Distribution Of Tumor Subtypes Research Articles

How Do Breast Cancer Patients Present Following COVID-19 Early Peak in a Breast Cancer Center in Turkey?

Coronavirus disease 2019 (COVID-19) has placed an unprecedented burden on healthcare systems and restricted resources for non-COVID patients worldwide. Treatment approaches and follow-up plans have been modified to prevent the risk of infection for patients and healthcare workers. Patients prefer to delay or cancel their treatments during the peak period of infection. We retrospectively reviewed the characteristics of patients with breast cancer who were consulted at our outpatient clinic right after early COVID-19 peak in May and June 2020 and compared them with the same period in 2017 to 2019. The number of patients who consulted at our outpatient medical oncology clinic declined in May and June 2020. This decline was regardless of stage and was larger in May than in June 2020. In general, the distribution of tumor subtypes [luminal, human epidermal growth factor receptor 2 (HER-2) positive, and triple negative] was not different from 2017 to 2020. Less than half of the patients received adjuvant chemotherapy following early COVID-19 peak in May and June 2020. Few patients received chemotherapy for metastatic disease, whereas many metastatic patients received endocrine therapy. None of the consulted new patients had a non-invasive disease. More patients received endocrine therapy than chemotherapy. The presentation patterns of patients with breast cancer after early COVID-19 peak differed from those during the same period in the last 3 years. The pandemic affected the number of new patients consulted and the way medical oncologists treat their patients.

Tumor subtypes and survival in male breast cancer

Male breast cancer is an uncommon disease, and population-based information regarding prognostic factors is limited. Most cases are hormone receptor (HR) positive; however, the association of tumor subtype with overall survival (OS) and breast cancer-specific survival (BCSS) is unclear. Using SEER data, we identified men with invasive breast cancer between 2010 and 2017 with known HR and HER2 status. We examined tumor subtypes by patient characteristics and performed multivariate Cox proportional hazards analyses to determine the associations of each variable with OS and BCSS. We included 2389 men with a median follow-up of 43months (IQR 19-68). Median age was 66years. Tumor subtype distribution was 84.1% HR+/HER2-, 12.7% HR+/HER2+ , 0.8% HR-/HER2+, and 2.3% triple-negative (TN). In univariate analysis, OS at 5years was 76.5% for HR+/HER2-, 65.1% for HR+/HER2+ , 84.2% for HR-/HER2+, and 48.1% for TN (p < 0.0001). Of all subtypes, TN had the worst BCSS (p < 0.0001). Stage, tumor subtype and race were significantly associated with OS and BCSS in multivariate analysis. Adjusted Cox hazard ratios for OS by tumor subtype with HR+/HER2- as reference were 1.55 for HR+/HER2+ (p = 0.001), 1.1 for HR-/HER2+ (p = 0.888), and 3.59 for TN (p < 0.001). We observed significant differences in survival outcomes by tumor subtype. Poor outcomes among men with HER2+ and TN disease suggest possible under-treatment, aggressive tumor biology, and/or more advanced disease at presentation. Studies to better understand the inferior survival for men with these subtypes are warranted and will likely require international collaboration.

Distribution of tumor subtypes in bilateral breast cancer: Comparison between synchronous and metachronous cancer.

This study was performed to evaluate patterns of breast cancer subtypes in Korean patients with synchronous (SBC) or metachronous bilateral breast cancer (MBC). We retrospectively reviewed records of 302 patients with SBC (n=161) or MBC (n=141) who received curative surgery at our hospital between 1995 and 2013. Expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was determined by immunohistochemistry (IHC) staining. We categorized breast cancers into the following subtypes: ER+ or PR+, HER2- (i.e., luminalA); ER+ or PR+, HER2+ (i.e., luminalB HER2+); ER-, PR- and HER2+ (i.e., HER2-enriched); ER-, PR- and HER2- (i.e., triple negative, TN). More patients with MBC were ≤40 years at the time of breast cancer diagnosis than patients with SBC (34.6%vs. 19.3%, P<0.01). The proportion of subtypes in SBC and MBC were as follows: luminalA, 65.8%vs. 45.0%; luminalB, HER2+, 9.0%vs. 8.5%; HER2-enriched, 4.1%vs. 12.1%; and TN, 11.2%vs. 31.2%, respectively (P<0.01). The 10-year overall survival rate in patients with SBC and MBC was 89.0% and 93.6%, respectively. The 10-year disease-free survival rate in patients with SBC and MBC was 79.6% and 80.9%, respectively. Locoregional recurrence was found in 2.5% of patients with SBC and 9.9% of patients with MBC. Distant metastasis occurred in 8.7% of patients with SBC and 4.9% of patients with MBC. The distribution of breast cancer subtypes was different between SBC and MBC. TN-subtype was profoundly more frequent in MBC whereas luminal-subtype was most frequently found among SBC.

Comprehensive transcriptome profiling of Taiwanese colorectal cancer implicates an ethnic basis for pathogenesis

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While both genetic and environmental factors have been linked to the incidence and mortality associated with CRC, an ethnic aspect of its etiology has also emerged. Since previous large-scale cancer genomics studies are mostly based on samples of European ancestry, the patterns of clinical events and associated mechanisms in other minority ethnic patients suffering from CRC are largely unexplored. We collected 104 paired and adjacent normal tissue and CRC tumor samples from Taiwanese patients and employed an integrated approach – paired expression profiles of mRNAs and microRNAs (miRNAs) combined with transcriptome-wide network analyses – to catalog the molecular signatures of this regional cohort. On the basis of this dataset, which is the largest ever reported for this type of systems analysis, we made the following key discoveries: (1) In comparison to the The Cancer Genome Atlas (TCGA) data, the Taiwanese CRC tumors show similar perturbations in expressed genes but a distinct enrichment in metastasis-associated pathways. (2) Recurrent as well as novel CRC-associated gene fusions were identified based on the sequencing data. (3) Cancer subtype classification using existing tools reveals a comparable distribution of tumor subtypes between Taiwanese cohort and TCGA datasets; however, this similarity in molecular attributes did not translate into the predicted subtype-related clinical outcomes (i.e., death event). (4) To further elucidate the molecular basis of CRC prognosis, we developed a new stratification strategy based on miRNA–mRNA-associated subtyping (MMAS) and consequently showed that repressed WNT signaling activity is associated with poor prognosis in Taiwanese CRC. In summary, our findings of distinct, hitherto unreported biosignatures underscore the heterogeneity of CRC tumorigenesis, support our hypothesis of an ethnic basis of disease, and provide prospects for translational medicine.

Abstract 4184: Tumor and risk factor characteristics among breast cancer patients from different geographic regions in Peru

Abstract There are few Latin American cohorts with available biospecimens that include women of high Indigenous American ancestry. The Peruvian population is characterized by a high degree of Native American (NA) ancestry, with this ancestral component varying between 56 to 100% on average, depending on the region. We have collected 1199 Peruvian samples from the Instituto Nacional de Enfermedades Neoplasicas in Lima. This cohort of patients represents a unique opportunity to study the molecular characteristics of breast cancer in the NA genetic and genomic background. Here we present a basic description of the women in the study and a comparison of tumor subtypes distribution and risk factor information of the patients by place of birth and residence. We explored differences in tumor subtype distribution and risk factors in relation to place of birth or residence in the three main geographical region of Peru. To test differences in proportions we used Chi2 or Fisher-exact tests. To test differences in means for continuous variables we used ANOVA or t-tests. Genetic ancestry was estimated using genome wide genotypes and the program ADMIXTURE. Tumor subtypes were defined using the following criteria: ER+/PR+/HER2- as luminal A, ER+/PR+/HER2+ as luminal B, ER-/PR-/HER2+ as HER2+ and ER-/PR-/HER2- as triple negative. Overall, the patients included in the study were relatively young (50 yrs, SD=11.0). The average number of full-term pregnancies was 3 (SD=1.8), the average age at first pregnancy 22 (SD=5.7) and age at menarche was 13 (SD=1.8). The tumor subtype distribution was 31% of Luminal B tumors, 24% luminal A, 12% HER2 and 12% triple negative and did not differ by place of birth or residence. We found that patients from the Coastal region were heavier and taller than those born in the Andean region (p&amp;lt;0.005). Women born in the Coastal region had the lowest age at menarche and a lower number of full-term pregnancies (p&amp;lt;0.0001). Similar trends were observed when we compared women by place of residence. Patients born in Lima, the Capital of Peru, smoke more (p&amp;lt;0.05), were heavier, had lower age at menarche, lower number of full term pregnancies and were diagnosed at a younger age, compared to women born outside the city (p&amp;lt;0.05). The distribution of NA genetic ancestry also varied by place of birth: patients born outside Lima had higher proportion of NA ancestry (78% SD=0.15 vs. 74%, SD=0.18, p&amp;lt;0.05). The distribution of tumor subtypes among women in the Peruvian breast cancer cohort did not differ by place of birth or residence. However, we found that for some breast cancer risk factors, exposures differed between women from different regions. Finally, given the relatively low observed values for reproductive and lifestyle related exposures and the high proportion of Indigenous American ancestry of Peruvian women, this cohort is likely to be particularly informative to study genetic predisposition to breast cancer. Citation Format: Valentina Zavala, Tatiana Vidaurre, Katie Marker, Jeannie Vásquez, L Tamayo, Renzo Florez, Sandro Casavilca, M Calderon, J Abugattas, H Gómez, H Fuentes, C Monge-Pimentel, S Song, D Cherry, Laura Fejerman. Tumor and risk factor characteristics among breast cancer patients from different geographic regions in Peru [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4184.

Prognostic factors and survival according to tumor subtype in newly diagnosed breast cancer with liver metastases: A competing risk analysis.

Population-based study for predicting the prognosis for breast cancer liver metastasis (BCLM) is lacking at present. Therefore, the present study aimed to evaluate newly diagnosed BCLM patients of different tumor subtypes and assess potential prognostic factors for predicting the survival for BCLM patients. Specifically, data were collected from the Surveillance, Epidemiology and End Results program from 2010 to 2014, and were assessed, including the data of patients with BCLM. Differences in the overall survival (OS) among patients was compared via Kaplan-Meier analysis. Other prognostic factors of OS were determined using the Cox proportional hazard model. In addition, the breast cancer-specific mortality was assessed using the Fine and Gray's competing risk model. A nomogram was also constructed on the basis of the Cox model for predicting the prognosis of BCLM cases. A total of 2,098 cases that had a median OS of 20.0 months were included. The distribution of tumor subtypes was as follows: 42.2% with human epidermal growth factor receptor 2 (Her2; -)/hormone receptor (HR; +), 12.8% with Her2(+)/HR(−), 19.1% with Her2(+)/HR(+) and 13.5% with triple negative breast cancer (TNBC). Kaplan-Meier analysis revealed that older age (>64 years), unmarried status, larger tumor, higher grade, no surgery, metastases at other sites, and TNBC subtype were associated with shorter OS. Additionally, multivariate analysis revealed that older age (>64 years), unmarried status, no surgery, bone metastasis, brain metastasis and TNBC subtype were significantly associated with worse prognosis. Thus, age at diagnosis, marital status, surgery, bone metastasis, brain metastasis and tumor subtype were confirmed as independent prognosis factors from a competing risk model. We also constructed a nomogram, which had the concordance index of internal validation of 0.685 (0.650–0.720). This paper had carried out the population-based prognosis prediction for BCLM cases. The survival of BCLM differed depending on the tumor subtype. More independent prognosis factors were age at the time of diagnosis, surgery, marital status, bone metastasis, as well as brain metastasis, in addition to tumor subtype. Notably, the as-constructed nomogram might serve as an efficient approach to predict the prognosis for individual patients.

Abstract P6-19-02: Tumor subtypes and survival in male breast cancer: SEER 2010-2014

Abstract Background: Male breast cancer (MaBC) is an uncommon disease, and population-based information regarding prognostic factors is limited. Most MaBC are hormone receptor (HR) positive, however, the association of tumor subtypes with overall survival (OS) and breast cancer-specific survival (BCSS) is unclear. The aim of this study was to analyze the characteristics of each tumor subtype and its impact on OS and BCSS. Methods: Using Surveillance, Epidemiology, and End Results (SEER) data, we identified men with invasive breast cancer between 2010 and 2014 with known estrogen receptor and progesterone receptor (together HR) status and human epidermal growth factor receptor 2 (HER2) status. Tumor subtypes were classified as: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple negative (TN). We examined tumor subtypes by patient (pt) characteristics and performed multivariate Cox proportional hazards analyses to determine the associations of each variable with OS and BCSS. Results: We included 1508 pts with a median follow-up of 24 months (range 0-60). Median age was 65 years (range 26-97). At diagnosis, 86.6% of tumors were ductal, 97.1% HR+, 42.1% T1, 55.7% N0, 7.9% M1. Tumor subtype distribution was: 85.5% HR+/HER2-, 11.6% HR+/HER2+, 0.9% HR-/HER2+ and 2% TN. Compared with other subtypes, pts with TN tumors had higher grade disease, presented with more advanced stage and died more often from breast cancer (all p&amp;lt;0.0001); whereas pts with HR+/HER2- tumors were older (p=0.02) and more often white (p=0.02). In univariate analysis, OS at 5 years for all HER2- and all HER2+ was 74.2% and 64.1%, respectively (p=0.002); while BCSS at 5 years for all HER2- and all HER2+ was 88.4% and 78.8%, respectively (p=0.009). Of all subtypes, TN had the worst OS and BCSS (p&amp;lt;0.0001). Breast cancer was the cause of death in 43.7% of HR+/HER2-, 54.2% of all HER2+ and 100% of TN (p&amp;lt;0.0001). In multivariate analyses for OS, older pts (Hazard ratio [HaR] 3 vs. &amp;lt;50 years; p=0.001), stage IV (HaR 9 vs. stage I; p&amp;lt;0.001), HR+/HER2+ tumors (HaR 1.9 vs. HR+/HER2-; p=0.003), TN tumors (HaR 8.5 vs. HR+/HER2-; p&amp;lt;0.001) and unmarried pts (HaR 1.9 vs. married; p=0.002) had significantly worse survival. In multivariate analyses for BCSS, stage IV (HaR 25.7 vs. stage I; p&amp;lt;0.001), HR+/HER2+ tumors (HaR 2.1 vs. HR+/HER2-; p=0.019), TN tumors (HaR 17 vs. HR+/HER2-; p&amp;lt;0.001) and unmarried pts (HaR 2.2 vs. married; p=0.009) had significantly worse survival. Conclusion: We observed significant differences in outcomes by tumor type in men with breast cancer which mirror those previously observed for women with breast cancer. Among the limited numbers of men with HER2+ and TN disease in our sample, outcomes were poor, suggesting possible under-treatment, aggressive tumor biology, and/or more advanced of disease at presentation. Studies to better understand the inferior survival for men with these subtypes are warranted and efforts to ensure appropriate treatment are paramount. Citation Format: Leone J, Freedman RA, Zwenger AO, Lin NU, Tolaney SM, Vallejo CT, Leone BA, Winer EP, Leone JP. Tumor subtypes and survival in male breast cancer: SEER 2010-2014 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-19-02.

Breast cancer subtype and survival among Indigenous American women in Peru

Latina women in the U.S. have relatively low breast cancer incidence compared to Non-Latina White (NLW) or African American women but are more likely to be diagnosed with the more aggressive “triple negative” breast cancer (TNBC). Latinos in the U.S. are a heterogeneous group originating from different countries with different cultural and ancestral backgrounds. Little is known about the distribution of tumor subtypes in Latin American regions. Clinical records of 303 female Peruvian patients, from the Peruvian National Cancer Institute, were analyzed. Participants were diagnosed with invasive breast cancer between 2010 and 2015 and were identified as residing in either the Selva or Sierra region. We used Fisher’s exact test for proportions and multivariable Cox Proportional Hazards Models to compare overall survival between regions. Women from the Selva region were more likely to be diagnosed with TNBC than women from the Sierra region (31% vs. 14%, p = 0.01). In the unadjusted Cox model, the hazard of mortality was 1.7 times higher in women from the Selva than the Sierra (p = 0.025); this survival difference appeared to be largely explained by differences in the prevalence of TNBC. Our results suggest that the distribution of breast cancer subtypes differs between highly Indigenous American women from two regions of Peru. Disentangling the factors that contribute to this difference will add valuable information to better target prevention and treatment efforts in Peru and improve our understanding of TNBC among all women. This study demonstrates the need for larger datasets of Latin American patients to address differences between Latino subpopulations and optimize targeted prevention and treatment.

Abstract 4240: Breast cancer characteristics and survival among different Indigenous American communities in Peru

Abstract Background: Breast cancer prognosis depends on stage at diagnosis and varies by intrinsic tumor subtype. In the US, the distribution of tumor subtypes has been shown to differ between racial/ethnic groups with African American and Latina women more likely to be diagnosed with the more aggressive “triple negative” breast cancer (TNBC) compared to Non-Latino White women. Latinos in the US originate from different countries with different cultures and ancestral genetic backgrounds, demonstrating the heterogeneity that exists. Information about the distribution of tumor subtypes in Latin American regions is limited. Methods: Data for these analyses come from The Peruvian National Cancer Institute . Includes clinical information for 303 patients diagnosed with breast cancer between 2010 and 2015 and who are members of Indigenous American communities. We analyzed women from different groups: the Quechuas (Group 1; N=223), Aimara (Group 2; N=9), Ashankinka/Nomatsigenga/Yenesha (Group 3; N=17), Awajun/Kichwa/Shawi/Shipibo-Konibo (Group 4; N=29) and other communities (Group 5; N=20). Some communities were combined based on previous literature describing their genealogical proximity. We compared tumor characteristics and survival between these groups using Fisher exact tests, T-tests, and a Cox Proportional Hazards model with predictors age at diagnosis, stage, tumor subtype, and treatment. Breast cancer subtype was defined as luminal A (ER/PR+/HER2-), luminal B (ER+/HER2+), HER2 overexpressing (ER/PR- HER2+) and triple negative (ER/PR- HER2-) based on immunohistochemistry. Results: Overall, tumors from the 303 Indigenous American women included in the present study were 37% luminal A, 20% luminal B, 23% HER2 overexpressing and 19% triple negative. Our analyses showed that women from group 1 were diagnosed at an older age (55 vs. 48-50, p&amp;lt;0.0001) and less frequently with TNBC compared to women from other groups (45% vs. 55-78%, p=0.06). Compared to group 1, women from the other groups a non-significant trend towards higher mortality (HR 1.5-1.9, p=0.272). In the full model, including age, stage, tumor subtype and treatment, the trend was no longer apparent. Whether the women had surgery had the strongest effect on survival (p=0.001) followed by stage (p=0.0012) and TNBC (p=0.0023). Conclusion: Differences in survival between the women of different indigenous communities with breast cancer in Peru are most likely due to differences in access to care. There could be environmental factors or subtle sub continental genetic differences influencing the risk of TNBC. However, the lower frequency of TNBC among the Quechuas could also be due to a reduced set of logistic barriers. The limited power of this study demonstrates the need for larger data sets for subgroup analysis in Latinas. The more we learn by analyzing diverse populations, the better equipped we will be to provide adequate care for all women. Citation Format: Lizeth I. Tamayo, Tatiana Vidaurre, Jeannie Navarro Vásquez, Sandro Casavilca, Jessica I. Aramburu, Monica Calderon, Daniel Cherry, Sikai Song, Garth H. Rauscher, Laura Fejerman. Breast cancer characteristics and survival among different Indigenous American communities in Peru [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4240.

Abstract B79: Breast cancer characteristics and survival among Indigenous American women from Peru

Abstract Background: Breast cancer prognosis depends on stage at diagnosis and varies by intrinsic tumor subtype. In the US, the distribution of intrinsic subtypes has been shown to differ between racial/ethnic groups with African American and Hispanic/Latina women more likely to be diagnosed with the more aggressive triple-negative breast cancer (TNBC) lacking expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), compared to non-Hispanic/Latino White women. Hispanics/Latinos in the US are a heterogeneous group originating from different countries with different cultures and ancestral backgrounds. Information about the distribution of tumor subtypes in Latin American regions is lacking. Methods: Data for these analyses come from the Instituto Nacional de Enfermedades Neoplásicas (the Peruvian National Cancer Institute), which diagnoses and treats ~20% of all breast cancers diagnosed in Peru. We have abstracted data from clinical records for 303 patients diagnosed with breast cancer between 2010 and 2015 and who are members of Indigenous American communities from the Andean Mountain region (N=232) or the Amazonian region (N=71). We compared tumor characteristics and survival between the two groups. Comparisons between the two regions were conducted using chi-squared tests, as well as a t-test for age at diagnosis. Breast cancer subtype was defined as luminal A (ER/PR+/HER2-), luminal B (ER+/HER2+), HER2 overexpressing (ER/PR- HER2+), and triple-negative (ER/PR- HER2-) based on immunohistochemistry. Survival analyses were conducted using a Cox proportional hazards model and included region, age at diagnosis, stage, and tumor subtype as predictors. Results: Overall, tumors from the 303 Indigenous American women from Peru included in the present study were 37% luminal A, 20% luminal B, 23% HER2 overexpressing, and 19% triple-negative. Our analyses showed that women from the Amazonian region were diagnosed at a younger age (50 vs. 55 mean age at diagnosis, P value =0.001), later stage (61% vs. 48% stage III or IV, P value=0.06), and more frequently with triple-negative tumors compared to women from the Mountain region (31% vs. 17%, P value =0.013). Women from the Amazonian region had a 70% higher mortality hazard than the women from the Mountain region in a model adjusted by age at diagnosis (hazard ratio 1.73, 95%CI 1.06-2.86, p=0.027). In the full model including stage and tumor subtype, the difference in the mortality hazard was no longer statistically significant (HR 1.20, 95%CI 0.71-2.03, p=0.493). Conclusion: Differences in tumor characteristics and survival between Indigenous American women from the Amazonian and Mountain Range regions in Peru could be due to variation in genetic predisposition to particular subtypes of the disease, variation in environmental exposures, as well as to differences in cancer awareness and access to care between the different groups. The more we learn by analyzing diverse populations and subpopulations and revealing heterogeneity within Latin American women, the better equipped we will be to provide adequate care for all women. Citation Format: Lizeth I. Tamayo, Tatiana Vidaurre, Jeannie Navarro Vasquez, Sandro Casavilca, Jessica Ivonne Aramburu Palomino, Monica Calderon, Garth H. Rauscher, Laura Fejerman. Breast cancer characteristics and survival among Indigenous American women from Peru [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B79.

Abstract IA40: Obesity in breast and ovarian cancers: Racial/ethnic disparities

Abstract IA40: Obesity in breast and ovarian cancers: Racial/ethnic disparities

Risk factors and survival outcomes in patients with breast cancer and lung metastasis: a population‐based study

The risk factors for morbidity and mortality in breast cancer lung metastases (BCLM) patients still remain poorly identified. The aim of this study was to assess the incidence and survival of BCLM and associated risk factors. Patients with BCLM were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate logistic regression analysis was used to determine the risk factors for BCLM. Predictors of factors associated with death were analyzed in Cox regression and Fine and Gray's test. Of the 11568 patients with stage IV breast cancer, 4213 (36.4%) had BCLM and 1214 (10.5%) had metastases confined to lungs. The median survival time for patients with BCLM was 21 months, and 15.5% of the patients were alive more than 3 years. The tumor subtype distribution was 45.3% HR−/HER2−, 12.2% HR+/HER2+, 7.8% HR−/HER2+, and 15.0% triple‐negative subtype. Compared with patients without BCLM, those with BCLM were more likely to be aged, female, black, higher tumor grade, HR−/HER2+, HR+/HER2+, and triple‐negative subtypes at diagnosis. Survival analysis showed that the aged, black race, HR−/HER2+, triple‐negative subtype, higher grade were the independent risk factor for BCLM patients’ survival, while HR+/HER2+ subtype, insured status, and married status suggested better prognosis. In conclusion, the incidence and prognosis of BCLM varied by tumor subtypes, age, and race. Elderly patients with HER2‐positive or triple‐negative tumors were more likely to have BCLM.

Racial Differences in PAM50 Subtypes in the Carolina Breast Cancer Study.

African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood. Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size. Molecular subtypes (Luminal A, Luminal B, HER2-enriched, and Basal-like) and ROR scores (high vs low/medium) were compared by race (blacks vs whites) and age (≤50 years vs > 50 years) using chi-square tests and analysis of variance tests. Black women of all ages had a statistically significantly lower frequency of Luminal A breast cancer (25.4% and 33.6% in blacks vs 42.8% and 52.1% in whites; younger and older, respectively). All other subtype frequencies were higher in black women (case-only odds ratio [OR] = 3.11, 95% confidence interval [CI] = 2.22 to 4.37, for Basal-like; OR = 1.45, 95% CI = 1.02 to 2.06, for Luminal B; OR = 2.04, 95% CI = 1.33 to 3.13, for HER2-enriched). Among clinically HR+/HER2- cases, Luminal A subtype was less common and ROR scores were statistically significantly higher among black women. Multigene assays highlight racial disparities in tumor subtype distribution that persist even in clinically defined subgroups. Differences in tumor biology (eg, HER2-enriched status) may be targetable to reduce disparities among clinically ER+/HER2- cases.

Contribution of clinical and socioeconomic factors to differences in breast cancer subtype and mortality between Hispanic and non-Hispanic white women.

To assess tumor subtype distribution and the relative contribution of clinical and sociodemographic factors on breast cancer survival between Hispanic and non-Hispanic whites (NHWs). We analyzed data from the California Cancer Registry, which included 29,626 Hispanic and 99,862 NHW female invasive breast cancer cases diagnosed from 2004 to 2014. Logistic regression was used to assess ethnic differences in tumor subtype, and Cox proportional hazard modeling to assess differences in breast cancer survival. Hispanics compared to NHWs had higher odds of having triple-negative (OR=1.29; 95% CI 1.23-1.35) and HER2-overexpressing tumors (OR=1.19; 95% CI 1.14-1.25 [HR-] and OR=1.39; 95% CI 1.31-1.48 [HR+]). In adjusted models, Hispanic women had a higher risk of breast cancer mortality than NHW women (mortality rate ratio [MRR]=1.24; 95% CI 1.19-1.28). Clinical factors accounted for most of the mortality difference (MRR=1.05; 95% CI 1.01-1.09); however, neighborhood socioeconomic status (SES) and health insurance together accounted for all of the mortality difference (MRR=1.01; 95% CI 0.97-1.05). Addressing SES disparities, including increasing access to health care, may be critical to overcoming poorer breast cancer outcomes in Hispanics.

Abstract 5275: Breast cancer characteristics among Indigenous American women from Peru

Abstract Background: Breast cancer prognosis depends on stage at diagnosis and varies by intrinsic tumor subtype. In the US, the distribution of intrinsic subtypes has been shown to differ between racial/ethnic groups, with African American and Hispanic/Latina women more likely to be diagnosed with the more aggressive “triple negative” breast cancer (TNBC), lacking expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), compared to Non-Hispanic/Latina White women. Hispanics/Latinos in the US are a heterogeneous group originating from different countries with different cultures and ancestral backgrounds. Information about the distribution of tumor subtypes in Latin American regions is lacking. Methods: Data for these analyses come from the Instituto Nacional de Enfermedades Neoplásicas (the Peruvian National Cancer Institute), which diagnoses and treats 20% of all breast cancers diagnosed in Peru. We have abstracted data from clinical records for 303 patients diagnosed with breast cancer between 2010 and 2015 and who self-reported as members of an Indigenous American community from the Andean Mountain region (indigenous subgroups: Quechuas, Aimaras, N=232) or the Amazonian region (indigenous subgroups: Shipibo-Konibo, Awajún, Ashaninka, Kichua, Ese Eja, Harakbut, Amahuaca, Shawi, Yanesha, Kakataibo, Nomatsigenga, N=71). We compared the distribution of age at diagnosis and tumor characteristics by region. Comparisons between the two regions were conducted using chi-squared tests, as well as a t-test for age at diagnosis. Breast cancer subtype was defined as luminal A (ER/PR+/HER2-), luminal B (ER+/HER2+), HER2 overexpressing (ER/PR- HER2+) and triple negative (ER/PR- HER2-) based on immunohistochemistry. Results: Overall, tumors from the 303 Indigenous American women from Peru included in the present study were 37% luminal A, 20% luminal B, 23% HER2 overexpressing and 19% triple negative. Our analyses showed that women from the Amazonian region were diagnosed at a younger age (50 vs. 55 mean age at diagnosis, P value =0.001), later stage (53.0% vs. 41.7% stage III or IV, P value=0.107) and more frequently with triple-negative tumors compared to women from the Mountain Region (30% vs. 16%, P value =0.115). Conclusion: Differences between Indigenous American women from the Amazonian and Mountain Range regions in Peru could be due to variation in genetic predisposition to particular subtypes of the disease, variation in environmental exposures, as well as to differences in cancer awareness and access to care between the different groups. The more we learn by analyzing diverse populations, subpopulations and revealing heterogeneity within Latin American women, the better equipped we will be to provide adequate care for all women. Citation Format: Lizeth I. Tamayo, Tatiana Vidaurre, Jeannie N. Vásquez, Sandro Casavilca, Jessica I. Palomino, Monica Calderon, Garth H. Rauscher, Laura Fejerman. Breast cancer characteristics among Indigenous American women from Peru [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5275. doi:10.1158/1538-7445.AM2017-5275

Overall survival (OS) of men and women with breast cancer according to tumor subtype: A population-based study.

1069 Background: The outcomes of male breast cancer (MBC) and female breast cancer (FBC) according to tumor subtype are poorly known. Our group previously reported the prognostic significance of tumor subtypes in MBC. The aim of this study was to analyze differences in OS between MBC and FBC according to tumor subtype compared with other factors. Methods: We evaluated men and women with microscopically confirmed invasive breast cancer between 2010 and 2013 with known estrogen receptor (ER) and progesterone receptor (PR) (together hormone receptor [HR]) status and human epidermal growth factor receptor 2 (HER2) status reported to the SEER program. Patients (pts) with other primary either before or after breast cancer were excluded. Pt characteristics were compared between MBC and FBC. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Results: We included 1,187 MBC and 166,054 FBC pts. Median age for MBC was 65 years (range 26-97) and for FBC was 60 years (range 18-108). Median follow-up was 21 months (range 1-48) for both groups. OS at 3 years for MBC and FBC was 85.6% and 90.4%, respectively (p = 0.0002). MBC pts were more frequently ductal, had higher grade, presented with more advanced stage and were more often HR+/HER2- (all p &lt; 0.0001). MBC had worse OS than FBC in HR+/HER2- (Hazard ratio [HaR] 1.5; p = 0.0005), HR+/HER2+ (HaR 2.8; p &lt; 0.0001) and triple negative (TN) (HaR 4.3; p &lt; 0.0001) (p for interaction &lt; 0.02). MBC had significantly worse OS than FBC in stage I and II, but similar OS in stage III and IV (p for interaction &lt; 0.01). In multivariate analysis adjusted for age, race, grade, stage, surgery, radiation and marital status; HR+/HER2+ was the only subtype with significant differences in OS between MBC and FBC (HaR 2.0; p = 0.002). Conclusions: In this cohort, we observed significant differences in the distribution of tumor subtypes between MBC and FBC. OS was significantly different in both groups. Men had worse OS in stage I and II while similar OS in stage III and IV. There were significant differences in OS according to tumor subtype; compared with women, men with HR+/HER2+ tumors had twice the risk of death.

Abstract P3-16-01: Immune characterization of inflammatory breast cancer and correlation to pathological complete response

Abstract Background: Treatment of inflammatory breast cancer (IBC) includes neoadjuvant chemotherapy (NAC) followed by mastectomy and radiation. Responses are limited however with low pathological complete response (pCR) rates and poor survival. Recent RNA expression studies suggest that activated T cell signaling pathways and immunomodulatory markers such as PD-L1 are associated with a higher pCR rate in IBC; however comprehensive studies of tumor infiltrating lymphocytes (TIL) and protein expression of immunomodulatory molecules are lacking. There is a critical need therefore to study molecular and immune determinants of therapeutic response in IBC, with the goal of identifying biomarkers and actionable strategies to improve treatment outcomes. Methods: Baseline core biopsies from 36 IBC patients, 22 with stage III and 14 with stage IV disease were evaluated. Of these, 21 stage III and 10 stage IV patients underwent mastectomy following NAC, the latter for palliative purposes. Tumor subtype distribution was 14 patients with HER2-/HR-, 6 with HER2+/HR-, 11 with HER2-/HR+, and 5 with HER2+/HR+ disease. TIL infiltration in the tumor stroma was quantified on H&amp;E slides based on consensus guidelines as well as by immunohistochemistry (IHC) staining for CD8. PD-L1 expression in the TIL and invasive tumor was evaluated by IHC in tumors with &amp;gt;1%TIL. Results: Stromal TIL were found in the invasive tumor on pretreatment biopsies in 26 (72%) patients, with TIL percentages ranging from 1% to 60% (mean=11.6; sd=13.8); of note, 1 patient biopsy sample only had tumor emboli on the tissue block and therefore was not evaluable. Higher TIL infiltrate was noted in stage III versus stage IV disease (mean TIL 11.6% versus 3.5%, p=0.028). Mean TIL infiltrate was 11.5% in HER2-/HR-, 10.0% in HER2+/HR-, 10.4% in HER2+/HR+, and 3.6% in HER2-/HR+ tumors (p=NS). At mastectomy, 7/21 stage III patients and 1/10 stage IV patients achieved a pCR. Mean TIL was 13.4% in the pCR group versus 8.2% in the non-pCR group (p=0.37) CD8 and PD-L1 staining was performed on samples with &amp;gt;1%TIL (n=15, of which 14 samples were available for additional staining). An average of 42% of TIL stained positive for CD8 (range 10-80%). There was no significant relationship between %CD8 and pCR, stage, or receptor status. None of these 14 patients demonstrated membranous PD-L1 positivity but all had focal weak cytoplasmic staining in the lymphocytes. Conclusions: Differences exist in the presence of stromal TIL in distinct groups within IBC (stage III versus stage IV disease and across histologic subtypes) and may contribute to differential responses to therapy. When comparing these results to published non-IBC literature (FinHER trial), our IBC patient cohort had lower TIL infiltrate in several histologic subtypes (HER2-/HR- 11.5% vs 25%, p=0.015), HER2+/HR-(10% vs 20%, p=0.10), and HER-/HR+ disease (3.6 vs 7.5%, p=0.01); TIL was comparable for HER2+/HR+ disease. Additional studies are underway (including multiplex analysis of myeloid and lymphoid markers, T cell receptor sequencing, and molecular profiling) in pre-treatment and surgical samples to better understand mechanisms of treatment response and resistance. Citation Format: Reddy SM, Wargo JA, Reuben A, Reuben J, Woodward W, Ueno N, Mittendorf EA, Krishnamurthy S. Immune characterization of inflammatory breast cancer and correlation to pathological complete response [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-16-01.

Abstract P1-12-02: Prognostic factors and survival according to tumor subtype in women presenting with breast cancer brain metastases at initial diagnosis

Abstract Background: Breast cancer represents one of the most common causes of brain metastases. The occurrence of this event is a catastrophic complication of metastatic breast cancer, associated with poor prognosis. However, the presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Because of this, the prognostic assessment and management of patients (pts) who present with BMIBCD is very challenging. The aim of this study was to analyze the influence of tumor subtype compared with other prognostic factors in the survival of pts who present with BMIBCD. Methods: We evaluated women with brain metastases at the time of initial diagnosis of microscopically confirmed breast cancer, reported to the Surveillance, Epidemiology and End Results (SEER) 18 registries program from 2010 to 2013. Pts with other primary malignancy either before or after breast cancer were excluded. Pt characteristics were compared between tumor subtypes. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS). Results: Seven hundred forty pts were included. Median age was 60 years (range 26-93). After a median follow-up of 6 months (range 1-48), median OS for the whole population was 10 months and 20.7% of pts were alive at 36 months. At diagnosis, brain was the only site of metastasis in 125 pts, whereas 66.2% of pts had metastases in bone, 33.2% in liver and 44.7% in lung. Tumor subtype distribution was: 46.6% hormone receptor (HR)+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% triple negative (TN). Pts with TN brain metastases had higher grade (p&amp;lt;0.0001), higher rate of brain only (p=0.001) and lung metastases (p=0.03), had lower rates of bone metastases (p&amp;lt;0.0001) and were more likely to die from breast cancer (p&amp;lt;0.0001). Univariate analysis showed that older age (p=0.0002), black race (p=0.004), lobular histology (p=0.01), unmarried pts (p=0.01), the presence of liver (p&amp;lt;0.0001) and lung metastases (p=0.002) and TN pts (median OS 6 months; p&amp;lt;0.0001) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8; p=0.001), lobular histology (hazard ratio 2.08; p=0.006), TN subtype (hazard ratio 2.25; p&amp;lt;0.001), liver metastases (hazard ratio 1.6; p=0.001) and unmarried pts (hazard ratio 1.39; p=0.04) had significantly shorter OS. Race, tumor grade, bone metastases, lung metastases and brain only metastases had no association with OS. Conclusions: To our knowledge, this is the largest study of BMIBCD. Although the prognosis of these pts is generally poor, it is important to notice that 20.7% of pts were still alive 3 years after diagnosis. There were substantial differences in OS according to tumor subtype, TN pts had the shortest OS. HR+/HER2- represented the largest proportion of cases, therefore these pts should not be ignored when designing clinical trials for pts with brain metastases. In addition to tumor subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases. Citation Format: Leone JP, Leone J, Zwenger AO, Iturbe J, Leone BA, Vallejo CT. Prognostic factors and survival according to tumor subtype in women presenting with breast cancer brain metastases at initial diagnosis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-12-02.

Abstract 3414: Ethnic disparities in breast cancer survival in Sarawak, Malaysia

Abstract Introduction: There are three distinct South-East Asian ethnic groups in Sarawak, Malaysia (Chinese, Malay, and natives) whose breast cancer incidence rates and the distribution of tumor subtypes were reported to be significantly different. It remains unclear whether survival varies among breast cancer cases in these ethnic groups. We aimed to evaluate the relationship between survival and ethnicity when taking into account tumor characteristics. Methods: We analyzed incident breast cancer cases who were enrolled and treated in Sarawak General Hospital, Malaysia, between 1992 and 2014. The association of ethnicity with survival (relapse-free survival and overall survival) was evaluated using multivariate Cox-proportional hazard model. Subgroup analysis was conducted for each tumor subtype defined by hormone receptor (HR+, ER+ or PR+; HR-, ER- and PR-) and HER2 status (HR+/HER2-, HR+/HER2+, HR-/HER2-, and HR-/HER2+). Results: Among 2,758 eligible cases (median follow-up years, 2.90 years), there were 636 deceased and 423 relapsed cases. While there was no significant difference in disease recurrence, overall survival varied significantly by ethnicity. Compared with Chinese women, Malay women had a higher proportion of mortality (HR = 1.50; 95% CI = 1.14-1.96; P = 0.0037). This disparity remained significant only among cases with HR+ tumors (HR = 1.91; 95% CI = 1.17-3.11; P = 0.0091 among HR+/HER2-; HR = 2.74; 95% CI = 1.30-5.77; P = 0.0079 among HR+/HER2+). There was no difference in survival between Chinese and native women overall or stratified by subtype. Conclusions: Our results showed that Malay women experienced worse survival compared to Chinese women particularly among cases with HR+ tumors. Future studies are needed to clarify the underlying factors for this association in order to develop intervention strategies to reduce disparity. Citation Format: Hyuna Sung, C.R. Beena Devi, Jennifer Guida, Tieng Swee Tang, William F. Anderson, Xiaohong R. Yang. Ethnic disparities in breast cancer survival in Sarawak, Malaysia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3414.

Abstract C43: Is the influence of high mammographic breast density on breast cancer incidence the same for non-Latina black and white women?

Abstract Background: Non-Latina Black (black) women, despite their lower BC incidence, are more likely to die from breast cancer compared to their nL White (white) counterparts. While differential access to care, comorbidities and BC aggressiveness are potential contributors to this difference, the potential impact of HMD on this disparity has rarely been explored. For example, nL black women are disproportionately diagnosed with more aggressive tumors that lack estrogen and progesterone receptors (ER and PR) and that are high grade. Therefore, if the association of HMD with breast cancer incidence varied by tumor subtype this could have implications for disparities in breast cancer aggressiveness and subsequent outcomes. Most of the conclusions establishing high mammographic breast density (HMD) as a risk factor for increased breast cancer incidence are derived from studies conducted primarily in whites, which jeopardizes generalizability. We sought to estimate the association between HMD and breast cancer incidence separately for white and black women and by tumor subtype, using data from a single, large healthcare organization. Methods: We used data from screening mammograms performed in women ages 18-100, between 2001 and 2010, probabilistically linked to incident BC cases recorded in the Illinois State Cancer Registry (ISCR) during 2001-2011. Each screening mammogram received a breast density score from the interpreting radiologist using the American College of Radiology Breast Imaging Reporting and Data System (BIRADS 1-4), defined as fatty (BIRADS 1), scattered fibroglandular (BIRADS 2), heterogeneously dense (BIRADS 3) or extremely dense (BIRADS 4). A mean BIRADS breast density score was calculated using available scores from both breasts at each exam. The mean was dichotomized as high (mean BIRADS score &amp;gt; 2.5) versus low (mean BIRADS score ≤2.5) and the dichotomous variable was modeled in logistic regression with generalized estimating equations (to account for multiple screens per woman) to estimate the association between breast density and the probability of a breast cancer diagnosis within 12 months of the screen. Models included age, race, family history, parity and exam year as covariates, and separate models were estimated for black and white women. Odds ratios were interpreted as rate ratios (RR) due to the rarity of the outcome (&amp;lt;1%). Model-based standardization (predictive margins) was use to estimate adjusted rate differences from the logistic regression models. Results: Included in this analysis were 616,466 screens on 201,348 white or black women during 2001-2010, and 4,104 BC in 3,706 women during 2001-2011 (overall rate of 6.7 per 1000 screens, 6.7 for whites and 6.5 for blacks, p=0.21). There were disparities in the distribution of tumor subtypes: breast cancers diagnosed in black women were more likely to be ER negative (23% vs. 15%, p&amp;lt;0.0001) and high grade (38% vs. 30%, p&amp;lt;0.0001) when compared to white women. Upon adjustment for age, family history, parity and exam year, HMD was associated with increased breast cancer incidence overall (RR=1.24, 95% CI: 1.16, 1.32, equivalent to an adjusted Rate Difference of 1.4 per 1000 screens). The association between HMD and breast cancer incidence was similar for whites (RR=1.26, 95% CI: 1.16, 1.36) and blacks (RR=1.19, 95% CI: 1.05, 1.34) and similar for ER positive (RR=1.23, 95% CI: 1.15, 1.31) and ER negative breast cancer (RR=1.29, 95% CI: 1.16, 1.45). HMD was modestly associated with incidence of low grade (RR=1.26, 95% CI: 1.12, 1.41), and moderate grade (RR=1.18, 95% CI: 1.08, 1.29) tumors, but more strongly associated with incidence of high grade tumors (RR=1.45, 95% CI: 1.30, 1.61). These RRs translated into adjusted Rate Differences of 0.4, 0.4 and 0.8 breast cancers per 1000 screens, respectively. Discussion: Our findings reiterate high breast density as a risk factor for breast cancer incidence. In addition, we found that the association was of roughly equal magnitude among white and black women, and of roughly equal magnitude for ER negative and ER positive tumors. The stronger association of HMD with high grade tumors, however, implies that HMD may be a more detrimental risk factor for black women who are more likely to experience higher grade tumors than white women. Citation Format: Katherine Y. Tossas-Milligan, Firas Dabbous, Garth Rauscher. Is the influence of high mammographic breast density on breast cancer incidence the same for non-Latina black and white women? [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C43.