Primary Invasive Breast Cancer Research Articles

Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy

BackgroundTriple negative breast cancer encompasses several biological entities with different outcomes and is a priority to identify which patients require more treatment to reduce the risk of recurrence and which patients need less treatment. Patients and methodsAmong the 210 women with first primary invasive apocrine non metastatic breast cancer operated on between January 1998 and December 2016 at the European Institute Oncology, Milan, we identified 24 patients with a pT1-pT2, node-negative, triple negative subtype and Ki-67 ≤ 20% who did not receive adjuvant chemotherapy (CT). We compared the outcome of this cohort with a similar group of 24 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features and also with a similar group of 12 patients with apocrine tumors who received adjuvant chemotherapy. ResultsThe median age was 64 and 61 years in the apocrine (w/o CT) and ductal group, respectively. The median value of Ki-67 expression was 12% in the apocrine group (w/o CT) and 16% in the ductal group (p < 0.001). After a median follow-up of 7.5 years, no patients in the apocrine group (w/o CT) experienced a breast cancer related event compared with 4 events in the ductal carcinoma group (Gray test p-value = 0.11). ConclusionsThe outcome of selected apocrine triple negative breast cancer patients who did not received adjuvant chemotherapy is excellent and supports a treatment de-escalation. Multicenter projects focusing on the possibility of avoiding adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted.

Impact of Delayed Neoadjuvant Systemic Chemotherapy on Overall Survival Among Patients with Breast Cancer.

Delays in the initiation of therapy among patients with early stage breast cancer (BC) can negatively affect outcomes. Patients treated with neoadjuvant systemic chemotherapy (NSC) usually display tumors with high-risk features. Considering these high-risk characteristics and the evidence supporting adverse outcomes associated with delays in adjuvant chemotherapy initiation, we sought to determine whether a delay in NSC initiation is associated with overall survival (OS). We identified patients diagnosed between January 1995 and December 2015 with invasive primary BC (stage I-III) who received NSC at MD Anderson Cancer Center. Patients were categorized according to their time from BC diagnosis to NSC (in days) into three subgroups: 0-30, 31-60, and ≥61 days. Primary endpoint was OS. Descriptive statistics and Cox's proportional hazard models were used. A total of 5,137 patients were included. Median follow-up was 6.5 years. The 5-year OS estimates according to time to NSC were 87%, 85%, and 83% in patients who received NSC within 0-30, 31-60, and ≥61 days after diagnosis, respectively (p = .006). In multivariable analysis, compared with time to NSC of 0-30 days, delayed NSC ≥61 days was associated with an increased risk of death (31-60 days: hazard ratio [HR] = 1.05 [95% confidence interval (CI) 0.92-1.19]; ≥61 days, HR = 1.28 [95% CI 1.06-1.54]). In stratified analyses, the association between delay in NSC initiation and increased risk of death was statistically significant for patients with stage I and II BC (31-60 days: HR = 1.22 [95% CI 1.02-1.47]; ≥61 days, HR = 1.41 [95% CI 1.07-1.86]) and among patients with HER2-positive tumors ( ≥61 days, HR = 1.86 [95% CI 1.21-2.86]). A delay in NSC initiation of more than 61 days after BC diagnosis was associated with an increased risk of death. Early initiation of NSC should be a priority; multidisciplinary teams must focus on coordination of care and patient-centered, timely treatment planning and delivery. The results of this study showed that a delay in neoadjuvant systemic chemotherapy initiation of more than 61 days after breast cancer diagnosis is associated with an increased risk of death; therefore, efforts must focus on early initiation of therapy, which should be a priority. Multidisciplinary teams must enhance coordination of care and patient-centered, timely treatment planning and delivery.

Peritumor to tumor apparent diffusion coefficient ratio is associated with biologically more aggressive breast cancer features and correlates with the prognostication tools.

PurposeThe apparent diffusion coefficient (ADC) is increasingly used to characterize breast cancer. The peritumor/tumor ADC ratio is suggested to be a reliable and generally applicable index. However, its overall prognostication value remains unclear. We aimed to evaluate the associations between the peritumor/tumor ADC ratio and histopathological biomarkers and published prognostic tools in patients with invasive breast cancer.Materials and methodsThis prospective study included 88 lesions (five bilateral) in 83 patients with primary invasive breast cancer who underwent preoperative 3.0-T magnetic resonance imaging. The lowest intratumoral mean ADC value on the slice with the largest tumor cross-sectional area was designated the tumor ADC, and the highest mean ADC value on the peritumoral breast parenchymal tissue adjacent to the tumor border was designated the peritumor ADC. The peritumor/tumor ADC ratio was then calculated. The tumor and peritumor ADC values and peritumor/tumor ADC ratios were compared with histopathological parameters using an unpaired t test, and their correlations with published prognostic tools were evaluated with Pearson’s correlation coefficient.ResultsThe peritumor/tumor ADC ratio was significantly associated with tumor size (p<0.001), histological grade (p = 0.005), Ki-67 index (p = 0.006), axillary-lymph-node metastasis (p = 0.001), and lymphovascular invasion (p = 0.006), but was not associated with estrogen receptor status (p = 0.931), progesterone receptor status (p = 0.160), or human epidermal growth factor receptor 2 status (p = 0.259). The peritumor/tumor ADC ratio showed moderate positive correlations with the Nottingham Prognostic Index (r = 0.498, p<0.001) and mortality predicted using PREDICT (r = 0.436, p<0.001).ConclusionThe peritumor/tumor ADC ratio was correlated with histopathological biomarkers in patients with invasive breast cancer, showed significant correlations with published prognostic indexes, and may provide an easily applicable imaging index for the preoperative prognostic evaluation of breast cancer.

Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer

BackgroundObesity induces molecular changes that may favor tumor progression and metastatic spread, leading to impaired survival outcomes in breast cancer. Adenylate cyclase-associated protein 1 (CAP1), an actin regulatory protein and functional receptor for the obesity-associated adipokine resistin, has been implicated with inferior cancer prognosis. Here, the objective was to investigate the interplay between body composition and CAP1 tumor expression regarding breast cancer outcome through long-term survival analyses.MethodsAmong 718 women with primary invasive breast cancer within the large population-based prospective Malmö Diet and Cancer Study, tumor-specific CAP1 levels were assessed following thorough antibody validation and immunohistochemical staining of tumor tissue microarrays. Antibody specificity and functional application validity were determined by CAP1 gene silencing, qRT-PCR, Western immunoblotting, and cell microarray immunostaining. Kaplan-Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of breast cancer-specific survival (BCSS) and overall survival (OS) according to body composition and CAP1 expression.ResultsStudy participants were followed for up to 25 years (median 10.9 years), during which 239 deaths were observed. Patients with low CAP1 tumor expression were older at diagnosis, displayed anthropometric measurements indicating a higher adiposity status (wider waist and hip, higher body mass index and body fat percentage), and were more prone to have unfavorable tumor characteristics (higher histological grade, higher Ki67, and estrogen receptor (ER) negativity). Overall, patients with CAP1-low tumors had impaired BCSS (adjusted hazard ratio: HRadj = 0.52, 95% CI 0.31–0.88) and OS (HRadj = 0.64, 95% CI 0.44–0.92) compared with patients having high CAP1 tumor expression. Further, analyses stratified according to different anthropometric measures or ER status showed that the CAP1-associated survival outcomes were most pronounced among patients with low adiposity status or ER-positive disease.ConclusionsLow CAP1 tumor expression was associated with higher body fatness and worse survival outcomes in breast cancer patients with effect modification by adiposity and ER status. CAP1 could be a novel marker for poorer survival outcome in leaner or ER-positive breast cancer patients, highlighting the need for considering body constitution in clinical decision making.

How Useful Are Tumor Markers in Detecting Metastases with FDG-PET/CT during Breast Cancer Surveillance?

Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5–43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0–108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4–10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9–30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and <0.001 for Q4), while no relevant heterogeneity between ORs emerged for CEA. Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.

Abstract D095: Plasma levels of polychlorinated biphenyls (PCBs) and breast cancer mortality: The Carolina Breast Cancer Study

Abstract Background: Polychlorinated biphenyls (PCBs) are a group of 209 synthetic organic chemicals, several of which are known carcinogens or endocrine disruptors. PCBs are hypothesized to influence the risk of developing breast cancer; however, whether PCBs influence the risk of mortality following breast cancer is poorly understood. We examined plasma levels of 17 PCB congeners in association with mortality among women who participated in the population-based Carolina Breast Cancer Study (CBCS). Methods: Participants included 456 white and 292 black women who were diagnosed with primary invasive breast cancer from 1993-1996, and who had PCB and lipid measurements from blood samples obtained on average 4.1 months after diagnosis. Using the National Death Index, we identified 392 deaths including 210 from breast cancer, over a median follow-up of 20.6 years. We used Cox regression to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and breast cancer-specific 5-year mortality, and 20-year mortality conditional on 5-year survival in relation to tertiles and continuous ln-transformed lipid-adjusted PCB levels. We also examined effect measure modification by race. Results: The highest (vs. lowest) tertile of PCB118 was associated with a 5-year breast cancer-specific mortality HR of 1.86 (95% CI=1.07-3.23). One-ln unit increases in PCB74, PCB99, PCB118, and total PCBs were associated with 5-year breast cancer-specific mortality HRs ranging from 1.33 (95% CI=1.02-1.74) for PCB74 to 1.40 (95% CI=1.02-1.92) for PCB118. By race, a one-ln unit increase in PCB74 was associated with a HR of 1.47 (95% CI=1.01-2.14) among black women and with a HR of 1.19 (95% CI=0.79-1.77) among white women (P-Interaction=0.05). Continuous PCB levels were associated with 20-year conditional all-cause mortality HRs ranging from 1.20 (95% CI=1.03-1.41) for a one-ln unit increase in PCB182+PCB187 to 1.37 (95% CI=1.12-1.68) for a one-ln unit increase in PCB118. PCBs were not associated with 5-year all-cause mortality or with 20-year conditional breast cancer-specific mortality. Conclusion: PCBs may increase the risk of short-term breast cancer-specific mortality as well as long-term all-cause mortality among women with breast cancer. Citation Format: Humberto Parada, Xuezheng Sun, Chiu-Kit Tse, Lawrence S. Engel, Andrew F. Olshan, Melissa A. Troester. Plasma levels of polychlorinated biphenyls (PCBs) and breast cancer mortality: The Carolina Breast Cancer Study [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 D095.

Abstract B128: The impact of race/ethnicity and insurance status on age-related differences in breast cancer survival

Abstract Background: A wealth of published data exists on factors that impact breast cancer survival, including race/ethnicity, health insurance, and other sociodemographic factors; however, there is limited research on whether associations differ by age at diagnosis. The purpose of this study was to assess risk of dying from breast cancer in older (≥ 60 years) versus younger women (&amp;lt; 60 years) according to race/ethnicity and insurance status. Methods: From the California Cancer Registry, we identified women with a first, primary invasive breast cancer, who were ages 18 and older, diagnosed between 2005 and 2015. Multivariable Cox proportional hazards regression was used to generate hazard rate ratios (HR) and 95% confidence intervals (CI) for risk of breast cancer-specific mortality for older vs younger patients, overall and by race/ethnicity and insurance status. HRs were also calculated for race/ethnicity and insurance status, stratified by age group. Results: Of the total population (n=192,932), 94,076 (48.7%) were diagnosed under the age 60 and 98,856 (51.2%) were aged 60 and older at diagnosis. Risk of dying from breast cancer was higher in older than younger patients (HR=1.35; 95% CI, 1.29-1.40) after multivariable adjustment, which varied in magnitude by race/ethnicity (P&amp;lt;0.0001). Larger mortality differences comparing older vs. younger patients were observed for Non-Hispanic White (NHW) (HR=1.43; 95% CI, 1.36-1.51) and Hispanic women (HR=1.37; 95% CI, 1.26-1.50), and smaller but significant differences were seen in Black (HR=1.17; 95% CI, 1.04-1.31) and Asian/Pacific Islander women (HR=1.15; 95% CI, 1.02-1.31). HRs comparing older to younger patients varied by insurance status (P&amp;lt;0.0001) with largest mortality differences observed for privately insured women (HR=1.51; 95% CI, 1.43-1.59), followed by Medicaid/military/other public insurance (HR=1.18; 95% CI, 1.10-1.26). Black vs. NHW women had a higher risk of dying regardless of age group, with higher HRs in younger (HR=1.36; 95% CI, 1.25-1.48) than in older (HR=1.11; 95% CI, 1.01-1.22) patients. In younger women, a higher risk of breast cancer mortality was observed in those with any Medicaid/military/other public insurance (HR=1.49; 95% CI, 1.41-1.58) and in those with no insurance (HR=1.96; 95% CI, 1.65-2.32), compared to patients with private health insurance. Among older women, higher risk of mortality was seen for those with any Medicaid/military/other public insurance (HR=1.13; 95% CI, 1.06-1.21) and those with no insurance (HR=1.57; 95% CI, 1.22-2.03), compared to privately-insured patients. Conclusion: Our results provide evidence for the continued disparity in survival in Black vs White women with breast cancer, which is magnified in younger women. Moreover, lack of health insurance continues to play a role in breast cancer survival, with uninsured women having the highest risk for breast cancer death, regardless of age. Citation Format: Yazmin San Miguel, Scarlett L Gomez, James D Murphy, Richard B Schwab, Corinne McDaniels-Davidson, Alison J Canchola, Alfredo A Molinolo, Jesse N Nodora, Maria E Martinez. The impact of race/ethnicity and insurance status on age-related differences in breast cancer survival [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 B128.

Abstract C026: Energy-related risk factors and breast cancer subtypes in African American women

Abstract Purpose: To investigate the association between energy-related risk factors and breast cancer subtypes in African American women. We hypothesized that African American women with triple negative breast cancer (TNBC), based on being negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, would be less likely to have energy-related risk factors than women with other breast cancer subtypes (1) estrogen receptor positive (ER+), and (2) estrogen receptor negative (ER-). Methods: African American women ages 25-75 years diagnosed with primary invasive breast cancer in 2009-2014 in Tennessee, South Carolina, and Georgia were eligible for the study. A total of 697 women (premenopausal n=156; postmenopausal n=541) provided information on energy-related risk factors in a telephone interview and consented to review of tumor tissue. Energy-related risk factors were defined as: no physical activity (54%), high meat intake (upper quartile), obese class II/III (32%), and high weight gain since age 18 (upper quartile). Breast cancer subtype was obtained from pathology reports that accompanied tumor tissue. Results: Although not significantly different, premenopausal (odds ratio (OR) 1.34) and postmenopausal (OR 1.26) women with TNBC were more likely to have high meat intake relative to women with ER+ disease. Premenopausal, but not postmenopausal, women with TNBC were also more likely to have high weight gain since age 18. Women with ER- disease were more likely to have high meat intake, be obese class II/III, and have high weight gain than women with ER+ disease which was more pronounced among premenopausal than postmenopausal women. Conclusions: Histologic subtyping is currently being performed on collected tissue to confirm the reported breast cancer subtypes in the pathology reports. The large number of African American women participating in our study can further our understanding of the relationships between energy-related risk factors and breast cancer subtypes in this population. Citation Format: Mieke Fortune, Steffie-Ann Dujon, Mary K Fadden, Loren Lipworth, Maureen Sanderson. Energy-related risk factors and breast cancer subtypes in African American women [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 C026.

ARID1A/BAF250a is significantly overexpressed in primary invasive breast cancer.

BackgroundARID1A (also known as BAF250a, p270 or SMARCF1) is a major component of the mammalian SWI/SNF family that is involved in the regulation of the chromatin structure. ARID1A gene mutations have been associated with many types of malignancies, including breast cancer. This study aimed to explore the expression of BAF250a protein in breast cancer and its association with the clinical and pathological characteristics and prognosis of breast cancer.MethodsWe assessed the BAF250a expression in 119 invasive breast carcinomas samples and 92 healthy control and correlated this expression pattern with various clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor (ER) status, progesterone receptor (PR) status. Immunohistochemical analysis of BAF250a, ER, PR, was carried out, and evaluation of stainings was performed.ResultsThe mean value of BAF250a expression in the experimental group was higher than in healthy control (P=0.001). The expression is unrelated to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (ER, PR).ConclusionsThese data suggest that BAF250a is overexpressed in breast cancers. BAF250a may play context-dependent tumor-promoting and tumor-suppressive roles in cancer.

Abstract C064: Hormone-related risk factors and breast cancer subtype in African American women

Abstract Purpose: To investigate the association between hormone-related risk factors and breast cancer subtype in African American women. We hypothesized that African American women with triple-negative breast cancer (TNBC) would have a lower prevalence of hormone-related risk factors than women with other breast cancer subtypes (1) hormone receptor [HR +/-] and human epidermal growth factor receptor 2 [HER2-] or (2) HR +/- and HER2+. Methods: African American women ages 25-75 years diagnosed with primary invasive breast cancer in 2009-2013 in Tennessee, South Carolina, and Georgia were eligible for the study. A total of 629 women (premenopausal n=175; postmenopausal n=454) provided information on hormone-related risk factors in a telephone interview and consented to review of tumor tissue; breast cancer subtype was obtained from pathology reports. Results: Although not significantly different, pre- and postmenopausal women with TNBC were more likely to have early age at menarche than women with other subtypes. Obesity was higher among pre- and postmenopausal women with HR+/- HER2+ disease and intermediate among women with TNBC relative to women with HR+/- HER2- disease. Oral contraceptive use was less likely among women with TNBC, significantly so for postmenopausal women (odds ratio=0.70, 95% confidence interval=0.53-0.91) than women with other subtypes. Conclusions: Histologic subtyping is currently being performed on collected tissue to confirm the reported breast cancer subtypes in the pathology reports. The large number of African American women participating in our study can further our understanding of hormone-related risk factors and their relationship with breast cancer subtypes in this population. Citation Format: Jennifer Davis, Cecilia Jimenez, Chrystina Clinton, Mary Kay Fadden, Loren Lipworth, Maureen Sanderson. Hormone-related risk factors and breast cancer subtype in African American women [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 C064.

Abstract B106: Racial/ethnic disparities in risk of breast cancer mortality by molecular subtype and stage at diagnosis

Abstract Background: Previous research has found significant survival disparities between African-American and white women among select stages and subtypes of breast cancer, however other racial/ethnic groups have been less well-studied. This study expands on previous research, examining differences in breast cancer-specific mortality across multiple racial and ethnic groups. Methods: Women diagnosed with a first primary invasive breast cancer between 2010 and 2016 who were between 20 and 85 years of age at diagnosis were identified in the SEER database. Subtypes were defined by joint hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Cox proportional hazards models for each stage and subtype were fit, with non-Hispanic white women as the reference group. Effect modification by age at diagnosis (&amp;lt;50, ≥50) was found, so models additionally including an interaction term for binary age at diagnosis, with a linear age term for the main effect, were fit. Four different models were fit to adjust for different sets of confounders, adding in additional covariates with each model. Results: After multivariable adjustment, younger African American women had greater risks of breast cancer-specific death for all stages of HR+/HER2-, stages II-IV of HR+/HER2+, stage III TN breast cancer, and stage I and IV of HR-/HER2+ breast cancer. Asian/Pacific Islander women generally had a lower hazard of breast cancer-specific death. Older Hispanic white women had a lower hazard of breast cancer-specific death for stages I-III HR+/HER2- and stage II TN breast cancer. Generally, insurance status explained in part the observed disparities; however, many of the observed disparities were still statistically significant after adjustment for tumor grade, treatment characteristics, and insurance status. Conclusions: These findings demonstrate that different racial/ethnic groups experience different risks of breast cancer-specific mortality by stage and subtype. By considering different models adjusting for different factors we were able to observe the extent to which these factors account for initially observed disparities. Insurance status, as a proxy for other health care and socioeconomic factors, may drive some of the observed differences in mortality; however, other factors, such as hormonal treatment or obesity, may be responsible for the remaining disparities. Efforts to address survival disparities should place additional focus on young African American women, as they experience meaningful disparities in breast cancer-specific mortality, particularly for HR+ subtypes. Citation Format: Nicole C Lorona, Kathleen E Malone, Christopher I Li. Racial/ethnic disparities in risk of breast cancer mortality by molecular subtype and stage at diagnosis [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 B106.

Abstract C108: Race and risk of subsequent aggressive breast cancer in women with ductal carcinoma in situ

Abstract Background: Ductal carcinoma in situ (DCIS) is a heterogeneous group of preinvasive neoplastic lesions in the breast. Black women with DCIS are more likely than White counterparts to subsequently develop invasive cancer in either breast. We examined the association between race and the risk of developing aggressive invasive breast cancer, characterized with hormone receptor (HR) negativity (both estrogen receptor and progesterone receptor negative) or intermediate-to-high risk Oncotype scores (≥18) in HR-positive subtypes, in women with DCIS. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) data, we identified 133,705 women with DCIS diagnosed between 1990 and 2015, and 12.9% were black. Cox proportional hazards regression was used to estimate relative risks (RRs) of subtypes of subsequent invasive breast cancer in either breast and metastatic breast cancer. Results: During a median follow-up of 90 months, 6889 women developed invasive breast cancer and 6384 had HR status available. The risks of HR-defined (Pheterogeneity=0.0004) and Oncotype score-defined (Pheterogeneity=0.046) invasive breast cancer subtypes after initial DCIS significantly varied by race. The RR of HR-negative invasive breast cancer was 1.86 (95% CI 1.57-2.20) and the RR of subsequent invasive subtypes with intermediate-to-high Oncotype scores was 1.29 (95% CI 1.00-1.67) in Black women with DCIS, which was independent of age, pathologic features and treatment. In women who had data on HR status in both primary DCIS and subsequent invasive breast cancer, the HR discordant rate was higher in Black patients than in White patients (21.2% versus 18.9%, P=0.003), which was largely driven by HR loss (15.4% versus 9.5%). Black race was more strongly associated with HR loss (RR=1.92, 95% CI 1.41-2.61, Pheterogeneity=0.03) than HR concordance (RR=1.24, 95% CI 1.09-1.41) and HR gain (RR=1.04, 95% CI 0.67-1.62). Conclusions: Black women with DCIS had higher risks of developing aggressive invasive breast cancer compared with White counterparts, which may contribute to their worse survival. Future studies examining biologic differences in the progression of DCIS for Black patients are warranted. Citation Format: Ying Liu, Graham Colditz. Race and risk of subsequent aggressive breast cancer in women with ductal carcinoma in situ [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 C108.

Matched Case-Control Study of Beans Intakes and Breast Cancer Risk in Urbanized Nigerian Women

Abstract Objectives To examine the association between dietary intake of beans and breast cancer in Nigerian women. Methods Overall 630 newly diagnosed patients with primary invasive breast cancer were age-matched (±5 years) with 630 controls from the Nigerian Integrative Epidemiology of Breast Cancer (NIBBLE) Study from 01/2014 to 07/2016. Dietary intakes were collected using a food frequency questionnaire (FFQ) to derive daily intake of beans. The daily bean intakes included intakes of beans alone, bean porridge, bean cake (akara), bean pudding (moinmoin), beans and corn (adalu) and bean soup (gbegiri). We categorized the daily bean intake into low, medium and high equally based on the distribution. Additional covariates included occupation, education, wealth index, contraceptive use, menopause status, number of pregnancies, breastfeeding, Body Mass Index, Waist to Hip Ratio and physical activity. Conditional logistic regression models were utilized to estimate the crude and adjusted Odds Ratio (OR) of total beans intake per day and breast cancer. Results The mean (SD) age of the cases was 42.5 (10.1) and controls was 41.5 (9.2) years. Among controls, almost 36% consume a high intake of total bean compared to 30% among cases, whereas among the cases 37.3% consumed the low intake of total bean compared to 31.6% among controls. In the multivariable, we found a significant association between total beans intakes and breast cancer (OR = 0.85; 95% CI: 0.74–0.97, p-value = 0.02). Comparing the highest category (approximately two portions or more a day) with the lowest category (less than one portion a day), the adjusted OR was 0.72 (95% CI: 0.52–0.98, p-value for trend = 0.04). Conclusions We found a significant association between high intakes of beans and reduce risks for breast cancer. Future studies are needed to evaluate the causality of this relationship and the specific component of beans that is responsible for this reduction. Funding Sources National Human Genome Research Institute of the National Institutes of Health's African Collaborative Center for Microbiome and Genomics Research grant, Award Number U54HG006947; the Fogarty International Center of the National Institutes of Health's Training Program in Nigeria for Non-communicable Diseases Research (TRAPING NCD), Award Number D43TW009106, the Maryland Department of Health's Cigarette Restitution Fund Program.

ABC trial (A011502): A randomized phase III double-blinded placebo-controlled trial of aspirin as adjuvant therapy breast cancer.

TPS600 Background: In-vitro and in-vivo evidence suggest that aspirin may have an anti-tumor effect. Multiple epidemiologic studies have reported improved breast cancer survival among regular aspirin users compared to non-users. Pooled data from randomized trials of aspirin for cardiovascular disease have also reported a decreased risk of metastatic cancer among aspirin users. However, the exact benefits and risks for breast cancer survivors need to be confirmed in a randomized controlled trial. Even if the clinical effect were modest, the global impact would be substantial since aspirin is inexpensive and widely available. Methods: The primary objective is to compare the effect of 300 mg daily aspirin versus placebo upon invasive disease-free survival (iDFS) in high risk HER2 negative breast cancer patients. Secondary objectives include effects on overall survival, cardiovascular disease, toxicity, and adherence. A biospecimen repository will be created for correlative analyses including tumor collection at baseline and blood and urine samples and questionnaires assessing lifestyle factors associated with inflammation (pain, sleep, stress, and depression) at baseline and 2 years. Study design: Subjects will be randomized (1:1) to aspirin 300 mg vs placebo daily for 5 years in a double-blinded fashion. Stratification factors include hormone receptor (HR) status (positive vs negative), body mass index ( &lt; or ≥ 30 kg/m2), and stage (II vs III). Subjects will be followed every 6 six months while on study drug, then annually for 10 years. Accrual goal is 2936 patients to reach 381 iDFS events. We have 80% power to detect HR 0.75 assuming 5-year iDFS on placebo of 77%. Eligibility: Eligible subjects include patients aged 18-70 diagnosed with a primary invasive HER2 negative breast cancer. If HR positive, tumors need to be node positive and diagnosed within the past 10 years. If HR negative, tumor can be node positive or T2-4N0 within 18 months of diagnosis. Subjects who are currently anticoagulated or those with a prior history of GI bleeding, atrial fibrillation, or myocardial infarction are excluded. Subjects who regularly use aspirin (defined as ≥ 5 days per week) need to stop 30 days prior to enrollment. Updated accrual numbers will be given at the time of presentation. Clinical trial information: NCT02927249 .

Inflammatory breast cancer (IBC) in native Hawaiians and Pacific Islanders: Frequency of IBC and impact of socioeconomic status on survival outcomes.

e19083 Background: IBC is one of the most aggressive types of breast cancer, accounting for only 1-4% of all breast cancer cases while causing 8-10% of breast cancer related deaths. Previous studies have demonstrated that IBC has distinct epidemiological characteristics, but the prevalence of IBC particularly in Native Hawaiian (NH) and Pacific Islander (PI) populations, and the socioeconomic disparities related to survival outcomes, are not fully understood. Our primary objective was to determine the frequency at which NH and PI breast cancer patients are diagnosed with IBC, and the association between socioeconomic status and overall survival (OS). Methods: Patients with newly-diagnosed primary invasive breast cancer were identified from January 1, 2000 through December 31, 2018 using Queen’s Medical Center Tumor Registry. Clinical T4d was used to differentiate IBC and non-IBC. OS was defined as the time from diagnosis to death or last follow-up. Patients who were alive at the date of last follow-up were censored. Univariate and multivariate cox proportional hazard models were used to assess the effects of variables of interest on OS. Results: A total of 3,715 patients were included in analysis. There were 98 (2.6%) patients with IBC and 3,617 (97.4%) with non-IBC. Proportion of IBC relative to non-IBC was significantly higher in PI (9.0%) than in White (W) (2.7%) (P &lt; 0.001). Proportion of IBC was higher in NH (4.7%) than W but the difference was not statistically significant (P = 0.08). In multivariate analysis among the non-IBC group, OS was significantly shorter for both PI and NH than W (HR 1.72, [95%CI, 1.13-2.6]; P = 0.01, HR 1.48 [95% CI, 1.14-1.93]; P = 0.003, respectively). There were no significant racial differences seen in OS among IBC patients. Being under or uninsured was also significantly associated with short OS outcomes among patients with non-IBC but not those with IBC. Conclusions: PI have a significantly high proportion of IBC relative to non-IBC. Race and insurance status were not associated with OS in IBC although they were significantly associated with short OS in non-IBC. This result suggests that in IBC, the potential effect of racial disparity on OS is negated by the aggressive and insidious nature of the cancer. The effect of a relatively small sample size cannot be excluded, and further study in a larger population is warranted.

Molecular profiles and treatment recommendations for invasive lobular carcinoma in a real-world prospective breast cancer registry.

e19291 Background: Invasive lobular carcinoma (ILC), the second most common histological breast cancer type, comprises 10-15% of breast tumors. Although ILC is thought to have a low risk of relapse, patient survival data vary. ILC treatment guidelines mirror those for invasive ductal carcinoma (IDC); however, these were extrapolated from trials that included predominantly IDC. The FLEX Registry captures data from real-world breast cancer patients; the current sub-study evaluated molecular profiles and treatment recommendations in ILC. Methods: The FLEX Registry (NCT03053193) includes stage I-III primary invasive breast cancer patients who receive 70-gene signature (70-GS)/80-gene signature (80-GS) testing and consent to full transcriptome and clinical data collection. This sub-analysis includes 335 ILC patients and 2,179 IDC patients enrolled from 2017 to present. 70-GS stratified tumors by risk of distant metastasis [High (HR), Low (LR), Ultralow (UL) Risk], and 80-GS classified tumors by molecular subtype (Luminal, HER2, or Basal type). Genomic and clinical data were compared for ILC and IDC using chi-square or Fisher’s exact test. Results: ILC represented 13% of FLEX cases (n = 335/2752); 81% were lymph node-negative, 99% ER-positive, and 94% HER2-negative. Clinical risk assessment (MINDACT criteria) classified 61% of ILC and 53% of IDC as low risk (p = 0.03). 70-GS risk distribution in ILC (18% UL, 51% LR, 31% HR) differed from IDC (13% UL, 34% LR, 53% HR; p &lt; 0.01). Discordance between 70-GS and clinical risk was greater in ILC (43%) than IDC (30%, p &lt; 0.01). 80-GS results also differed between ILC (98% Luminal, 1.6% HER2, 0.3% Basal) and IDC (85% Luminal, 3% HER2, 11% Basal; p &lt; 0.01). Inclusion of chemotherapy (CT) in treatment plans was associated with 70-GS risk (p &lt; 0.01); treatment plans that disagreed with 70-GS results were associated with discordant clinical risk (p &lt; 0.05). Treatment plans disagreed with 70-GS in 15% of ILC and 12% of IDC total cases (p = 0.08), and more frequently in HR cases (25% in ILC, 14% in IDC; p &lt; 0.01). Conclusions: The FLEX Registry includes patients with ILC consistent with real-world breast cancer frequencies. ILC demonstrated genomic risk and subtype profiles distinct from IDC. Treatment plans largely agreed with 70-GS results; however, discordance was more frequent in HR ILC than IDC. Future studies will evaluate clinical outcomes; however, these results demonstrate the added value of molecular profiling in ILC and the utility of real-world registry data in evaluating uncommon breast tumor types. Clinical trial information: NCT03053193 .

Molecular subtypes of invasive breast cancer: correlation between PET/computed tomography and MRI findings

The aim of the study was to investigate the diagnostic value of fluorodeoxyglucose-18 (FDG)-PET/computed tomography (CT) and MRI parameters in determining the molecular subtypes of invasive breast cancer. Data from 55 primary invasive breast cancer masses in 51 female patients who underwent pre-treatment PET/CT and MRI scans, and histopathological diagnosis at the authors' center were retrospectively reviewed. The relationship between FDG-PET/CT and MRI parameters, including maximum and mean standard uptake values (SUVmax and SUVmean, respectively), mean metabolic index (MImean) and metabolic tumor volume (MTV) values obtained from FDG-PET, and shape, margin, internal contrast-enhancement characteristics, kinetic curve types, functional tumor volume (FTV), apparent diffusion coefficient (ADC) values obtained from MRI was evaluated. Subsequently, differences among molecular subtypes (i.e. luminal A, luminal B, c-erbB-2 positive, and triple-negative) in terms of PET/CT and MRI parameters were evaluated. The luminal B subtype of invasive breast cancer had higher SUVmax and SUVmean (P = 0.002 and P = 0.017, respectively) values than the luminal A subtype. In addition, the triple-negative subtype had a higher SUVmax (P = 0.028) than the luminal A subtype. There was a statistically significant positive correlation between pathological tumor volume (PTV) and SUVmean (P = 0.019, r = 0.720). SUVmax and ADC were negatively correlated (P = 0.001; r = -0.384). A very strong positive correlation was detected between MTV and FTV (P = 0.000; r = 0.857), and between MTV and PTV (P = 0.006, r = 0.796), and between FTV and PTV (P = 0.006, r = 0.921). Results of the present study suggest that SUVmax was superior to MRI findings in predicting molecular subtypes and that MRI was superior to PET/CT in predicting PTV.

SUN-122 Nuclear PDCD4 Expression Predicts Good Clinical Outcome in Luminal A-Like and Luminal B-Like Breast Cancer Subtypes

Hormone receptor-positive (HR+, estrogen and/or progesterone receptor-positive) and HER2-negative breast cancer (BC) subtype is a biologically heterogeneous entity that comprises 70% of BCs. This subtype includes both luminal (Lum) A- and B-like subtypes, which have differences in prognosis and sensitivity to endocrine therapies. The development of biomarkers guiding treatment decisions in these settings is required. Tumor suppressor PDCD4 (programmed cell death 4), which can be found both in the nucleus (NPDCD4) or the cytoplasm (CPDCD4), inhibits tumor growth and metastasis, and its loss is associated with poor prognosis in solid tumors. To explore the clinical relevance of PDCD4 in BC, we analyzed its expression by immunohistochemistry in a cohort of 619 patients with primary invasive BC. We found that 34.7% of patients showed NPDCD4 and 21.3% showed CPDCD4. NPDCD4 positivity, but not CPDCD4, was associated with lower clinical stage (P = 0.0003), with presence of more differentiated tumors (P = 6.4x10-6), and with estrogen and progesterone receptor (PR) expression (P = 9.2x10-9 and P = 2.8x10-9, respectively). Kaplan-Meier analysis revealed that NPDCD4 expression was associated with a longer overall survival (OS) and disease-free survival (DFS) in LumA-like (P = 0.008 and P = 0.028, respectively) and LumB-like (P = 0.004 and P = 0.012, respectively) subtypes. Interestingly, patients with LumB-like tumors displaying NPDCD4 presented estimated OS and DFS rates similar to the ones observed in patients with LumA-like tumors also expressing NPDCD4, indicating that its presence improves the clinical outcome of LumB-like patients. Multivariate Cox regression analysis identified NPDCD4 as an independent predictor of good clinical outcome in both LumA-like (HR: 0.45, 95% CI 0.22-0.96, P = 0.038) and LumB-like (HR: 0.28, 95% CI 0.10-0.80, P = 0.018) subtypes. We validated our results by in silico analysis using expression data from the METABRIC cohort. Bioinformatics analysis of BC cells from the Cancer Cell Line Encyclopedia revealed a positive correlation between PDCD4 and PR expression (P = 0.015). Since LumB-like tumors present a higher risk of resistance to endocrine therapy and both PR and PDCD4 levels in this subtype are lower than in the LumA-like one, we postulated that the presence of PR may modulate PDCD4 expression. Silencing of PR expression in HR+ cells decreased PDCD4 protein levels while reconstitution of PR in a PR-null cell line increased them, confirming PR requirement for PDCD4 modulation. In line with PDCD4 physiological function, its knockdown increased cell migration capability of HR+ BC cells, whereas its restoration led to a decrease in cell migration of HR-negative BC models. Our findings identified NPDCD4 positivity as a novel biomarker of clinical outcome in LumA- and B-like subtypes and revealed PDCD4 reconstitution as a novel therapeutic strategy in BC.

Epidemiological, clinical and diagnostic profile of breast cancer patients treated at Potchefstroom regional hospital, South Africa, 2012-2018: an open-cohort study.

IntroductionBreast cancer is the second most diagnosed cancer worldwide. We aimed to depict the diagnostic approach as well as the epidemiological and clinical profile of patients with breast cancer at Potchefstroom regional hospital, South Africa.MethodsThis descriptive open-cohort study included patients with primary invasive breast cancer, confirmed by histology results and treated at the hospital from 01 January 2012 to 31 December 2018. Data such as demographics, patient history, histology, breast clinical findings, physical mass description and diagnostic investigations were captured from hospital registries and patient files.ResultOne-hundred thirty-eight patients (mean age 56.2 (SD: 14.4) (95% CI 54.6-59.7) years) met inclusion criteria. Most patients were female (98.6%), from African (67.4%) or Caucasian (23.9%) descent. Findings included mostly left-sided breast involvement (51.8%), lesions in the upper-outer quadrant (43.1%), extensions to the skin (25.6%, N = 39), and tumour size of 2 ≤ 5 cm (49.3%), or > 5 cm (39.1%). Most patients (57.9%, N = 135) were categorised as BIRADS-5, with a ductal pattern (89.6%) (p < 0.01). Patients mostly presented in stages II to IV of disease (89.1%; p < 0.05). Late-stage (stages III-IV) at time of diagnosis (n = 84) was significantly associated with mass location (p = 0.006; Cramér's V = 0.280), tumour size (p < 0.001, Cramér's V = 0.239), and skin changes (p = 0.027, Cramér's V = 0.492).ConclusionMost patients consulted at a late-stage of the disease, indicating a need for the promotion of breast awareness campaigns, early detection, and timeous referral.

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.