Prior Breast Research Articles

Abstract PS7-07: Predicting breast cancer risk for women veterans

Abstract BackgroundAccurate breast cancer risk assessment allows personalized approach in breast cancer screening and/or prevention. Breast cancer risk prediction models have been developed. Independent prospective validation however was needed before broad clinical applications. The Department of Veterans Affairs (VA) Million Veteran Program (MVP) is one of the largest biobanks in the world. Important attributes include: large sample size (>830,000, April 20), national coverage, multi-ethnic representation, access to bio-specimens from which multi-omics measurements have been conducted, thousands of biomedical phenotypes derived from our baseline and life style surveys and electronic health records (EHR). About 9% of MVP registrants are women. Breast cancer risk prediction models were evaluated in a prospective cohort of women in MVP. MethodologyMore than 350000 MVP participants completed genotyping to date. Breast cancer diagnoses were captured from the EHR. Ethnicity was determined by a supervised learning algorithm, Harmonized Ancestry and Race/Ethnicity (HARE), that used genetically inferred ancestry to refine self-identified race/ethnicity. Clinical breast cancer risk prediction instruments were based on personal health, lifestyle, demographics, family history, and environmental exposure. Polygenic Risk Score used in this study is comprised of 313 single nucleotide polymorphisms (PRS313). Clinical risk models tested were: BPC3, Lit and Breast Cancer Risk Assessment Tool (BCRAT, a version of the Gail’s model). The BPC3 and Lit models were tested by deploying the iCARE (Individualized Cancer Absolute Risk Estimator) with or without incorporation of PRS313. The BCRAT was deployed in the R package “BCRA” (Breast Cancer Risk Assessment v. 2.1 by F. Zhang). The performance of the risk prediction models was assessed by Area under the Receiver Operating Characteristic Curve (AUC-ROC). The observed absolute risk over expected absolute risk was compared for each decile. Results35133 genetic females were identified without a prior breast cancer diagnosis. By HARE definition, 10717 were African Americans (AA), 317 non-Hispanic Asians (ASIAN), 19941 non-Hispanic whites (EU), 1803 Hispanic (HIS) and 1355 unassigned. The median age of this cohort at MVP entry was 55. 369 subjects developed incident breast cancers with a median follow up of 4 years. These new cases were identified from Cancer Registry (292 cases) and EHR search for compatible ICD plus CPT codes (77 cases). The breast cancer incidence rate was 2.6/1000/year. iCARE-lit model was tested in 2731 AA women (38 incident breast cancers), 9027 EU women (111 incident breast cancers), and 10254 non-AA women (122 incident breast cancers) that had comprehensive risk factor evaluation (<4 missing). The AUC with the iCARE-lit model alone is 0.569 for AA, 0.563 for EU, and 0.565 for non-AA. Incorporation of PRS313 into the iCARE-lit model improved the AUC to 0.573 for AA, 0.645 for EU and 0.638 for non-AA. Additionally, iCARE-lit plus PRS313 estimated that 15% (AA), 7.3% (EU) and 7.7% (non-AA) of the women would have a lifetime risk of >20%. The iCARE-BPC3 had similar performance as iCARE-lit. The AUC of BCRAT alone was 0.648 for EU (20550 with 179 incident breast cancers) and 0.661 for AA (10462 with 96 incident breast cancers). Incorporation of PRS313 to BCRAT improved the AUC to 0.682 (EU) and 0.658 (AA). BCRAT plus PRS313 estimated that 5.6% (AA) and 4.4% (EU) of the women would have a lifetime risk of >20%. DiscussionWe prospectively evaluated and validated the performance of breast cancer risk prediction models as reported from case control studies. Longer follow up of more women in MVP will provide better assessment esp. for AA women. Prospective validation of these risk prediction models provides strong rationale for further development of these models in the clinical setting. Citation Format: Shiuh-Wen Luoh, Cynthia Brandt, Sally Haskell, Lina Gao, Byung Park, Paul Spellman, Saiju Pyarajan, Million Veteran Program, Nallakkandi Rajeevan, Jessica Minnier. Predicting breast cancer risk for women veterans [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 PS7-07.

Abstract PS7-02: The relationship of established breast cancer risk factors with breast cancer subtypes

Abstract Background: Molecular characterization of breast tumors has revealed four subtypes which differ in expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Breast cancer subtypes have different prognosis and unique risk factors. Breast cancer risk assessment models mainly reflect risk of ER/PR+ HER2- tumors, the most common subtype, and may not reflect risk of other subtypes. The study objective was to compare associations of established breast cancer risk factors across invasive breast cancer subtypes. Methods: The study population included women aged 40-84 years who had a screening mammogram at Massachusetts General Hospital, Newton Wellesley Hospital, or the University of Pennsylvania from 2006-2015. Patients completed a risk factor questionnaire and additional risk factors were ascertained from clinical records. Women with prior breast cancer, breast implants, or BRCA1/2 mutations were excluded. Women diagnosed with breast cancer within 6 months were excluded to remove those with cancer at the time of risk assessment. Tumor characteristics were obtained from linkage with hospital and state cancer registries. For invasive tumors, subtype was defined based on immunohistochemistry as ER and/or PR+ HER2-, ER and/or PR+HER2+, ER and PR- HER2+, or ER and PR and HER2- (triple negative breast cancer, TNBC). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer using time from mammogram to cancer diagnosis or censoring. Separate Cox models were fit for each subtype, and patients who developed DCIS or another subtype, died, or were alive and cancer free on December 31, 2017 were censored. Age, biopsy history, atypical hyperplasia, age at menarche, age at first live birth, family history, race, BMI, and breast density at the time of screening were included in the models. Results: The study population (N=197,836) had a mean age of 54 years and 74% of patients were white, 15% were Black, and 11% were other races. During a mean follow-up of 6.3 years, 4,510 (2.3%) women developed breast cancer. Of these cancers, 1068 (24%) were DCIS. Of the invasive cancers, 2675 (77%) were ER/PR+HER2-, 290 (8%) were ER/PR+HER2+, 108 (3%) were ER/PR-HER2+, 264 (8%) were TNBC and 105 (3%) had missing subtype. For ER/PR+HER2- cancers, all risk factors were consistent with the literature and statistically significant. Breast density was associated with increased risk of all four subtypes compared to women with less dense breasts. Atypical hyperplasia was strongly associated with HER2+ cancers (HR=2.97 CI 1.63-5.40 p<0.01), less strongly associated with ER/PR+HER2- cancers, and not significantly associated with TNBC. Black women had higher risk of TNBC than white women (HR=2.61 CI 1.91-3.57 p<0.01). Conclusion Our results highlight both similarities and heterogeneity in risk factors across breast cancer subtypes. Prior diagnosis of atypical hyperplasia was more strongly associated with HER2+ compared to HER2- tumors. While it is well known that Black women have higher risk of TNBC, it is striking that the more than two-and-a-half-fold increased risk persisted even with comprehensive adjustment for breast cancer risk factors in a screened population. These results suggest that additional factors, such as genetics, biomarkers, and environmental exposures should be included in risk assessment to better capture risk of less common breast cancer subtypes such as TNBC. Risk factors for breast cancer subtypes among 197,836 women undergoing screening mammography*ER/PR+ HER2- N=2674ER/PR+ HER2+ N=290ER/PR-HER2+ N=108ER/PR/HER2- N=264HR,95% CIpHR,95% CIpHR,95% CIpHR,95% CIpBlack vs. white unadjusted0.67,0.58-0.77<0.010.73,0.48-1.090.120.91,0.49-1.680.772.61,1.96-3.46<0.01Black vs. white multivariate*0.72,0.63-0.83<0.010.75,0.49-1.150.191.23,0.65-2.330.532.61,1.91-3.57<0.01Atypical Hyperplasia*1.38,1.02-1.870.042.77,1.42-5.42<0.013.89,1.03-14.70.040.43,0.06-3.140.401 FDR** vs. none1.46,1.32-1.63<0.011.16,0.82-1.650.391.93,1.18-3.160.011.11,0.75-1.630.602 FDR** vs. none2.12,1.67-2.71<0.011.17,0.44-3.150.751.90,0.47-7.760.372.81,1.44-5.49<0.01BMI ≥25 vs. <25 kg/m2*1.37,1.25-1.50<0.011.35,1.04-1.750.031.07,0.71-1.640.741.29,0.97-1.730.08Dense vs. non-dense breasts1.55,1.42-1.69<0.011.75,1.34-2.29<0.011.97,1.25-3.10<0.011.65,1.26-2.17<0.01*Adjusted for all factors in the table and additionally age, biopsy, age at menarche, age at first live birth**FDR= first degree relative with breast cancer Citation Format: Anne Marie McCarthy, Tara Friebel, Wei He, Michaela Welch, Sarah Ehsan, Kevin Hughes, Alan Semine, Jinbo Chen, Despina Kontos, Susan Domchek, Emily Conant, Aditya Bardia, Constance Lehman, Katrina Armstrong. The relationship of established breast cancer risk factors with breast cancer subtypes [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 PS7-02.

Abstract PS3-17: Patient and provider determinants of breast cancer screening among Ontario women age 40-49: A population based retrospective cohort study

Abstract Background: For women aged 40-49, Canadian guidelines recommend individualized-decision making (based on risk assessment, values, and preferences) rather than routine screening mammography (SM). In this age group, family physicians are the gatekeepers to access SM; however, studies indicate substantial variability in practice patterns. There are few population-based data regarding uptake and patient/provider determinants of SM in this age group. We describe the uptake and frequency of SM and identify patient and provider level associations with SM in Ontario women aged 40-49. We hypothesized that SM would vary by provider characteristics and women’s demographics, suggesting lack of guideline-concordant care. Methods: This population-based retrospective cohort study linked health administrative databases to form a cohort of all Ontario women aged 40-49 between April 1, 2009 to March 31, 2019. Mammograms were identified using Ontario Health Billing codes. In order to identify mammograms that were specifically for screening, women were excluded if they had any prior breast MRI, mammogram, cancer diagnosis, oncologist visit, or breast surgical procedure. Sub-cohorts were created to identify women who had (a) at least one SM (“screen cohort”) and (b) 3 or more SM (“routine screen cohort”). Following SM, women were censored from cohorts if they had any cancer diagnosis, breast surgical procedure, oncologist visit, or death; however, breast cancer related outcomes were tracked for 6 months following SM, regardless of whether a censoring event occurred. Patient and provider characteristics were extracted for women in each cohort. A multivariable regression model was used to identify predictors of routine SM. Results: Of 2 million eligible women, 743 274 (35.6%) received a mammogram, 532 782 (25.5%) received at least one SM, and 90 651 (4.3%) received routine SM (3 or more). Table 1 demonstrates cohort characteristics. There were 0.32 and 0.52 mammograms per woman per year in the screen and routine screen cohort respectively. Call-backs were similar for women after the first SM compared to the third SM (9.5% vs 9.3%); however, there were more biopsies (3.2% vs 1.8%) and breast cancers diagnosed (1.2% vs 0.45%) within six months of the first SM. Compared to the full cohort, women in the routine screen cohort were more likely to have a family physician at cohort entry, be in higher-income quintiles, receive annual health exams, and receive have pap smears (p<0.001). Women in the screen cohort were more likely to have female providers and providers that were primarily paid fee for service versus capitation (p<0.001). Multivariable analysis will be reported at the meeting. Conclusions: Less than 5% of Ontario women 40-49 undergo routine SM. SM is associated with patient demographics related to higher socioeconomic status which could be related to higher risk of breast cancer and/or increased access to care. SM is also associated with some provider demographics which could be independent of breast cancer risk, suggesting lack of individualized risk assessment. Qualitative work is ongoing to explore this hypothesis. This information can inform guideline implementation strategies. Table 1: Patient and Provider Characteristics of ScreeningCharacteristicpercent (%) unless otherwise notedAll Women 40-49Screen Cohort (1 or more SM)Routine Screen Cohort (3 or more SM)Patient CharacteristicsAge at Cohort entryMean (median)42.5 (40)42.8 (42)41.7 (41)Age at Cohort exitMean (median)47.3 (50)48.5 (50)49.1 (50)Family Physician at Cohort entry90.0 %92.3%94.8%Income – top quintile20.7%22.3%24%Rurality Category – most urban76.3%79.0%81.2%Birth Location – Canada74.4%72.2%71.6%Annual Health Exams: at least one51.1%72.1%75.3%Pap Smear: at least one68.4%86.6%92.9%Provider CharacteristicsFemale44.8%47.2%52.1%Canadian Graduates70.3%70.3%72.1%Fee for Service model48.0%55.0%58.8% Citation Format: Michelle B Nadler, Alex Marchand-Austin, Peter C. Austin, Alexandra Desnoyers, Brooke E. Wilson, Aisha Lofters, Noah Ivers, Eitan Amir. Patient and provider determinants of breast cancer screening among Ontario women age 40-49: A population based retrospective cohort study [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 PS3-17.

Abstract PS7-16: Increased cancer mortality after second primary malignancy among breast cancer survivors

Abstract Background: Due to advances in early detection and treatment, the number of breast cancer survivors in the US is expected to increase to 5 million by 2030. Although it is well established that breast cancer survivors are at increased risk of second primary malignancy (SPM), there is limited data on the impact of a SPM on overall and cancer-specific mortality compared to women with a first primary cancer. This information could inform prognosis for women with breast cancer as well as screening and treatment recommendations. Methods: A retrospective cohort study was conducted using the Surveillance, Epidemiology, and End Results (SEER) 18 database, which collected cancer incidence and mortality from 18 US cancer registries (represents 28% of US population) between 2000 and 2016. For this analysis, we focused on the top 10 SPM in breast cancer survivors: breast cancer, lung cancer, colorectal cancer, uterine cancer, lymphoma, melanoma, thyroid cancer, pancreatic cancer, ovarian cancer, and leukemia. Propensity scores were used to match SPM with first primary cancer 1:1 on race, primary site, year of diagnosis, age of diagnosis, tumor stage, and treatments (surgery, chemotherapy, and radiotherapy). Hazard ratio (HR) and 95% confidence interval (CI) for cancer-specific death comparing SPM to first primary cancer were estimated from Cox proportional hazard regression, accounting for competing risk of death from conditions other than cancer. Subgroup analyses were conducted by SPM tumor stage, SPM primary site, and time interval between first breast cancer and SPM diagnosis. Results: The study population included 31,712 breast cancer survivors with SPM and 1,471,886 women with first primaries. Women with SPM were older (mean age of 66.6 years) than first primary cancers (mean age of 62.1 years). 52.8% of SPM and 47.5% of first primary cancers were diagnosed at local stage. Women with SPM had higher cancer mortality than women with first primary cancer (HR: 1.27, 95%CI: 1.23-1.30). Mortality difference was larger among local stage SPM (HR: 1.95, 95%CI: 1.82-2.08) and regional stage (HR: 1.40, 95%CI: 1.33-1.47) than for distant stage (HR:1.10, 95%CI:1.06-1.14). Among the top 10 SPM, increased mortality was observed for thyroid cancer (HR: 3.02, 95%CI: 1.96-4.67), breast cancer (HR: 2.26, 95%CI: 2.11-2.42), and melanoma (HR: 1.76, 95%CI: 1.36-2.28). There was no statistically significant difference in mortality for second lung (HR: 1.06, 95%CI: 1.00-1.17) and pancreatic cancer (HR: 0.93, 95%CI: 0.82-1.06). Larger mortality difference comparing SPM to first primary cancer was observed for SPM diagnosed within 5 years (HR: 1.39, 95%CI: 1.35-1.44) than after 5 years (HR: 1.09, 95%CI: 1.04-1.13). Conclusion: Breast cancer survivors with a SPM had higher cancer-specific mortality overall and for several cancers compared to women diagnosed with the same type of cancer for the first time suggesting that prior breast cancer is an important prognostic factor. Our results support the evaluation of improved risk stratification and/or novel screening and treatment approaches to improve outcomes from second cancer in breast cancer survivors. Citation Format: Zhengyi Deng, Miranda R Jones, Kala Visvanathan. Increased cancer mortality after second primary malignancy among breast cancer survivors [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 PS7-16.

Preservation of the Implant in Nipple-Sparing Mastectomies: A Retrospective Cohort Study.

Mastectomies are an integral part of breast cancer treatment for many patients.1 Of those patients, a significant number have previously undergone breast augmentation before being diagnosed with breast cancer. Therefore, we developed the novel technique of performing nipple- and implant-sparing mastectomies (NISMs) for women with prior breast augmentations. This study will assess the plausibility of using NISMs versus nipple-sparing mastectomies (NSMs) in this subgroup of patients by comparing the complication rates. Data were collected on age, tumor size, tumor grade, receptors, and the interval between mastectomy and implant exchange for both groups. Descriptive statistics were used to summarize patient characteristics. Independent samples t tests, χ2 tests, and Fisher exact tests were used to compare the NISM and NSM cohorts. Logistic regression was used to assess the association between complications and mastectomy type and was summarized as an odds ratio with a 95% confidence interval. Fifteen patients underwent an NISM and 35 patients underwent an NSM. The overall rate of complications was less in NISM cases than in NSM cases (20% vs 27%). However, this difference was not statistically significant (odds ratio, 0.54; 95% confidence interval, 0.18-1.64; P = 0.278). The overall complication rate was lower with NISMs compared with NSMs. Nipple- and implant-sparing mastectomy is a novel, viable, and safe option for patients with breast cancer and a history of submuscular breast augmentation.

Systematic Review and Meta-Analysis of Complications Following Mastectomy and Prosthetic Reconstruction in Patients With and Without Prior Breast Augmentation.

There is limited evidence available in the literature with regard to the complication profile of mastectomy and immediate prosthetic reconstruction in augmented patients. The aim of this systematic review and meta-analysis was to compare postoperative complications between women with vs without prior augmentation undergoing skin- or nipple-sparing mastectomy and immediate prosthetic reconstruction. A systematic search was conducted in February 2020 for studies comparing women with vs without prior augmentation undergoing skin- or nipple-sparing mastectomy and immediate prosthetic reconstruction with documentation of postoperative complications. Outcomes analyzed included early, late, and overall complications. Pooled odds ratios (ORs) with 95% CIs were obtained through meta-analysis. Our meta-analysis, which included 6 studies comparing 241 breasts with prior augmentation and 1441 without, demonstrated no significant difference between the 2 groups in rates of early (36.7% vs 24.8%: OR, 1.57; 95% CI, 0.94-2.64; P = 0.09), late (10.1% vs 19.9%: OR, 0.53; 95% CI, 0.06-4.89; P = 0.57), and overall complications (36.5% vs 31.2%: OR, 1.23; 95% CI, 0.76-2.00; P = 0.40). Subgroup analysis showed a significantly higher rate of hematoma formation in the augmented group (3.39% vs 2.15%: OR, 2.68; 95% CI, 1.00-7.16; P = 0.05), but no difference in rates of seroma, infection, mastectomy skin flap necrosis, and prosthesis loss. Our meta-analysis suggests that prior augmentation does not significantly increase overall postoperative complications in women undergoing skin- or nipple-sparing mastectomy and immediate prosthetic reconstruction. However, the significantly higher rate of hematoma formation in augmented patients warrants further investigation and preoperative discussion.

A case of IVIg responsive paraneoplastic SOX1 peripheral neuropathy in a male with breast carcinoma

Background and aimsSOX1 antibodies are generally associated with small cell lung cancer and anti-Hu antibody overlap is common. This case demonstrates isolated anti-SOX1 antibodies with an uncommon tumor type, and relapse of a paraneoplastic syndrome with recurrence of tumor. MethodsWe describe a case of a 65-year-old male with a paraneoplastic peripheral neuropathy and anti-SOX1 antibody positivity in the context of a prior male breast Grade 2 ductal carcinoma, in remission at the time of the initial neurological presentation. ResultsTreatment response to intravenous immunoglobulin (IVIg) was demonstrated. After period of clinical stability on IVIg in the context of remission of breast carcinoma, the patient experienced a relapse of his neuropathy. This was associated with tumor recurrence and again responded to tumor excision, radiotherapy and IVIg. InterpretationMale breast carcinoma has not previously been associated with anti-SOX1 antibody positive paraneoplastic neuropathy.

Six-year experience of oncoplastic volume replacement using local perforator flaps

Local perforator flaps may be utilised to correct volume defects after breast-conserving surgery (BCS), improving the cosmetic outcome and avoiding the need for contralateral symmetrising surgery. The aims of this study were to assess longer term oncological outcomes following local perforator flap reconstruction, and to demonstrate the learning curve associated with incorporating such techniques within routine clinical practice. We report a consecutive case series of 116 local perforator flaps performed between January 2014 and May 2020. Data collected included patient demographics, tumour characteristics, surgical procedure data, complications and follow-up outcomes. All breast cancer patients are followed with annual mammographic surveillance for a minimum of five years. Of 116 procedures, 101 were performed as immediate partial breast reconstruction and 15 as delayed reconstructive procedures for patients who had prior breast surgery. The overall complication rate was 15%; the majority were minor surgical site infections, 1.7% required haematoma evacuation. At a median follow-up of 37 months, there were no local cancer recurrences. Three patients who underwent delayed reconstruction required revision procedures, and one required a contralateral symmetrisation procedure. One patient in the immediate reconstruction group required additional lipofilling. Over time, the mean lesion size selected for immediate local flap reconstruction increased, operative times decreased and the proportion of day case procedures increased. Our data confirm that local perforator flaps are associated with low morbidity, excellent oncological outcomes and long-term durability. The use of local flaps can increase the range of indications for BCS, reducing mastectomy rates and the associated revision and symmetrising procedures associated with them.

COVID-19 Vaccine-Related Axillary and Cervical Lymphadenopathy in Patients with Current or Prior Breast Cancer and Other Malignancies: Cross-Sectional Imaging Findings on MRI, CT, and PET-CT.

Breast radiologists are increasingly seeing patients with axillary adenopathy related to COVID-19 vaccination. Vaccination can cause levels I–III axillary as well as cervical lymphadenopathy. Appropriate management of vaccine-related adenopathy may vary depending on clinical context. In patients with current or past history of malignancy, vaccine-related adenopathy can be indistinguishable from nodal metastasis. This article presents imaging findings of oncology patients with adenopathy seen in the axilla or neck on cross-sectional imaging (breast MRI, CT, or PET-CT) after COVID-19 vaccination. Management approach and rationale is discussed, along with consideration on strategies to minimize false positives in vaccinated cancer patients. Time interval between vaccination and adenopathy seen on breast MRI, CT, or PET-CT is also reported.

The Association Between Periodontal Disease and Breast Cancer in a Prospective Cohort Study.

Periodontal disease may be associated with increased breast cancer risk, but studies have not considered invasive breast cancer and ductal carcinoma in situ (DCIS) separately in the same population. We assessed the relationship between periodontal disease and breast cancer in a large prospective cohort study. The Sister Study followed women without prior breast cancer ages 35 to 74 years from 2003 to 2017 (N = 49,968). Baseline periodontal disease was self-reported, and incident breast cancer was ascertained over a mean follow-up of 9.3 years. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression, adjusting for multiple potential confounders, including smoking status. Heterogeneity in risk for invasive breast cancer versus DCIS was also estimated. About 22% of participants reported a history of periodontal disease at baseline. A total of 3,339 incident breast cancers (2,607 invasive breast cancer, 732 DCIS) were identified. There was no clear association between periodontal disease and overall breast cancer risk (HR = 1.02; 95% CI, 0.94-1.11). However, we observed a nonstatistically significant suggestive increased risk of invasive breast cancer (HR = 1.07; 95% CI, 0.97-1.17) and decreased risk of DCIS (HR = 0.86; 95% CI, 0.72-1.04) associated with periodontal disease, with evidence for heterogeneity in the risk associations (relative HR for invasive breast cancer versus DCIS = 1.24; 95% CI, 1.01-1.52). A case-only analysis for etiologic heterogeneity confirmed this difference. We observed no clear association between periodontal disease and overall breast cancer risk. The heterogeneity in risk associations for invasive breast cancer versus DCIS warrants further exploration.

Abstract PO-079: Mixed success and persistent disparities in outcomes related to breast density legislation: A national survey

Abstract Little is known about whether women residing in states with mandated dense breast notification (DBN) have improved awareness, knowledge, or discussion with their doctors, or whether there are disparities by sociodemographic characteristics. We conducted a cross-sectional, national telephone survey to assess the primary outcomes intended by DBN legislation: informing women about personal breast density, increasing awareness of its making effect and association with increased cancer risk, and prompting discussions with providers. Specific efforts were made to include women from all race/ethnic groups, education strata, and literacy levels. Women aged >40 reporting a mammogram in <2 years, with no prior breast cancer diagnosis and having heard of the term ‘breast density’ were eligible. We conducted chi-square analyses for each outcome, comparing each by state DBN legislation status, age, income, race/ethnicity, health literacy, and two clinical breast cancer risk factors (family history, prior breast biopsy). Paired comparisons within each sociodemographic factor were tested using Z-tests (α=0.05). Multivariable, binary logistic regressions predicted each outcome using all variables above entered simultaneously as predictors. Secondary analyses tested whether sociodemographic differences in outcomes were moderated by state DBN status via interaction terms. The sample included 2,306 women; 1,782 residing in DBN states and 524 in non-DBN states. Half of the participants were white (50.3%), 23.1% non-Hispanic black, 14% Hispanic, 8.2% Asian, and 4.4% ‘other’. Women in DBN states were 1.55 (95% CI = 1.20, 1.99) times more likely to have received personal breast density information compared to women in non-DBN states after controlling for sociodemographic and risk factors. Those with lower incomes, Asian women, and those with lower health literacy were less likely to report receiving personal breast density information. Overall, 39% had a discussion with their provider about breast density, with women in DBN states being 1.82 times more likely to have done so (95% CI= 1.40, 2.37). There were no differences between women in DBN vs. non-DBN states related to knowledge of masking bias (OR=.99, 0.71, 1.39) or understanding that breast density is a cancer risk factor (OR=0.93, 0.71, 1.22). Hispanic and lower income women had less knowledge about these topics. Interaction models failed to reveal moderating effects of state DBN status, indicating that DBN legislation does not appear to be mitigating or worsening the observed sociodemographic differences. Findings suggest that mandated DBNs have had partial success informing women about their breast density. However, we saw few indications that DBNs increased knowledge and observed less knowledge among women with low income, racial/ethnic minority status and lower literacy. This ‘one size fits all’ policy approach to relaying breast density information appears to be inadequate in reducing disparities in breast density awareness and knowledge. Citation Format: Nancy R. Kressin, Jolie Wormwood, Tracy A. Battaglia, Priscilla J. Slanetz, Christine M. Gunn. Mixed success and persistent disparities in outcomes related to breast density legislation: A national survey [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-079.

Abstract PO-151: Risk factors associated with breast cancer subtypes among Black women that have undergone screening mammography

Abstract Purpose: This study explores the associations of breast density and reproductive risk factors with invasive breast cancer subtypes in Black women. Background: Well- established risk factors for breast cancer have been extensively studied in White populations but fewer studies have examined these factors in Black populations. Black women are more likely to be diagnosed with triple negative breast cancer (TNBC), a more aggressive subtype with poorer prognosis than estrogen receptor (ER) and/or progesterone receptor (PR) positive, HER2 negative (ER/PR+HER2-) breast cancer. This study assesses the associations of breast density and reproductive risk factors with ER/PR+HER2- and TNBC subtypes among Black women. Methods: Black women who underwent screening mammography at the University of Pennsylvania between 2010-2015 were included. Eligible women were older than 40 years, had no prior breast cancer, no breast implants, and no known BRCA1/2 mutation. Data collection included a questionnaire completed at the time of screening and electronic medical records abstraction. Outcomes of interest included invasive breast cancer subtypes: ER and/or PR+ HER2-, TNBC, as determined by immunohistochemistry. Women were censored at death, date diagnosed with DCIS or another subtype of breast cancer, or on December 31, 2017 if they were alive and cancer free. Known breast cancer risk factors examined included age at screening, age at menarche, breast density (extremely or heterogeneously dense vs. scattered or almost entirely fatty), family history, BMI, and parity. Among parous women, age at first live birth, number of births and any history of breastfeeding were examined. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. Results: Among 24,857 Black women, mean age was 56.2 (40- 84) and 268 (1%) developed invasive breast cancer during a mean follow up of 4.32 years; 179 (67%) of those cancers were ER/PR+ HER- and 51 (19%) were TNBC. Factors found to increase risk across both subtypes included family history and dense breasts. Having dense breasts increased risk of ER/PR+ HER2- breast cancer by over 70% (HR: 1.73, 95%CI 1.24-2.40)) and TNBC more than twofold (HR: 2.57, 1.40-4.72). Among ER/PR+/HER2-breast cancers, older age at menarche was protective (>=14 vs <12, HR: 0.39, 0.23-0.68), yet among TNBC, older age at menarche increased risk (12- 13 vs. <12, HR: 4.34, 1.32-14.24; >=14 vs. <12, HR: 3.78, 1.05-12.74). Additionally, among parous women, in ER/PR+ HER2- cancers, increased parity was protective (3-4 births vs. 1-2: HR: 0.61, 0.40-0.95). Breast feeding and age at first live birth were not significantly associated with either breast cancer subtype. Conclusion: We observed a stronger association of breast density for TNBC than ER/PR+ HER2- breast cancer. In addition, later age at menarche was associated with increased risk of TNBC but protective for ER/PR+HER2- disease. These results highlight the importance of assessing risk factors for tumor subtypes in Black women. Citation Format: Tara Friebel, Sarah Ehsan, Susan Domchek, Despina Kontos, Emily Constant, Anne Marie McCarthy. Risk factors associated with breast cancer subtypes among Black women that have undergone screening mammography [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-151.

Alopecia neoplastica: An uncommon presentation of metastatic breast carcinoma

<p>Cutaneous metastasis may correspond to the initial clinical presentation of hidden internal malignancies. In patients presenting said neoplasia, clinical manifestations of breast cancer reaches 23.9%. Considering that neoplastic alopecia appears as an unusual pattern of the said metastasis, this report describes a case of such uncommon neoplastic alopecia which presents itself as a cutaneous metastasis of rapid progression in a patient with prior breast cancer history. We present a 47-year-old female patient reporting lesions at the scalp, and who was asymptomatic with a 1-year evolution. The patient reported prior breast cancer history and presence of lung metastasis, and was undergoing chemotherapy at the time of consultation. A dermatological evaluation showed only a nodular lesion with erythematous surface and a diameter measuring about 4 cm, firm in consistency, and immovable. She was routed to the Department of Dermatological Surgery, and the results from histopathology were consistent with a diagnosis of metastatic breast adenocarcinoma. Neoplastic alopecia appears as an unusual form of cutaneous metastasis which is predominantly described in association with breast cancer. The lesion’s clinical features play a crucial role at the differential diagnosis, as the presence of erythema could distinguish neoplastic alopecia from alopecia areata. The existence of cutaneous metastasis leads to unfavorable outcomes. As a conclusion, cutaneous evaluation of patients is essential for treating visceral metastases, since the forms of cutaneous metastasis are diverse and can also affect the scalp.</p>

Does Prior Breast Augmentation Affect Outcomes After Mastectomy With Reconstruction? An Analysis of Postoperative Complications and Reoperations.

The purpose of this study is to evaluate how prior breast augmentation impacts rates of complications and risk for reoperation after mastectomy with concurrent breast reconstruction. Patients undergoing nipple-sparing, skin-sparing, or simple mastectomy with implant-based reconstruction from 2008 to 2018 were identified in a prospective database. Postoperative complications and reoperations were then analyzed comparing patients with prior augmentation to patients without history of previous breast surgery. A total of 468 patients were identified with a median follow-up of 4 years. Of these, 72 had prior augmentation mammoplasty. These patients underwent nipple-sparing (52, 72%), skin-sparing (15, 21%), or simple (5, 7%) mastectomy with immediate direct-to-implant (46, 61%) or tissue expander (26, 35%) reconstruction. On univariate analysis, this cohort had a lower body mass index (23.3 vs 25.3, P = 0.003), a higher rate of nipple-sparing mastectomy (72% vs 54%, P = 0.01), and a higher prevalence of stage I disease (44% vs 33%, P = 0.04). Differences in age, comorbidities, reconstructive techniques, tumor size, and neoadjuvant/adjuvant therapies were not significant. Overall complication rate between patients with or without prior augmentation did not significantly differ (51% vs 50%, P = 0.83); no significant differences in rates of surgical site infection, hematoma, mastectomy skin flap/wound necrosis, nipple complications, implant loss, or capsular contracture were found. Analysis of reoperations between patients with and without prior augmentation revealed no significant differences in average number of subsequent planned, unplanned, or total reoperations. On multivariate analysis, prior breast augmentation was found to be associated with significantly increased risk for undergoing ≥1 unplanned reoperation (odds ratio, 2.28; 95% confidence interval, 1.28-4.05, P = 0.005). Prior augmentation mammoplasty does not significantly affect rates of postoperative complications after mastectomy with concurrent reconstruction. Although prior augmentation does not affect number of subsequent reoperations on average, it does increase the risk of experiencing 1 or more unplanned reoperation after mastectomy with reconstruction.

Family communication of genetic test results among women with inherited breast cancer genes.

Identification of inherited breast cancer may guide care. These benefits can be amplified through communication of genetic test results with at-risk family members and subsequent family testing (FT). Females with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about family communication (FC) of genetic test results and FT. Comparisons were made across genes. The 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and most were non-Hispanic whites (89%) with a prior breast cancer diagnosis (61%). When controlling for other variables, FC was higher among younger participants (p<.0001), those with high FC self-efficacy (p=.019), and those with P/LP variants in BRCA1/2 compared to PALB2 (p =.040) and ATM/CHEK2 (p =.032). Higher rates of FC and FT were also observed among female relatives and relatives of closer kinship. Overall 94% of participants would find one or more resources helpful with FC and 70% reported using FC resources when telling family members about their genetic test result. The three most commonly used resources included the following: (a) a family sharing letter (38%); (b) printed materials (30%); and (c) web-based information (23%). Among the 86% who spoke with a genetic counselor (GC), 93% were given at least one FC resource and the three most common resources GCs provided to participants overlapped with the resources participants would find helpful and those that were used. Our results suggest lower FC and FT rates among women with P/LP variants in genes other than BRCA1/2, the reasons for which should be evaluated in future studies. As more data to refine cancer risks and management are generated across these other inherited breast cancer genes, strategies to improve FC and FT are needed to amplify the benefits of genetic testing.

Mutational and Copy Number Profiling of Circulating Tumor DNA in Acute Myeloid Leukemia Using Targeted Next Generation Sequencing

The assessment of circulating tumor DNA (ctDNA), released by tumor cells undergoing apoptosis or necrosis, has established utility in solid tumors due to the advantage of a non-invasive "liquid biopsy" replacing multiple site-specific biopsies. However, its role in acute myeloid leukemia (AML) is uncertain, where a significant proportion of variants detected in the bone marrow (BM) may not be detected in ctDNA (Short, Blood Adv 2020). We have previously demonstrated the possibility of comprehensive genomic characterization of lymphoid malignancy from ctDNA using a single targeted next generation sequencing (NGS) hybridization-based panel (Blombery, BJH 2017). We aimed to assess the performance of this same genomic approach in ctDNA and to compare it against BM in AML. In addition, we aimed to assess the integration of a sensitive variant caller (Mutect2; Benjamin, bioRxiv 2019) to the bioinformatics suite in an attempt to improve low-level variant detection. Nineteen patients were identified from sequential patients with AML treated at our institutions where paired ctDNA and BM aspirate DNA were available. ctDNA was analyzed using a hybridization-based NGS panel targeting genes recurrently mutated in hematological malignancy followed by a suite of bioinformatics tools including HaplotypeCaller (GATK)/Mutect2 (GATK) for variant calling, CNSpector/CNSpectorX (Markham, Sci Reports 2019) for copy number variation (CNV) assessment and GRIDSS (Cameron, Genome Res 2017) for structural variant detection. The cohort clinical details are summarized in Table 1; none had documented extramedullary disease at time of collection. A total of 66 unique variants in 27 genes were detected, summarized in Figure 1. Median number of variants detected was 3 per patient sample, including NPM1 (n=6), IDH1/2 (n=4) and FLT3 point mutation (n=2). Three patient samples had FLT3-ITD detected by fragment length analysis; none were detected by the NGS panel in either ctDNA or BM. Variant allele frequency (VAF) from both compartments were highly correlated (R2 0.87). Higher VAFs in ctDNA were more commonly observed for kinase activating mutations (12/17 variants) and TP53 (5/6). Using HaplotypeCaller alone, 58 and 61 variants were detected in the BM and ctDNA, respectively. Of the 2 variants "specific" to the BM, both (IDH1 and NRAS) were called by Mutect2 in ctDNA and confirmed by visual inspection of sequence read alignments. Of the 5 variants "specific" to the ctDNA, 4 were detected in the BM at low VAF: CBL (n=2), KRAS and TET2. One discrepant case was patient #15 with prior breast cancer: KRAS G13D 21% in ctDNA but absent in the BM. Analysis by Mutect2 additionally detected 3 variants not called by HaplotypeCaller: NRAS and KIT in both ctDNA and BM, and TP53 P278R (VAF 6%) specific to the ctDNA in patient #9 with normal karyotype AML without history of prior malignancy. Overall, 3/5 variants in ctDNA and 6/6 in BM with low VAF were kinase activating mutations. We then performed genome-wide alignment of off-target reads to generate a low-resolution digital karyotype and CNV from ctDNA (Figure 2) which was compared with CNV and conventional karyotyping from BM. CNVs were detected in ctDNA in 10/11 patients with abnormal karyotype (Figure 1). Of these, 6/7 with non-complex abnormal karyotypes had consistent ctDNA CNVs including (i) 3 patients (#1, #10 and #15) with either rearranged/amplified KMT2A by FISH were all found to have gains at 11q23.3-qter, and (ii) 1 patient (#4) had 2 marker chromosomes of unknown origin on karyotyping which were resolved as additional copies of 4p using ctDNA sequencing. Although no CNVs were detected in all 8 patients with normal karyotype, analysis of B-allele frequency from ctDNA revealed one patient (#5) with copy neutral loss of heterozygosity (CN-LOH) in 7q (with a concurrent EZH2 mutation &amp;gt;95% VAF). In summary, we have demonstrated the ability to detect sequence variants, perform low-resolution digital karyotyping, CNV detection and CN-LOH detection from ctDNA in AML using a single hybridization based NGS assay. When using this approach, we show a high degree of concordance for both sequence variant and CNV detection, supporting the use of ctDNA as an alternative to BM (e.g. in cases of dry tap, hypocellular AML or failed karyotyping). Finally, using a sensitive variant caller, additional mutations were able to be detected in the ctDNA, the significance of which require evaluation in future studies. Disclosures Tiong: Amgen: Consultancy, Honoraria; Pfizer: Consultancy; Servier: Consultancy. Wilson:Illumina: Other: Illumina Diagnostic Genomics Scholarship. Bajel:Novartis: Honoraria; Astellas: Honoraria; Abbvie: Honoraria; Amgen: Honoraria, Speakers Bureau; Pfizer: Honoraria. Blombery:Invivoscribe: Honoraria; Novartis: Consultancy; Janssen: Honoraria; Amgen: Consultancy.

Oocyte Donation, Gestational Carriers, and Adoption for Breast Cancer Survivors

The purpose of this review is to describe and compare the use of oocyte donation, gestational carriers, and adoption for family building specifically in women with a history of breast cancer. Oocyte donation is an effective and safe option for women whose exposure to gonadotoxic cancer therapy has resulted in primary ovarian insufficiency, or for women with a familial cancer syndrome who are concerned about genetic risk to their offspring. A gestational carrier may also be considered—with or without oocyte donation—depending on the patient’s acceptance of ovarian stimulation and pregnancy in the context of prior breast cancer or ongoing endocrine therapy. Lastly, adoption is a frequently considered option for family building by many breast cancer survivors. Assisted reproductive technology and adoption offer breast cancer survivors the opportunity to expand their families despite the challenges that the diagnosis may pose.

Case 287.

History A 60-year-old woman was diagnosed with a new right upper lobe stage I lung adenocarcinoma and underwent video-assisted thoracoscopic surgery (VATS) for right upper lobectomy. Her postoperative course was complicated by a large pneumothorax after chest tube removal on postoperative day 3. This was managed with repeat right-sided chest tube placement on the same day. The second chest tube was removed on postoperative day 8 without complications. A 2-week postoperative clinic visit was unremarkable. Postoperative chest radiographs on postoperative days 1, 3, and 8 (Fig 1a-1c) are provided. Subsequently, chest CT scanning was performed as part of routine 6-month postsurgical lung cancer surveillance follow-up (Figs 2, 3). The patient had no clinical complaints at routine follow-up. Physical examination revealed well-healed VATS scars in the chest wall. Laboratory results were within normal limits, including a normal white blood cell count of 6400/μL. Her surgical history included prior left upper lobectomy for remote left upper lobe stage IIIA adenocarcinoma and prior bilateral breast implantation for cosmesis. On the basis of chest CT findings, the patient was transferred from an outside institution.

Pathology Examination of Breast Reduction Specimens: Dispelling the Myth.

Background:More than 100,000 reduction mammaplasties are performed in the United States each year. There is large variance in reported incidence of cancerous/high-risk lesions, ranging from 0.06% to 4.6%. There has been debate whether histological review of breast reduction specimen is necessary. This study aimed to determine the incidence of cancerous/high-risk lesions and to evaluate risk factors for their occurrence.Methods:A retrospective review was conducted for all patients who underwent reduction mammaplasty in 2018 by the senior author. Variables collected included demographics, comorbidities, history of breast surgery, family/personal history of breast cancer, weight of specimen, and pathologic findings. All specimens underwent pathologic evaluation and categorized as benign, proliferative, or malignant.ResultsA total of 155 patients underwent 310 reduction mammaplasties. Pathologic evaluations found that 11 patients (7.1%) had positive findings, 9 (5.8%) had proliferative lesions, and 2 (1.29%) had cancerous lesions. Patients with pathology were older (P = 0.038), had a family history of breast cancer (P = 0.026), and had a greater weight of resected tissue (P = 0.005). Multivariable analysis showed family history of breast cancer (P = 0.001), prior breast surgery (P = 0.026), and greater weight of resected breast tissue (P = 0.008) had a higher likelihood of positive pathology.Conclusions:These findings demonstrate an incidence of positive pathology higher than that reported and illustrate the importance of histologic review of breast reduction specimens. Family history of breast cancer, prior breast surgery, and a greater weight of resected tissue increase risk for proliferative/cancerous lesions.

Comparative Performance of Artificial Intelligence Algorithms for Screening Mammography.

HomeRadiology: Imaging CancerVol. 2, No. 6 PreviousNext Research HighlightsFree AccessComparative Performance of Artificial Intelligence Algorithms for Screening MammographyMichio TayaMichio TayaMichio TayaPublished Online:Nov 27 2020https://doi.org/10.1148/rycan.2020209034MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major Focus: To evaluate the performance of three commercially available artificial intelligence algorithms in screening mammography assessment in an external population both independently and in combination with radiologists.■ Key Result: One of the three artificial intelligence algorithms had significantly higher accuracy for breast cancer detection (area under receiver operating characteristic curve of 0.96 vs 0.92 vs 0.92; P < .001). Combining this best algorithm with first-reader radiologists achieved the highest accuracy at 88.6% sensitivity and 93.0% specificity.■ Impact: A commercially available artificial intelligence algorithm can assess screening mammograms with comparable diagnostic accuracy as radiologists. Whether such an algorithm can act as independent readers prospectively in a screening population remains unanswered.Screening mammography is currently the clinical standard for early detection of breast cancer. However, performance of individual radiologists in screening mammography programs varies widely. Efforts to develop artificial intelligence (AI) algorithms for screening mammography have yielded mixed outcomes owing to variability in quality of training data and study methodology. External validation studies comparing the performance of different AI algorithms in a screening population are lacking.This external validation study compared the diagnostic performance of three commercially available AI algorithms both independently and in combination with radiologists in a retrospective population-based screening cohort. Women with implants or prior breast cancer were excluded. The study population included 739 women with pathology-verified breast cancer diagnosed at screening or within 12 months and 8066 randomly sampled healthy controls with negative findings by 2-year cancer-free follow-up. The AI algorithm determined suspicion of cancer on a continuous scale from 0 to 1.0 with a decision threshold for normal and abnormal set at the mean specificity of the first-reader radiologist (96.6%).Algorithm 1 performed significantly better than the other two algorithms with area under receiver operating characteristic curve of 0.96 versus 0.92 versus 0.92 (P < .001). No significant difference in sensitivity existed compared with radiologist consensus at the same specificity (81.9% vs 85.0%, P = .11), despite the algorithm having no inputs from prior imaging or clinical history. When choosing an operating point corresponding to the U.S. Breast Cancer Surveillance Consortium benchmark of 88.9% specificity, algorithm 1’s sensitivity of 88.6% was comparable to the benchmark sensitivity of 86.9%.In combination with a radiologist where abnormal was defined by either the algorithm or radiologist, the cancer detection rate increased 8% from 5.32 per 1000 for algorithm 1 alone to 5.76 per 1000 in combination with the first reader with a corresponding 77% increase in recall rate from 39.1 to 69.1 per 1000.The most accurate algorithm was trained on the largest training set and utilized pixel-level annotations and higher capacity network architecture, despite training on a patient population and vendor system different from the external validation data set. In conclusion, only one of the three algorithms performed at an independent level comparable to radiologists, setting the groundwork for prospective trial evaluation of AI systems in screening mammography.Highlighted ArticleSalim M, Wåhlin E, Dembrower K, et al. External evaluation of 3 commercial artificial intelligence algorithms for independent assessment of screening mammograms. JAMA Oncol 2020;6(10):1581–1588. doi: 10.1001/jamaoncol.2020.3321Highlighted ArticleSalim M, Wåhlin E, Dembrower K, et al. External evaluation of 3 commercial artificial intelligence algorithms for independent assessment of screening mammograms. 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