History Of Lobular Carcinoma Research Articles

Self-reported barriers to screening breast MRI among women at high risk for breast cancer.

Annual screening breast MRI is recommended for women at high (≥ 20% lifetime) breast cancer risk, but is underutilized. Guided by the Health Services Utilization Model (HSUM), we assessed factors associated with screening breast MRI among high-risk women. From August 2020-January 2021, we recruited an online convenience sample of high-risk women ages 25-85 (N = 232). High-risk was defined as: pathogenic genetic mutation in self or first-degree relative; history of lobular carcinoma in situ; history of thoracic radiation; or estimated lifetime risk ≥ 20%. Participants self-reported predisposing factors (breast cancer knowledge, health locus of control), enabling factors (health insurance type, social support), need factors (perceived risk, screening-supportive social norms, provider recommendation), and prior receipt of screening breast MRI. Multivariable logistic regression analysis with backward selection identified HSUM factors associated with receipt of screening breast MRI. About half (51%) of participants had received a provider recommendation for screening breast MRI; only 32% had ever received a breast MRI. Breast cancer knowledge (OR = 1.15, 95% CI = 1.04-1.27) and screening-supportive social norms (OR = 2.21, 95% CI = 1.64-2.97) were positively related to breast MRI receipt. No other HSUM variables were associated with breast MRI receipt (all p's > 0.1). High-risk women reported low uptake of screening breast MRI, indicating a gap in guideline-concordant care. Breast cancer knowledge and screening-supportive social norms are two key areas to target in future interventions. Data were collected during the COVID-19 pandemic and generalizability of results is unclear. Future studies with larger, more heterogeneous samples are needed to replicate these findings.

Metastatic Carcinoma to the Brain with Mucinous Features in a Patient in Remission with History of Breast Lobular Carcinoma Triple Positive: A Case Report

Introduction: Breast cancer remains to be the most frequently diagnosed cancer in woman accounting for more than 2 million cases per year where it can metastasize to several organs in the body with brain metastasis being one of the most dreaded sequelae of it. Whole-brain radiosurgery, with or without surgical resection, or stereotactic radiosurgery remains to be the predominant treatment modality whereby surgical resection is limited to cases having a sole lesion identified or when located in excisable cortical regions. Case description: We presented the case of a 71-year old female patient with history of Lobular carcinoma in situ triple positive with brain metastatic carcinoma with mucinous features consistent with breast origin while being in remission after she underwent bilateral mastectomies 6 years prior to presentation with negative PET scan for any lesion other than that in the brain. Conclusion: Finding of brain metastasis with pathological features discordant with primary pathology of breast cancer, in a patient who is in remission years after undergoing bilateral mastectomies raises the question of the histological differentiation between the metastatic lesion and the primary source at the cellular level, and reflects on the relationship with receptor expression be it PR, ER or HER2.

Synchronous and metachronous bilateral breast cancer among women with a history of lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) confers increased cancer risk in either breast, but it remains unclear if this population is at increased risk for bilateral breast cancer (BC) development. Here we report bilateral BC incidence among women with a history of LCIS. Women with classic-type LCIS diagnosed from 1980 to 2017 who developed unilateral BC (UBC) or bilateral BC were identified. Bilateral BC was categorized as synchronous (bilateral BC diagnosed < 6months apart; SBBC) or metachronous (bilateral BC diagnosed ≥ 6months apart; MBBC). Five-year incidence rates of bilateral BC among this population were evaluated. Comparisons were made to identify factors associated with bilateral BC. At 7years' median follow-up, 249/1651 (15%) women with LCIS developed BC; 34 with bilateral BC (2%). There were no clinicopathologic feature differences between those with UBC and bilateral BC. SBBC occurred in 18 without significant differences versus UBC. Among 211 with UBC and a contralateral breast at risk, 16 developed MBBC at a median follow-up of 3years. MBBC patients were less likely to receive endocrine therapy and more likely to receive chemotherapy versus UBC. Tumor histology was not associated with MBBC. Estimated 5-year MBBC risk was 6.4%. Index estrogen/progesterone receptor positivity and endocrine therapy were the only factors associated with MBBC risk. Bilateral BC occurred in 2% of women with LCIS history at median follow-up of 7years. Similar to the general BC population, a decrease in MBBC is seen among women with a history of LCIS who develop hormone receptor-positive disease and those who receive endocrine therapy, highlighting the protective effects of this treatment.

Abstract PS8-05: Randomized controlled trial of decision support tools for patients and providers to increase breast cancer chemoprevention

Abstract Background: Breast cancer chemoprevention with selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) have been shown in randomized controlled trials to reduce breast cancer incidence by 50-65% among high-risk women. However, chemoprevention is still underutilized with fewer than 5% of high-risk women offered chemoprevention agreeing to take the medications. Reasons for low chemoprevention uptake include inadequate knowledge about chemoprevention among patients and healthcare providers, concerns about side effects, competing comorbidities, and time constraints during the clinical encounter. To address these barriers to chemoprevention uptake, we developed decision support tools for patients and providers. Methods: We conducted a randomized controlled trial of standard educational materials alone or combined with web-based decision support tools, RealRisks and BNAV, among 300 high-risk women and 50 healthcare providers, respectively. Patient eligibility criteria included: 1) women, age 35-75 years; 2) high-risk for breast cancer, defined as a 5-year invasive breast cancer risk ≥1.67% according to the Gail model or history of lobular carcinoma in situ (LCIS); 3) no prior use of a SERM or AI; 4) No personal history of breast cancer; 5) Access to the internet. Providers included primary care providers, such as internists, family practitioners, gynecologists, and nurse practitioners, and specialists, such as breast surgeons and medical oncologists. The RealRisks decision aid (DA) is available in English and Spanish and includes interactive modules to communicate personalized breast cancer risk and the risks and benefits of chemoprevention. The BNAV tool includes self-paced learning modules on breast cancer risk factors and chemoprevention and was made available to all providers through the electronic health record (EHR) dashboard. The primary endpoint was chemoprevention uptake at 6 months as assessed via the EHR. Secondary outcomes included validated measures of perceived breast cancer risk, breast cancer worry, chemoprevention knowledge, self-efficacy, decision conflict, chemoprevention attitudes, intention, and informed choice, which were administered to patients at baseline, 1 month, and 6 months after randomization. Results: Among 282 evaluable high-risk women enrolled from November 2016 to March 2020, mean age was 57 years (SD, 9.9), including 59% white, 14% black, 21% Hispanic, and 6% other. Mean 5-year invasive breast cancer risk was 2.98% (SD, 1.42), including 67% of women with benign breast disease and 64% with a first-degree family history of breast cancer. Comparing the intervention and control arms at 1 month, there were significant differences among high-risk women in accurate breast cancer risk perceptions (56% vs. 39%, p=0.017), adequate chemoprevention knowledge (49% vs. 27%, p&amp;lt;0.001), informed choice (41% vs. 23%, p=0.003), and mean decision conflict (34.0 vs. 47.0, p&amp;lt;0.001). There were no significant differences between the two groups in other patient-reported outcomes. Among patients who completed their 6-month follow-up, only 2.3% of high-risk women in the intervention arm and 3.8% in the control arm initiated a SERM or AI for breast cancer chemoprevention. Conclusions: With short-term follow-up, exposure to our decision support tools was associated with improvement in decision antecedents (accurate breast cancer risk perceptions, adequate chemoprevention knowledge) and decision quality (increased informed choice, reduced decision conflict). However, actual chemoprevention uptake in both arms remained low at less than 5%. Future research should focus on targeting high-risk women with LCIS or atypical hyperplasia and better incorporating decision support into clinic workflow through EHRs and patient portals. Citation Format: Katherine D Crew, Gauri Bhatkhande, Thomas Silverman, Tarsha Jones, Jennie Mata, Ashlee Guzman, Ting He, Jill Dimond, Rita Kukafka. Randomized controlled trial of decision support tools for patients and providers 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 PS8-05.

Chemoprevention Uptake for Breast Cancer Risk Reduction Varies by Risk Factor.

The efficacy of chemoprevention for breast cancer risk reduction has been demonstrated in randomized controlled trials; however, use remains low. We sought to determine whether uptake differed by risk factors, and to identify reasons for refusal and termination. Women seen in a high-risk clinic from October 2014 to June 2017 considered eligible for chemoprevention (history of lobular carcinoma in situ, atypia, family history of breast/ovarian cancer, genetic mutation, or history of chest wall radiation) were retrospectively identified. Breast cancer risk factors were compared among those with and without chemoprevention use, and compliance was noted. Overall, 1506 women were identified, 24% with prior/current chemoprevention use. Women ≥ 50years of age were more likely to use chemoprevention than women < 50years of age (28% vs. 11%, p < 0.001). Chemoprevention use by risk factor ranged from 7 to 40%. Having multiple risk factors did not increase use. Significant variation by risk factor was present among women ≥ 50years of age (p < 0.001), but not among women < 50years of age (p = 0.1). Among women with a documented discussion regarding chemoprevention (575/1141), fear of adverse effects was the most common refusal reason (57/156; 36%). The majority of women (61%) who initiated chemoprevention completed 5years. Chemoprevention use among women at increased risk for breast cancer remains low, with more frequent use among women ≥ 50years of age. These data highlight the need for ongoing educational efforts and counseling, as the majority who begin therapy complete 5years of use. Given the fear of adverse effects as well as low uptake, particularly among women < 50years of age, alternative risk-reducing strategies are needed.

Abstract OT3-01-02: Randomized controlled trial of web-based decision support tools for high-risk women and primary care providers to increase breast cancer chemoprevention

Abstract Background: Breast cancer chemoprevention with selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) is under-utilized despite several randomized controlled trials demonstrating a 40-65% decrease in breast cancer incidence among high-risk women. Reasons for low chemoprevention uptake include inadequate time for counseling, insufficient knowledge about SERMs and AIs, and concerns about side effects. Intervention trials of clinical decision support tools designed to increase chemoprevention uptake have been met with limited success. We have developed web-based decision aids (DAs), RealRisks for high-risk women and BNAV for primary care providers (PCPs). Our intervention differs from the prior literature in that we are targeting both patients and PCPs with personalized risk reports and education about the risks and benefits of chemoprevention. Our patient-centered decision aid is available in English and Spanish and has been rigorously tested in multi-ethnic women with varying health literacy. We hypothesize that standard educational materials combined with RealRisks and BNAV will increase uptake of SERMs or AIs among high-risk women in the primary care setting. Trial Design: We are conducting a randomized controlled trial at Columbia University Medical Center (CUMC) in New York, NY, consisting of standard educational materials combined with RealRisks and BNAV or standard educational materials alone among 300 high-risk women stratified by Hispanic ethnicity and menopausal status. Women in the intervention arm are given access to the RealRisks DA, and, based on their responses, an action plan is generated summarizing their breast cancer risk profile, risks/benefits of SERMs and AIs, and personal preferences for chemoprevention. PCPs are given their patient's tailored risk report, which is the providers' view of the action plan, and are invited to access the BNAV tool. Eligibility Criteria: 1) Women, aged 35-75 years; 2) 5-year invasive breast cancer risk ≥1.67% or lifetime risk ≥20% according to the Gail model (Breast Cancer Risk Assessment Tool) or history of lobular carcinoma in situ; 3) No prior use of SERM or AI; 4) No prior history of breast cancer; 5) PCP at CUMC; 6) English- or Spanish-speaking. Specific Aims: The primary endpoint is chemoprevention uptake of a SERM or AI at 6 months based upon documentation in the electronic health record. Secondarily, we use validated surveys to assess breast cancer and chemoprevention knowledge, accuracy of perceived breast cancer risk and worry, decision self-efficacy, and informed choice at baseline, 1 month, 6 months, and post-clinical encounter with the patients' PCP. PCPs will complete a 1-time survey on personal and professional characteristics and practice patterns. Statistical Methods: With a total sample size of 300 (150 per arm), assuming a Type 1 error of 5% and a 10% drop-out rate (effective sample size of 270), we will have &amp;gt;80% power to detect a difference in chemoprevention uptake of 1% in the control arm and 10% in the active intervention arm. Target Accrual: 300. Seventy-eight participants accrued as of June 2017. Accrual completion expected November 2018. Contact: Katherine Crew, CUMC, kd59@cumc.columbia.edu Citation Format: Vanegas A, Vargas JM, Kukafka R, Crew KD. Randomized controlled trial of web-based decision support tools for high-risk women and primary care providers to increase breast cancer chemoprevention [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-01-02.

The Association of Mammographic Density and Molecular Breast Cancer Subtype.

Background: Mammographic density (MD) is associated with increased breast cancer risk, yet limited data exist on an association between MD and breast cancer molecular subtypes.Methods: Women ages 18 years and older with breast cancer and available mammograms between 2003 and 2012 were enrolled in a larger study on MD. MD was classified by the Breast Imaging Reporting and Data System (BI-RADS) classification and by volumetric breast percent density (Volpara Solutions). Subtype was assigned by hormone receptor status, tumor grade, and mitotic score (MS). Subtypes included: Luminal-A (ER/PR+ and grade = 1; ER/PR+ and grade = 2 and MS = 1; ER+/PR- and grade = 1; n = 233); Luminal-B (ER+ and grade = 3 or MS = 3; ER+/PR- and grade = 2; ER/PR+ and grade = 2 and MS = 2; n = 79); Her-2-neu+ (H2P; n = 59); triple-negative (ER/PR-, Her-2-; n = 86). Precancer factors including age, race, body mass index (kg/m2), family history of breast cancer, and history of lobular carcinoma in situ were analyzed.Results: A total of 604 patients had invasive cancer; 457 had sufficient information for analysis. Women with H2P tumors were younger (P = 0.011) and had the highest volumetric percent density (P = 0.002) among subgroups. Multinomial logistic regression (LA = reference) demonstrated that although quantitative MD does not significantly differentiate between all subtypes (P = 0.123), the association between MD and H2P tumors is significant (OR = 1.06; confidence interval, 1.01-1.12). This association was not seen using BI-RADS classification in bivariable analysis but was statistically significant (P = 0.047) when controlling for other precancer factors.Conclusions: Increased MD is more strongly associated with H2P tumors when compared with LA.Impact: Delineating risk factors specific to breast cancer subtype may promote development of individualized risk prediction models and screening strategies. Cancer Epidemiol Biomarkers Prev; 26(10); 1487-92. ©2017 AACR.

Role of breast magnetic resonance imaging in predicting residual lobular carcinoma in situ after initial excision

Breast magnetic resonance (MR) imaging is a useful screening modality in detecting suspicious lesions in patients with a history of lobular carcinoma in situ (LCIS). This study aimed to evaluate the effectiveness of breast MR imaging in detecting remnant LCIS lesions after initial excision. Between 2011 and 2015, 29 patients with LCIS who underwent initial excision were enrolled. Breast ultrasonography and breast MR imaging was conducted after initial excision. Imaging findings were compared with pathologic results. There were nine (31.0%) cases with positive margins after initial excision; they were LCIS (n=8) and atypical lobular hyperplasia (n=1). Residual lesions were identified in 12 cases; they were invasive lobular carcinoma (n=1; 3.4%), LCIS (n=9; 31.0%), atypical lobular hyperplasia (n=1; 3.4%), and papillary carcinoma in situ (n=1; 3.4%). Prior to the second operation, these lesions could be detected in seven cases using ultrasonography (sensitivity, 53.3%; specificity, 100%) and in 10 cases using breast MR imaging (sensitivity, 83.3%; specificity, 100%). Breast MR imaging showed higher sensitivity than breast ultrasonography in detecting remnant LCIS lesions. If a suspicious lesion was found using breast MR imaging, a second operation should be considered because of the possibility of multifocality, even if LCIS was confirmed at the initial operation.

Accuracy of screening mammography in women with a history of lobular carcinoma in situ or atypical hyperplasia of the breast.

Women with lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH), atypical ductal hyperplasia (ADH), or atypical hyperplasia (AH) are at increased breast cancer (BC) risk. We investigated the accuracy and outcomes of mammography screening in women with histology-proven LCIS, ALH, ADH, or AH history who had screening through Breast Cancer Surveillance Consortium-affiliated mammography facilities. Screens from two cohorts, defined by LCIS/ALH or ADH/AH history, were compared to two cohorts without such history mammogram-matched for age-group, breast density, family history, screen-year, and mammography registry. Overall 359 BCs (277 invasive BC) occurred within 1 year from screening among 52,380 screens. In the LCIS/ALH cohort [versus comparator screens] cancer incidence rates, cancer detection rates (CDR), and interval cancer rates (ICR) were significantly higher (all P < 0.001); although ICR was 4.4/1,000 screens [versus 0.9/1,000; P < 0.001] the proportion that were interval cancers did not differ between compared cohorts (P = 0.43); screening sensitivity was 76.1 % [versus 82.3 %; P = 0.43], however, specificity was significantly lower at 85.1 % [versus 90.7 %; P < 0.0001]. In the ADH/AH cohort [versus comparator] cancer rates and CDR were significantly higher (P < 0.001); although ICR was 2.6/1,000 screens [versus 0.9/1,000; P = 0.002] the proportion that were interval cancers did not differ between cohorts (P = 0.74); screening sensitivity was 81.0 % [versus 82.6 %; P = 0.74] and specificity was lower at 86.2 % [versus 90.2 %; P < 0.0001]. Mammography screening sensitivity in LCIS/ALH and ADH/AH cohorts did not significantly differ from that of matched screens, however, specificity was lower, and ICRs were higher (reflecting underlying cancer rates). Adjunct screening may be of value in these women if it reduces ICR without substantially reducing specificity.

Cigarette smoking, physical activity, and alcohol consumption as predictors of cancer incidence among women at high risk of breast cancer in the NSABP P-1 trial.

NSABP P-1 provides an opportunity to examine the association of behavioral factors with prospectively monitored cancer incidence and interactions with tamoxifen. From 1992 to 1997, 13,388 women with estimated 5-year breast cancer risk greater than 1.66% or a history of lobular carcinoma in situ (87% younger than age 65; 67% postmenopausal) were randomly assigned to tamoxifen versus placebo. Invasive breast cancer, lung cancer, colon cancer, and endometrial cancer were analyzed with Cox regression. Predictors were baseline cigarette smoking, leisure-time physical activity, alcohol consumption, and established risk factors. At median 7 years follow-up, we observed 395, 66, 35, and 74 breast cancer, lung cancer, colon cancer, and endometrial cancer, respectively. Women who had smoked were at increased risk of breast cancer (P = 0.007; HR = 1.3 for 15-35 years smoking, HR = 1.6 for ≥ 35 years), lung cancer (P < 0.001; HR = 3.9 for 15-35 years, HR = 18.4 for ≥ 35 years), and colon cancer (P < 0.001; HR = 5.1 for ≥ 35 years) versus never-smokers. Low activity predicted increased breast cancer risk only among women assigned to placebo (P = 0.021 activity main effect, P = 0.013 activity-treatment interaction; HR = 1.4 for the placebo group) and endometrial cancer among all women (P = 0.026, HR = 1.7). Moderate alcohol (>0-1 drink/day) was associated with decreased risk of colon cancer (P = 0.019; HR = 0.35) versus no alcohol. There were no other significant associations between these behaviors and cancer risk. Among women with elevated risk of breast cancer, smoking has an even greater impact on breast cancer risk than observed in past studies in the general population. Women who smoke or are inactive should be informed of the increased risk of multiple types of cancer.

Abstract B17: The evaluation of breast cancer chemoprevention uptake in a high-risk cohort

Abstract Background: Population-based estimates in the United States indicate that uptake of breast cancer chemoprevention has remained low despite more than a decade of scientific evidence demonstrating clinical benefit. The objective of our study was to evaluate the uptake of breast cancer chemoprevention in a high-risk clinical setting. Methods: We evaluated the uptake of chemoprevention (tamoxifen, raloxifene or exemestane) 2007 to 2011 among 1,151 healthy women at high risk of breast cancer who were seen at the MD Anderson Cancer Center and enrolled in a high-risk breast cancer cohort. We used stepwise multivariable logistic regression to determine patient-related factors associated with use of chemoprevention. Results: Mean age of the cohort was 60 years; 85% of the women were white, 6% black and 9% of other ethnicities. Chemoprevention use was reported among 29% of women (n=340) (22% tamoxifen, 7% raloxifene). Among women with a history of lobular carcinoma in situ (LCIS), a proliferative breast lesion or Gail 5-year risk ≥1.66%, the uptake of chemoprevention was 52%, 42% and 14%, respectively. In multivariable analysis, history of osteoporosis (p=0.0034), prior use of hormone replacement therapy (p=0.0002) and elevated Gail model 5 year risk &amp;gt;3.0% (p=0.003) were positively associated with uptake of chemoprevention. Conclusion: Women seen in a high-risk clinical setting may be more motivated to use chemoprevention and uptake was highest among women with a history of LCIS or a proliferative breast lesion. Individualized strategies are needed to improve breast cancer chemoprevention uptake among different subsets of high-risk patients. Citation Format: Scott Nimmons, Arvind Bambhroliya, Bevers Teresa, Jun Ying, Powel Brown, Elise Cook, Lonzetta Newman, Abenaa Brewster. The evaluation of breast cancer chemoprevention uptake in a high-risk cohort. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B17.

Differences in Mammographic Density Decline over Time in Breast Cancer Cases and Women at High Risk for Breast Cancer

Abstract Introduction: High absolute breast density and increased breast density over time are strongly associated with breast cancer risk, and breast density generally decreases with increasing age. We examined mammographic density data from members of the Women At Risk High-Risk Registry at Columbia University Medical Center (WAR), a cohort defined as at high risk for breast cancer due to family history of breast cancer, history of lobular carcinoma in situ, and/or benign breast disease, to determine changes in their breast density over time. Methods: Within the WAR cohort of 1598 women, we conducted a nested case-control study of 66 incident cases of invasive breast cancer and 70 women without cancer, matched on age and time between first and second mammogram. For each participant, we collected two mammograms (for the cases, both mammograms occurred before cancer diagnosis), to examine differences in absolute density, percent density, and change in density between cases and controls. The average time between first and second mammogram was 4.6 years for both cases and controls, with a range of between 1 and 15 years. Results: Using linear regression with change in percent density as the outcome, and time between first and second mammogram as the independent variable, we found that among women without breast cancer, density decreased as time between first and second mammogram increased (β = −2.15, p = 0.005). In contrast, there was no overall change in density among the cases associated with time between first and second mammogram (β = 0.69, p = 0.39). In an ANCOVA comparing the slopes of the regression lines, the slopes were significantly different for cases versus controls (p = 0.009). Conclusion: In a cohort of women at high risk for breast cancer, breast density does not decrease as time between mammograms increases, for women who go on to develop breast cancer. For women who do not develop breast cancer, breast density decreases significantly over time.

Abstract P3-02-11: Screening Magnetic Resonance Imaging (MRI) of the breast in women at increased lifetime risk for breast cancer: A retrospective single institution study.

Abstract Background: Multiple factors are associated with an increased lifetime risk of breast cancer, including inheritance of an abnormal BRCA 1/2 gene, history of lobular carcinoma in situ (LCIS) or atypical hyperplasia, family history of breast cancer or previous chest wall radiation. In 2007, the American Cancer Society released updated guidelines for breast cancer screening based on risk stratification. These guidelines added annual MRI screening to mammography for women with greater than or equal to a 20–25% lifetime risk. Breast MRI screening trials have consistently demonstrated a higher sensitivity of MRI for malignancy compared with mammography, with an additional cancer yield from MRI of approximately 3%. The purpose of this study was to evaluate MRI screening outcomes in women with an increased risk for breast cancer evaluated in an established breast subspecialty clinic within the University of Wisconsin (UW) Hospital and Clinics. Methods: Patients (Pts) were included if they were seen by a UW breast center nurse practitioner, medical or surgical oncologist between 1/1/2007–3/1/2011 with a diagnosis code of: family history of breast or ovarian cancer, genetic susceptibility to malignant neoplasm or genetic carrier, Hodgkin's disease, LCIS, or atypical hyperplasia. Pts with a co-existing diagnosis of invasive breast cancer or ductal carcinoma in situ prior to initial encounter were excluded. Demographic information, breast cancer risk factors, estimated lifetime risk of breast cancer and screening recommendations were abstracted from the medical record. Results of subsequent breast imaging examinations (including breast MRI, diagnostic and screening mammography, and image-guided biopsies) were analyzed with the use of the mammography information system (PenRad™). Results: Of 276 women who met the inclusion criteria, 148 underwent at least 1 screening breast MRI. The majority of MRI screened pts were premenopausal (82%) and Caucasian (96.6%) with a mean age of 42.5 (range 20–68) at their initial encounter. Eighty five percent had a first degree relative with breast cancer and 72.3% of pts undergoing MRI screening had a documented lifetime risk of breast cancer of 20% or greater using a validated model. Within this MRI-screened cohort, 18.2% had a known genetic predisposition to breast cancer. Over the time assessed, 307 MRIs were performed in the 148 pts. Biopsy was recommended and performed based on the results of the MRI in 31 of 307 exams (10%). Ten cancers were detected for a positive predictive value based on biopsy performed of 32% and an overall cancer yield of 3.3% (10 of 307 MRI exams). All cancers were stage 0 - II. All pts are currently with no evidence of disease. Conclusion: Breast MRI has a high positive predictive value and cancer yield with an acceptable biopsy rate in a diverse group of high risk women undergoing breast MRI at an academic center outside of a clinical trial. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-11.

P4-11-21: A Retrospective Analysis of Women at Increased Lifetime Risk for Breast Cancer: Referral Patterns to Subspecialty Providers, Recommendations and Outcomes.

Abstract Background: Inheritance of an abnormal BRCA 1/2 gene, a family history of breast cancer (BrCa), or a personal history of lobular carcinoma in situ (LCIS), atypical hyperplasia, or chest wall radiation can significantly increase an individual's lifetime risk for developing BrCa. In 2007, the American Cancer Society (ACS) released updated guidelines for screening in women with a lifetime risk of BrCa ≥20-25%. These guidelines added MRI screening to annual mammography. The objective of our analysis is to characterize patients referred after the release of the 2007 ACS guidelines to subspecialty providers specifically for evaluation of BrCa risk and analyze subsequent screening and risk reduction recommendations in the cohort of patients (pts) with a predicted increased lifetime risk for BrCa. Methods: Pts seen at a single center (University of Wisconsin [UW]) between 1/2007-3/2011 by medical, surgical and/or gynecology-oncology for an increased lifetime risk of BrCa were identified by billing codes or evaluation in the UW Breast Cancer Prevention, Assessment and Tailored Health Screening (PATHS) Clinic. Pts with a personal history of BrCa prior to 1/2007 are excluded. Patients with a known genetic predisposition to BrCa, family history of breast cancer, or a personal history of LCIS, atypical hyperplasia or chest wall radiation are included in this analysis. All charts will be evaluated for documentation of the individual's lifetime risk of BrCa and method used for risk-assessment, recommended and performed screening tests, concordance with ACS screening guidelines, patient adherence to initial and subsequent screening recommendations, and uptake of risk reduction strategies. Call-back rates for additional or follow-up imaging and/or biopsy following BrCa screening and characteristics of all new BrCa diagnoses will be collected. Results: 240 eligible pts were seen during the study period. 15% of pts referred had a known genetic predisposition to BrCa. Most pts (75%) were referred for a family history of BrCa. The majority of these pts had a predicted lifetime risk of BrCa in excess of 20%, with less than 10% of patients being referred having a lifetime risk &amp;lt;20%. The remaining pts were referred for a personal history of LCIS, atypical hyperplasia or previous radiation to the chest wall. Results including subspecialty provider BrCa risk assessment, screening and risk-reduction recommendations, patient uptake and adherence, outcomes of screening and characteristics of diagnosed BrCa cases will be presented. Conclusion: Pts with a predicted increased lifetime risk for BrCa are often evaluated by oncology subspecialty providers. The primary factor related to referral is family history of BrCa. The majority of patients referred to a subspecialty provider have a calculated lifetime risk for BrCa in excess of 20%. This study evaluates provider assessment of BrCa risk and subsequent recommendations for screening and discussion of risk reduction strategies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-21.

Screening Breast MR Imaging in Women with a History of Lobular Carcinoma in Situ

To assess the utility of screening magnetic resonance (MR) imaging in the detection of otherwise occult breast cancers in women with a history of lobular carcinoma in situ (LCIS). This HIPAA-compliant study received institutional review board approval. The need for informed consent was waived. Retrospective review of the database yielded 670 screening breast MR studies obtained between January 2003 and September 2008 in 220 women with a history of LCIS. MR and mammographic findings were reviewed. Number of cancers diagnosed, method of detection, and tumor characteristics were examined. The cumulative incidence of developing breast cancer as detected with MR imaging and mammography was calculated. Breast density was examined as a prognostic factor in the cumulative incidence analysis. Biopsy was recommended in 63 lesions seen in 58 (9%) of 670 screening MR studies. Eight additional lesions were identified at short-term follow-up MR imaging for a total of 71 lesions in 59 patients. Twelve cancers (20%) were identified in 60 lesions sampled. Biopsy was recommended in 26 additional lesions identified at mammography; biopsy was performed in 25 of these lesions and revealed malignancy in five (20%). Overall, 17 cancers were detected in 14 patients during the study period. Of these, 12 were detected with MR imaging alone, and five were detected with mammography alone. Of the 12 cancers detected at MR imaging, there were nine invasive cancers and three cases of ductal carcinoma in situ (DCIS). Of the five cancers detected at mammography, two were invasive and three were DCIS. MR imaging is a useful adjunct modality with which to screen women with a history of LCIS at high-risk of developing breast cancer, resulting in a 4.5% incremental cancer detection rate. Sensitivity in the detection of breast cancers with a combination of MR imaging and mammography was higher than sensitivity of either modality alone.

Abstract PD05-02: Genome-Wide Associations of Breast Events and Functional Genomic Studies in High-Risk Women Receiving Tamoxifen or Raloxifene on NSABP P1 and P2 Prevention Trials. A Pharmacogenomics Research Network-RIKEN-NSABP Collaboration

Abstract Background: NSABP P1 and P2 are the largest prevention trials of tamoxifen and raloxifene in women at high risk of developing breast cancer. Both agents have been shown to decrease, but not eliminate breast cancer risk in these women. The goal of our study was to identify single nucleotide polymorphisms (SNPs) associated with development of breast cancer in high-risk women treated with tamoxifen or raloxifene. Methods: We performed a nested matched case-control genome-wide association study (GWAS) in subjects entered on the P2, which included only postmenopausal women, and subjects at least 50 years old entered on the P1 phase III prevention trials who were treated with tamoxifen or raloxifene. Cases were defined as subjects who developed invasive breast cancer or ductal carcinoma in situ and each was matched to two controls based on trial (P1, P2), age at trial entry, Gail risk score, history of lobular carcinoma in situ, and time on study. The study was restricted to the 94% of subjects self-identified as Caucasian. Genotyping was performed with the Illumina Human610-Quad chip. Eigenstrat analyses were performed to control for population stratification. SNPs were imputed within 200 Kb on either side of regions containing SNPs with p ≤ 3E-05. CYP2D6 genotyping was performed on all subjects. Results: The GWAS included 592 cases and 1171 controls. 547,356 SNPs were used in the analyses after removing 14,019 for call rates less than 98%, 30,560 for minor allele frequencies &amp;lt;1%, and 301 with Hardy-Weinberg equilibrium p-value &amp;lt;1E-06. Eigenvectors did not alter the results when used as covariates. Eleven genotyped SNPs with p-values ranging from 2.12E-06 to 9.98E-06 (conditional logistic regression with eigenvector adjustment) were identified; and 22 SNPs with p &amp;lt; 4E-05 were identified by imputation around these SNPs on chromosomes (Chr) 4, 8, 9, 13, 16 and 22, which were then genotyped with the Invader platform. Following imputation and genotyping, initial functional genomic studies have focused on 8 SNPs on Chr 16 (p-values 1.81E-06 to 9.55E-06, with the lowest p-value for an imputed and fine mapped SNP), all of which were in ZNF423, a gene known to encode a protein that associates with SMAD family members. In lymphoblastoid cell lines genotyped for the 2 top SNPs in ZNF423 (rs8060157 and rs11076499) and stably transfected with estrogen receptor-α, the variant and wild type SNPs displayed striking differences in estradiol-induced expression of ZNF423, SMAD3, BRCA1, and BRCA2. Conclusions: This GWAS revealed SNPs associated with the development of breast cancer in high-risk women treated with tamoxifen or raloxifene. Genome-wide significance was not achieved, but SNPs in ZNF423 identified on Chr 16 were associated with differential expression of ZNF423, SMAD3, BRCA1, and BRCA2 in response to estradiol in vitro, providing direction for future research. (Supported in part by NIH grants U01GM61388, U01GM63173, P50CA116201, U10CA77202, U10CA37377, U10CA69974, U24CA114732, and the Biobank Japan Project funded by the Ministry of Education, Culture, Sports, Science and Technology, Japan) Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD05-02.

The Role of MRI in Breast Cancer Screening

The 2009 NCCN Clinical Practice Guidelines in Oncology for Breast Cancer Screening and Diagnosis include significant updates for the role of MRI in screening women at increased risk for breast cancer. The NCCN now recommends considering breast MRI as an adjunct to annual mammography and clinical breast examination for women who have a BRCA1 or -2 mutation or who have a first-degree relative who has a BRCA1 or -2 mutation but who have not undergone genetic testing themselves; those who are determined to have a lifetime risk greater than 20% based on models that are highly dependent on family history; and those with a history of lobular carcinoma in situ. MRI is also recommended for patients who underwent radiation treatment to the chest between 10 and 30 years of age, and in those who carry or have a first-degree relative who carries a genetic mutation in the TP53 or PTEN genes (Li-Fraumeni, Cowden, and Bannahyan-Riley-Ruvalcaba syndromes). MRI is specifically not recommended for screening women at average risk for breast cancer. This article describes the peer-reviewed, published clinical research trials evaluating breast MRI in high-risk patients, on which the NCCN guidelines were based, and provides suggestions for future research.

Accuracy of self-reported breast cancer among women undergoing mammography

This study estimated the sensitivity and specificity of self-reported breast cancer and their associations with patient factors and pathologic findings using data from the Breast Cancer Surveillance Consortium. We included 24,631 women with and 463,804 women without a prior diagnosis of breast cancer who completed a questionnaire (including breast cancer history) at participating US mammography facilities between 1996 and 2006. We determined "true" cancer status using cancer registries and pathology databases. Multivariable logistic regression models were used to examine associations with patient factors and pathologic findings. Sensitivity of self-reported breast cancer was higher for women with invasive cancer (96.9%) than for those with ductal carcinoma in situ (DCIS) (90.2%). Specificity was high overall (99.7%) but much lower for women with a history of lobular carcinoma in situ (LCIS) (65.0%). In multivariable models, women reporting older ages, a nonwhite race/ethnicity, or less education had lower sensitivities and specificities. Sensitivity was reduced when there was evidence of prior DCIS, especially when this diagnosis had been made more than 2 years before questionnaire completion. Women reporting a family history of breast cancer had higher sensitivity. Evidence of prior LCIS was associated with lower specificity. The accuracy of self-reported breast cancer depends on the respondent's characteristics and prior diagnoses. Accuracy is lower among nonwhite women and women reporting less education. There appears to be uncertainty surrounding breast findings such as DCIS and LCIS. These results have important implications for research relying on self-report and for patient communication and care.

Economic evaluation of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan

Raloxifene was approved for chemoprevention against breast cancer among high-risk women in addition to tamoxifen by the US Food and Drug Administration. This study aims to evaluate cost-effectiveness of these agents under Japan's health system. A cost-effectiveness analysis with Markov model consisting of eight health states such as healthy, invasive breast cancer, and endometrial cancer is carried out. The model incorporated the findings of National Surgical Adjuvant Breast and Bowel Project P-1 and P-2 trial, and key costs obtained from health insurance claim reviews. Favourable results, that is cost saving or cost-effective, are found by both tamoxifen and raloxifene for the introduction of chemoprevention among extremely high-risk women such as having a history of atypical hyperplasia, a history of lobular carcinoma in situ or a 5-year predicted breast cancer risk of ⩾5.01% starting at younger age, whereas unfavourable results, that is ‘cost more and gain less’ or cost-ineffective, are found for women with a 5-year predicted breast cancer risk of ⩽5.00%. Therapeutic policy switch from tamoxifen to raloxifene among postmenopausal women are implied cost-effective. Findings suggest that introduction of chemoprevention targeting extremely high-risk women in Japan can be justifiable as an efficient use of finite health-care resources, possibly contributing to cost containment.

Percutaneous core biopsy in patients with a history of LCIS

11555 Background: Patients with a history of lobular carcinoma in situ (LCIS) routinely undergo increased radiologic surveillance for early detection of breast cancer (BC). This screening often results in abnormal imaging and subsequent percutaneous core biopsy (PCB) for tissue diagnosis. If the PCB reveals LCIS, the standard of care is surgical excision (SE). The purpose of this study was to compare the pathology of PCB and final surgical excisional pathology in patients with LCIS. Methods: A retrospective review of the Breast Service Surgical Database was performed for patients with a previous surgical biopsy demonstrating LCIS. All patients with previous or simultaneous diagnosis of BC were excluded. All LCIS patients underwent yearly mammography and biannual clinical breast examination (CBE). Additional screening ultrasound or MRI was performed at the discretion of the physician. Each PCB was recorded as an individual event. All subsequent pathology was reviewed and recorded. Results: A total of 559 patients were identified with a diagnosis of LCIS. After receiving this diagnosis, 26 patients underwent bilateral total mastectomies. The remaining 533 patients were followed for a median of 36 months. During this time 89 PCB were performed for abnormal imaging. All patients had a normal CBE at the time of PCB. Conclusions: At a median follow-up of 36 months, PCB detected BC in 27/89 (30.3%) of patients who underwent PCB for abnormal imaging. Two of the 6 (33%) patients with ADH on PCB had BC at excision. While none of the patients with LCIS on PCB had BC at definitive excision, PCB remains an important aspect of LCIS management. Summary of Percutaneous Core Biopsy Pathology and Surgical Excision Pathology PCB Pathology Number SE Surgical Excision Pathology BC Benign ADH/ALH LCIS Benign (n=44) 4 0 0 1 3 ADH (n=6) 6 1 1 1 2 LCIS (n=12) 10 2 2 6 0 Cancer (n=27) 25 1 3 4 17 Total (n=89) 45 5 6 12 22 No significant financial relationships to disclose.