associated with non‐referral. No other factors were associated with genetic referral for all eligible cancers combined, although differences were seen in specific cancers. Race was a significant factor only for breast cancer, with fewer Asians than Whites referred. Health disparities in referral to genetics for HBOC cancers are mitigated in a comprehensive integrated health care system.
Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing.
A ...prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system.
Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p < .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process.
Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results.
•All women with ovarian cancer offered genetic testing by their gynecologic oncologist underwent testing.•Only 67% of those undergoing standard of care pretest counseling underwent genetic testing.•Time to test result was faster when the gynecologic oncologists ordered genetic testing than standard care.•Patients, providers and genetic counselors reported high satisfaction with point of care genetic testing.
Kaiser Permanente Northern California is a large integrated health care delivery system in the United States that has guidelines for referring women with newly diagnosed BRCA1-and BRCA2-associated ...cancers for genetic counseling. This study assesses adherence to genetic counseling referral guidelines within this health system.
Chart review was performed to identify patients with cancer who met the following pathology-based Kaiser Permanente Northern California guidelines for referral for genetic counseling: invasive breast cancer, younger than age 40; nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer, younger than age 60; women with synchronous or metachronous primary cancers of the breast and ovaries; and male breast cancer. We assessed compliance with referral guidelines. An electronic notice was sent to the managing physician of patients with newly diagnosed cancer to assess the feasibility of this intervention.
A total of 340 patients were identified with breast cancer at younger than age 40 or with ovarian, peritoneal, or tubal cancer between January and June, 2008. Upon chart review, 105 of these patients met pathology-based criteria for referral to genetic counseling, of whom 47 (45%) were referred within the 2-year study period. Of the 67 subjects with breast cancer, 40 subjects (60%) were referred. In contrast, only 7 (21%) of 33 patients with ovarian cancer were referred (P < 0.001). A pilot study was performed to test the feasibility of notifying managing oncologists with an electronic letter alerting them of eligibility for genetic referral of patients with new diagnosis (n = 21). In the 3 to 6 months after this notification, 12 of these 21 patients were referred for counseling including 5 of 7 patients with a diagnosis of ovarian cancer.
There is a missed opportunity for referring patients to genetic counseling, especially among patients with ovarian cancer. A pilot study suggests that alerting treating physicians is a feasible strategy to increase appropriate referral.
Background
We compared the results of hereditary cancer multigene panel testing among patients ≤ 45 years of age diagnosed with ductal carcinoma in situ (DCIS) versus invasive breast cancer (IBC) in ...a large integrated health care system.
Methods
A retrospective cohort study of hereditary cancer gene testing among women ≤ 45 years of age diagnosed with DCIS or IBC at Kaiser Permanente Northern California between September 2019 and August 2020 was performed. During the study period, institutional guidelines recommended the above population be referred to genetic counselors for pretesting counseling and testing.
Results
A total of 61 DCIS and 485 IBC patients were identified. Genetic counselors met with 95% of both groups, and 86.4% of DCIS patients and 93.9% of IBC patients (
p
= 0.0339) underwent gene testing. Testing differed by race/ethnicity (
p
= 0.0372). Among those tested, 11.76% (
n
= 6) of DCIS patients and 16.71% (
n
= 72) of IBC patients had a pathogenic variant (PV) or likely pathogenic variant (LPV) based on the 36-gene panel (
p
= 0.3650). Similar trends were seen in 13 breast cancer (BC)-related genes (
p
= 0.0553). Family history of cancer was significantly associated with both BC-related and non-BC-related PVs in IBC, but not DCIS.
Conclusion
In our study, 95% of patients were seen by a genetic counselor when age was used as an eligibility criterion for referral. While larger studies are needed to further compare the prevalence of PVs/LPVs among DCIS and IBC patients, our data suggest that even in younger patients, the prevalence of PVs/LPVs in BC-related genes is lower in DCIS patients.
Compare detection of Lynch syndrome in endometrial cancer between regions of a health care system with different screening strategies.
A retrospective study of endometrial cancer (EC) cases from 2 ...regions of an integrated health care system (Kaiser Permanente Northern (KPNC) and Southern (KPSC) California). Within KPNC, immunohistochemistry tumor screening (IHC) was physician ordered and risk-based; within KPSC, IHC was universal and automated. Clinical risk factors associated with abnormal IHC and Lynch Syndrome (LS) were identified.
During the study, there were 2045 endometrial cancers: 1399 in the physician-order group and 646 in the universal testing group. In the physician-order group: among women < age 60, 34% underwent IHC; 9.6% were abnormal, and 3% were possible LS after methylation testing; among women ≥60, 11% underwent IHC, 3% were abnormal and <1% were possible LS. In the universal group, 87% of women age <60 had IHC, 19.4% were abnormal, and 6% were possible LS; Among women age ≥60, 82% underwent IHC, 26% were abnormal, and 2% were possible LS. There were no differences in LS cases between the physician-order group and the universal group in either age strata (<60: 3% vs. 3.6%, p=0.62; ≥60: <1% vs. 1%, p=0.63) Factors associated with LS were younger age (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.04–0.29) and lower body mass index (BMI), (OR 0.38 95% CI 0.18–0.80).
Universal IHC screening did not result in increased LS detection in EC.
•Significant factors associated with an abnormal IHC screen included endometrioid histology and tumor grade >1.•Significant factors associated with Lynch Syndrome were younger age and lower BMI.•Universal IHC screening did not lead to increased detection of Lynch Syndrome compared to risk-based IHC screening.•Uptake of IHC screening was inconsistent when a physician order was required.
