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Although the benefits of surveillance mammography for older breast cancer survivors have not been quantified prospectively, it is unlikely that mammography provides substantial benefit (and possible that mammography is harmful) to women with limited life expectancy and a low risk for in-breast cancer events.We identified 1268 women aged 77 and older with a history of Stage I-III breast cancer, who did not undergo bilateral mastectomy, were diagnosed with cancer at least three years prior to study entry, and who had consented to be surveyed as part of the Mayo Clinic Breast Disease Registry. We mailed them a one-time survey asking about their experiences with surveillance mammography. Women with metastatic disease were excluded. The primary endpoint was whether or not women reported at least one mammogram since breast cancer surgery.Eight hundred forty-six of 1268 (67%) returned the survey, 734 of whom were eligible for analysis. The median age at the time of survey was 82, and the median time since cancer diagnosis was 12 years. Ninety-three percent reported having had at least one mammogram since their initial breast cancer surgery. Seventy-nine percent reported that they had surveillance mammography annually over the prior three years, including 76% of the 491 aged 80+ and 64% of the 189 aged 85 + .Most older breast cancer survivors who have residual breast tissue are undergoing annual mammograms. Additional educational materials may be beneficial for patients and clinicians to better individualize plans for surveillance mammography in older breast cancer survivors.

PURPOSE To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC). RESULTS The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC. CONCLUSION The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.

PURPOSE The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years. METHODS A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs. RESULTS The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in BRCA1, BRCA2, and PALB2 were found in 3.42% of women diagnosed with estrogen receptor (ER)–negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in CHEK2, PALB2, BRCA2, and BRCA1 were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in BRCA1, BRCA2, and PALB2. CONCLUSION This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with BRCA1 and BRCA2 PVs and perhaps with PALB2 and CHEK2 PVs should be considered for magnetic resonance imaging screening.

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

Introduction: The utilization of self reported chemotherapy treatment data is common in epidemiologic research but there is little understanding of its accuracy and limitations. Methods: The Mayo Clinic Breast Disease Registry (MCBDR) has over 9,600 participants enrolled within one year of a first breast cancer diagnosis. Participants receive annual follow up surveys through the mail to capture data on breast cancer treatments and outcomes. We compared nurse abstracted medical record chemotherapy data to self reported chemotherapy data from women diagnosed with stage 0 to 3 breast cancer that completed five consecutive annual follow up surveys. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) statistics were assessed for the report of broad chemotherapy receipt (yes, no, DK) within each yearly survey compared to the gold standard medical record data. To assess the accuracy of the self reported use of specific chemotherapy regimens, a sub cohort known as the “congruent sub cohort” was created for each survey year that included subjects that agreed with the nurse abstractors report of their broad chemotherapy usage. Sensitivity, specificity, PPV, NPV, and concordance statistics were calculated for the congruent sub cohorts followed by an assessment of the proportion of subjects providing correct responses for all chemotherapy regimens queried compared to those that had at least one discrepancy with the nurse abstracted data and the proportion of subjects with 0, 1, 2 and 3 or more discrepancies within each survey year. Results: For the 430 survey respondents, the average age was 59.5 years (SD 11.7) with a range of 29 to 94. The mean time between diagnosis and the year 1 follow up survey was 13.5 months, with an average of 61.2 months between diagnosis and the year 5 survey. The respondents were 97% white, 100% female, and 53.5% had a bachelor’s degree or higher. The self-reported receipt of chemotherapy had substantial agreement across all 5 follow up surveys with the nurse abstracted treatment data from the medical record with kappa values ranging from 0.70 (0.63 to 0.76) to 0.64 (0.57 to 0.71). For subjects in the congruent sub cohort (N=125, 120, 122, 121, and 121 subjects across the 5 survey years, respectively), self reported use of specific chemotherapy regimens were reported with an average concordance of 90% across the 5 annual surveys, however only 23% had perfect agreement with nurse abstracted data. The average number of discrepant responses provided by subjects was 1.2, with at least 12% of subjects reporting 3 or more erroneous responses for the specific chemotherapy regimens each survey year. Discussion: This study supports previous findings that self-reported chemotherapy usage may be utilized when resources are unavailable for medical record abstraction, but may have less utility when analyzing specific chemotherapy regimens. Citation Format: Nicole L. Larson, Kathryn J. Ruddy, Feven Abraha, Denise M. Herman, Fergus J. Couch, Janet E. Olson. Accuracy of self reported chemotherapy usage in annual follow up surveys for a breast cancer registry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 748.

BackgroundCopy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data.ResultsGene burden tests detected the strongest association for deletions in BRCA1 (P= 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P= 0.0008), ATM (P= 0.002) and BRCA2 (P= 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci.ConclusionsThis is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.

BACKGROUND: The American Cancer Society recommends at least 150 minutes of moderate and/or strenuous exercise and muscle-strengthening activities each week for adults. Exercise has been associated with decreased breast cancer mortality and adverse symptoms. This study’s purpose is to understand prevalence and predictors of inadequate aerobic exercise in patients recently diagnosed with breast cancer to inform interventions to increase exercise participation. METHODS: Patients seen at least once at Mayo Clinic Rochester were prospectively enrolled within one year of an initial breast cancer diagnosis in the Mayo Clinic Breast Disease Registry after providing informed consent. This analysis includes those who completed a baseline survey with self-reported exercise data using the Godin Leisure-Time Exercise Questionnaire. This longitudinal cohort study was approved by the Mayo Clinic institutional review board. RESULTS: 1,738 participants reported their usual weekly quantity of moderate and strenuous exercise an average of 95 days (SD 71 days, range 0-365) after diagnosis. Table 1 displays participant characteristics overall and by whether participants reported at least 150 minutes of moderate and/or strenuous activity weekly (“met guidelines”) or not (“did not meet guidelines”). Overall, 39% of participants met guidelines, including 56% of those aged 18-39 years, 40% of those aged 40-69 years, and 27% of those aged 70+ years. CONCLUSION: Older age was associated with less likelihood of meeting exercise guidelines (all age groups vs 70+, p < 0.05). A more diverse cohort will be needed to evaluate differences by gender and race/ethnicity. There did not appear to be any obvious impact on exercise level by time since diagnosis (during the first year after diagnosis) or educational status, though substantial missing data limit conclusions related to the latter. Additional research is needed to assess exercise levels later in survivorship and the impact of various treatment modalities on exercise habits Table 1. Patient and tumor characteristics Citation Format: Paulina S. Marell, Janet E. Olson, Joerg Herrmann, Nicole L. Larson, Nathan K. LeBrasseur, Stacy D. D'Andre, Andrea L. Cheville, Toure Barksdale, Charles L. Loprinzi, Fergus J. Couch, Kathryn J. Ruddy. Factors associated with exercise participation in patients with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5868.

Objective: To better understand the characteristics associated with a participant's willingness to consent to the Mayo Clinic Biobank (MCB) and examine factors associated with willingness to participate in follow-up studies embedded within MCB that require re-contact and participant approval. Participants and Methods: Consent rates were compared across patient demographics to the MCB. Rates of participation to follow-up studies were also compared across demographics and request types. Results: Among 272,102 Mayo Clinic patients invited to the MCB, 48,314 (19%) consented across the three recruitment sites within 90 days of initial invitation. A significant age by gender interaction was identified, showing young males consent at a lower rate than young females and older males consent at a higher rate than older females. Over the recruitment time frame of 2009–2015, there was a significant decrease in consent rates (decline of 2.5%/year). Of the 57,041 consented MCB participants, 33,487 participants (59%) have been invited to participate in follow-up studies via re-contact. Follow-up studies of the MCB may require participants to provide additional samples, complete questionnaires, and/or release their identity to a research team. MCB participants have been invited to enroll in a median of two studies (IQR: 1–3). Seventy-one percent of participants consented to at least one follow-up study, with individual follow-up study consent rates ranging from 14 to 87% depending on study type, with a median consent rate of 61% (IQR: 47–70%). Studies requesting return of a questionnaire had the highest participation rates. White participants, older participants, and participants with some college or a degree were significantly more likely to participate to follow-up studies, while there was no association with gender. Conclusion: Consent rates among younger and non-white patients were lower than in older, white patients. However, we also found that participation rates among those already enrolled in the biobank were much higher than those seen in new recruitment efforts, external to an existing biobank. We thus demonstrate an important way that biobanks can advance precision medicine goals: through provision of populations from which studies can draw participants for future studies.

Three-dimensional (3D) imaging is increasingly being incorporated into a variety of medical specialties: surgery and radiology being but two prominent examples. Image-intensive disciplines, such as anatomic pathology (AP), represent excellent potential candidates for further exploration of this innovative technology. Multiple potential use cases exist within AP, involving patient care, education, and research. These use cases broadly include direct utilization of the 3D digital assets for viewing on a 2D screen, populating 3D extended reality platforms (virtual reality, augmented reality, and mixed reality) as well as generation of 3D printed photorealistic specimen models. Herein, these use cases are explored with specific regard to our experiences and yet unrealized potential. Future directions and considerations are also discussed.