Genetic Counseling, Testing, and Family Communication Into Survivorship After Diagnosis of Breast Cancer.

PURPOSE: To examine receipt of genetic testing and communication with relatives about results into survivorship after diagnosis of breast cancer. METHODS: Women age 20-79 years diagnosed with early-stage breast cancer in 2014-2015 and reported to the Georgia and Los Angeles County SEER registries were surveyed approximately 7 months and 6 years after diagnosis (n = 1,412). We asked about genetic counseling, testing, and communication with relatives about results. We categorized women into indications for testing on the basis of clinical guidelines at the time of diagnosis and at the time of the follow-up survey (FUPs). RESULTS: A total of 47.4% had indications for genetic testing at any time: 28.0% at baseline and an additional 19.4% at the time of the FUPs (only); 71.9% (95% CI, 67.4 to 76.4) of those with a baseline indication reported genetic testing versus 53.3% (95% CI, 47.3 to 59.2) with an indication at FUPs only and 35.0% (95% CI, 31.6 to 38.4) with no indication (P < .001). There were no significant racial or ethnic differences in receipt of testing, controlling for age and clinical indications (P = .239); results for genetic counseling were similar. Only 3.4% of survivors had direct-to-consumer genetic testing (DTCt) for cancer. Testers who reported a pathogenic variant (n = 62) were much more likely to have talked to most or all their first-degree adult relatives about genetic testing than those with a variant of unknown significance (n = 49) or a negative finding (n = 419): 62.7% versus 38.8% and 38.0%, respectively (P < .001). CONCLUSION: Many women with indications for genetic counseling and testing into survivorship do not receive it. But those tested reach out to family members on the basis of the clinical relevance of their results. Very few patients obtained DTCt, which suggests that these tests do not substitute for clinical testing in breast cancer survivors.

Deciding to Attend the Emergency Department: Experiences of Patients With Inflammatory Arthritis.

OBJECTIVE: Patients may use emergency departments (EDs) to meet their health needs when ambulatory care systems are not sufficient. We aim to describe contributing factors to the decision made by persons with inflammatory arthritis (IA) to present to the ED, as well as their experiences of ED care and postdischarge follow-up. METHODS: An embedded mixed-methods approach was taken to contextualize quantitative data with associated free-text responses from an online survey distributed to residents of Alberta with a known IA condition and an ED visit. RESULTS: Eighty-two persons (63% aged 16-55 years, 48% female, 50% urban residents) with rheumatoid arthritis (48%), psoriatic arthritis (12%), spondyloarthritis (6%), or gout (34%) completed the survey. Presenting concerns were arthritis flare (37%), chest pain (15%), injury (12%), and infection (11%). Of all visits, 29% proceeded directly to the ED, 35% attempted accessing ambulatory care first, and 32% arrived for a return visit. In presentations for arthritis flare, patients were aware of the rheumatology service being contacted by the ED provider for advice in just 9% of events. Challenges in healthcare system coordination and system pressures resulted in patients requiring ED attendance to assess their concern. The quality of communication and relationality developed between patients with IA and healthcare providers informed experiences of ED care. CONCLUSION: Modifying rheumatology ambulatory care models could better meet patient needs and ultimately reduce avoidable ED use by patients with IA.

Burnout and fatigue amongst internal medicine residents: A cross-sectional study on the impact of alternative scheduling models on resident wellness.

BACKGROUND: Fatigue and burnout are prevalent among resident physicians across Canada. Shifts exceeding 24 hours are commonly purported as detrimental to resident health and performance. Residency training programs have employed strategies towards understanding and intervening upon the complex issue of resident fatigue, where alternative resident scheduling models have been an area of active investigation. This study sought to characterize drivers and outcomes of fatigue and burnout amongst internal medicine residents across different scheduling models. METHODS: We conducted cross-sectional surveys were among internal medicine resident physicians at the University of Alberta. We collected anonymized socioeconomic demographics and medical education background, and estimated associations between demographic or work characteristics and fatigue and burnout outcomes. RESULTS: Sixty-nine participants competed burnout questionnaires, and 165 fatigue questionnaires were completed (response rate of 48%). The overall prevalence of burnout was 58%. Lower burnout prevalence was noted among respondents with dependent(s) (p = 0.048), who identified as a racial minority (p = 0.018), or completed their medical degree internationally (p = 0.006). The 1-in-4 model was associated with the highest levels of fatigue, reported increased risk towards personal health (OR 4.98, 95%CI 1.77-13.99) and occupational or household harm (OR 5.69, 95%CI 1.87-17.3). Alternative scheduling models were not associated with these hazards. CONCLUSIONS: The 1-in-4 scheduling model was associated with high rates of resident physician fatigue, and alternative scheduling models were associated with less fatigue. Protective factors against fatigue are best characterized as strong social supports outside the workplace. Further studies are needed to characterize the impacts of alternative scheduling models on resident education and patient safety.

Germline Genetic Testing After Cancer Diagnosis.

Importance: Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention. Objective: To describe the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019. Design, Setting, and Participants: Observational study including patients aged 20 years or older who had been diagnosed with any type of cancer between January 1, 2013, and March 31, 2019, that was reported to statewide Surveillance, Epidemiology, and End Results registries in California and Georgia. These patients were linked to genetic testing results from 4 laboratories that performed most germline testing for California and Georgia. Main Outcomes and Measures: The primary outcome was germline genetic testing within 2 years of a cancer diagnosis. Testing trends were analyzed with logistic regression modeling. The results of sequencing each gene, including variants associated with increased cancer risk (pathogenic results) and variants whose cancer risk association was unknown (uncertain results), were evaluated. The genes were categorized according to their primary cancer association, including breast or ovarian, gastrointestinal, and other, and whether practice guidelines recommended germline testing. Results: Among 1 369 602 patients diagnosed with cancer between 2013 and 2019 in California and Georgia, 93 052 (6.8%) underwent germline testing through March 31, 2021. The proportion of patients tested varied by cancer type: male breast (50%), ovarian (38.6%), female breast (26%), multiple (7.5%), endometrial (6.4%), pancreatic (5.6%), colorectal (5.6%), prostate (1.1%), and lung (0.3%). In a logistic regression model, compared with the 31% (95% CI, 30%-31%) of non-Hispanic White patients with male breast cancer, female breast cancer, or ovarian cancer who underwent testing, patients of other races and ethnicities underwent testing less often: 22% (95% CI, 21%-22%) of Asian patients, 25% (95% CI, 24%-25%) of Black patients, and 23% (95% CI, 23%-23%) of Hispanic patients (P < .001 using the χ2 test). Of all pathogenic results, 67.5% to 94.9% of variants were identified in genes for which practice guidelines recommend testing and 68.3% to 83.8% of variants were identified in genes associated with the diagnosed cancer type. Conclusions and Relevance: Among patients diagnosed with cancer in California and Georgia between 2013 and 2019, only 6.8% underwent germline genetic testing. Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.

Primary care provider attitudes about and tendency to use non-recommended surveillance tests after curative breast cancer treatment.

PURPOSE: Little is known about the factors contributing to the receipt of non-recommended surveillance testing among early-stage breast cancer survivors. We assessed primary care providers (PCP) attitudes about and tendency to order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors post-adjuvant chemotherapy. METHODS: A stratified random sample of PCPs identified by early-stage breast cancer survivors were surveyed (N = 518, 61% response rate). PCPs were asked how likely they would be to order bone scans, imaging and/or tumor marker testing using a clinical vignette of an early-stage asymptomatic patient where these tests are non-recommended. A composite tendency to order score was created and categorized by tertiles (low, moderate, high). PCP-reported factors associated with high and moderate tendency to order non-recommended testing (vs. low) were estimated using multivariable, multinomial logistic regression. RESULTS: In this sample, 26% reported a high tendency to order non-recommended surveillance tests during survivorship for early-stage breast cancer survivors. PCPs who identified as family practice physicians and PCPs reporting more confidence in ordering surveillance testing were more likely to report a high tendency to order non-recommended testing (vs. low) ((aOR family practice 2.09, CI 1.2, 3.8; aOR more confidence 1.9, CI 1.1, 3.3). CONCLUSIONS: In this population-based sample of PCPs caring for breast cancer survivors, over a quarter of PCPs reported they would order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors. Efforts to better support PCPs and disseminate information about appropriate surveillance for cancer survivors are warranted.

Cascade Genetic Risk Education and Testing in Families With Hereditary Cancer Syndromes: A Pilot Study.

PURPOSE: Cascade genetic risk evaluation in families with hereditary cancer can reduce the burden of disease but the rate of germline genetic testing in relatives of patients at risk is low. METHODS: We identified all 277 women diagnosed with breast cancer in Georgia in 2017 who linked to a clinically actionable germline pathogenic variant through a Surveillance, Epidemiology, and End Results registry-variant linkage initiative. We surveyed them, and then invited eligible respondents to an online platform hosted by a navigator that offered cancer genetic risk education and germline genetic testing to untested relatives. We randomly assigned patient-family clusters at the time of the patient enrollment offer to free versus $50 (USD) test cost. Patients invited relatives to join the study through personalized e-mail. Enrolled relatives received online cancer genetic education and the opportunity to order clinical germline genetic testing through the platform. The primary outcome was the number of relatives who ordered genetic testing. RESULTS: One hundred twenty-five of 277 patients completed surveys (45.2%). Most respondents were eligible for the trial offer (113 of 125; 90.4%). In the free testing arm, 20 of 56 eligible patients participated (35.7% of eligible respondents) and they invited 28 relatives: 12 relatives enrolled and 10 ordered testing. In the $50 (USD) arm, 16 of 57 eligible patients participated (28.1%) and they invited 38 relatives: 18 relatives enrolled and 17 ordered testing. CONCLUSION: Cascade genetic testing in families with hereditary cancer syndromes accrued through a population-based cancer registry can be achieved through an online platform that offers genetic risk education and low-cost testing to relatives. A modest charge did not appear to influence the percentage of participating patients, numbers of participating relatives, and numbers of relatives who received genetic testing.

Rheumatology Image of the Month: A Low Resource Innovation With Measurable Results.

OBJECTIVES: Strategies to increase confidence in rheumatology knowledge are valuable for medical trainees and residents. A web-based teaching innovation was implemented in an attempt to increase rheumatology exposure for internal medicine residents. METHODS: An Image of the Month webpage was established, where a practicing rheumatologist would post a new image that could be answered online by internal medicine residents. Cumulative data was analyzed to determine the extent and change in rheumatology exposure. RESULTS: The Image of the Month webpage posted images for a total of 76 months between July 2010 to May 2017, with a total of 1326 submitted responses. The proportion of residents who only participated in Image of the Month and only did a rheumatology rotation averaged 36.1% and 16.5%, respectively. The proportion of residents who only participated in Image of the Month was higher than the proportion who only did a rheumatology rotation for all of the 7 time periods assessed. A total of 491 residents participated in Image of the Month, with an average of 54.9% of residents participating each year. Overall, on average, 52 residents had 1 or more submissions, 3.6 entries were submitted per resident, and 17.4 entries were submitted per month. Junior residents (PGY1) participated more often than senior residents (PGY3). CONCLUSIONS: The Image of the Month webpage successfully improves internal medicine resident exposure to rheumatology with minimal resources and manpower required. Further study is necessary to determine the impact this exposure may have on the abilities and confidence levels of internal medicine residents.

Biological Sex Inequality in Rheumatology Wait Times During the COVID-19 Pandemic.

OBJECTIVE: To examine the effect of biological sex on wait times to first rheumatology appointment in a central triage system before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Deidentified data of all referred patients between November 2019 and June 2022 were extracted from the electronic medical record. Variables, including time from referral to first appointment, biological sex, referral period, urgency status, age, and geographic location were collected and analyzed. RESULTS: Twelve thousand eight hundred seventeen referrals were identified. Wait times increased by 24.23 days in the peri-COVID period (P < 0.001). In the pre-COVID period, there was no significant difference in wait times by biological sex or age. Triage urgency was a predictor of wait time, with semiurgent referrals seen 8.94 days (95% CI -15.90 to -1.99) sooner than routine referrals and urgent referrals seen 25.42 days (95% CI -50.36 to -0.47) sooner than routine referrals. In the peri-COVID period, there was a significant difference in wait time by biological sex with women waiting on average 10.03 days (95% CI 6.98-13.09) longer than men (P < 0.001). Older patients had shorter wait times than younger patients, with a difference of -4.64 days for every 10-year increase in age (95% CI -5.49 to -3.78). Triage urgency continued to be a predictor of wait time. CONCLUSION: Women and younger patients appear to have been affected by wait time increases during the COVID-19 pandemic. This finding should be further investigated to determine its pervasiveness across other specialities and to better understand the underlying cause of this finding.

Comparing Entrustable Professional Activity Scores Given by Faculty Physicians and Senior Trainees to First-Year Residents.

Introduction Competency by Design (CBD) began on July 1, 2019, for postgraduate year 1 (PGY1) Canadian Core Internal Medicine (CIM) residents. Many entrustable professional activity (EPA) observations allow for assessment by either a faculty physician, senior medicine resident (SMR), or subspecialty resident (SSR). However, few studies exist that compare EPA scores and comments given by faculty vs senior trainees (SMRs and SSRs). This study aimed to identify differences in EPA scores and comments given to PGY1 residents by faculty physicians vs senior trainees. Methods Scores and comments of EPAs completed between July 1, 2019, and June 30, 2020, for 35 CIM PGY1 residents were extracted anonymously from the University of Alberta CBD platform. Scores from faculty vs senior trainees were compared with the Mann-Whitney U test and the Kruskal-Wallis test. Word counts for positive and constructive comments written by faculty vs senior trainees were compared with the independent t-test and one-way ANOVA. The most common two-word phrases in comments were identified with QI Macros software (Denver, CO: KnowWare International, Inc.). Results A total of 2226 EPAs were observed. Faculty physicians gave significantly lower EPA scores overall compared to senior trainees (U = 501706, P <0.001). Constructive comments written by faculty (M = 14.06, SD = 16.84) had lower word counts compared to senior trainees (M = 15.85, SD = 16.43) for overall EPAs (t{2224} = -2.528, P = 0.012). Conclusion Faculty physicians gave lower EPA scores and had lower word counts on constructive comments, compared to senior trainees. These results may help the ongoing implementation of Competence by Design.

Chemotherapy Regimens Received by Women With BRCA1/2 Pathogenic Variants for Early Stage Breast Cancer Treatment.

BACKGROUND: Genetic testing is widespread among breast cancer patients; however, no guideline recommends using germline genetic testing results to select a chemotherapy regimen. It is unknown whether breast cancer patients who carry pathogenic variants (PVs) in BRCA1 and/or 2 (BRCA1/2) or other cancer-associated genes receive different chemotherapy regimens than noncarriers. METHODS: We linked Surveillance, Epidemiology, and End Results registry records from Georgia and California to germline genetic testing results from 4 clinical laboratories. Patients who 1) had stages I-III breast cancer, either hormone receptor (HR) positive and HER2 negative or triple negative (TNBC), diagnosed in 2013-2017; 2) received chemotherapy; and 3) were linked to genetic results were included. Chemotherapy details were extracted from Surveillance, Epidemiology, and End Results text fields completed by registrars. We examined whether PV carriers received more intensive regimens (HR-positive,HER2-negative: ≥3 drugs including an anthracycline; TNBC: ≥4 drugs including an anthracycline and platinum) and/or less standard breast cancer agents (a platinum). All statistical tests were 2-sided. RESULTS: Among 2293 patients, 1451 had HR-positive, HER2-negative disease, and 842 had TNBC. On multivariable analysis of women with HR-positive, HER2-negative disease, receipt of a more intensive chemotherapy regimen varied statistically significantly by genetic results (P = .02), with platinum receipt more common among BRCA1/2 PV carriers (odds ratio = 2.44, 95% confidence interval = 1.36 to 4.38; P < .001). Among women with TNBC, chemotherapy agents did not vary significantly by genetic results. CONCLUSION: BRCA1/2 PV carriers with HR-positive, HER2-negative breast cancer had twofold higher odds than noncarriers of receiving a platinum, as part of a more intensive chemotherapy regimen. This likely represents overtreatment and emphasizes the need to monitor how genetic testing results are managed in oncology practice.

Staff and resident perceptions on the introduction of a team based multi-specialty resident night shift system.

OBJECTIVES: To determine the perceptions of staff and resident physicians on the impact of implementation of a new team based multi-specialty resident night shift system. METHODS: An electronic survey was distributed anonymously to all resident physicians in the Core Internal Medicine residency program at the University of Alberta. A similar survey was distributed to staff physicians in the 4 specialties impacted by this new system: hematology, respirology, nephrology and gastroenterology. RESULTS: 74 physicians completed the survey. A majority of respondents (67%) indicated the new system was a positive change. Most shared it was better than traditional 1 in 4 call (65%), with resident physicians appreciating the team based nature of the system (65%), and just more than half of residents (55%) indicating this system improved their overall wellness. Most respondents (78%) did not feel the additional handover required had a negative impact. Respondents indicated daytime teaching and feedback improved as a result of this system (52%) with most others indicating it had no impact, although overnight feedback remained a challenge. CONCLUSION: The implementation of this new team based system was well accepted by both staff and resident physicians across a number of domains. Future study is required to determine its impact on access and quality of care.

Association of Genetic Testing Results With Mortality Among Women With Breast Cancer or Ovarian Cancer.

BACKGROUND: Breast cancer and ovarian cancer patients increasingly undergo germline genetic testing. However, little is known about cancer-specific mortality among carriers of a pathogenic variant (PV) in BRCA1/2 or other genes in a population-based setting. METHODS: Georgia and California Surveillance Epidemiology and End Results (SEER) registry records were linked to clinical genetic testing results. Women were included who had stages I-IV breast cancer or ovarian cancer diagnosed in 2013-2017, received chemotherapy, and were linked to genetic testing results. Multivariable Cox proportional hazard models were used to examine the association of genetic results with cancer-specific mortality. RESULTS: 22 495 breast cancer and 4320 ovarian cancer patients were analyzed, with a median follow-up of 41 months. PVs were present in 12.7% of breast cancer patients with estrogen and/or progesterone receptor-positive, HER2-negative cancer, 9.8% with HER2-positive cancer, 16.8% with triple-negative breast cancer, and 17.2% with ovarian cancer. Among triple-negative breast cancer patients, cancer-specific mortality was lower with BRCA1 (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.35 to 0.69) and BRCA2 PVs (HR = 0.60, 95% CI = 0.41 to 0.89), and equivalent with PVs in other genes (HR = 0.65, 95% CI = 0.37 to 1.13), vs noncarriers. Among ovarian cancer patients, cancer-specific mortality was lower with PVs in BRCA2 (HR = 0.35, 95% CI = 0.25 to 0.49) and genes other than BRCA1/2 (HR = 0.47, 95% CI = 0.32 to 0.69). No PV was associated with higher cancer-specific mortality. CONCLUSIONS: Among breast cancer and ovarian cancer patients treated with chemotherapy in the community, BRCA1/2 and other gene PV carriers had equivalent or lower short-term cancer-specific mortality than noncarriers. These results may reassure newly diagnosed patients, and longer follow-up is ongoing.

Perceived financial decline related to breast reconstruction following mastectomy in a diverse population-based cohort.

BACKGROUND: Despite mandated insurance coverage for breast reconstruction following mastectomy, health care costs are increasingly passed on to women through cost-sharing arrangements and high-deductible health plans. In this population-based study, the authors assessed perceived financial and employment declines related to breast reconstruction following mastectomy. METHODS: Women with early-stage breast cancer (stages 0-II) diagnosed between July 2013 and May 2015 who underwent mastectomy were identified through the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles and were surveyed. Primary outcome measures included patients' appraisal of their financial and employment status after cancer treatment. Multivariable models evaluated the association between breast reconstruction and primary outcomes. RESULTS: Among 883 patients with breast cancer who underwent mastectomy, 44.2% did not undergo breast reconstruction, and 55.8% underwent reconstruction. Overall, 21.9% of the cohort reported being worse off financially since their diagnosis (25.8% with reconstruction vs 16.6% without reconstruction; P = .002). Women who underwent reconstruction reported higher out-of-pocket medical expenses (32.1% vs 15.6% with expenses greater than $5000; P < .001). Reconstruction was independently associated with a perceived decline in financial status (odds ratio, 1.92; 95% confidence interval, 1.15-3.22; P = .013). Among women who were employed at the time of their diagnosis, there was no association between reconstruction and a perceived decline in employment status (P = .927). CONCLUSIONS: In this diverse cohort of women who underwent mastectomy, those who elected to undergo reconstruction experienced higher out-of-pocket medical expenses and self-reported financial decline. Patients, providers, and policymakers should be aware of the potential financial implications related to reconstruction despite mandatory insurance coverage.

Multiple imputation with missing data indicators.

Multiple imputation is a well-established general technique for analyzing data with missing values. A convenient way to implement multiple imputation is sequential regression multiple imputation, also called chained equations multiple imputation. In this approach, we impute missing values using regression models for each variable, conditional on the other variables in the data. This approach, however, assumes that the missingness mechanism is missing at random, and it is not well-justified under not-at-random missingness without additional modification. In this paper, we describe how we can generalize the sequential regression multiple imputation imputation procedure to handle missingness not at random in the setting where missingness may depend on other variables that are also missing but not on the missing variable itself, conditioning on fully observed variables. We provide algebraic justification for several generalizations of standard sequential regression multiple imputation using Taylor series and other approximations of the target imputation distribution under missingness not at random. Resulting regression model approximations include indicators for missingness, interactions, or other functions of the missingness not at random missingness model and observed data. In a simulation study, we demonstrate that the proposed sequential regression multiple imputation modifications result in reduced bias in the final analysis compared to standard sequential regression multiple imputation, with an approximation strategy involving inclusion of an offset in the imputation model performing the best overall. The method is illustrated in a breast cancer study, where the goal is to estimate the prevalence of a specific genetic pathogenic variant.

Internet search results correlate with seasonal variation of sarcoidosis.

BACKGROUND: The etiology and pathophysiology of sarcoidosis remains unclear, with epidemiologic studies limited by its relatively low prevalence. The internet has prompted patients to seek information about medical diagnoses online; Google Trends provides access to an anonymized version of this data, which has a new role in epidemiology. We hypothesize that there is seasonal variation in the relative search interest of sarcoidosis, which would suggest seasonal variation in the incidence of sarcoidosis. METHODS: Google Trends was used to assess the relative search volume from 2010 to 2020 for "sarcoidosis" and "sarcoid" in 7 countries. ANOVA with multiple comparisons was performed to compare the mean relative search volume by month and by season for each country, with a p-value less than 0.05 indicating statistical significance. RESULTS: Our analysis revealed a significant seasonal variation in search popularity in 4 of the 7 countries and in the Northern Hemispheric countries combined. Direct comparison showed search terms to be more popular in spring, specifically March & April, than in the winter. Southern Hemisphere data was not statistically significant but showed a trend towards a nadir in December and a peak in September and October. CONCLUSIONS: Overall, these findings suggest seasonal variation with a possible peak in spring and nadir in winter. This supports the hypothesis that sarcoidosis has seasonal variation and is more commonly diagnosed in spring, but more evidence is needed to support this, as well as investigation into the pathophysiology of sarcoidosis to explain this phenomenon.

The Influence of Applicant and Reviewer Gender on Resident Selection for Internal Medicine.

BACKGROUND: While gender bias in medicine, including physician training, has been well described, less is known about gender bias in the selection process for post graduate residency training programs. This analysis reviews the potential role of gender on resident selection for an internal medicine residency program. METHODS: File review and interview overall and component scores were analyzed based on the gender of the applicant. File review scores were further analyzed based on the reviewer's gender. RESULTS: Women applicants scored higher than men applicants on their file review. There were no differences in any one component score except for leadership in art. Women file reviewers scored applicants higher than men file reviewers, but there was no difference between gender scores. There was no difference in overall or component interview scores between men or women applicants. Scoring did not impact the expected rank performance of applicants based on gender at any stage of the selection process. CONCLUSIONS: While higher scores were observed in women applicants upon their file review, and women reviewers provided higher file review scores, this did not appear to impact the expected number of women and men applicants at each stage of the applicant process. This suggests a potential lack of gender bias at these stages of applicant selection.

Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019.

PURPOSE: Genetic testing is important for breast and ovarian cancer risk reduction and treatment, yet little is known about its evolving use. METHODS: SEER records of women of age ≥ 20 years diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia were linked to the results of clinical germline testing through 2019. We measured testing trends, rates of variants of uncertain significance (VUS), and pathogenic variants (PVs). RESULTS: One quarter (25.2%) of 187,535 patients with breast cancer and one third (34.3%) of 14,689 patients with ovarian cancer were tested; annually, testing increased by 2%, whereas the number of genes tested increased by 28%. The prevalence of test results by gene category for breast cancer cases in 2017 were BRCA1/2, PVs 5.2%, and VUS 0.8%; breast cancer-associated genes or ovarian cancer-associated genes (ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53), PVs 3.7%, and VUS 12.0%; other actionable genes (APC, BMPR1A, MEN1, MUTYH, NF2, RB1, RET, SDHAF2, SDHB, SDHC, SDHD, SMAD4, TSC1, TSC2, and VHL) PVs 0.6%, and VUS 0.5%; and other genes, PVs 0.3%, and VUS 2.6%. For ovarian cancer cases in 2017, the prevalence of test results were BRCA1/2, PVs 11.0%, and VUS 0.9%; breast or ovarian genes, PVs 4.0%, and VUS 12.6%; other actionable genes, PVs 0.7%, and VUS 0.4%; and other genes, PVs 0.3%, and VUS 0.6%. VUS rates doubled over time (2013 diagnoses: 11.2%; 2017 diagnoses: 26.8%), particularly for racial or ethnic minorities (47.8% Asian and 46.0% Black, v 24.6% non-Hispanic White patients; P < .001). CONCLUSION: A testing gap persists for patients with ovarian cancer (34.3% tested v nearly all recommended), whereas adding more genes widened a racial or ethnic gap in VUS results. Most PVs were in 20 breast cancer-associated genes or ovarian cancer-associated genes; testing other genes yielded mostly VUS. Quality improvement should focus on testing indicated patients rather than adding more genes.

Predicted Chemotherapy Benefit for Breast Cancer Patients With Germline Pathogenic Variants in Cancer Susceptibility Genes.

Breast cancer patients increasingly undergo genetic testing. To examine chemotherapy indications for germline pathogenic variant (PV) carriers, we linked results of germline testing to Georgia and California Surveillance, Epidemiology, and End Results registry records, including 21-gene recurrence score (RS) results, for breast cancer patients diagnosed in 2013-2017. All statistical tests were 2-sided. Patients (N=37 349) had RS results of whom 714 had BRCA1, BRCA2, CHEK2, ATM, PALB2, or Lynch syndrome (MLH1, MSH2, MSH6, PMS2) PVs. For women aged 50 years or older at breast cancer diagnosis, RS often exceeded the chemotherapy benefit threshold (≥26) with BRCA1 (71.7% vs 14.4% with none; P <.001), PALB2 (37.1%; P = .001), and BRCA2 (44.3%; P < .001) PVs. Results were similar for women diagnosed at younger than 50 years of age. PVs in BRCA1, but not BRCA2, PALB2, ATM, CHEK2, or Lynch syndrome genes, were associated with elevated RS on multivariable analysis (P < .001). Results may inform RS testing decisions in breast cancer patients with PVs.