Previous Diagnosis Of Breast Cancer Research Articles

Fertility-related information received by young women and men with cancer – a population-based survey

Background Infertility is a well-known sequela of cancer treatment. Despite guidelines recommending early discussions about risk of fertility impairment and fertility preservation options, not all patients of reproductive age receive such information. Aims This study aimed to investigate young adult cancer patients’ receipt of fertility-related information and use of fertility preservation, and to identify sociodemographic and clinical factors associated with receipt of information. Materials and Methods A population-based cross-sectional survey study was conducted with 1010 young adults with cancer in Sweden (response rate 67%). The inclusion criteria were: a previous diagnosis of breast cancer, cervical cancer, ovarian cancer, brain tumor, lymphoma or testicular cancer between 2016 and 2017, at an age between 18 and 39 years. Data were analyzed using logistic regression models. Results A majority of men (81%) and women (78%) reported having received information about the potential impact of cancer/treatment on their fertility. A higher percentage of men than women reported being informed about fertility preservation (84% men vs. 40% women, p < .001) and using gamete or gonadal cryopreservation (71% men vs. 15% women, p < .001). Patients with brain tumors and patients without a pretreatment desire for children were less likely to report being informed about potential impact on their fertility and about fertility preservation. In addition, being born outside Sweden was negatively associated with reported receipt of information about impact of cancer treatment on fertility. Among women, older age (>35 years), non-heterosexuality and being a parent were additional factors negatively associated with reported receipt of information about fertility preservation. Conclusion There is room for improvement in the equal provision of information about fertility issues to young adult cancer patients.

Abstract PS8-11: Recruitment strategies for enrollment of high-risk women to a randomized controlled trial of web-based decision support tools to increase breast cancer chemoprevention

Abstract Background: Less than 10 % of those identified as eligible for clinical trials are recruited. Recruitment for chemoprevention trials poses challenges as it is often difficult to identify unaffected patients at high risk for cancer. Barriers to recruitment include personal perceptions of the benefits, fear of trials, low recruitment of minorities, language barriers, transportation costs, and complex study designs. In this study, we identified five potential sources of recruitment that could be collectively leveraged to identify women at high risk for breast cancer to improve recruitment yield. Methods: A total of 300 high-risk women and 50 healthcare providers were recruited and randomized to access web-based decision support tools in combination with standard educational materials or standard educational materials alone. Patient inclusion criteria included: 1) women, age 35-75 years; 2) English or Spanish-speaking; 3) no previous breast cancer diagnosis; 4) no prior use of selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). Five broad strategies were considered for identification and recruitment of women at high risk for breast cancer: 1) in-person recruitment during routine screening mammography with survey administration for breast cancer risk assessment according to the Gail model; 2) collection of breast cancer risk factors from the electronic health record (EHR) for risk assessment according to the Breast Cancer Surveillance Consortium (BCSC) risk calculator; 3) identification of women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) using ICD-9/10 diagnostic codes from the EHR; 4) high-risk women with clinic appointments and referred by enrolled providers; 5) women who responded to recruitment flyers and online recruitment distributed throughout the medical center and community. Results: A total of 6229 high-risk women were identified using these recruitment sources, of which 3663 were contacted by email, mailed letter, and/or phone for participation in our clinical trial. Of these contacted women, 16.4% were identified through in-person recruitment during screening mammography, 35.8% through breast cancer risk factors in the EHR, 14.5% had a diagnosis of AH or LCIS identified in the EHR, 28.7% had appointments with enrolled providers, and 4.5% responded to recruitment flyers or online recruitment. Women from the different recruitment sources varied by mean age (64.7 years for mammography and 44.9 years for recruitment flyers), race/ethnicity (73.7% non-white from mammography and 45.5% from breast cancer risk factors in the EHR), and mean 5-year breast cancer risk (2.56% identified from the EHR and 1.34% from recruitment flyers). Of 300 consented patients, 44.7% came from provider referrals (12.7% recruitment yield [number consented/number contacted]) and 27.3% from mammography (13.6% recruitment yield). Comparing enrolled to unenrolled patients, there were significant differences in mean age (57.3 vs. 58.7 years, p=0.027), proportion of non-whites (41.5% vs. 54.7%, p&amp;lt;0.001), and mean 5-year breast cancer risk (3.0% vs. 2.2%, p&amp;lt;0.001). Conclusions: We were able to identify a large cohort of women at high risk from breast cancer from multiple different recruitment sources. Our recruitment yield was highest among direct referrals from healthcare providers and in-person recruitment from mammography. Consented patients tended to be younger, include more non-Hispanic whites, and have a higher risk of breast cancer compared to the overall pool of high-risk women identified. We were able to successfully recruit a racially-ethnically diverse study population to a randomized controlled trial of decision support for breast cancer chemoprevention. Citation Format: Gauri Bhatkhande, Thomas Silverman, Jennie Mata, Ashlee Guzman, Ting He, Jill Dimond, Tarsha Jones, Rita Kukafka, Katherine Crew. Recruitment strategies for enrollment of high-risk women to a randomized controlled trial of web-based decision support tools to increase breast cancer chemoprevention [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-11.

Lifestyle Characteristics in Women Carriers of BRCA Mutations: Results From an Italian Trial Cohort

BackgroundWomen with deleterious mutations in BRCA1/2 have a high lifetime penetrance of developing breast cancer and/or ovarian cancer. Genetic and/or environmental factors may influence BRCA penetrance, and identifying modifiable exposures might be valuable for prevention. Patients and MethodsWe implemented a multicenter prospective 2-arm (1:1) randomized controlled trial to investigate whether a Mediterranean dietary intervention with moderate protein restriction would reduce potential modulators of BRCA penetrance such as insulin-like growth factor 1 (IGF-1), body weight, and metabolic risk factors. We studied the baseline characteristics of women with BRCA-positive disease who joined the trial cohort, focusing on the relationships between selected lifestyle exposures, metabolic/anthropometric parameters, and BRCA-related cancer. ResultsA total of 502 women (304 with a previous diagnosis of breast cancer and/or ovarian cancer and 198 unaffected) with deleterious BRCA mutations, with or without a previous cancer, aged 18 to 70 years and without metastases were included. Late age at menarche and pregnancy were negatively associated with BRCA-related cancer, especially in women with BRCA1-positive disease. Higher fat mass and the presence of 4 or 5 metabolic risk factors were significantly associated with BRCA-related cancer (hazard ratio, 1.87, 95% confidence interval, 1.21-2.88; and hazard ratio, 1.87, 95% confidence interval, 1.11-3.19, respectively), with greater effect in BRCA2-positive women. ConclusionsOur findings confirm previous observations about reproductive factors in women with BRCA disease and suggest a potential impact of metabolic factors in BRCA-related cancer. The prospective follow-up of the trial cohort will enable us to study the environmental modulators of BRCA penetrance and their impact in relation to the history of BRCA-related cancer. [ClinicalTrials.gov NCT03066856]

Limbal stem cell deficiency secondary to systemic paclitaxel (Taxol) for breast cancer: a case report

BackgroundPaclitaxel (PTX) is an antineoplastic drug widely used in treatments for ovarian, breast, and small-cell lung cancer. Although ocular effects associated with PTX have been previously described, very few studies have specifically reported systemic PTX as a contributing factor for limbal stem cell deficiency (LSCD), which is characterized by the loss of stem cell and barrier function of the limbus leading to progressive pain and reduction in visual acuity. Described here is a unique case where a patient was diagnosed with LSCD secondary to PTX use for the treatment of breast cancer, at doses of PTX far lower than what is reported in current literature.Case presentationA 73-year-old woman with a previous diagnosis of breast cancer with liver metastasis presented with a complaint of increasing pain in the left eye more than the right, along with decreasing visual acuity in both eyes following 3 months of PTX therapy for recurrent liver metastases. Upon examination, best-corrected visual acuity was 20/100 in the right eye and counting fingers on the left. Peripheral neovascularization, stromal scarring, and features of limbal stem cell deficiency (LSCD) were noted on the right cornea. A central neurotrophic ulcer with thinning to 50% and 360 degrees of conjunctivalization were noted on the left. After the discontinuation PTX with doxorubicin as the substitute, there was no further progression of her LSCD, and stabilization of her ocular surface was achieved.ConclusionAlthough chemotherapy induced LSCD is a relatively rare adverse event, it is essential for clinicians starting new chemotherapy agents to consider the potential ocular toxicities that may result in their use. Ophthalmology review is recommended for patients after starting PTX therapy to assess for signs of LSCD, particularly in patients where drug toxicity can be aggravated due to impaired hepatic function.

Mammographic density change in a cohort of premenopausal women receiving tamoxifen for breast cancer prevention over 5 years

BackgroundA decrease in breast density due to tamoxifen preventive therapy might indicate greater benefit from the drug. It is not known whether mammographic density continues to decline after 1 year of therapy, or whether measures of breast density change are sufficiently stable for personalised recommendations.MethodsMammographic density was measured annually over up to 5 years in premenopausal women with no previous diagnosis of breast cancer but at increased risk of breast cancer attending a family-history clinic in Manchester, UK (baseline 2010-2013). Tamoxifen (20 mg/day) for prevention was prescribed for up to 5 years in one group; the other group did not receive tamoxifen and were matched by age. Fully automatic methods were used on mammograms over the 5-year follow-up: three area-based measures (NN-VAS, Stratus, Densitas) and one volumetric (Volpara). Additionally, percentage breast density at baseline and first follow-up mammograms was measured visually. The size of density declines at the first follow-up mammogram and thereafter was estimated using a linear mixed model adjusted for age and body mass index. The stability of density change at 1 year was assessed by evaluating mean squared error loss from predictions based on individual or mean density change at 1 year.ResultsAnalysis used mammograms from 126 healthy premenopausal women before and as they received tamoxifen for prevention (median age 42 years) and 172 matched controls (median age 41 years), with median 3 years follow-up. There was a strong correlation between percentage density measures used on the same mammogram in both the tamoxifen and no tamoxifen groups (all correlation coeficients > 0.8). Tamoxifen reduced mean breast density in year 1 by approximately 17–25% of the inter-quartile range of four automated percentage density measures at baseline, and from year 2, it decreased further by approximately 2–7% per year. Predicting change at 2 years using individual change at 1 year was approximately 60–300% worse than using mean change at 1year.ConclusionsAll measures showed a consistent and large average tamoxifen-induced change in density over the first year, and a continued decline thereafter. However, these measures of density change at 1 year were not stable on an individual basis.

Absence of detectable effect of radiotherapy and chemotherapy for breast cancer on the presence of low voltage areas in patients receiving left atrial catheter ablation

Purpose Radiation and chemotherapy for breast cancer are known to cause side effects to the heart. However, it still remains unclear whether those therapies affect left atrium fibrosis. We sought to examine the effects of radiation and chemotherapy on the electroanatomic features of the left atrium (LA) in patients who received catheter ablation for LA arrhythmias and underwent radiation and/or chemotherapy prior to the procedure. Methods and results We compared 38 patients who underwent catheter ablation for LA arrhythmias and had a previous diagnosis of breast cancer with 38 patients without breast cancer. LA low voltage zones (LVZ) were analysed during the electrophysiological (EP) study. The existence of LA LVZ did not differ significantly between both groups (71.1% vs. 76.3%, p = .602; 13.7cm2 (IQR 0;20.6cm2) vs. 7.0cm2 (IQR 1.6;21.1cm2), p = .690). Also scar distribution revealed no difference between both groups. However, an involvement of the anterior wall was common in both groups (65.8% vs. 73.7%, p = .454). Patients with breast cancer and persistent AF showed a trend towards greater LA scar areas 14.5% vs. 6.9%, p = .383) compared to the control group. Age and LA volume index were the only independent predictors for greater LA scarring. Conclusions Thoracic irradiation and chemotherapy for breast cancer do not lead to an increase in LA scar area or a changed distribution of LA scarring. However, patient with breast cancer showed a tendency towards greater LA scar areas. Patient’s age and LA volume index were identified as independent predictors for LA scar development.

Participation in breast cancer screening among breast cancer survivors –A nationwide register-based cohort study

The aim of this study was to analyse if breast cancer survivors without other breast imaging surveillance attend population-based screening differently than women not previously diagnosed with breast cancer. Further, to analyse if any differences depended on the women’s age and years since previous cancer diagnosis.The study was a register-based retrospective cohort study of all women invited to participate in the national breast cancer screening programme in 2015–2016. Participation rates were calculated for breast cancer survivors without breast imaging within 21 months (2–4 years, 4–6 years, 6–10 years and more than 10 years after diagnosis) and for women without previous breast cancer. Relative differences in participation rates between the two groups were calculated.A total of 679,990 women were included in the study (2.6% breast cancer survivors).For breast cancer survivors, participation rates increased with increasing number of years since the previous cancer diagnosis peaking at 80.3% if the cancer diagnosis was more than 10 years ago. For women with no previous breast cancer, participation rate was 80.3%.The relative difference in participation was highest close to the breast cancer diagnosis and for the youngest women participation rates remained lower among breast cancer survivors even more than 10 years after the diagnosis.In conclusion, regardless of age and years since previous breast cancer diagnosis, breast cancer survivors had lower or similar participation rates than women with no previous cancer diagnosis. This indicated that as many as one fifth of the breast cancer survivors are at risk of inadequate surveillance.

Medical Maximizing-Minimizing Preferences in Relation to Low-Value Services for Older Women with Hormone Receptor-Positive Breast Cancer: A Qualitative Study.

Multiple studies have demonstrated the safety of omitting therapies in older women with breast cancer. Despite de-implementation guidelines, up to 65% of older women continue to receive one or more of these low-value services. Previous work has investigated the role of both provider and patient attitudes as barriers to de-implementation; however, the importance of the patient's maximizing-minimizing preferences within this context remains unclear. In this qualitative study, we conducted 30 semi-structured interviews with women ≥ 70years of age without a previous diagnosis of breast cancer to elicit perspectives on breast cancer treatment in relation to their medical maximizing-minimizing preferences, as determined by the single-item maximizer-minimizer elicitation question (MM1). We used an interpretive description approach in analysis to produce a thematic survey. Participants were relatively evenly distributed across the MM1 (minimizer, n = 8; neutral, n = 13; maximizer, n = 9). Despite being told of recommendations allowing for the safe omission of sentinel lymph node biopsy and post-lumpectomy radiotherapy, maximizers consistently stated preferences for more medical intervention and aggressive therapies over minimizers and neutral individuals. Medical maximizing-minimizing preferences in older women correspond with preferences for breast cancer treatment options that guidelines identify as potentially unnecessary. Increased awareness of patient-level variability in maximizing-minimizing preferences may be valuable in developing optimal intervention strategies to reduce utilization of low-value care.

P1361Impact of radiation/chemotherapy for breast cancer on the electroanatomic features in patients receiving catheter ablation for left atrial arrhythmia

Abstract Background Atrial fibrillation (AF) is a common cardiac arrhythmia and catheter ablation a viable treatment option for patients with AF. Extensive left atrial (LA) scars, frequently seen in patients with persistent AF, can limit its efficacy. Radiation for breast cancer treatment is known to have serious long-term effects (e.g. fibrosis) on the targeted tissue. At the same time, chemotherapy often leads to organ dysfunction. We sought to examine the effects of radiation and chemotherapy on the electroanatomic features of the LA in patients who received catheter ablation for left atrial arrhythmias with prior breast cancer treatment. Methods and Results We compared 38 patients (mean age 68.4 ± 7.1 years) who underwent catheter ablation for LA arrhythmia and had a previous diagnosis of breast cancer with 38 patients (mean age 65.4 ± 7.3 years) without breast cancer who formed our control group. LA scar area, as well as its distribution was measured during the electrophysiology (EP) study and graded according to the Utah classification. The existence of LA scarring did not differ significantly between both groups (71.1% vs. 76.3%, p = 0.602). LA scar area (excluding PVs) was 107.5cm2 ± 19.0cm2 in the breast cancer group compared to 110.1cm2 ± 18.5cm2 in the control group (p = 0.536). The distribution of the scar area revealed no significant difference between both groups, however an involvement of the anterior wall was common (65.8% vs. 73.7%; p = 0.454). We further investigated whether the location of breast cancer had an impact on the LA scar development of the patients in our study cohort. Here, we found no significant difference in the amount of LA scarring when comparing patients with left-sided breast cancer to patients with right-sided breast cancer (66.7% vs. 73.9%). In a sub-analysis patients with breast cancer and persistent AF showed a non-significant trend towards greater LA scar areas (17.4cm2 vs. 6.8cm2) in comparison to patients of the control group with similar LA volumes. The patient’s age (&amp;gt;65 years) was the only independent predictor for greater LA scarring we could identify. Neither former radiotherapy, nor chemotherapy showed a positive correlation with greater LA scarring. Conclusion There is no change in the distribution as well as an increase of the extent of LA scars after thoracic irradiation and/or chemotherapy. A trend towards greater LA scar areas was seen in patients with breast cancer and persistent AF. The patient’s age was identified as an independent predictor for LA scar development.

Abstract A030: Empowering Latinas to obtain breast cancer screenings: Comparing intervention effects and cost effectiveness

Abstract Purpose: Latinas suffer disproportionately from breast cancer relative to non-Latina Whites, partially due to lower guideline-concordant screening. Multiple approaches are used to address this disparity including educational interventions and empowerment-related interventions, wherein a subset of the population is trained to share information with other members of the priority population. However, little is known about the relative effects of these different approaches. Objective: To analyze preliminary data regarding the effectiveness and cost-effectiveness of education and empowerment approaches. Methods: This ongoing, quasiexperimental trial is situated in two lower-income Latino communities in Chicago. Eligibility criteria include: 1) age of 52-74; 2) no mammography use within past 2 years; 3) no previous breast cancer diagnosis; and 4) no prior health volunteerism experience. Women are assigned to a cohort and participate in a three-week intervention (education: breast cancer, diet, physical activity; empowerment: breast cancer, sharing information with networks, health volunteerism). For women who wish to obtain mammography (from either arm), the study team provides navigation to free/low-cost services. Data collected at baseline, post-intervention, and six-month follow-up include standard demographics and self-reported mammography use, which are verified by study navigation records. The perspective for cost-effectiveness analyses was the community-based organization implementing the program. Cost data include overhead, non-personnel, and personnel costs (per task, per person encounter). Cost data were standardized to US dollars in 2018 and extrapolated to the duration of study implementation. Results: Our current sample is 97 women (51 education; 46 empowerment). Most women were 52-64 years old (70%), had insurance (58%), had less than a 9th grade education (60%), had an annual household income of &amp;lt;$15,000 (67%), and were born in Mexico (86%). More empowerment participants obtained a mammogram than education participants, after adjusting for age, education, income, insurance, mammography history, and mammography plans (47% vs. 74%; OR = 3.2, 95%CI [1.1, 9.00], p=.001). The empowerment intervention was also less expensive. The costs for education and empowerment interventions were $32,919 and $24,983 ($645 and $490 per person), respectively. Hence, empowerment appears to be a dominant strategy. Discussion: Empowerment approaches may be more effective and more cost effective in promoting mammography than education approaches among non-adherent Latinas. Limitations concern generalizability due a non-probability based sample, and limited ability for causal inferences due to a lack of randomization. Next steps include incorporating participants' costs and including unintended effects (e.g., number of non-participant women obtaining mammography). Citation Format: Yamile Molina, Liliana G. San Miguel, Catherine Pichardo, Genesis Rios, Leslie Diaz, Stephanie Cardenas, Esmeralda Cardoso-Mendoza, Juanita Arroyo, Maria Medina, Nora Coronado, Araceli Lucio, Olivia Hernandez, Surrey Walton. Empowering Latinas to obtain breast cancer screenings: Comparing intervention effects and cost effectiveness [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A030.

Abstract B011: Empowering Latinas to obtain breast cancer screenings: Comparing interventions’ behavioral and network effects

Abstract Purpose: Multiple approaches have been used to address Latinas’ disproportionate breast cancer burden, including educational interventions and empowerment related interventions, wherein a subset of the population is trained to share information with other members of the priority population. However, little work has compared their effects. Objective: To analyze data regarding the effectiveness of education and empowerment approaches on participant behaviors and network dissemination. Methods: This quasi-experimental trial was conducted in two lower-income Latino communities in Chicago between 2017-2019. Eligibility criteria include: 1) age of 52-74; 2) no mammography use within past 2 years; 3) no previous breast cancer diagnosis; and, 4) no prior health volunteerism experience. Women were assigned to a cohort and participate in a three-week intervention (education: breast cancer, diet, physical activity; empowerment: breast cancer, sharing information with networks, health volunteerism). For women who wished to obtain mammography (from either arm), the study team provided navigation to free/low-cost services. Data were collected at baseline, post-intervention, and six-month follow-up included standard demographics; self-reported mammography use, which were verified by study navigation records; and a modified version of Burt’s General Social Survey tool for egocentric data collection. All analyses accounted for cohort clustering and adjusted for relevant covariates (age, education, income, insurance status, baseline mammography intention, social network size, baseline proportion of network engaged about breast cancer). Results: There was a total of 145 women who enrolled in the study, of which 126 completed the intervention (64 empowerment, 62 education). Approximately 70% of participants were 52-64 years old, 57% were insured, 58% had less than a 9th grade education, had an annual household income of &amp;lt;$15,000 (44%), and 83% were born in Mexico. More empowerment participants had greater odds of obtaining a mammogram relative to education participants, 47% vs 84%; OR = 6.1, 95%CI [2.3, 15.5], p&amp;lt;.0001. Simultaneously, relative to education participants, empowerment participants talked to more women about breast cancer (M = 5.4 SD = 4.7 vs M= 2.6, SD = 2.6; Std B = 2.7, 95%CI [1.3, 4.0], p&amp;lt;.0001) as well as had greater odds of endorsing a specific type of breast cancer screening (69% vs 39%, OR = 3.6, 95%CI[1.7, 7.4], p =.001) and disseminating breast cancer information in public locations (48% vs 23%, OR = 3.2, 95%CI [1.6, 6.7], p = .002). Discussion: Empowerment approaches appear to be more effective at promoting mammography among non-adherent Latinas and enabling community-wide dissemination of evidence-based breast health information, when compared to education approaches. Limitations concern generalizability due a non-probability based sample, and limited ability for causal inferences due to a lack of randomization. Citation Format: Yamilé Molina, Liliana G. San Miguel, Catherine Pichardo, Genesis Rios, Juanita Arroyo, Maria Medina, Nora Coronado, Araceli Lucio, Olivia Hernandez. Empowering Latinas to obtain breast cancer screenings: Comparing interventions’ behavioral and network effects [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B011.

Diagnostic yield and clinical utility of germline genetic testing following somatic testing in breast cancer patients.

1092 Background: Germline genetic testing is recommended for breast cancer patients with specific presentations or family histories. Separately, tumor DNA sequencing is increasingly used to inform therapy, most often in patients with advanced disease. Recent NCCN and ESMO guidelines recommend germline testing following somatic testing, under specific circumstances and for specific genes. We examined the utility of germline findings in patients referred for both test modalities. Methods: We reviewed somatic and germline mutations in a consecutive series of patients who: (a) had a current or previous breast cancer diagnosis, (b) were referred for germline testing, and (c) previously received tumor sequencing. Diverse reasons for germline testing included: a tumor finding of potential germline origin, treatment or surgical planning, personal or family history, and patient concern. Results: 227 patients met study criteria of whom 88 (39%) harbored a pathogenic germline variant (PGV) in a high or moderate risk cancer predisposition gene. Mutations in certain genes were most likely to be of germline origin, and most PGVs were potentially actionable (Table). 13% of PGVs were not reported by tumor tests as either germline or somatic findings, usually a result of tumor test limitations. Of note, 27 of the patients with PGVs (31%) had these variants uncovered only after presenting with a second, possibly preventable, malignancy. Conclusions: Germline testing following tumor sequencing often yielded findings that may impact care. Indeed, the 39% PGV rate we observed suggests that such testing may be underutilized. We observed actionable PGVs missed by somatic tests, PGVs uncovered in patients’ second malignancies, and PGVs not within germline reflex testing criteria. These results reinforce the utility of germline testing separate from somatic testing in appropriate patients. [Table: see text]

Use of an Online Breast Cancer Risk Assessment and Patient Decision Aid in Primary Care Practices.

Background: U.S. Preventive Services Task Force (USPSTF) recommendations for mammography screening, genetic counseling and testing for pathogenic BRCA1/2 mutations, and use of risk-reducing medications require assessment of breast cancer risk for clinical decision-making, but efficient methods for risk assessment in clinical practice are lacking. Materials and Methods: A cross-sectional study evaluating a web-based breast cancer risk assessment and decision aid (MammoScreen) was conducted in an academic general internal medicine clinic. All eligible women, 40-74 years of age without previous diagnosis of breast or ovarian cancer and who were enrolled in the Epic MyChart patient portal were invited. MammoScreen uptake and completion rates and consistency between breast cancer risk determined by MammoScreen and existing risk information in the Epic record were measured. Patient and physician experiences were summarized from interviews. Results: Of 448 invited participants, 339 (75.7%) read their MyChart invitation and 125 (36.9%) who read invitations enrolled in the study; 118 (94.4% of enrolled) completed MammoScreen. Twenty-one women were categorized as above-average risk from either MammoScreen data or the chart review and 7 (33.3%) were identified by both sources. Physicians and patients believed MammoScreen was easy to use and was helpful in identifying risks and facilitating shared decision-making. Conclusions: Breast cancer risk assessment and mammography screening decision support were efficiently implemented through a web-based tool for patients sent through an electronic patient portal. Integration of patient decision aids with risk algorithms in clinical practice may help support the implementation of USPSTF recommendations that include risk assessment and shared decision-making.

Continuation of Annual Screening Mammography and Breast Cancer Mortality in Women Older Than 70 Years.

Randomized trials have shown that initiating breast cancer screening between ages 50 and 69 years and continuing it for 10 years decreases breast cancer mortality. However, no trials have studied whether or when women can safely stop screening mammography. An estimated 52% of women aged 75 years or older undergo screening mammography in the United States. To estimate the effect of breast cancer screening on breast cancer mortality in Medicare beneficiaries aged 70 to 84 years. Large-scale, population-based, observational study of 2 screening strategies: continuing annual mammography, and stopping screening. U.S. Medicare program, 2000 to 2008. 1058013 beneficiaries aged 70 to 84 years who had a life expectancy of at least 10 years, had no previous breast cancer diagnosis, and underwent screening mammography. Eight-year breast cancer mortality, incidence, and treatments, plus the positive predictive value of screening mammography by age group. In women aged 70 to 74 years, the estimated difference in 8-year risk for breast cancer death between continuing and stopping screening was -1.0 (95% CI, -2.3 to 0.1) death per 1000 women (hazard ratio, 0.78 [CI, 0.63 to 0.95]) (a negative risk difference favors continuing). In those aged 75 to 84 years, the corresponding risk difference was 0.07 (CI, -0.93 to 1.3) death per 1000 women (hazard ratio, 1.00 [CI, 0.83 to 1.19]). The available Medicare data permit only 8 years of follow-up after screening. As with any study using observational data, the estimates could be affected by residual confounding. Continuing annual breast cancer screening past age 75 years did not result in substantial reductions in 8-year breast cancer mortality compared with stopping screening. National Institutes of Health.

Abstract P6-10-16: High circulating levels of adrenomedullin are associated with metabolic syndrome and low cardiorespiratory fitness in BRCA1 and BRCA2 mutation carriers

Abstract BACKGROUND: Risk factors for cardiovascular disease (CVD) and breast cancer overlap substantially. Identification of the underlying mechanisms associated with this co-occurrence is of great public health importance. Adrenomedullin (AM) is an almost ubiquitously expressed peptide with vasodilator and natriuretic properties. Previous studies have observed a link between high AM levels and worse prognosis in patients with myocardial infarction and heart failure, indicating a crucial role in the pathophysiology of CVD. Moreover, AM is expressed in 80% of sporadic breast cancers, and the degree of expression is associated with tumour growth, local tumour progression and bone metastases. High plasma AM levels are linked to arterial hypertension, diabetes, obesity and smoking. Preliminary evidence suggests that AM influences the osteoclast differentiation mediated by Receptor Activator of NF-κB Ligand (RANKL), an important signalling pathway in BRCA1-associated breast tumorigenesis. OBJECTIVE: Besides an elevated risk of breast cancer, recent studies revealed that BRCA mutation carriers are potentially at higher cardiovascular risk. The value of AM in BRCA mutation carriers is unknown. The aim of this study was to examine circulating plasma AM levels in BRCA mutation carriers and assess their association with modifiable risk factors. METHODS: AM concentrations were measured in 290 BRCA1/2 mutation carriers without overt CVD, participating in the randomized controlled LIBRE study (NCT numbers: NCT02087592, NCT02516540), by an immunoassay (sphingotest® bio-ADM®). Subjects were classified into high versus low AM levels based on the median plasma AM level in the entire cohort (13.9 pg/mL). Univariate logistic regression models were used to estimate the odds ratio (OR) of having high circulating AM levels by metabolic syndrome (MetS), cardiorespiratory fitness (CRF), body mass index (BMI), circulating insulin, smoking, current age, BRCA mutation status (BRCA1 or BRCA2) and previous diagnosis of breast cancer. MetS was defined in accordance with the criteria of the Third Adult Treatment Panel (ATP III). CRF was measured by peak oxygen uptake (VO2peak) assessed on a cycle ergometer via standardized cardiopulmonary exercise testing. RESULTS: Of all women (median age: 43 years), 57.9% had a previous diagnosis of breast cancer. The median time between diagnosis and study entry was 3 years (range: 0-32 years). Women fulfilling the criteria of metabolic syndrome had over 17 times higher odds of having increased AM levels compared to those who did not meet the criteria (OR = 17.49, p &amp;lt; 0.001). Moreover, high AM levels were associated with lower VO2peak (OR = 0.91, p &amp;lt; 0.001), higher BMI (OR = 1.24, p &amp;lt; 0.001) and higher circulating insulin levels (OR = 1.1, p &amp;lt; 0.001). AM levels were higher in women who have ever smoked (OR = 1.73, p = 0.022), and AM levels increased with the number of pack-years smoked (OR = 1.03, p = 0.06). AM levels were not associated with age (p = 0.143), BRCA mutation status (p = 0.51) or previous diagnosis of breast cancer (p = 0.48). After adjustment for confounding variables, we observed that MetS (OR = 10.78, p = 0.002) and VO2peak (OR = 0.92, p = 0.001) were independent determinants of circulating AM. CONCLUSIONS: This is the first study in BRCA mutation carriers that has linked circulating AM levels to MetS and CRF. The long-term clinical implications of these findings are yet to be determined. Conflict of interest: The study is funded by the German Cancer Aid (Deutsche Krebshilfe) within the Priority Program “Primary Prevention of Cancer” (Grant no. 110013). JS and OH are employed by Sphingotec GmbH, a company having patent rights in and commercializing the bio-ADM assay. SG and MK received grants from Sphingotec GmbH. JL, MYD, MB and MH have nothing to disclose. Citation Format: Jacqueline Lammert, Sabine Grill, Maryam Yahiaoui-Doktor, Maryam Basrai, Joachim Struck, Oliver Hartmann, Martin Halle, Marion Kiechle. High circulating levels of adrenomedullin are associated with metabolic syndrome and low cardiorespiratory fitness in BRCA1 and BRCA2 mutation carriers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-16.

Radiographic Surveillance of Patients with Non-BRCA1/2 Pathogenic Variants.

The National Comprehensive Cancer Network (NCCN) developed clinical practice guidelines for germline pathogenic variants in highly penetrant genes, such asTP53andPTEN, and in moderately penetrant genes, such asCHEK2, ATM andPALB2. Whether the practice of radiographic surveillance of patients with pathogenic variants in genes other than BRCA1/2 complies with current NCCN guidelines remains unclear. Retrospective review of patients identified with pathogenic variants in genes other than BRCA1/2 from 2007 through 2017 to determine if radiographic surveillance was in accordance with NCCN guidelines for mammography and consideration of magnetic resonance imaging (MRI). Exclusions included variants of unknown significance, pathogenic variants not associated with an increased risk of breast cancer, and previous breast cancer diagnosis. After exclusions, 35 patients with pathogenic variants in ATM, CDH1, CHEK2, NBN, PALB2, PTEN, and STK11 genes were reviewed to assess whether radiographic surveillance was in accordance with NCCN guidelines. Guidelines for those with variants in ATM, CHEK2 and NBN includes annual mammography with tomosynthesis and consideration of breast MRI at age 40, variants in CDH1 and PALB2 at age 30, variants in PTEN at age 30-35 or 5-10 years before the earliest family breast cancer, and variants in STK11 at age 25. Of these 35 patients, 11 (31%) received mammography only; 11 (31%) received mammography and MRI, and 13 (37%) received no radiographic surveillance. Two of the 35 (6%) patients who received radiographic surveillance were diagnosed with ductal carcinoma in situ or invasive breast cancer. Thirty-one percent of patients with pathogenic variants in genes other than BRCA1/2 received both mammography and MRI. Thirty-seven percent of patients with these highly penetrant and moderately penetrant genes received no radiographic follow-up, clearly demonstrating an opportunity for improvement.

Influence of mammography screening in the treatment of women diagnosed with breast cancer

Introduction: Apart from non-melanoma skin tumors, breast cancer is the most prevalent neoplasm among women in Brazil and worldwide. Breast cancer is a very heterogeneous disease, a fact attributed to the plasticity of its cells. Therefore, the stratification of tumors is critical to achieving better clinical outcomes. Breast cancer screening often allows diagnosing the disease in its earlier stages, manifested as smaller tumors, and still without lymph node involvement. The multiple prognostic factors that must be taken into account when considering the eligibility for treatment, such as age, reproductive status, type of cancer, and severity of the disease, make it impossible to establish clear approach guidelines for the disease, given the many different clinical situations. Objectives: To evaluate the influence of mammography screening in the treatment of women with a previous diagnosis of breast cancer. Methodology: This is an observational, descriptive, cross-sectional study conducted with primary and secondary data and a quantitative approach. The research was carried out in a high-complexity hospital in the far-south of Santa Catarina, Southern Brazil, and assessed patients with a previous diagnosis of breast cancer, from 2012 to 2017, who were on oncological outpatient follow-up. Results: Among the 99 patients analyzed, 58.6% undergo the examination annually, and 49.5% were diagnosed less than 12 months after the last mammography. Stage I diseases were more frequent, corroborating the finding that 74.7% of patients were submitted to conservative surgeries and 68.7% to sentinel lymph node biopsy, instead of more extensive procedures. With respect to the treatment of choice, patients with annual or biennial mammography frequency had surgical and chemotherapeutic outcomes similar to those of women who had no set frequency or who had never had a screening, that is, 72.4% of patients with annual frequency and 100% of patients with biennial frequency were submitted to conservative surgery, as occurred with 85% of patients with no set frequency and 66% of those who had never had the test. Conclusion: Patients who had annual mammographies and those diagnosed less than 12 months after the last mammography presented smaller tumors at diagnosis, but these characteristics did not influence the type of treatment chosen.

Impact of mammography screening on the treatment of women diagnosed with breast cancer

Objective: To evaluate the influence of mammographic screening on the treatment of women with previous diagnosis of breast cancer. Method: Cross-sectional, descriptive, observational study, with primary and secondary data collection and quantitative approach. It was performed in a high complexity hospital in the South region of Santa Catarina, Brazil, where patients with previous history of breast cancer were evaluated during the period from 2012 to 2017, and who were undergoing oncological follow-up at the same hospital. The variables were expressed as frequency and percentage. Inferential statistical analyses were performed with a significance level of alpha = 0.05 and, therefore, 95% confidence interval. Therefore, the confidence interval was 95%. Associations between variables were investigated using the Pearson’s χ² and the likelihood ratio tests. Results: Among the 99 analyzed patients, 58.6% annually performed the examination and 49.5% had elapsed less than 12 months between the last performed mammogram and the diagnosis. There was a higher frequency of stage I disease, corroborating the results that 74.7% of patients underwent breastconserving surgeries and 68.7% underwent sentinel lymph node biopsy, rather than extensive surgeries. Regarding the treatment of choice, patients with annual or biennial mammographic frequency had similar surgical and chemotherapeutic outcomes in relation to patients who had a mammogram without defined frequency or who had never undergone it. Conclusion: Patients who underwent mammography on an annual frequency and those whose time between the last mammogram and the diagnosis of cancer was less than 12 months had tumors of lesser extent at diagnosis; however, it did not influence the type of treatment chosen.

Influence of the Mediterranean diet on the production of short-chain fatty acids in women at risk for breast cancer (LIBRE)

AbstractBackground: A number of small intervention studies suggested that a Mediterranean diet (MedD) and physical activity can lower the risk for breast cancer. LIBRE is the first large multicenter RCT to test the effect of these lifestyle factors on the incidence of breast cancer in women at risk because of BRCA mutations(1). LIBRE also offers to unravel underlying mechanisms such as the role of short-chain fatty acids (SCFA) for beneficial effects of such lifestyle interventions.Methods: We examined the effect of the lifestyle intervention on the production of SCFA measured in feces by gas chromatography. From the ongoing LIBRE trial we included all complete datasets (171 women; mean age 44 ± 11 years). Both women with and without previous breast cancer diagnosis were recruited (diseased; non-diseased). The participants were randomized into an intervention group (IG) trained for MedD and physical activity, and a usual care control group (CG). Adherence to the MedD was assessed at baseline and after 3 months (V1) using the validated Mediterranean Diet Adherence Screener (MEDAS) and the EPIC food frequency questionnaire (FFQ).Results: At baseline there was no difference in SCFA levels between the groups. In the IG the MEDAS score increased substantially by 2.5 points (p &lt; 0.001), in the CG only mildly by 0.4 points (p &lt; 0.05). Correspondingly, the intake of fibers increased solely in the IG. In the course of the study the amount of caproic acid decreased in the control group (p &lt; 0.001). At V1 non-diseased women showed higher amounts of acetic acid (p = 0.042), n-butyric acid (p = 0.023), n-valeric acid (p = 0.018) and iso-valeric acid (p = 0.031). There were several correlations between the intake of different fibers and fecal SCFA. For example, the sum of poly- and oligosaccharides correlated with acetic acid (p = 0.001; r = 0.316), propionic acid (p = 0.034; r = 0,251), n-butyric acid (p = 0.010; r = 0.316) and iso-valeric acid (p = 0.012; r = 0.306). There was no correlation between the MEDAS and SCFA.Discussion: A lifestyle change towards a MedD and increased physical activity did not change the levels of SCFA in feces, although an increase of fiber intake was documented in the IG. To further analyze SCFA metabolism in this target population, gut microbiota composition and function (metabolites) are currently analyzed.

Breast cancer in patients with brca mutation: case series

Introduction: Women who inherit a deleterious mutation in BRCA face substantially increased risks of developing breast cancer, estimated in 70%. Even though the annual screening with magnetic resonance and mammography promotes the early detection of the disease, the gold standard for the primary prevention of breast cancer is still bilateral mastectomy. Objectives: To characterize breast cancer with mutation in the BRCA gene. Method: This is a retrospective study, case series. We included all patients who had tested positive for BRCA mutation and who had a previous or current diagnosis of breast cancer from 1999 to 2019. The study was approved by the Research Ethics Committee of Universidade Federal do Piauí, report n. 2.817.502. Results: We found 10 patients with previous breast cancer, or at the time when they had a mutation in the BRCA gene. They were all female, with mean age of 39.4 years at diagnosis, average of 3.6 cases of cancer in the family. Five (50.0%) were triple negative tumors, mean size of 6.7cm, 9 invasive carcinomas, 2 stage IIIB, 3 cases with invasion and impairment of axillary lymph nodes. Three underwent bilateral salpingo-oophorectomy, and 6 underwent bilateral or contralateral risk-reducing mastectomy procedures. All patients were submitted to chemotherapy, being 6 neadjuvant and 5 associated with radiotherapy. As to type of mutation, 6 presented mutation for BRCA1, and 4 for BRCA2. Two patients died because of the disseminated disease. Only one patient is still being followed-up, after 29 months, with annual mammography, resonance and clinical examination, and did not accept risk-reducing mastectomy or salpingo-oophorectomy. Conclusions: The mean age of breast cancer diagnosis was 39.4 years. Half of the patients were triple negative, and most had mutation in BRCA1. Two patients died because of the disseminated disease.