Diagnosis Of Invasive Breast Cancer Research Articles

Abstract D094: Associations among state-level racial inequality, individual-level unfair treatment, and incident breast cancer in a risk-enriched cohort

Abstract Background: There is a small but growing body of evidence suggesting that structural inequality is associated with racial disparities in breast cancer stage at diagnosis and mortality. Less is known about the potential relationship between structural inequality and breast cancer incidence or subtypes. To address this gap, we developed a multidimensional state-level measure of racial inequality and assessed whether higher levels of inequality are associated with 1) higher odds of an invasive breast cancer diagnosis, and 2) among those diagnosed, higher odds of an estrogen receptor negative (ER-) vs. positive (ER+) tumor. Methods: The Sister Study is a longitudinal cohort of women who had a sister diagnosed with breast cancer, but did not have a personal history of the disease at enrollment. Leveraging this cohort, we generated state-level composite scores (range = 1-5) summarizing differences between non-Hispanic white and black residents across four domains: educational attainment, employment & occupational status, political participation, and incarceration. Data for the racial inequality measure were drawn from publicly available sources and linked to the participants’ state of residence at the time of enrollment. An individual-level measure of unfair treatment due to race was included as a proximal exposure to racial inequality. Invasive breast cancer diagnoses and subtypes were recorded through September 2016. The final analytic sample was limited to non-Hispanic white (n= 38,760) and black (n=4,061) Sister Study participants and their states of residence (n=40). Two-level population average models were constructed to assess the relationship among state- and individual-level factors and the odds of 1) an invasive breast cancer diagnosis (n=1,475) and 2) ER subtype among women with invasive breast cancer (1,278 ER+ cases; 197 ER- cases). Results: Adjusting for self-reported race, education, age, and epidemiologic risk factors (e.g., breast feeding history, menopausal status), we found that women residing in states with higher levels of racial inequality did not have higher odds of invasive breast cancer. However, among women diagnosed with an invasive breast cancer, we found higher odds of ER- vs. ER+ subtype among women living in states with higher levels of racial inequality (OR range = 1.7 – 2.6 for inequality composite scores of 3-5 vs. 1; p-values of <0.001 to 0.04). The proximal measure of unfair treatment due to race was also a significant factor in the fully-adjusted model, with women reporting 2 or more incidents of unfair treatment having a 2.6 times higher odds of an ER- diagnosis than women reporting no such incidents. Conclusions: In this relatively small sample of invasive breast cancer cases, structural and interpersonal experiences with racial inequality were associated with greater odds of the ER- vs. ER+ subtype, but not with the overall odds of an invasive breast cancer diagnosis. Reanalysis using a longer follow-up period may provide greater insight into this novel association. Citation Format: Erin Linnenbringer, Sarah Humble, Sarah Gehlert, Dale P Sandler. Associations among state-level racial inequality, individual-level unfair treatment, and incident breast cancer in a risk-enriched cohort [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D094.

Abstract B112: Influence of cholesterol screening on breast cancer detection and survival in the Breast Cancer Care in Chicago Study

Abstract Background: The utilization of non-cancer-related screening tests may result in a screening-related comorbidity that also serves as a marker for overall increased preventive health care use, including for breast cancer detection. Previous studies have found that a diagnosis of either hypertension or cholesterol has been associated with earlier stage at diagnosis for breast cancer. We sought to replicate these findings in a racially and ethnically diverse sample of patients in the population-based Breast Cancer Care in Chicago (BCCC) study. Methods: Participants included 989 non-Hispanic White (NHW), African American (AA), and Hispanic female breast cancer patients diagnosed between 2005 to 2008 who completed an interview. All patients resided in Chicago, Illinois, and were between the ages of 30-79 years at the time of their first primary in situ or invasive breast cancer diagnosis. Comorbid conditions were defined from interviews and medical record abstractions. Multivariable logistic regression and Cox proportional hazards (PH) models were used to estimate the associations of comorbid conditions with mode of detection (screen-detected vs. symptomatic), breast cancer-specific survival (BCSS), and overall survival (OS). Results: Overall, 33% of BC patients had hypertension and 9% had high cholesterol (HC). A diagnosis of hypertension was not associated with mode of breast cancer detection or survival. Screen-detection was nearly 30 percentage points higher for patients with vs. without a diagnosis of HC (78% vs. 49%, PD=0.29, 95% CI: 0.19, 0.39). HC was present in 9% of NHW BC patients and 8% of AA and Hispanic BC patients. The association of HC with screen-detection varied widely by race/ethnicity, being strongest among AA patients (PD=0.41, 95% CI: 0.28, 0.54), more moderate for NHW patients (PD=0.27, 95% CI: 0.14, 0.40), and absent among Hispanic patients (PD=0.05, 95% CI: -0.21, 0.31). With adjustment for age, race/ethnicity, income, education, affluence, disadvantage, insurance status, presence of a regular provider, and time of last clinical breast exam and last mammogram, HC remained associated with screen-detection (PD=0.21, 95%CI: 0.10, 0.32). A diagnosis of high cholesterol was associated with a large but imprecise reduction in age-adjusted BCSS (HR=0.43, 95% CI: 0.14, 1.3) and OS (HR=0.50, 95% CI: 0.21, 1.1). Multivariable-adjusted HRs were 0.54 (95% 0.17, 1.7) and 0.55 (0.24, 1.2), respectively. Conclusion: High cholesterol may be a potent marker for contact with a primary care physician and willingness to utilize preventive services. We found a particularly strong association of high cholesterol with early detection among AA patients. This association remained after robust control for preventive breast health care variables, suggesting that it is an independent predictor of screen-detected BC. A larger study is required to have sufficient sample to examine subsequent associations with BCSS and OS among racial/ethnic subgroups. Citation Format: Alpana Kaushiva, Susan Hong, Katherine Tossas-Milligan, Garth Rauscher. Influence of cholesterol screening on breast cancer detection and survival in the Breast Cancer Care in Chicago Study [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B112.

Androgen receptor expression inversely correlates with histological grade and N stage in ER+/PgRlow male breast cancer.

Androgen Receptor (AR) positivity is often displayed in breast cancer and especially in Male Breast Cancer (MBC), where it appears to be a heterogeneous feature, with its expression ranging between 38 and 81% of cases. Given the fact that circulating androgens represent the most important sex hormones in males and that breast carcinogenesis is characteristically subjected to hormonal mechanisms, our purpose was to investigate the clinicopathological significance of AR in MBC assessing if its expression could be associated with parameters of tumor aggressiveness. Clinical and pathological data were retrospectively reviewed for male patients with a diagnosis of invasive breast cancer. AR status was detected by immunohistochemistry on formalin-fixed, paraffin-embedded tumoral tissue sections. Correlations between AR expression and histopathological features were assessed using univariate and multiple comparisons where appropriate, assuming P values < 0.05 as statistically significant. The study included 44 consecutive male patients. AR expression ranged between 10 and 98% and the majority of cases presented a moderate to high expression of this receptor. Adopting a 20% PgR cut-off, statistical analyses highlighted a different behavior of AR: in ER+/PgRhigh group, it positively correlated with the other steroid receptors pointing out the importance of hormonal cross-talk: in ER+/PgRlow group, AR status inversely correlated with histological gradeand lymph node status. Hormonal factors reveal to play a crucial role in MBC carcinogenesis and progression. Intriguingly, in ER+/PgRlow tumors AR expression significantly correlates with lymph node status, hinting at a favorable biological role of AR in this tumor subgroup.

ER, PR, and HER2 expression in Ugandan breast cancer patients: An evaluation of in-country RT-PCR compared to IHC.

e19009 Background: Breast cancer, the most common cancer in sub-Saharan Africa (SSA), is characterized by poor survival. An accurate assessment of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2) status, typically via immunohistochemistry (IHC), is considered essential to provide prognostic data and guide therapeutic decision-making. However, due to inaccessible IHC services, these data are often unavailable in many parts of SSA; alternate methods need to be explored. Given the lab infrastructure developed in response to the HIV pandemic, RT-PCR testing is more readily accessible and feasible in SSA. Here we assess the potential of RT-PCR in evaluating the receptor status of women with breast cancer in Uganda. Methods: We enrolled women with a new diagnosis of invasive breast cancer at the Uganda Cancer Institute. Demographic and clinical data were obtained. A formalin-fixed paraffin embedded (FFPE) specimen was utilized for quantitative RT-PCR, using a validated assay for the detection of the ER, PR and HER2. Receptor expression levels were expressed as relative quantity (RQ) compared to housekeeping genes (CALM2). HER2 IHC results were categorized as negative (score 0 or 1+) or positive (3+); 2+ results (n=6) were excluded as FISH testing was not performed. Unstained slides were sent to the Fred Hutchinson Cancer Research Center for IHC. Receiver operating characteristic (ROC) analysis was applied to compare RT-PCR to IHC (gold standard). Results: We analyzed interim data (anticipated N=100 of an ongoing study) from 32 women aged 35 to 56 years. The majority of women (25, 78%) presented with advanced stage disease. Of the 32 cancers, 18 were ER+ (56%), 10 were PR+ (31%), 9 were HER2+ (28%) and 8 were triple negative (25%) by IHC. From ROC analysis, the AUC were 0.94, 0.95, and 0.81 for ER, PR, and HER2 respectively with high sensitivity and specificity (Table). Conclusions: Despite the tremendous need, the ability to detect the ER, PR, and HER2 via IHC in SSA is limited. Here we demonstrate the favorable test characteristics of RT-PCR when compared to IHC. Given the relatively wide accessibility of RT-PCR and endocrine therapy for breast cancer, as well as the recent inclusion of trastuzumab in the WHO’s Essential Medicines List, the results of this study have both direct diagnostic and therapeutic implications. Clinical trial information: NCT03518242 . [Table: see text]

Breast cancer in women aged 80 years and older: Clinical characteristics and treatment patterns according to biologic subtype.

e12594 Background: Older age is associated with poorer breast cancer-specific survival (BCSS) outcomes, despite a higher prevalence of biologically favorable disease. We sought to evaluate differences in the clinical characteristics and management of older women according to biologic subtype of breast cancer. Methods: The Surveillance, Epidemiology, and End Results (SEER) treatment database was queried to identify all women aged 80 years or older with a first diagnosis of invasive breast cancer between 2010 and 2016. Patients were subgrouped according to biologic subtype and clinical and treatment-related variables were compared. Multivariable logistic regression was then performed to determine factors independently associated with receipt of breast-conserving surgery (BCS) and adjuvant radiation. Results: Overall, 27,375 women with a median age of 84 (range, 80-108 years) met inclusion criteria. The majority of older women were diagnosed with HR+HER2- breast cancer (78.9%), followed by HER2+ (11.0%) and triple-negative breast cancer (TNBC) (10.0%). In women with stage I-III disease, non-operative management was employed in 13.4% of HR+HER2- patients, compared to 16.7% of HER2+ patients and 11.0% of TNBC (p &lt; 0.001). In those undergoing surgery, BCS was most common in HR+HER2- patients (80.9%), compared to HER2+ (68.9%) and TNBC (67.8%; p &lt; 0.001). Axillary surgery was performed in 74.0% of early stage patients with HR+HER2- disease, compared to patients with HER2+ (77.8%) and TNBC (79.3%; p &lt; 0.001). In adjusted analyses controlling for stage and clinical variables, women aged 80 years or older with HER2+ breast cancer and TNBC had a lower likelihood of BCS (ORHER2+ 0.72, 95% CI 0.65-0.80; ORTNBC 0.72, 95% CI 0.65-0.81), and an increased likelihood of adjuvant radiation (ORHER2+ 1.14, 95% CI 1.02-1.27; ORTNBC 1.40, 95% CI 1.25-1.57). Conclusions: One fifth of women with breast cancer over age 80 are diagnosed with HER2+ and triple-negative subtypes, which are associated with more aggressive local therapy. Further studies are warranted to determine if higher rates of adjuvant radiation optimize local control in older HER2+ and TNBC patients at increased risk for early locoregional recurrences.

Onset of cardiovascular disease risk factors in women with and without a history of breast cancer: The Pathways Heart Study.

12017 Background: Women with a history of breast cancer (BC) are at increased long-term risk of dying from cardiovascular disease (CVD). However, the onset of CVD risk factors in women with BC has not been well-described. We compared risk of incident CVD risk factors in women with and without BC enrolled in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records. All invasive BC cases diagnosed between 2005-2013 were identified and matched 1:5 with controls on birth year, race/ethnicity and KPNC membership at the date of BC diagnosis. Cox regression models assessed the hazard of incident hypertension (based on diagnosis codes and filled prescriptions), dyslipidemia (based on diagnosis codes, filled prescriptions, and lab values), and diabetes (KPNC Diabetes Registry). Models were adjusted for baseline BMI, menopausal status, smoking status, neighborhood median household income, education, prevalent CVD conditions, and other baseline CVD risk factors. Subgroups of women who received chemotherapy, radiation therapy, and endocrine therapy were compared with controls. Results: A total of 14,942 women with a new diagnosis of invasive BC were identified and matched to 74,702 controls. On average, women were 62.0 years, 28.3 kg/m2BMI, 64.9% non-Hispanic white. Overall, cases were more likely to develop hypertension (HR: 1.18, 95% CI: 1.13, 1.24) and diabetes (HR: 1.23, 95% CI: 1.16, 1.31). Across the board, receipt of any of the three therapies (chemotherapy, radiation therapy and endocrine therapy) was associated with increased risk of hypertension and diabetes, compared to controls. Risk-factor specific hazard ratios for receipt of chemotherapy were (HR 1.18, 95% CI: 1.10, 1.27) and (HR 1.38, 95% CI: 1.26, 1.51), for hypertension and diabetes, respectively. For receipt of radiation therapy, risk-factor specific hazard ratios were (HR: 1.17, 95% CI: 1.09, 1.26) and (HR: 1.15, 95% CI: 1.04, 1.27), for hypertension and diabetes, respectively. Risk-factor specific hazard ratios for receipt of endocrine therapy were (HR: 1.22, 95% CI: 1.14, 1.30) and (HR: 1.16, 95% CI: 1.06, 1.27), for hypertension and diabetes, respectively. Conclusions: The risk of developing hypertension and diabetes is increased in women with BC who received chemotherapy, radiation therapy, and/or endocrine therapy. Future studies should examine the roles of CVD risk factor diagnosis and management on cardiometabolic risk in women with a BC history.

Risk of cardiovascular disease in women with and without a history of breast cancer: The Pathways Heart Study.

12016 Background: Breast cancer (BC) survivors are at increased risk of cardiovascular disease (CVD) following diagnosis, as compared to women without BC. To provide a population-based estimate of CVD risk in BC survivors, we compared risk of CVD events in women with and without BC history enrolled in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records. All invasive BC cases diagnosed between 2005-2013 were identified and matched 1:5 with non-BC controls on birth year, race/ethnicity and KPNC membership at date of BC diagnosis. Cox regression models were used to assess differences in the hazard of four major CVD events (ischemic heart disease (IHD), heart failure (HF), cardiomyopathy, and stroke). Models were adjusted for factors known to influence risk of breast cancer or CVD.Other CVD events included arrhythmia, cardiac arrest, carotid disease, myocarditis/pericarditis, transient ischemic attack, valvular disease, and venous thromboembolism (VTE). We additionally examined subgroups of cases who received chemotherapy, radiation, and endocrine therapy, and their controls. Results: A total of 14,942 women with a new diagnosis of invasive BC were identified and matched to 74,702 women without BC history. On average, women were 62.0 years, 28.3 kg/m2BMI, 64.9% non-Hispanic white. Among all cases and controls, there were no significant differences in hazard of developing IHD, cardiomyopathy, and stroke; there was a borderline difference in HF (HR: 1.08, 95% CI: 0.99, 1.19). Cases were more likely to have a cardiac arrest (HR: 1.39, 95% CI: 1.09, 1.78) and develop VTE (HR: 1.97, 95% CI: 1.74, 2.23). Women treated with chemotherapy were more likely than controls to develop HF (HR: 1.44, 95% CI: 1.21, 1.72), cardiomyopathy (HR: 2.01, 95% CI: 1.02, 3.98), and VTE (HR: 3.15, 95% CI: 2.62, 3.79). Women who received radiation therapy were more likely to develop carotid disease (HR: 5.49, 95% CI: 1.22, 24.66) and VTE (HR: 1.65, 95% CI: 1.35, 2.03) than controls. Women who received endocrine therapy were more likely to experience a cardiac arrest (HR: 1.49, 95% CI: 1.07, 2.09) and develop VTE (HR: 1.70, 95% CI: 1.42, 2.03) than controls. Conclusions: Women with BC were at increased risk of heart failure, cardiomyopathy, cardiac arrest, VTE and carotid disease. These risks varied by cancer treatment, with higher risk in those who received chemotherapy. Future studies should explore the effects of chemotherapy class and radiation dose exposure on diverse CVD endpoints in BC survivors.

Mediation of black/white disparities in triple negative breast cancer by socioeconomic position, reproductive factors and diabetes in the Nurses’ Health Study Cohorts I &amp; II.

1565 Background: The higher rates of triple negative (TN) breast cancer (BC) observed among black compared to white women may be attributable to social and reproductive factors, as well as biological conditions like diabetes mellitus type 2. We examine the extent to which the black/white race disparity in TNBC is transmitted through these factors. Methods: Data are from the Nurses’ Health Study I and II prospective cohorts and include non-Hispanic (nH) black (n = 97) and nH white (n = 8,876) women aged 25-55 years at enrollment with invasive BC diagnoses. Participant characteristics are self-reported or drawn from medical records. We estimated average controlled direct associations (ACDA) using logistic regression with model-based standardization to evaluate the age/body mass index (BMI)-adjusted prevalence difference for TN versus luminal A/B type BC by race, and performed a series of ACDA (with comparison of rescaled coefficients (RC)) controlling for diabetes, mean family income before diagnosis (cont.), husband’s education ( &lt; college, college, graduate school), parental ownership of participant’s childhood home (yes/no), age at menarche (cont.), age at first birth (cont.), parity (integer), and breastfeeding (BF) (parous/never BF, parous/ever BF). Results: Compared to nH whites, nh black women had higher prevalence of TNBC (24.5% v. 45.4%; p &lt; 0.01), higher prevalence of diabetes (5.5% v. 11.3%; p = 0.01), lower prevalence of BF (59.2% v. 46.6%; p = 0.02), higher mean BMI (26.1 v. 29.9; p &lt; 0.01), and lower mean family income ($17,304 v. 15,750; p &lt; 0.01). BMI, age, and menopause were positively associated with prevalence of diabetes. In the age/BMI adjusted model, nH black women were 20%-points more likely than nH whites to have TNBC (95% Confidence Interval (CI): 0.11, 0.29). This disparity was reduced to 18.1% after also adjusting for BF (95% CI: 0.09, 0.28), to 13.7% after additionally adjusting for socioeconomic indicators (95% CI: 0.02, 0.25), and to 13.3% after adjusting for all potential mediators (95% CI: 0.01, 0.26). Based on the method of RC, socioeconomic indicators accounted for the largest fraction of mediated effects and BF accounted for most of main effect attenuation associated with reproductive factors; diabetes accounted for negligible effect. Conclusions: Our findings support the hypothesis that observed racial differences in TNBC diagnoses may be at least partially mediated by differences in socioeconomic position and reproductive patterns, namely breastfeeding.

Pathogenic Variants in CHEK2 Are Associated With an Adverse Prognosis in Symptomatic Early-Onset Breast Cancer.

Checkpoint kinase 2 (CHEK2) is frequently included in multigene panels. We describe the associated outcomes among carriers of CHEK2 pathogenic variants in young patients with symptomatic breast cancer. Participants (N = 2,344) in the Prospective Outcomes in Sporadic Versus Hereditary Breast Cancer study had a diagnosis of primary invasive breast cancer at age ≤ 40 years. Summary statistics were used to compare tumor characteristics among CHEK2+ carriers with those who were CHEK2-. Kaplan-Meier curves were used to demonstrate overall survival (OS) and distant disease-free survival. Overall, 53 of the 2,344 participants (2.3%) had a pathogenic CHEK2 variant. CHEK2+-associated tumors were significantly more likely to be grade 2, estrogen receptor and progesterone receptor-positive compared with CHEK2- tumors (grade 2, n = 28 of 52 [53.8%] v n = 803 of 2,229 [36.0%]; P = .029). CHEK2-associated tumors were significantly more likely to have nodal involvement (N1, n = 37 of 53 [69.8%] v 1,169 of 2,253 [51.9%]; P = .0098) and demonstrated a trend toward multifocality. A higher proportion of participants with CHEK2+ variants with invasive breast cancer were obese than were those with CHEK2- variant (28.3% v 18.8%; P = .039). Univariate and multivariable analyses revealed that OS and distant disease-free survival were significantly worse in CHEK2+ versus CHEK2- carriers (OS hazard ratio, 1.58; 95% CI, 1.01 to 2.48; P = .043). This work highlights the adverse prognosis associated with breast cancer in carriers of CHEK2 pathogenic variants. It also identifies a potential association among obesity, family history, and breast cancer risk in young CHEK2 gene carriers.

Dioxin exposure and breast cancer risk in a prospective cohort study

BackgroundDioxins are persistent organic pollutants generated from industrial combustion processes such as waste incineration. To date, results from epidemiologic studies of dioxin exposure and breast cancer risk have been mixed. ObjectivesTo prospectively examine the association between ambient dioxin exposure using a nationwide spatial database of industrial dioxin-emitting facilities and invasive breast cancer risk in the Nurses’ Health Study II (NHSII). MethodsNHSII includes female registered nurses in the US who have completed self-administered biennial questionnaires since 1989. Incident invasive breast cancer diagnoses were self-reported and confirmed by medical record review. Dioxin exposure was estimated based on residential proximity, duration of residence, and emissions from facilities located within 3, 5, and 10 km around geocoded residential addresses updated throughout follow-up. Cox regression models adjusted for breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsFrom 1989 to 2013, 3840 invasive breast cancer cases occurred among 112,397 participants. There was no association between residential proximity to any dioxin facilities (all facilities combined) and breast cancer risk overall. However, women who resided within 10 km of any municipal solid waste incinerator (MSWI) compared to none had increased breast cancer risk (adjusted HR = 1.15, 95% CI: 1.03, 1.28), with stronger associations noted for women who lived within 5 km (adjusted HR = 1.25, 95% CI: 1.04, 1.52). Positive associations were also observed for longer duration of residence and higher dioxin emissions from MSWIs within 3, 5, and 10 km. There were no clear differences in patterns of association for ER + vs. ER-breast cancer or by menopausal status. DiscussionResults from this study support positive associations between dioxin exposure from MSWIs and invasive breast cancer risk.

Association of Medicaid Expansion Under the Affordable Care Act With Insurance Status, Cancer Stage, and Timely Treatment Among Patients With Breast, Colon, and Lung Cancer

The effect of the Patient Protection and Affordable Care Act's Medicaid expansion on cancer care delivery and outcomes is unknown. Patients with cancer are a high-risk group for whom treatment delays are particularly detrimental. To examine the association between Medicaid expansion and changes in insurance status, stage at diagnosis, and timely treatment among patients with incident breast, colon, and non-small cell lung cancer. This quasi-experimental, difference-in-differences (DID) cross-sectional study included nonelderly adults (aged 40-64 years) with a new diagnosis of invasive breast, colon, or non-small cell lung cancer from January 1, 2011, to December 31, 2016, in the National Cancer Database, a hospital-based registry capturing more than 70% of incident cancer diagnoses in the United States. Data were analyzed from March 8 to August 15, 2019. Residence in a state that expanded Medicaid on January 1, 2014. The primary outcomes were insurance status, cancer stage, and timely treatment within 30 and 90 days of diagnosis. A total of 925 543 patients (78.6% women; mean [SD] age, 55.0 [6.5] years; 14.2% black; and 5.7% Hispanic) had a new diagnosis of invasive breast (58.9%), colon (14.6%), or non-small cell lung (26.5%) cancer; 48.3% resided in Medicaid expansion states and 51.7% resided in nonexpansion states. Compared with nonexpansion states, the percentage of uninsured patients decreased more in expansion states (adjusted DID, -0.7 [95% CI, -1.2 to -0.3] percentage points), and the percentage of early-stage cancer diagnoses rose more in expansion states (adjusted DID, 0.8 [95% CI, 0.3 to 1.2] percentage points). Among the 848 329 patients who underwent cancer-directed therapy within 365 days of diagnosis, the percentage treated within 30 days declined from 52.7% before to 48.0% after expansion in expansion states (difference, -4.7 [95% CI, -5.1 to -4.5] percentage points). In nonexpansion states, this percentage declined from 56.9% to 51.5% (difference, -5.4 [95% CI, -5.6 to -5.1] percentage points), yielding no statistically significant DID in timely treatment associated with Medicaid expansion (adjusted DID, 0.6 [95% CI, -0.2 to 1.4] percentage points). This study found that, among patients with incident breast, colon, and lung cancer, Medicaid expansion was associated with a decreased rate of uninsured patients and increased rate of early-stage cancer diagnosis; no evidence of improvement or decrement in the rate of timely treatment was found. Further research is warranted to understand Medicaid expansion's effect on the treatment patterns and health outcomes of patients with cancer.

Abstract P6-08-21: Prevalence of HER2 positivity in germline BRCA 1/2-associated breast cancers (gBRCA1/2-BC)

Abstract Purpose: To define the prevalence of HER2 positive breast cancer (HER2+ BC) in women with gBRCA1/2-BC and to determine whether there are significant differences in the prevalence of HER2 positivity in BRCA1 mutation carriers compared to BRCA2 mutation carriers. Background: It is estimated that 5-10% of patients with breast cancer have a BRCA1 or BRCA2 mutation. Two poly ADP ribose polymerase inhibitors (PARPi) have been approved for metastatic HER2-negative gBRCA1/2-BC, as trials excluded those with HER2+ BC and gBRCA1/2 mutations. Most often, breast tumors in BRCA1 carriers lack the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 receptor or gene amplification (HER2). BRCA2 tumors have similar rates of ER positivity as sporadic controls, but are less likely to be HER2+. The prevalence of HER2 positivity among BRCA1 and BRCA2 mutation carriers has been variably reported in the literature. The prevalence of HER2 positivity has generally been reported as lower among BRCA1 carriers than BRCA2 carriers. The prevalence of HER2 positivity in BRCA1 carriers and BRCA2 carriers has ranged from 0-10% and 0-13% respectively. The true prevalence of HER2+ breast cancer in gBRCA1/2-BC remains poorly defined. Methods: In this study, we assessed the prevalence of HER2 positivity among a cohort of 137 BRCA1 and BRCA2 mutation carriers who consented for participation in a single institution risk assessment program registry between 2009 and 2019. To be eligible for this study, participants had to have a documented diagnosis of invasive breast cancer and be a confirmed BRCA1 or BRCA2 mutation carrier. Participants with all stages of invasive breast cancer were included. Fisher’s exact tests and univariate logistic regression were used to analyze differences between BRCA1 and BRCA2 mutation carriers. Results: 69 BRCA1 mutation carriers and 68 BRCA2 carriers were included in the study. Only 38 BRCA1 mutation carriers and 41 BRCA2 mutation carriers had complete HER2 data and were included in this analysis for prevalence. 12.6 % (10/79) of the study participants had HER2+ invasive breast cancer; 3 of these participants were BRCA1 carriers and 7 were BRCA2 carriers. The prevalence of HER2 positivity in BRCA1 carriers was 7.9%. The prevalence of HER2 positivity among BRCA2 carriers was 17.0% (7/41). In this small sample, the prevalence of HER2 positivity in BRCA 2 mutation carriers was numerically higher than that in BRCA1 mutation carriers, although this difference was not statistically significant (p= 0.3145). Conclusion: In this analysis, the rates of HER2 positivity among BRCA1 mutation carriers are consistent with the range of rates previously reported (0-10%). However, the rates of HER2 positivity in BRCA2 mutation carriers (17.0%) are higher than those previously reported (0-13%). This study included participants who received breast cancer treatment at our institution where their HER2 status was verified with a pathology report, but also participants who received their breast cancer treatment at outside institutions. In the latter, HER2 status most often was obtained by verbal self-reporting. It is possible that this led to over-reporting of positive HER2 status in either BRCA1 or BRCA2 mutation carriers. Thus, estimates of HER2 positivity might be slightly overestimated. Despite some variation in HER2 positivity rates among BRCA1 and BRCA2 mutation carriers, this study demonstrates that HER2 positive breast cancers may not be as rare in gBRCA1/2-BC as previously reported in initial studies (0-3% in either BRCA1 or BRCA2 carriers). Given that BRCA1/2 mutation carriers could potentially derive therapeutic benefit from drugs, such as PARPi, it is important that future studies include gBRCA1/2-BC with HER2 positive breast cancer. Citation Format: Kristen Whitaker, Elias Obeid, Lori Goldstein, Mary Daly. Prevalence of HER2 positivity in germline BRCA 1/2-associated breast cancers (gBRCA1/2-BC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-21.

Abstract OT3-12-01: Effect of home-based high-intensity interval training and behavioral modification using information and communication technology on cardiorespiratory fitness and exercise habits among sedentary breast cancer survivors: The habit-B randomized controlled trial in progress

Abstract Maintaining high levels of physical activity not only helps to maintain and improve physical health and quality of life, but also plays a role in reducing adverse effects due to cancer treatments. Moreover, a greater degree of cardiorespiratory fitness is associated with reduced risk of all-cause mortality in breast cancer survivors. However, there are no home-based programs for improving cardiorespiratory fitness using body weight exercises for breast cancer survivors. This study assesses the efficacy of the newly developed habit-B program (12-weeks, high-intensity interval training exercise, exercise counseling + guidance, home-based exercise support using information and communication technology, and a wearable device (fitbit versa®)) on peak oxygen uptake (VO2peak; mL/kg/min) compared with treatment as usual. This is a parallel-group, single blind, randomized controlled trial. Subjects are sedentary women aged 20 to 59 years who have received breast surgery in the past 2 to 13 months after diagnosis of invasive breast cancer (Stage I-IIa) and have never received chemo-therapy except for hormone therapy. The primary outcome is difference of change in VO2peak between the groups after 12 weeks. The planned sample size is 60 patients to detect the increase of 2.0 ml/kg/min change in VO2peak with a one-sided significance level of 2.5% and 80% power. The effects of this program on exercise habits, physical activity, physical fitness, fatigue, health-related quality of life, and psychological distress are also be investigated. We have already enrolled 6 subjects as of 2019.7.2, and study will be planned to be finished by 2020 April. Citation Format: Katsunori Tsuji, Eisuke Ochi, Yoichi Shimizu, Aya Kuchiba, Tomomi Narisawa, Yuri Ishino, Ryo Okubo, Taro Ueno, Taichi Shimazu, Takayuki Kinoshita, Naomi Sakurai, Yutaka Matsuoka. Effect of home-based high-intensity interval training and behavioral modification using information and communication technology on cardiorespiratory fitness and exercise habits among sedentary breast cancer survivors: The habit-B randomized controlled trial in progress [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-12-01.

Abstract OT3-02-02: Radiomics of multi-parametric MRI associated with axillary lymph node metastasis and prognostic in patients with breast cancer: A multicenter RBC-001 study

Abstract Background: Axillary lymph node status has a guiding significance in the operative schemes. However, sensitivity and noninvasive for prediction of lymph node metastasis and survival of currently evidences is limited. This study aims to establish a deep learning algorithms of multi-parametric MRI radiomics for identifying lymph node metastasis and prognostic prediction, and investigate the relationship between the radiomics and tumor microenvironment in early stage breast cancer. Methods: RBC-01 is a multicentre, ambispective cohort study aims to assess multi-parametric MRI radiomics-based prediction model for identifying metastasis lymph nodes and prognostic prediction in early stage breast cancer. Patients are recruited from Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Sun Yat-sen University Cancer Center, Tungwah hospital of Sun Yat-sen University, and Shunde Hospital of Southern Medical University in China. Patients from Sun Yat-sen Memorial Hospital of Sun Yat-sen University are training cohort, and the independent validation cohort were built by patients from other centers. Eligible women could be aged from 18 to 75 years old with pathological diagnosis of early stage invasive breast cancer, without distant organ metastasis, and completed the breast MRI examination before therapy. PyRadiomics is used to extract patients’ breast cancer region, paratumor region, and axillary lymph nodes in multi-parametric MRI. To avoid MRI data heterogeneity bias, all MRI data are subjected to imaging normalization and resampled to the same resolution before feature extraction. The least absolute shrinkage and selection operator, random forest and supporting vector machine models are used to select the most useful radiomics characteristics from the training cohort, and then test by validation cohorts. The correlation between radiomics features and tumor microenvironment is also planned to investigate. Combined with independent risk factors, a radiomics nomogram was built with a multivariate logistic regression model. Decision curve analysis was performed with the combined training and validation set to estimate the clinical usefulness of the nomogram. The primary endpoint is disease-free survival. Secondary endpoints are lymph node metastasis prediction and overall survival. The trial is registered with ClinicalTrials.gov, number NCT04003558, and Chinese Clinical Trail Registry, number ChiCTR1900024020. Citation Format: Herui Yao, Yujie Tan, Yunfang Yu, Chuanmiao Xie, Qiugen Hu, Jie Ouyang, Chenchen Li, Kai Chen, Nian Lu, Xiaohong Li, Rong Zhang, Jiafan Ma, Ying Wang, Jianli Zhao. Radiomics of multi-parametric MRI associated with axillary lymph node metastasis and prognostic in patients with breast cancer: A multicenter RBC-001 study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-02-02.

Abstract P2-12-08: Triaging breast care center patients to supportive care services based on the Athena Breast Health Network online intake form and the patient-reported outcomes measurement information system (PROMIS)

Abstract Background: The Athena Breast Health Network is a multi-site effort aimed at integrating cutting-edge research and clinical care for breast cancer screening and treatment. At the University of California, San Francisco (UCSF) Breast Care Center (BCC), an Athena-based electronic Health Questionnaire System (eHQS) is distributed to all new patients. This questionnaire assesses self-reported personal and familial health history, comorbidities, and Patient-Reported Outcome Measurement and Information System (PROMIS) quality of life domains. Based on these responses, patients are proactively triaged to genetic counseling, psycho-oncology, onco-fertility, smoking cessation, peer support, nutritional counseling, behavioral sleep, and social work. These referrals are based on pre-defined thresholds, such as Ashkenazi Jewish Ancestry (referral to Genetic Counseling), or PROMIS Depression and Anxiety scores greater than or equal to 9 and 11, respectively. This analysis aims to assess the eHQS as a means to refer patients to supportive care services and assess if high-need patients (those with the highest symptom burden as assessed by quality of life PROMIS scores) are referred to services more frequently. Patients and Methods: Since Athena’s launch in 2013, over 6,000 patients have completed the online intake questionnaire at the UCSF BCC, 4,984 of whom have consented to research. 3,627 patients completed all relevant data to this study and were used in our analysis. A review of patient referrals was conducted to assess the number of referrals as a result of eHQS completion. PROMIS T-Scores in 8 domains (depression, anxiety, fatigue, sleep-related impairment and disturbance, cognitive function, applied cognition and physical function) were calculated with the Health Measures system and compared across patients stratified by age and cancer type and against the US general population. Results: When compared to the US population as a whole, PROMIS scores indicate that UCSF BCC patients have impaired quality of life in every assessed PROMIS domain except for depression. As age increases, PROMIS scores across multiple domains (depression, anxiety, sleep disturbance, cognitive function) increase, signifying lower symptom burden. Importantly, high symptom burden in the anxiety PROMIS domain was suggestive of lower quality of life scores in 6 out of the other 7 assessed PROMIS domains. 39% (1408 patients) of all analyzed BCC patients received at least one referral to a supportive care service. 721 of 1450 (50%) patients with an Invasive Breast Cancer (IBC) diagnosis and 246 of 571 (43%) patients with a DCIS diagnosis triggered at least one referral. 31% of all patients received a referral to genetic counseling, 16.3% to psycho-oncology, 11% to behavioral sleep, 8% to nutritional counseling, 7.6% to social work, 2.4% to smoking cessation, and 1.6% to onco-fertility. When compared to patients with DCIS or without a cancer diagnosis, patients with IBC are most likely to receive a referral to genetic counseling and psychosocial services. Referrals to supportive care services are less frequent as age increases. Conclusion: The Athena online intake form at the UCSF BCC effectively triages patients with high levels of anxiety (PROMIS &amp;gt; 8) and depression (PROMIS &amp;gt;10) to supportive care services. Preliminary results regarding the correlation between anxiety and overall poor quality of life suggest that referrals to psycho-oncology may be most efficacious in decreasing symptom burden. Using these analyses, we aim to refine our use of the eHQS to tailor the most relevant and effective referrals to the highest-need patients. Citation Format: Madeline Matthys, André Dempsey, Amrita Basu, Emily Wong, Nickolas Dreher, Irene Acerbi, Suzanne Ackerson, Laura Esserman, Athena Breast Health Network Investigators and Advocate Partners, Michelle Melisko, Laura van 't Veer. Triaging breast care center patients to supportive care services based on the Athena Breast Health Network online intake form and the patient-reported outcomes measurement information system (PROMIS) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-08.

Abstract OT3-09-02: A large-scale multicenter phase II study evaluating the protective effect of a tissue selective estrogen complex (TSEC) in women with newly diagnosed ductal carcinoma in situ (DCIS)

Abstract Background: TSECs were developed to treat menopausal symptoms after progesterone containing hormone replacement therapy was found to significantly increase the risk of invasive breast cancer (IBC). The first of this class of agents combines conjugated estrogens (CE), a collection of steroidal estrogens that collectively have both estrogen receptor (ERα) agonistic and antagonistic activity, and bazedoxifene (BZA), a third generation selective estrogen receptor modulator that does not stimulate the mammary gland or endometrium. The FDA approved CE/BZA for treatment of menopausal symptoms and osteoporosis after five randomized placebo controlled trials demonstrated the safety, efficacy and tolerability of CE/BZA in healthy postmenopausal women. Since then, a substantial body of evidence has emerged suggesting that CE/BZA may have additional therapeutic benefits in women. It is widely accepted that progression to IBC occurs through both epithelial and stromal mechanisms. Recent in vitro and in vivo data provide support that CE/BZA prevents progression to IBC through its effects on both epithelium and stroma. In epithelial cells, CE/BZA antagonizes estrogen-induced proliferation and expression of markers of ERα activity and also degrades ERα protein. In the stroma, CE/BZA increases expression of the scavenger receptor CD36 and consequently, reduces expression of extracellular matrix proteins (ECM) and pro-inflammatory cytokines that have been shown to contribute to the development of pro-tumorigenic microenvironment. Based on these preliminary data, we hypothesized that CE/BZA will have an anti-tumorigenic effect in the breast. Our ultimate objective is to provide postmenopausal women diagnosed with DCIS a novel and safe therapeutic option to prevent progression to IBC. Specific Aims: Aim 1: To assess epithelial contributions by determining if a short intervention of CE/BZA will have antagonistic activity in breast epithelium of postmenopausal women with ER + DCIS. Aim 2: To assess stromal contributions by determining if a short intervention of CE/BZA will alter expression of stromal markers of progression in breast tissue of postmenopausal women with ER + DCIS. Aim 3: To determine if a short intervention of CE/BZA is well tolerated and safe in postmenopausal women with ER + DCIS. Trial Design: We are currently conducting a multicenter randomized placebo controlled window of opportunity trial with CE/BZA in post-menopausal women with DCIS, a non-obligate precursor to IBC. The duration of intervention is 28 ± 7 days prior to surgical resection to enable comparison of CE/BZA on the breast using the diagnostic core biopsy and surgical sample. To date 33/166 women have enrolled in the trial. Eligibility Criteria: Post-menopausal women between 18-79 years of age diagnosed with ER (+) DCIS (&amp;gt;1cm on imaging) undergoing surgery are eligible. Women must not be on current hormonal therapy, have a current or past diagnosis of IBC, other ER sensitive tumors or have recurrent DCIS. Statistics: Results will be compared between diagnostic biopsy and surgical resection specimens and contrasted between the CE/BZA intervention group and placebo group using Fisher’s exact test for categorical variables and independent sample t-tests, or rank sum tests for continuous data. For RNAseq data, transcripts that have &amp;gt;1.5-fold expression change (at 20% FDR) between control and experimental samples will be used for downstream analysis, such as to plot heat maps, pathway and gene ontology analysis. Summary: At the conclusion of this study, we will have the first direct evidence of the potential benefits of CE/BZA therapy on DCIS lesions in the human breast, along with an initial assessment of symptoms and pharmacogenomics that will inform the design of future studies. Citation Format: Swati A. Kulkarni, Geoffrey Greene, Thea Tlsty, Luis Blanco, Judy Garber, Al George, Fred Rademaker, Seema A Khan, Nora Hansen, Kevin Bethke, Rebecca Aft, Julia Tchou. A large-scale multicenter phase II study evaluating the protective effect of a tissue selective estrogen complex (TSEC) in women with newly diagnosed ductal carcinoma in situ (DCIS) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-09-02.

Abstract P5-03-02: Cancer risks associated with pathogenic variants in the ataxia telangiectasia mutated (ATM) gene

Abstract Background: Germ-line pathogenic variants (PV) in ATM are often considered low-to-moderate penetrance risk factors for breast cancer (BC), conferring a two-fold increased BC risk among heterozygous PV carriers. Several other cancers have been associated with ATM PV such as melanoma, thyroid cancer, prostate cancer, pancreatic cancer, gastro-esophageal cancers, colorectal cancer, and ovarian cancer. Estimating the diverse cancer risks attributable to ATM PVs may present challenges due to the low-to-moderate penetrance of ATM PV for some cancers, requiring large samples of tested patients to estimate risk with precision, and the potential for substantial variability in penetrance of particular ATM PV such as the c.7271T&amp;gt;G PV reported by previous studies. We investigated cancer risks with ATM PV in a large clinical testing dataset. Methods: Results of 614,344 individuals undergoing clinical analysis of ATM as part of a multi-gene hereditary cancer gene panel between 09/2013 and 06/2019 were reviewed. Patient age, sex, ancestry, personal and family cancer history were extracted from a test requisition form. PV included variants classified as suspected deleterious or deleterious (hereafter referred to as pathogenic). Risk estimates are estimated using multivariate logistic regression and are reported as odds ratios (OR) with 95% confidence intervals (CI). Results: PV in ATM were identified in 4,372/614,344 (0.7%) individuals: 4,155/592,881 (0.7%) females and 217/21,463 (1.0%) males. 1,603/4,155 (38.6%) of female ATM PV carriers had invasive BC or DCIS. Overall, ATM PV were associated with a 2-fold increased risk for invasive BC [OR 2.01, 95% CI 1.86-2.16] and DCIS [OR 1.82, 95% CI 1.62-2.04]. A prevalent missense PV c.7271T&amp;gt;G, predicted to lead to inactivation of ATM kinase activity and that has previously been described as high penetrance (Goldgar DE et al, Breast Cancer Res 2011), represented 5.1% (n=223) of all ATM PV, and was associated with a particularly high risk of invasive BC [OR 3.80, 95% CI 2.78-5.19] but no increased risk of DCIS. Significantly elevated risks of pancreatic cancer, gastric cancer, prostate cancer, ovarian cancer, colon cancer and melanoma were also observed among ATM PV carriers (see Table 1). Median age of invasive BC diagnosis was similar in carriers and non-carriers of ATM PV. Conclusions: ATM PV are associated with 1.5-fold to &amp;gt;4-fold increased cancer risks across a variety of disease sites, including invasive BC (2-fold increased risk). Cancer risks also demonstrate mutation-specific variability, as suggested by the 4-fold increased risk of invasive BC in carriers of the ATM PV c.7271T&amp;gt;G. Larger and/or pooled studies are critical to further refine the breadth and magnitude of ATM-associated cancer risk and to improve clinical management guidelines for ATM PV carriers. Table 1: Odds ratios for cancer risks in c.7271T&amp;gt;G and all other ATM PV carriersAll ATM PVs (excluding c.7271T&amp;gt;G)c.7271T&amp;gt;GCancer OR (95% CI)p-valueOR (95% CI)p-valueBreast, Invasive1.94 (1.79, 2.09)&amp;lt;0.00013.80 (2.78, 5.19)&amp;lt;0.0001Breast, DCIS1.83 (1.62, 2.05)&amp;lt;0.00011.63 (0.97, 2.74)0.0624Breast, Lobular invasive0.94 (0.73, 1.21)0.62330.84 (0.27, 2.64)0.7671Breast, Male1.44 (0.86, 2.42)0.16884.24 (0.46, 39.15)0.2032Ovarian1.55 (1.32, 1.82)&amp;lt;0.00011.99 (0.99, 4.02)0.0532Colorectal1.51 (1.25, 1.82)&amp;lt;0.00011.67 (0.67, 4.18)0.2693Endometrial1.10 (0.88, 1.39)0.39610.89 (0.28, 2.81)0.8401Melanoma1.44 (1.14, 1.81)0.00182.16 (1.00, 4.64)0.0491Prostate2.61 (1.93, 3.52)&amp;lt;0.00014.37 (0.70, 27.26)0.1146Pancreatic4.18 (3.17, 5.49)&amp;lt;0.00012.50 (0.34, 18.21)0.3660Gastric3.09 (1.73, 5.53)0.0001—— Citation Format: Michael J Hall, Katie Larson, Ryan Bernhisel, Elisha Hughes, Eric Rosenthal, Nanda Singh, Johnathan M Lancaster, Allison W Kurian. Cancer risks associated with pathogenic variants in the ataxia telangiectasia mutated (ATM) gene [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-03-02.

Photodynamic Therapy in Primary Breast Cancer.

Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment. The photosensitizer verteporfin (0.4 mg/kg) was administered intravenously followed by exposure to escalating light doses (20, 30, 40, 50 J; 3 patients per dose) delivered via a laser fiber positioned interstitially under ultrasound guidance. MRI (magnetic resonance imaging) scans were performed prior to and 4 days after PDT. Histological examination of the excised tissue was performed. PDT was well tolerated, with no adverse events. PDT effects were detected by MRI in 7 patients and histology in 8 patients, increasing in extent with the delivered light dose, with good correlation between the 2 modalities. Histologically, there were distinctive features of PDT necrosis, in contrast to spontaneous necrosis. Apoptosis was detected in adjacent normal tissue. Median follow-up of 50 months revealed no adverse effects and outcomes no worse than a comparable control population. This study confirms a potential role for PDT in the management of early breast cancer.

Usefulness of cytological approach for invasive breast cancer diagnosis compared with alternative intrinsic subtype classification approach

Usefulness of cytological approach for invasive breast cancer diagnosis compared with alternative intrinsic subtype classification approach

The Association Between Ultrasound Features and Biological Properties of Invasive Breast Carcinoma Is Modified by Age, Tumor Size, and the Preoperative Axilla Status.

To investigate the value of ultrasound (US) feature-based models in predicting the proliferation and invasiveness of invasive breast cancer (IBC) and to compare the performance of models based solely on US features with models that combined US features, patient age, tumor size, and axilla status from US. With ethical approval, 746 patients with a pathologic diagnosis of IBC were reviewed for preoperative clinical, US, and postoperative pathologic data. The proliferation and invasiveness properties of the IBC included the histologic grade and Ki-67 status and lymphovascular invasion (LVI) and axillary lymph node metastasis (ALNM), respectively. Logistic regression analyses were used to identify independent risk factors for tumor proliferation and invasiveness. Posterior echo enhancement, calcification, a tumor size larger than 2 cm, and suspicion of ALNM from axillary US were independent risk factors for a high histologic grade and high Ki-67 expression of IBC (P < .05). A posterior echo shadow, patient age younger than 45 years, and suspicious findings on axillary US imaging were independent variables for predicting the presence of LVI and ALNM in IBC (P < .05). Calcification was the independent factor for predicting LVI (P = .013). The predictive performance of the combined models was improved compared with the US feature-based models, with a higher accuracy rate and negative predictive value. The area under curve of the combined models was also significantly higher than that of the single models (P < .05). Compared with the US feature-based models, the combined models yielded better predictive performance. This may provide a more robust model to predict the tumor biological properties of IBC before surgery.