Abstract PS11-08: MRI improves multi-modal AI system for breast cancer diagnosis and prognosis

Rapid developments in cancer genetics and hereditary cancer risk assessments have enabled the identification of individuals at elevated risk for hereditary malignancies to guide enhanced cancer screening and prevention efforts. Multigene panel testing has emerged as the standard approach as emphasized in the National Comprehensive Cancer Network (NCCN) guidelines. The purpose of this study was to investigate the frequency of other pathogenic mutations identified through multigene panel testing in individuals who previously tested negative for germline BRCA1/2 and assess the clinical impact of panel testing. Patients either previously diagnosed with breast cancer or with a family history of breast or ovarian cancer that had also been seen by Oncology Genetics at a single institution and tested negative for BRCA1/2 genes but had not undergone prior multigene panel testing were invited via a letter to return for an additional genetic counseling visit to discuss multigene panel testing. Patients were also able to opt-in to a survey component of the study and received an email to fill out the Multidimensional Impact of Cancer Risk Assessment (MICRA) and Cancer Worry Scale (CWS). Surveys were completed prior to the initial genetic counseling appointment and repeated after discussion of the multigene panel test results. A total 24 women met with a genetic counselor of which 22 (92%) had a personal history of breast cancer, 1 (4%) had a family history of breast cancer, and 1 (4%) had a family history of ovarian cancer. The mean age was 52.6 years (range, 42-68) and 100% of women were Caucasian. Of the 24 women, 17 (71%) completed multigene panel testing. Of the women that underwent testing, 7 (41%) had negative results, 6 (35%) had variants of unknown significance (VUS), and 4 (24%) had a pathogenic mutation identified in another gene (CDKN2A, CHEK2, and CFTR). There was no significant change in MICRA or CWS scores after multigene panel results were reviewed in the 9 patients that completed both pre- and post-genetic testing surveys. The mean/median summary MICRA scores pre- and post-counselling were 30 (SD 12.4), median 26 (min 18, max 56), and 21.2 (SD 15.4), median 21 (min 3, max 43), respectively (p=0.19, Wilcoxon signed ranks test). The mean/median summary CWS scores pre- and post-counselling were 14.3 (SD 5), median 15 (min 7, max 24), and 13.6 (SD 2.59), median 14 (min 10, max 17), respectively (p=0.53, Wilcoxon signed ranks test). Of the 4 patients with newly identified pathogenic mutations, 2 started new screening protocols and 1 underwent a prophylactic mastectomy. In conclusion, multigene panel testing identified pathogenic mutations in a subset of individuals who previously tested negative for BRCA1/2 genes leading to changes in clinical management. The completion of multigene panel testing did not lead to a significant increase in MICRA or CWS scores. Key limitations of this study include a small sample size and an all Caucasian population. Citation Format: Devon Miller, Stephanie Pritzl, Angela Tess, Jessica Gooding, Lisa Barroilhet, Lori Dubenske, Kari Wisinski. Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-09-03.

Objectives: Germline mutations in cancer susceptibility genes other than BRCA1 and BRCA2 (BRCA1/2) are found in approximately 6% of women with ovarian, fallopian tube, or primary peritoneal cancer. Our objective was to sequence BRCA1/2-negative ovarian cancer patients with a family history of ovarian or breast cancer to identify inherited mutations that may explain the familial risk. Methods: We used a targeted capture, massively parallel sequencing test called BROCA on ovarian cancer probands with a family history of ovarian or breast cancer, or a personal history of breast cancer. BROCA testing included all known breast and ovarian cancer genes. Only clear loss of function mutations were included. 118 probands were ascertained from a gynecologic oncology tissue bank or outside referrals and provided informed consent. A family history of ovarian cancer was defined as having a first or second degree relative with ovarian cancer. A family history of breast cancer was defined as having a first or second degree relative with pre-menopausal breast cancer, or 2 or more regardless of menopausal status. Subjects were only included in one category. Results: Of 118 ovarian cancer probands, 22 (18.6%) were found to carry deleterious mutations in non-BRCA1/2 cancer susceptibility genes. 8/29 (27.6%) ovarian cancer patients with a personal history of breast cancer had mutations in 7 genes (2 CHEK2, 2 RAD51D, 1 BRIP1, 1 TP53, 1 ATM, and one with both PALB2 and PMS2). This included mutations found in 2/5 (40%) who also had a family history of ovarian cancer and 4/10 (40%) who also had a family history of breast cancer. 38 patients had a family history of ovarian cancer with no personal history of breast cancer; 9/38 (23.7%) had mutations in 5 genes (3 BRIP1, 3 RAD51C, 1 RAD51D, 1 TP53, and 1 ATM). Finally, 5/51 (9.8%) ovarian cancer patients with a family history of breast cancer and no personal history of breast cancer had mutations in 5 genes (1 MSH6, 1 FAM175A, 1 NBN, 1 PALB2, and 1 CHEK2). Conclusions: Germline mutations in DNA-repair genes are present in a substantial fraction of BRCA1/2-negative ovarian cancer patients with a personal or family history suggestive of inherited disease. These women may benefit from multiplex gene testing. The detection of inherited mutations in these women may be useful to identify the risk of other cancers, to inform family members of possible risk, and to direct therapy by suggesting candidates for PARP inhibitor therapy. Citation Format: B. Norquist, M. Harrell, T. Walsh, J. Mandell, S. Bernards, K. Agnew, M. Lee, K. Pennington, M.C. King, E. Swisher. Germline mutations in cancer susceptibility genes in BRCA1 and BRCA2 negative families with ovarian and breast cancer [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr AS09.

Breast Cancer Survivors: Does the Screening MRI Debate Continue?

MRI Screening of Women with a Personal History of Breast Cancer.

Commentary on Graubard et al., [p. 2430][1] In 2010, it is projected that there will be 207,090 diagnoses and 39,840 deaths from breast cancer among women in the United States. Approximately 10,300 will be diagnosed before the age of 40 ([1][2]), the age when the American Cancer Society ([2][3])

BACKGROUND AND PURPOSE The benefits of breast MRI for screening women at high risk of developing BC is established, but its role in women with a personal history of BC or dense breasts is unknown. We sought to estimate the performance of annual surveillance MRI added to mammography in women at moderately increased BC risk due to a personal history of breast cancer and/or a high-risk breast lesion and dense breasts. METHOD AND MATERIALS We performed a retrospective chart review of the clinical, radiological, and pathological parameters of women who received annual, concurrent surveillance breast MRI and mammography between 04/2013 and 12/2015. We included women who met all of the following criteria: age<69; prior diagnosis of high-risk lesion (ADH, ALH, LCIS), DCIS, or invasive BC; heterogeneously (50-75%) or extremely dense (>75%) breasts; and did not qualify for our provincial MRI screening program for high risk women (calculated lifetime BC risk ≥ 25%). Results of each scan were analyzed using descriptive statistics and Chi squared for comparisons between subgroups. RESULTS A total of 199 patients (267 MRI exams) were included in this study. The mean age at initial diagnosis was 45 years and at subsequent diagnosis of DCIS or invasive cancer was 53 years. Mean time to new diagnosis was 86 months (range 14-202). All 15 cancers diagnosed during the study period were MRI detected: 11 invasive stage I (66% IDC, 7% ILC) and 4 DCIS (27%). Of these 15, all but 1 were mammographically occult. Five (33%) were found in the breast ipsilateral to the original lesion. The cancer detection rate was 6% (12/199) on the first screening round and 4.7% (3/64) on the second screening round. Specificity and positive predictive value respectively for MRI exams increased from 77% and 22% on the first screening round to 88% and 30% on the second round. Of women who developed BC, 57% had a history of breast or ovarian cancer in a first degree relative. None of the 72 women who were on hormonal therapy at the time of surveillance imaging had a new cancer detected compared to 11% (14/125) of those who were not on hormonal therapy (p=0.0025). CONCLUSIONS The incremental early-stage BC detection rate and specificity of MRI in this population are comparable to what is observed in screening women at high risk. The addition of annual MRI to mammography should be considered for surveillance of women with a personal history of BC / premalignant lesion and heterogeneous / extremely dense breasts, particularly if they have a family history of BC and are not on hormonal therapy. Citation Format: Nadler M, Al Attar H, Curpen B, Martel AL, Balasingham S, Zhang L, Eisen A, Warner E. Magnetic resonance imaging (MRI) surveillance for patients with dense breasts and a previous breast cancer (BC) and/or high risk lesion [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-02-06.

Germline genetic testing for cancer risk offers opportunities for decision-making about screening and clinical risk management for individuals and their family members. Despite increasing availability of cancer genetic testing, Black individuals are still much less likely to receive or engage with testing compared to non-Hispanic white individuals. We sought to identify individual level factors influencing knowledge about and attitudes toward cancer genetic testing among Black women with and without breast cancer. Participants included 925 women from the Black Women’s Health Study who had previously provided a biospecimen for research and were invited to have their cancer genetic research findings confirmed via a CLIA-certified laboratory and learn their results as part of a randomized controlled trial. Prior to confirmation testing, all women completed a baseline questionnaire about personal and family history of cancer; prior genetic testing for hereditary cancer; and knowledge, attitudes, and confidence in one’s ability to use genetic information (genetics self-efficacy). We used linear regression to evaluate individual-level factors influencing cancer genetics knowledge, attitudes, and self-efficacy. Overall, mean knowledge score was 12.3 out of 16 (SD, 2.5); there were no differences in knowledge score between women who had a personal history of breast cancer and those who did not. While the majority of women answered most questions correctly, 20-30% of women were unable to correctly answer questions about validity of test results, clinical implications of a variant of uncertain significance, and legal protections against health insurance discrimination. Younger age, higher educational attainment, being married, and having had prior genetic testing were statistically significant predictors of higher total knowledge score. There were no differences in mean knowledge scores by first degree family history of breast cancer or personal history of breast or other cancer. Predictors of favorable attitudes and genetics self-efficacy included younger age, higher educational attainment, and being married. Women with a personal history of breast cancer had somewhat more favorable attitudes toward genetic testing compared to those with no prior history of breast cancer. In multivariable adjusted models, higher total knowledge was associated with more favorable attitudes and higher self-efficacy. In this cohort of highly educated Black women, overall cancer genetics knowledge was relatively high; however, evaluation of individual knowledge questions revealed opportunities for improvement in specific areas. Older women, those with lower educational attainment, and women who are not married or living as married may benefit from more targeted education about genetic cancer testing. Further, despite the role genetic testing currently plays in guiding cancer treatment, Black women who had breast cancer did not have higher knowledge scores than those without breast cancer and therefore may also benefit from targeted education. Citation Format: Kimberly A. Bertrand, Michelle Trevino-Talbot, Maggie Rudderman, Maureen Flynn, Howard J. Cabral, Julie R. Palmer, Catharine Wang. Knowledge, attitudes, and self-efficacy toward cancer genetic testing among Black women with and without breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B101.

Background - There is suggestive evidence of familial clustering of breast and prostate cancer in first-degree relatives; women with a family history of prostate cancer are at increased risk of breast cancer. Few studies have investigated joint family history of breast and prostate cancer and prostate cancer risk, and no study to date has examined lethal prostate cancer. Methods - We studied 42,672 from the Health Professionals Follow-up Study between 1996 to 2012. During follow-up, 4,258 prostate cancer cases were diagnosed, of whom 380 were lethal disease. Men self-reported family history of breast and prostate cancer, including in siblings or parents. Using cause-specific hazards regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) of the association between family history and prostate cancer risk and progression. Results - About 8% of men had a family history of prostate cancer, 8.7% had a family history of breast cancer, and 1.4% of men had a family history of both breast and prostate cancer. A family history of prostate cancer was significantly associated with an increased risk of prostate cancer (HR: 1.69; 95% CI: 1.54-1.85). Increased risk was higher for men with a father diagnosed with prostate cancer (HR: 1.64 95% CI: 1.49-1.80) than for men with a diagnosis in a brother(s) (HR: 1.51 95% CI: 1.27-1.80). A positive family history of breast cancer was associated with a small, but significant 22% increased risk (HR: 1.22; 95% CI: 1.11-1.35). Familial breast cancer in a sister (HR: 1.22 95% CI: 1.06-1.41) increased risk more than familial breast cancer in a mother (HR: 1.12; 95% CI: 0.99-1.25). Men with a family history of both prostate and breast cancer had a 52% (HR: 1.52; 95%CI: 1.23-1.88) increased risk of prostate cancer compared to men with no family history of either cancer. Risk of lethal prostate cancer was also significantly increased for men with a positive family history of prostate cancer (HR: 1.64; 95% CI: 1.20-2.24), as well as for men with a family history of breast cancer (HR: 1.47; 95% CI: 1.07-2.01). Conclusions - These results support the findings of familial aggregation of breast and prostate cancer, and for the first time suggest an association between familial breast cancer and lethal prostate cancer. Data from this prospective study have translational relevance for family counseling of cancer patients. Citation Format: Lauren E. Barber, Travis A. Gerke, Sarah C. Markt, Giovanni Parmigiani, Lorelei A. Mucci. A family affair: Prostate cancer risk and family history of breast or prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2543.

10524 Background: Pathogenic variants in CDH1 ( CDH1+) are associated with hereditary diffuse gastric cancer (HDGC), with an increased risk for DGC (~40-83%) and lobular breast cancer (BC) (~64%) [1]. The National Cancer Center Network recommends the inclusion of CDH1 in multi-gene panel testing (MGPT) for patients with significant history of BC, given its classification as a high-risk BC gene [2]. Management includes prophylactic gastrectomy or consideration of annual endoscopic biopsies and high-risk breast screening, with consideration of prophylactic mastectomy. Several studies have identified CD H1+ patients who do not meet the International Gastric Linkage Consortium’s diagnostic criteria for HDGC [3.4,5,6]. These studies have brought concerns of CDH1 pathogenic variants in patients with low risk phenotypes, given the potential for total gastrectomy to reduce DGC risk. Our study aims to investigate our cohort of patients with a personal and/or family history of BC to determine if there is a significant number of CDH1+ patients with a non-classical presentation of HDGC. Methods: 17,208 families with a history of BC who underwent MGPT were seen in a Clinical Cancer Genetics (CCG) high-risk breast clinic between August 2013 and July 2022. They were identified using a prospectively maintained MD Anderson Cancer Center CCG database. Families were categorized by their history of GC and CDH1 status. Results: Among the families, 10,202 (59%) had a proband with a personal history of BC, with a mean age of onset of 51 years. 49 families (0.28%) were CDH1+. 21 CDH1+ families (43%) had no personal and/or family history of GC. Overall, 0.12% of families within the cohort were CDH1+ and had no family history of GC. A chi-square goodness of fit test was performed comparing observed (O) versus expected frequencies (E) (O/E) of families that were: 1) CDH1+ and had a history of GC (28/28), 2) CDH1+ and no history of GC (21/21), 3) CDH1 – (benign variant or variant of unknown significance (VUS)) and a history of GC (180/164), and 4) CDH1- and no history of GC (16,979/16,995). O was determined by using a general population risk of GC (0.81%) and estimated risk of DGC for CDH1+ individuals (58.2%). The X2 was determined to be 1.576, with a p-value of 0.66483. Conclusions: In comparison to the expected frequency of incidental CDH1+ families identified via MGPT, we found that there was not a significant difference in expected and observed frequencies of families based on CDH1 status and presence of GC. These results likely reflect the incomplete penetrance and variable expressivity of HDGC, in addition to reported cases of occult signet ring cell carcinomas in biopsy samples or surgical pathology that has been reported in low risk presenting families [7]. We seek to validate these results with cohort of patients in which the diffuse gastric cancer pathology is known and to expand the analysis in patients specifically with a personal history of lobular breast cancer.

BACKGROUND Risk reducing bilateral salpingo-oophorectomy (rrBSO) can provide up to a 90% reduction in the risk of developing ovarian cancer in women who are carriers of pathogenic variants in the BRCA1 and BRCA2 genes. National guidelines recommend risk reducing rrBSO once childbearing is complete and/or between the ages of 35-45. Previous studies have found that a large percentage of women who are eligible for rrBSO do not undergo the procedure and surgery is often done at later ages than recommended in the national guidelines. Research on factors associated with the uptake and timing of rrBSO is limited. Our study describes the percentages of women who are BRCA1 or BRCA2 carriers who elected rrBSO and ascertains the timing of the surgery relative to recommended age guidelines. We also identify patient characteristics associated with uptake of rrBSO. METHODS We conducted a retrospective cohort study in a large, integrated healthcare system in Southern California. The study population included women who were identified as BRCA1 or BRCA2 carriers in our electronic health record by ICD 9 and ICD 10 codes, and by review of our internal Cancer DNA database. Inclusion criteria included adults 18 years and older who were members of Kaiser Permanente Southern California between 2008 - 2018. Exclusion criteria included patients with an established diagnosis of ovarian cancer, with rrBSO at the time of study entry, and who were KP members for less than 12 months. Crude logistic regression models were used to determine odds ratios and 95% confidence intervals for associations between patient variables and uptake of rrBSO. RESULTS Of the 2,592 patients in the cohort, 1,326 were BRCA1 carriers and 1,266 were BRCA2 carriers. 1,003 (38.6%) women underwent rrBSO at a median age of 48.0 years (IQR: 42.0, 57.0). For the entire cohort, 38.6% identified as Caucasian, 30% identified as Hispanic/Latin American/Caribbean, 9.4% identified as Ashkenazi Jewish, 8.6% identified as Asian/Pacific Islander, and 1.5% identified as Black/African, and 1.4% identified as Near East/Middle Eastern. The baseline characteristics of our cohort can be seen in Table 1. Ovarian malignancy was incidentally detected on pathology evaluation in 1.5% of patients who elected rrBSO. The odds of rrBSO were lower among those who had used oral contraceptives for more than one year compared to those who hadn’t (OR=0.18, 95% CI: 0.11-0.30). A family history of ovarian cancer or breast cancer were also associated with higher odds of rrBSO, (OR=1.45, 95% CI: 1.21-1.73) and (OR=1.75; 95% CI: 1.48-2.08), respectively. The odds of rrBSO were also higher for those with a personal history of breast cancer (OR=2.29, 95% CI: 1.95-2.70). CONCLUSIONS In this large cohort of women who were BRCA1 and BRCA2 carriers and who were eligible for rrBSO, only a third of patients underwent risk reducing surgery. Among those who did undergo surgery, the median age at the time of procedure was higher than what is recommended in national guidelines. Family history of breast cancer and/or ovarian cancer, as well as personal history of breast cancer were associated with women selecting rrBSO. Table 1.No Oophorectomy (N=1589)rrBSO (N=1003)Total (N=2592)p valueAge at BRCA diagnosis<0.00011 N158910032592 Mean (SD)43.9 (15.73)49.5 (11.11)46.1 (14.38) Median42.048.345.5 Range(18.1-95.7)(19.8-79.7)(18.1-95.7)Gene0.03522 BRCA1839 (52.8%)487 (48.6%)1326 (51.2%) BRCA2750 (47.2%)516 (51.4%)1266 (48.8%)Race/Ethnicity0.01002 African72 (4.5%)61 (6.1%)133 (5.1%) Ashkenazi Jewish134 (8.4%)110 (11%)244 (9.4%) Asian/Pacific Islander138 (8.7%)86 (8.6%)224 (8.6%) Black24 (1.5%)14 (1.4%)38 (1.5%) Hispanic/Latin American/Caribbean486 (30.6%)291 (29%)777 (30%) Multiple2 (0.1%)2 (0.2%)4 (0.2%) Native American/Alaskan2 (0.1%)0 (0%)2 (0.1%) Near East/Mideast24 (1.5%)13 (1.3%)37 (1.4%) White/Caucasian (Western/Northern/Central European)611 (38.5%)389 (38.8%)1000 (38.6%) Other77 (4.8%)37 (3.7%)114 (4.4%) Unknown19 (1.2%)0 (0%)19 (0.7%)Oral contraceptive use ≥ 1 year<0.00012 N1456 (91.6%)987 (98.4%)2443 (94.3%) Y133 (8.4%)16 (1.6%)149 (5.7%)Family history of ovarian cancer0.00012 N1236 (77.8%)710 (70.8%)1946 (75.1%) Y353 (22.2%)293 (29.2%)646 (24.9%)Family history of breast cancer<0.00012 N650 (40.9%)284 (28.3%)934 (36%) Y939 (59.1%)719 (71.7%)1658 (64%)Personal history of breast cancer<0.00012 N1094 (68.8%)492 (49.1%)1586 (61.2%) Y495 (31.2%)511 (50.9%)1006 (38.8%)Age at prophylactic surgery NN/A893893 Mean (SD)49.6 (10.36)49.6 (10.36) Median48.048.0 Q1, Q342.0, 57.042.0, 57.0 Range(21.0-80.0)(21.0-80.0)Ovarian cancer<0.00012 N1589 (100%)988 (98.5%)2577 (99.4%) Y0 (0%)15 (1.5%)15 (0.6%)1Kruskal Wallis 2Chi-Square Citation Format: Karen W Kwan, Stephanie W Morton, Joanie Chung. Timing and acceptance of bilateral prophylactic salpingo-oophorectomy among BRCA1 and BRCA2 mutation carriers enrolled in an integrated community-based health care system [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 P2-09-04.

Accurate estimation of carrier probabilities of cancer susceptibility gene mutations is an important part of pre-test genetic counselling. Many predictive models are available but their applicability in the Asian population is uncertain. We evaluated the performance of five BRCA mutation risk predictive models in a Chinese cohort of 647 women, who underwent germline DNA sequencing of a cancer susceptibility gene panel. Using areas under the curve (AUCs) on receiver operating characteristics (ROC) curves as performance measures, the models did comparably well as in western cohorts (BOADICEA 0.75, BRCAPRO 0.73, Penn II 0.69, Myriad 0.68). For unaffected women with family history of breast or ovarian cancer (n = 144), BOADICEA, BRCAPRO, and Tyrer-Cuzick models had excellent performance (AUC 0.93, 0.92, and 0.92, respectively). For women with both personal and family history of breast or ovarian cancer (n = 241), all models performed fairly well (BOADICEA 0.79, BRCAPRO 0.79, Penn II 0.75, Myriad 0.70). For women with personal history of breast or ovarian cancer but no family history (n = 262), most models did poorly. Between the two well-performed models, BOADICEA underestimated mutation risks while BRCAPRO overestimated mutation risks (expected/observed ratio 0.67 and 2.34, respectively). Among 424 women with personal history of breast cancer and available tumor ER/PR/HER2 data, the predictive models performed better for women with triple negative breast cancer (AUC 0.74 to 0.80) than for women with luminal or HER2 overexpressed breast cancer (AUC 0.63 to 0.69). However, incorporating ER/PR/HER2 status into the BOADICEA model calculation did not improve its predictive accuracy.

The relationship between family history of breast, ovarian and endometrial cancer and risk of breast cancer was analysed using data from a case-control study of breast cancer conducted in the greater Milan area, Northern Italy. The cases studied were 3415 women (median age 52 years, range 23-74) who had histologically confirmed breast cancer diagnosed within the year preceding the interview. The controls were 2916 women (median age 54 years; range 21-74) in hospital for a spectrum of acute illnesses excluding gynaecological, hormonal or neoplastic conditions. A total of 375 cases (11.0%) and 128 controls (4.4%) reported a history of breast cancer in first degree relatives. Compared with women with no family history of breast cancer, the RR was 2.7 (95% confidence interval [CI] : 2.2-3.3) in those with one first degree relative affected and 2.8 (95% CI : 1.3-5.7) in those with two or more affected relatives. In comparison with women without family history of ovarian cancer the RR of breast cancer was 1.4 (95% CI : 0.9-2.3) for those reporting one or more first degree relatives with ovarian cancer. However, the multivariate estimate for family history of ovarian cancer, including a term for familial breast cancer, decreased to 0.8 (95% CI : 0.5-1.4). The risk of breast cancer was similar in women reporting a family history of breast cancer (RR = 2.2) and in those reporting a family history of both breast and ovarian cancer (RR = 2.5), in comparison with women reporting no family history of breast and/or ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Introduction: Family history (FH) of breast cancer (BC) is an independent risk factor for BC, regardless the presence of a germline mutation in a BC predisposition gene. Women with a FH of BC could be diagnosed at earlier stages due to increased awareness and screening. Nevertheless, other factors could be associated with diagnosis at later stages such as early onset, fear, and misinformation. Objective: To determine if women with a family history of breast cancer present earlier stages of disease. Methods: This single institution study was conducted at the Oncogenetics Department of Hospital Sirio-Libanês (Brasília DF, Brazil). Eligibility included patients with a personal history of BC who received genetic counseling between 2017 and 2025, and a genetic testing result without a pathogenic/probably pathogenic germline variant in a BC gene. Lack of FH data was an exclusion criteria. Data were collected retrospectivelly from medical charts. FH of BC was defined as a BC cancer diagnosis in 1st, 2nd, and/or 3rd degree relatives (defined as close relatives). For patients who received neoadjuvant therapy, BC stage was based on clinical staging and pathological or clinical staging were used for the remaining cases. Chi-square test was used for comparison of patients with and without a FH of BC. Results: Among 161 patients, 155 met study criteria. Median age of BC diagnosis was 49 years (23.0-87.0), 6 patients were diagnosed during pregnancy or breastfeeding, 6 had bilateral synchronous BC and 7 metastatic de novo disease. Out of 155 patients, 88 (56.7%) had at least one close relative with BC (FH+), including 37 (23.9%) with a family member affected before 50 years and 7 (4.5%) with bilateral BC. In total, 68 (43.8%) patients were diagnosed due to symptoms, 68 (43.8%) through screening, 3 incidentally found during mamoplasty and in 16 cases presentation was not specified. Among those screen-detected cancers (n=68), 22 (32.3%) were detected by ultrasound, 35 (51.5%) by mammogram, 7 (10.3%) by MRI, and in 4 cases the diagnostic modality was unavailable. There were no differences between groups (FH+ vs FH-) regarding age of BC diagnosis, menopausal status, BC presentation, and BC stage. Conclusion: In this BC Brazilian cohort from a private health setting without a cancer predisposition syndrome, a family history of BC did not impact BC stage at diagnosis. Cancer risk assessment based on risk models such as Tyrer Cuzick could inform the benefit of BC screening with MRI in this scenario. Citation Format: B. Resendes, R. Sandoval, T. Correa, A. Castro, Z. Souza, I. Guttieres. The impact of family history on breast cancer stage: data from a Brazilian breast cancer cohort without inherited predispositions [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-05-13.

e12583 Background: For women with certain high risk germline mutations, preventive surgical procedures (PSP) have been shown to reduce the risk of cancer. Uptake of these PSP, however, is highly variable among the population at risk. Rate of contralateral mastectomies is reported to be lower among African American (AA) and Asian women compared to Whites. Low socioeconomic status (SES) is reported to impact decision making concerning PSP, but the data remains scant due to associated low healthcare access. Our comprehensive cancer center is notable for providing state of the art care at a public safety net hospital, Harris Health System (HHS), where the population is > 80% racial and ethnic minorities, 60% uninsured and predominantly of low SES. Patients who meet the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing are provided with the opportunity for counseling and testing. We therefore evaluated the likelihood of PSP among our patients with known germline mutations. Methods: We performed a retrospective chart review of a prospectively maintained database of patients who were offered genetic counseling and testing at HHS. We included patients diagnosed with high-risk mutations in BRCA1, BRCA2, PALB2, ATMand CHEK2 between 10/1/2009-09/30/2019 . We abstracted data on date of birth, race and ethnicity, history of breast cancer, breast cancer subtype, family history of breast or ovarian cancers. We collected data on whether the patients had undergone any PSP: bilateral or contralateral mastectomy, salpingectomy, or BSO. We used descriptive statistics to compare patient profiles in each mutation category. We performed univariate and multivariate logistic regression to evaluate whether differences in race, ethnicity, family history of breast or ovarian cancer, or personal history of breast cancer contributed to the likelihood of undergoing PSP. Results: Our dataset identified a total of 202 patients who had a pathogenic mutation in one of the genes above. This included 108 BRCA1, 57 BRCA2, 26 PALB2, 8 ATM and 4 CHEK2 mutation carriers. Sixty-one percent of the mutation carries identified as Hispanic, 18% as AA, 10% as White and 3% as Asian, 31% of the population never had a history of breast cancer. Sixty-three percent of the patients underwent at least one PSP. The results of the regression analysis identified personal history of breast cancer as the only predictor of undergoing PSP, OR 2.77, p = 0.002, which remained significant on the multivariate analysis with OR 4.4, p < 0.001. There were no statically significant findings with regards to race, ethnicity or family history of breast or ovarian cancers. Conclusions: Among our population racially diverse patients with low SES, history of breast cancer significantly increases the likelihood of opting to have prophylactic PSP. We will use this information to tailor our approach towards patient education and future quality improvement projects.

Breast cancer screening, surveillance, and diagnostic imaging services were profoundly limited during the initial phase of the coronavirus disease 2019 (COVID-19) pandemic. To develop a risk-based strategy for triaging mammograms during periods of decreased capacity. This population-based cohort study used data collected prospectively from mammography examinations performed in 2014 to 2019 at 92 radiology facilities in the Breast Cancer Surveillance Consortium. Participants included individuals undergoing mammography. Data were analyzed from August 10 to November 3, 2020. Clinical indication for screening, breast symptoms, personal history of breast cancer, age, time since last mammogram/screening interval, family history of breast cancer, breast density, and history of high-risk breast lesion. Combinations of clinical indication, clinical history, and breast cancer risk factors that subdivided mammograms into risk groups according to their cancer detection rate were identified using classification and regression trees. The cohort included 898 415 individuals contributing 1 878 924 mammograms (mean [SD] age at mammogram, 58.6 [11.2] years) interpreted by 448 radiologists, with 1 722 820 mammograms in individuals without a personal history of breast cancer and 156 104 mammograms in individuals with a history of breast cancer. Most individuals were aged 50 to 69 years at imaging (1 113 174 mammograms [59.2%]), and 204 305 (11.2%) were Black, 206 087 (11.3%) were Asian or Pacific Islander, 126 677 (7.0%) were Hispanic or Latina, and 40 021 (2.2%) were another race/ethnicity or mixed race/ethnicity. Cancer detection rates varied widely based on clinical indication, breast symptoms, personal history of breast cancer, and age. The 12% of mammograms with very high (89.6 [95% CI, 82.3-97.5] to 122.3 [95% CI, 108.1-138.0] cancers detected per 1000 mammograms) or high (36.1 [95% CI, 33.1-39.3] to 47.5 [95% CI, 42.4-53.3] cancers detected per 1000 mammograms) cancer detection rates accounted for 55% of all detected cancers and included mammograms to evaluate an abnormal mammogram or breast lump in individuals of all ages regardless of breast cancer history, to evaluate breast symptoms other than lump in individuals with a breast cancer history or without a history but aged 60 years or older, and for short-interval follow-up in individuals aged 60 years or older without a breast cancer history. The 44.2% of mammograms with very low cancer detection rates accounted for 13.1% of detected cancers and included annual screening mammograms in individuals aged 50 to 69 years (3.8 [95% CI, 3.5-4.1] cancers detected per 1000 mammograms) and all screening mammograms in individuals younger than 50 years regardless of screening interval (2.8 [95% CI, 2.6-3.1] cancers detected per 1000 mammograms). In this population-based cohort study, clinical indication and individual risk factors were associated with cancer detection and may be useful for prioritizing mammography in times and settings of decreased capacity.