Larson, Nicole L.

Abstract Background Physical activity is associated with decreased breast cancer recurrence and mortality, as well as fewer treatment-related symptoms. Nevertheless, most breast cancer survivors do not meet physical activity guidelines. The purpose of this manuscript is to characterize physical activity trends over time in breast cancer survivors. Methods Mayo Clinic Breast Disease Registry participants received surveys at baseline and at 1 and 4 years after diagnosis; breast cancer recurrence and/or metastatic disease were exclusion criteria. Participants were considered to be meeting guidelines if they self-reported at least 150 minutes of moderate-intensity (eg, fast walking) and/or strenuous (eg, jogging) physical activity per week. Statistical analyses include analysis of covariance methods, paired t tests, conditional logistic regression models, and McNemar tests of homogeneity. Results A total of 171 participants were included in the analysis. The amount of total physical activity decreased over time (P = .07). Mild-intensity physical activity (eg, easy walking) decreased most over time (P = .05). Among participants aged 18-49 years, mild-intensity (P = .05) and moderate-intensity (P = .02) physical activity decreased over time. Strenuous-intensity physical activity levels decreased over time among participants with a normal body mass index (P = .002) and with obesity (P = .01). Conclusions We found a trend-level decrease in total physical activity over time, driven mostly by a decrease in mild-intensity physical activity. Young breast cancer survivors are especially likely to reduce their physical activity over time. Further research on implementing physical activity guidelines in clinical practice is warranted.

Abstract 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.

PURPOSE To estimate the risk of contralateral breast cancer (CBC) among women with germline pathogenic variants (PVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2. METHODS The study population included 15,104 prospectively followed women within the CARRIERS study treated with ipsilateral surgery for invasive breast cancer. The risk of CBC was estimated for PV carriers in each gene compared with women without PVs in a multivariate proportional hazard regression analysis accounting for the competing risk of death and adjusting for patient and tumor characteristics. The primary analyses focused on the overall cohort and on women from the general population. Secondary analyses examined associations by race/ethnicity, age at primary breast cancer diagnosis, menopausal status, and tumor estrogen receptor (ER) status. RESULTS Germline BRCA1, BRCA2, and CHEK2 PV carriers with breast cancer were at significantly elevated risk (hazard ratio > 1.9) of CBC, whereas only the PALB2 PV carriers with ER-negative breast cancer had elevated risks (hazard ratio, 2.9). By contrast, ATM PV carriers did not have significantly increased CBC risks. African American PV carriers had similarly elevated risks of CBC as non-Hispanic White PV carriers. Among premenopausal women, the 10-year cumulative incidence of CBC was estimated to be 33% for BRCA1, 27% for BRCA2, and 13% for CHEK2 PV carriers with breast cancer and 35% for PALB2 PV carriers with ER-negative breast cancer. The 10-year cumulative incidence of CBC among postmenopausal PV carriers was 12% for BRCA1, 9% for BRCA2, and 4% for CHEK2. CONCLUSION Women diagnosed with breast cancer and known to carry germline PVs in BRCA1, BRCA2, CHEK2, or PALB2 are at substantially increased risk of CBC and may benefit from enhanced surveillance and risk reduction strategies.

Abstract 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.

Abstract Background: Eyebrow and eyelash loss are widely recognized as consequences of some chemotherapies, but prevalence and predictors are understudied. The purpose of this study was to evaluate real world experiences of eyebrow and eyelash loss during treatment for breast cancer. Methods: Breast cancer survivors participating in the ongoing prospective Mayo Clinic Breast Disease Registry (MCBDR) were mailed a survey one year after diagnosis. Respondents were asked to recall their severity of eyebrow and eyelash loss since diagnosis, measured from “no loss” to “a little loss” to “a lot of loss” to “complete loss”. Results: 524 participants were mailed a survey including these questions between May 2020 and November 2020; the median time from diagnosis to survey completion was 12 months (range 6 months). Of the 265 participants whose responses were available for analysis (median age 60.8 years), 88 (33%) had received chemotherapy, including 39 (44%) who received doxorubicin and cyclophosphamide, 16 (18%) who received docetaxel and cyclophosphamide, 56 (64%) who received paclitaxel, and 11 (13%) who received carboplatin. 173 (65%) had received endocrine therapy: 56 (32%) of patients who received endocrine therapy received tamoxifen, and 115 (66%) received aromatase inhibitors. 124 (47%) reported at least a little eyebrow loss, and 22 (8%) reported complete loss. Forty-seven percent reported at least a little eyelash loss, and 27 (10%) reported complete loss (Table 1). In the subgroup of 88 patients who received chemotherapy, the rates of at least a little eyebrow and eyelash loss were 50% and 55%, respectively, and rates of complete loss were 8% and 9%. Rates of eyebrow and eyelash loss did not appear to differ significantly by age. Conclusion: Eyebrow and eyelash loss are frequently reported during breast cancer-directed therapy. Future investigations into the incidence and treatment of this side effect are needed. Table 1.<55 years old55+ years oldEyebrow Loss (N)%Eyelash Loss (N)%Eyebrow Loss (N)%Eyelash Loss (N)%No Loss4551%4753%9655%9353%A Little Loss2629%2225%3922%3922%A lot of loss1011%1112%2715%2514%Complete Loss89%910%148%1810%Funding Source: Breast Cancer Research Foundation (CLL) Clinic Citation Format: Elizabeth Cathcart-Rake, Charles L Loprinzi, Fergus Couch, Janet Olson, Brittany Dulmage, Maryam Lustberg, Nicole Larson, Kathryn J Ruddy. Eyebrow/eyelash loss among survivors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-11.

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.

Abstract 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.

Abstract 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<5x10-8 as genome-wide significant, and p-values<1x10-5 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-values<1x105. 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.