Survival, treatment regimens and medical costs of women newly diagnosed with metastatic triple-negative breast cancer.

Individuals diagnosed with metastatic triple-negative breast cancer (mTNBC) suffer worse survival rates than their metastatic non-TNBC counterparts. There is little information on survival, treatment patterns, and medical costs of mTNBC patients in Asia. Therefore, this study aimed to examine 5-year survival, regimens of first-line systemic therapy, and healthcare costs of mTNBC patients in Taiwan. Adult females newly diagnosed with TNBC and non-TNBC as well as their survival data, treatment regimens and costs of health services were identified and retrieved from the Cancer Registry database, Death Registry database, and National Health Insurance (NHI) claims database. A total of 9691 (19.27%) women were identified as TNBC among overall BC. The 5-year overall survival rate of TNBC and non-TNBC was 81.28% and 86.50%, respectively, and that of mTNBC and metastatic non-TNBC was 10.81% and 33.46%, respectively. The majority of mTNBC patients received combination therapy as their first-line treatment (78.14%). The 5-year total cost in patients with metastatic non-TNBC and with mTNBC was NTD1,808,693 and NTD803,445, respectively. Higher CCI scores were associated with an increased risk of death and lower probability of receiving combination chemotherapy. Older age was associated with lower 5-year medical costs. In sum, mTNBC patients suffered from poorer survival and incurred lower medical costs than their metastatic non-TNBC counterparts. Future research will be needed when there are more treatment options available for mTNBC patients.

Systemic therapy, survival and end-of-life costs for metastatic triple-negative breast cancer: retrospective SEER-Medicare study of women age ≥65 years.

Aim: To analyze therapy for metastatic triple-negative breast cancer (mTNBC), factors contributing to survival and costs. Patients & methods: Using 2010-2016 SEER-Medicare data, we identified women (≥65 years) with mTNBC. Results: Of 302 eligible patients, 152 (50%) received systemic therapy. In multivariable regression analyses, only age <75 years was associated with therapy receipt (odds ratio: 2.91; 95% CI: 1.79-4.74); and only systemic therapy significantly reduced risk of death (hazard ratio: 0.34; 95% CI: 0.26-0.44). Median overall survival was 13.4 (95% CI: 11.3-15.1) vs 3.3 months (95% CI: 2.7-3.9) in therapy vs no-therapy cohorts. Mean per-patient-per-month costs <30 days before end-of-life/follow-up were $14,100 and $15,600 (2019 USD), respectively. Conclusion: Poor outcomes and high costs indicate need for more effective mTNBC therapy.

Validation and comparison of Breast Graded Prognostic Assessment scores in patients with breast cancer and brain metastases.

PURPOSE: Brain metastases (BM) occur in 15-35% of patients with metastatic breast cancer, conferring poor prognosis and impairing quality of life. Clinical scores have been developed to classify patients according to their prognosis. We aimed to check the utility of the Breast Graded Prognostic Assessment (B-GPA) and its modified version (mB-GPA) and compare them in routine clinical practice. METHODS: This is an ambispective study including all patients with breast cancer BM treated in a single cancer comprehensive center. We analyzed the overall survival (OS) from BM diagnosis until death. The Kaplan-Meier method and Cox proportional hazard regression model were used in the analyses. ROC curves were performed to compare both scores. RESULTS: We included 169 patients; median age was 50 years. HER2-positive and triple negative patients were 33.7% and 20.7%, respectively. At the last follow-up, 90% of the patients had died. Median OS was 12 months (95% confidence interval 8.0-16.0 months). OS was worse in patients with > 3 BM and in patients with triple negative subtype. CONCLUSIONS: In our series, we confirm that B-GPA and mB-GPA scores correlated with prognosis. ROC curves showed that B-GPA and mB-GPA have similar prognostic capabilities, slightly in favor of mB-GPA.

Optimized tumour infiltrating lymphocyte assessment for triple negative breast cancer prognostics.

The tumour microenvironment has been shown to be a valuable source of prognostic information for different cancer types. This holds in particular for triple negative breast cancer (TNBC), a breast cancer subtype for which currently no prognostic biomarkers are established. Although different methods to assess tumour infiltrating lymphocytes (TILs) have been published, it remains unclear which method (marker, region) yields the most optimal prognostic information. In addition, to date, no objective TILs assessment methods are available. For this proof of concept study, a subset of our previously described TNBC cohort (n = 94) was stained for CD3, CD8 and FOXP3 using multiplex immunohistochemistry and subsequently imaged by a multispectral imaging system. Advanced whole-slide image analysis algorithms, including convolutional neural networks (CNN) were used to register unmixed multispectral images and corresponding H&E sections, to segment the different tissue compartments (tumour, stroma) and to detect all individual positive lymphocytes. Densities of positive lymphocytes were analysed in different regions within the tumour and its neighbouring environment and correlated to relapse free survival (RFS) and overall survival (OS). We found that for all TILs markers the presence of a high density of positive cells correlated with an improved survival. None of the TILs markers was superior to the others. The results of TILs assessment in the various regions did not show marked differences between each other. The negative correlation between TILs and survival in our cohort are in line with previous studies. Our results provide directions for optimizing TILs assessment methodology.

Real-world effectiveness outcomes in patients diagnosed with metastatic triple-negative breast cancer.

Aim: This study examined treatment patterns and effectiveness outcomes of patients with metastatic triple-negative breast cancer (mTNBC) from US community oncology centers. Materials & methods: Eligible patients were females, aged ≥18 years, diagnosed with mTNBC between 1 January 2010 and 31 January 2016. Kaplan-Meier and Cox regression methods were used. Results: Sample comprised 608 patients with average age of 57.5 years and 505/608 patients (83.1%) received systemic treatment. Overall survival (OS) from first-line treatment found that African-American patients had shorter OS than White (9.3 vs 13.7 months; hazard ratio: 1.35; p = 0.006). Conclusion: More than 15% of women with mTNBC were not treated, indicating a high unmet need. Overall prognosis remains poor, which highlights the opportunity for newer therapies to improve progression-free survival and OS.

Racial/Ethnic Disparities in All-Cause Mortality among Patients Diagnosed with Triple-Negative Breast Cancer.

It is unclear whether racial/ethnic disparities in triple-negative breast cancer (TNBC) mortality remain after accounting for clinical characteristics, treatment, and access-to-care-related factors. In this study, women with a primary diagnosis of TNBC during 2010-2014 were identified from the National Cancer Database. Hazard ratios (HR) and 95% confidence intervals (CI) for 3- and 5-year all-cause mortality associated with race/ethnicity were estimated using Cox proportional hazards models with stepwise adjustments for age, clinical characteristics, treatment, and access-to-care-related factors. Of 78,708 patients, non-Hispanic (NH) black women had the lowest 3-year overall survival rates (79.4%), followed by NH-whites (83.1%), Hispanics (86.0%), and Asians (87.1%). After adjustment for clinical characteristics, NH-blacks had a 12% higher risk of dying 3 years post-diagnosis (HR, 1.12; 95% CI, 1.07-1.17), whereas Hispanics and Asians had a 24% (HR, 0.76; 95% CI, 0.70-0.83) and 17% (HR, 0.83; 95% CI, 0.73-0.94) lower risk than their NH-white counterparts. The black-white disparity became non-significant after combined adjustment for treatment and access-to-care-related factors (HR, 1.04; 95% CI, 0.99-1.09), whereas the white-Hispanic and white-Asian differences remained. Stratified analyses revealed that among women aged less than or equal to 50 with stage III cancer, the elevated risk among NH-blacks persisted (HR, 1.20; 95% CI, 1.04-1.39) after full adjustments. Similar results were seen for 5-year mortality. Overall, clinical characteristics, treatment, and access-to-care-related factors accounted for most of the white-black differences in all-cause mortality of TNBC but explained little about Hispanic- and Asian-white differences. SIGNIFICANCE: These findings highlight the need for equal healthcare to mitigate the black-white disparity and for investigations of contributors beyond healthcare for lower mortality among Asians and Hispanics.

Does a ketogenic diet as an adjuvant therapy for drug treatment enhance chemotherapy sensitivity and reduce target lesions in patients with locally recurrent or metastatic Her-2-negative breast cancer? Study protocol for a randomized controlled trial.

BACKGROUND: Recent studies have indicated that a ketogenic diet can be used as an adjuvant therapy to enhance sensitivity to chemotherapy and radiotherapy in cancer patients. However, there are no sufficient data and no consistent international treatment guidelines supporting a ketogenic diet as an adjuvant therapy for metastatic breast cancer. Therefore, this trial was designed to observe whether irinotecan with a ketogenic diet can promote sensitivity to chemotherapy and remit target lesions in locally recurrent or metastatic Her-2-negative breast cancer patients. METHODS/DESIGN: This trial aims to recruit 518 women with locally recurrent or metastatic breast cancer admitted to the Liaoning Cancer Hospital and Institute (Shenyang, China) in northeast China. All patients will be randomly assigned into the combined intervention group (n = 259) or the control group (n = 259), followed by treatment with irinotecan + ketogenic diet or irinotecan + normal diet, respectively. The primary endpoints are sensitivity to irinotecan and the objective response rate of target lesions; the secondary endpoints include quality of life scores (EORTC QLQ-C30), progression-free survival, overall survival time, incidence of adverse events, and cost-effectiveness. The endpoints will be evaluated at baseline (before drug administration), during treatment, 4 weeks after treatment completion, and every 3months (beginning 2 months after treatment completion). DISCUSSION: This trial attempts to investigate whether irinotecan treatment with a ketogenic diet for locally recurrent or metastatic breast cancer among women in northeast China can enhance the disease's sensitivity to chemotherapy and reduce target lesions. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR1900024597. Registered on 18 July 2019. Protocol Version: 1.1, 24 February 2017.

CinéBreast-factors influencing the time to first metastatic recurrence in breast cancer: Analysis of real-life data from the French ESME MBC database.

PURPOSE: The Time to First Metastatic Recurrence (TFMR) could be considered as an indirect reflection of the tumour growth kinetics which plays an important role in cancer. Molecular subtypes such as expression of estrogen receptor are known predictive factors of TFMR. The CinéBreast study aimed to identify predictive factors of the time to TFMR. METHODS: The French Epidemiological Strategy and Medical Economics (ESME) Metastatic Breast Cancer (MBC) Database (NCT03275311) was used, which contains data from a cohort of metastatic breast cancer patients from 2008 to 2016 using retrospective data collection. It is a national multi-centre database. The impact of TFMR on overall survival (OS) since first metastasis was also evaluated. RESULTS: Among 16 702 patients recorded in the ESME MBC database, 10 595 had an initially localised breast cancer with hormone receptor (HR) and HER2 status available, with a metastatic recurrence. Median follow up was 56 months. Median TFMR was 59 months (<24: 20%, 24-60: 31%, 60-120: 25%, >120: 24%). HER2+ and TNBC were respectively 4 times and 12 times (p < 0.0001) more likely to have a recurrence within 2 years when compared to the luminal subgroup. Short TFMR and HR-/HER2-subtype significantly correlated with a poor OS in multivariate analysis. Some patients with MBC (20% in HER2+, 10% in ER+/HER2-and <5% in the ER-/HER2-) were long-term survivors in all 3 subgroups. CONCLUSIONS: In this large-scale real-life data study, patients with a TNBC metastatic recurrence had a shorter TFMR. Short TFMR significantly correlated with worse overall survival.

Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series.

Multigene expression signatures provide a molecular subdivision of early breast cancer associated with patient outcome. A gap remains in the validation of such signatures in clinical treatment groups of patients within population-based cohorts of unselected primary breast cancer representing contemporary disease stages and current treatments. A cohort of 3520 resectable breast cancers with RNA sequencing data included in the population-based SCAN-B initiative (ClinicalTrials.gov ID NCT02306096) were selected from a healthcare background population of 8587 patients diagnosed within the years 2010-2015. RNA profiles were classified according to 19 reported gene signatures including both gene expression subtypes (e.g. PAM50, IC10, CIT) and risk predictors (e.g. Oncotype DX, 70-gene, ROR). Classifications were analyzed in nine adjuvant clinical assessment groups: TNBC-ACT (adjuvant chemotherapy, n = 239), TNBC-untreated (n = 82), HER2+/ER- with anti-HER2+ ACT treatment (n = 110), HER2+/ER+ with anti-HER2 + ACT + endocrine treatment (n = 239), ER+/HER2-/LN- with endocrine treatment (n = 1113), ER+/HER2-/LN- with endocrine + ACT treatment (n = 243), ER+/HER2-/LN+ with endocrine treatment (n = 423), ER+/HER2-/LN+ with endocrine + ACT treatment (n = 433), and ER+/HER2-/LN- untreated (n = 200). Gene signature classification (e.g., proportion low-, high-risk) was generally well aligned with stratification based on current immunohistochemistry-based clinical practice. Most signatures did not provide any further risk stratification in TNBC and HER2+/ER- disease. Risk classifier agreement (low-, medium/intermediate-, high-risk groups) in ER+ assessment groups was on average 50-60% with occasional pair-wise comparisons having <30% agreement. Disregarding the intermediate-risk groups, the exact agreement between low- and high-risk groups was on average ~80-95%, for risk prediction signatures across all assessment groups. Outcome analyses were restricted to assessment groups of TNBC-ACT and endocrine treated ER+/HER2-/LN- and ER+/HER2-/LN+ cases. For ER+/HER2- disease, gene signatures appear to contribute additional prognostic value even at a relatively short follow-up time. Less apparent prognostic value was observed in the other groups for the tested signatures. The current study supports the usage of gene expression signatures in specific clinical treatment groups within population-based breast cancer. It also stresses the need of further development to reach higher consensus in individual patient classifications, especially for intermediate-risk patients, and the targeting of patients where current gene signatures and prognostic variables provide little support in clinical decision-making.

The persisting puzzle of racial disparity in triple negative breast cancer: looking through a new lens.

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors and absence of amplification of human epidermal growth factor receptor (HER2). This disease has no approved treatment with a poor prognosis particularly in African-American (AA) as compared to European-American (EA) patients. Gene ontology analysis showed specific gene pathways that are differentially regulated and gene signatures that are differentially expressed in AA as compared to EA. Such differences might underlie the basis for the aggressive nature and poor prognosis of TNBC in AA patients. In-depth studies of these pathways and differential genetic signature might give significant clues to improve our understanding of tumor biology associated with AA TNBC to advance the prognosis and survival rates. Along with gene ontology analysis, we suggest that post-translational modifications (PTM) could also play a crucial role in the dismal survival rate of AA TNBC patients. Further investigations are necessary to explore this terrain of PTMs to identify the racially disparate burden in TNBC.

Overall survival, costs and healthcare resource use by number of regimens received in elderly patients with newly diagnosed metastatic triple-negative breast cancer.

AIM: This analysis estimated the overall survival, treatment patterns and economic burden of elderly metastatic triple-negative breast cancer patients. MATERIALS & METHODS: Patients (≥66 years) with metastatic triple-negative breast cancer were identified from the SEER-Medicare database. Treatment patterns were defined in terms of first, second and third or more regimens. Healthcare resource use and costs were reported over the follow-up period and over the treatment duration of each regimen. RESULTS:  A total of 51% of patients did not receive chemotherapy. Taxanes were most commonly used. Median survival was 7 months. The mean cumulative (per patient per month) cost per patient was US$73,586 (US$10,084). Mean cost in first and second regimen were US$26,950 and US$33,347. CONCLUSION: About half of patients did not receive chemotherapy. Receipt of increasing regimens led to higher mean costs and healthcare resource use.

Biomarker assessment of the CBCSG006 trial: a randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

Background: CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods: Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results: Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46-9.00] months for GP arm and 6.07 (95% CI 5.32-6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions: GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration: ClinicalTrials.gov, NCT01287624.

Health Disparities and Triple-Negative Breast Cancer in African American Women: A Review.

Importance: Variation in cancer incidence and outcome has well-documented correlations with racial/ethnic identity. In the United States, the possible genetic and ancestral hereditary explanations for these associations are confounded by socioeconomic, cultural, and lifestyle patterns. Differences in the breast cancer burden of African American compared with European/white American women represent one of the most notable examples of disparities in oncology related to racial/ethnic identity. Elucidating the source of these associations is imperative in achieving the promise of the national Precision Medicine Initiative. Observations: Population-based breast cancer mortality rates have been higher for African American compared with white American women since the early 1980s, largely reflecting declines in mortality that have been disproportionately experienced among white American patients and at least partly explained by the advent of endocrine therapy that is less effective in African American women because of the higher prevalence of estrogen receptor-negative disease. The increased risk of triple-negative breast cancer in African American women as well as western, sub-Saharan African women compared with white American, European, and east African women furthermore suggests that selected genetic components of geographically defined African ancestry are associated with hereditary susceptibility for specific patterns of mammary carcinogenesis. Disentangling health care access barriers, as well as reproductive, lifestyle, and dietary factors from genetic contributions to breast cancer disparities remains challenging. Epigenetics and experiences of societal inequality (allostatic load) increase the complexity of studying breast cancer risk related to racial/ethnic identity. Conclusions and Relevance: Oncologic anthropology represents a transdisciplinary field of research that can combine the expertise of population geneticists, multispecialty oncologists, molecular epidemiologists, and behavioral scientists to eliminate breast cancer disparities related to racial/ethnic identity and advance knowledge related to the pathogenesis of triple-negative breast cancer.

Identification of novel prognostic indicators for triple-negative breast cancer patients through integrative analysis of cancer genomics data and protein interactome data.

Triple negative breast cancers (TNBCs) are highly heterogeneous and aggressive without targeted treatment. Here, we aim to systematically dissect TNBCs from a prognosis point of view by building a subnetwork atlas for TNBC prognosis through integrating multi-dimensional cancer genomics data from The Cancer Genome Atlas (TCGA) project and the interactome data from three different interaction networks. The subnetworks are represented as the protein-protein interaction modules perturbed by multiple genetic and epigenetic interacting mechanisms contributing to patient survival. Predictive power of these subnetwork-derived prognostic models is evaluated using Monte Carlo cross-validation and the concordance index (C-index). We uncover subnetwork biomarkers of low oncogenic GTPase activity, low ubiquitin/proteasome degradation, effective protection from oxidative damage, and tightly immune response are linked to better prognosis. Such a systematic approach to integrate massive amount of cancer genomics data into clinical practice for TNBC prognosis can effectively dissect the molecular mechanisms underlying TNBC patient outcomes and provide potential opportunities to optimize treatment and develop therapeutics.

Imaging and histologic prognostic factors in triple-negative breast cancer and carcinoma in situ as a prognostic factor. / Valoración de los factores pronósticos radiopatológicos del cáncer de mama triple negativo y análisis del carcinoma in situ como factor pronóstico.

OBJECTIVES: To analyze what factors in magnetic resonance imaging (MRI) and histological study of triple-negative breast cancers are related to tumor recurrence and to shorter disease-free survival. To analyze survival and recurrence in function of the presence of an in situ component. MATERIAL AND METHODS: This was a retrospective study of MRI staging examinations in 122 women with triple-negative breast cancer done from 2007 through 2014. In the MRI, we evaluated morphological variables (size, margins, morphology, internal signal in T2-weighted sequences) and dynamic variables (perfusion and diffusion). In the histological study, we evaluated Ki67, p53, CK5/6, nuclear grade, and Scarff-Bloom grade, as well as the presence of an in situ component and tumor grade (high grade or not high grade). We compared the variables between patients with tumor recurrence and those without, and we conducted a survival analysis. RESULTS: Non-nodular enhancement was more common in patients with tumor recurrence (p=0.038) and was associated with shorter disease-free survival (p=0.023). Neither diffusion restriction (p=0.079) nor ki67 (p=0.052) was associated with a worse prognosis. An in situ component was detected in 44% of triple-negative tumors, and a greater proportion of patients in the group with tumor recurrence had an in situ component; however, the presence of an in situ component was not associated with shorter survival (p = 0.185). CONCLUSION: Non-nodular enhancement was associated with a worse prognosis. Diffusion restriction, ki67, and the presence of an in situ component were not associated with shorter disease-free survival.

Neighborhood socioeconomic deprivation, tumor subtypes, and causes of death after non-metastatic invasive breast cancer diagnosis: a multilevel competing-risk analysis.

The purpose of this study is to examine the associations of neighborhood socioeconomic deprivation and triple-negative breast cancer (TNBC) subtype with causes of death [breast cancer (BC)-specific and non-BC-specific] among non-metastatic invasive BC patients. We identified 3,312 patients younger than 75 years (mean age 53.5 years; 621 [18.8 %] TNBC) with first primary BC treated at an academic medical center from 1999 to 2010. We constructed a census-tract-level socioeconomic deprivation index using the 2000 U.S. Census data and performed a multilevel competing-risk analysis to estimate the hazard ratios (HR) and 95 % confidence intervals (CI) of BC-specific and non-BC-specific mortality associated with neighborhood socioeconomic deprivation and TNBC subtype. The adjusted models controlled for patient sociodemographics, health behaviors, tumor characteristics, comorbidity, and cancer treatment. With a median 62-month follow-up, 349 (10.5 %) patients died; 233 died from BC. In the multivariate models, neighborhood socioeconomic deprivation was independently associated with non-BC-specific mortality (the most- vs. the least-deprived quartile: HR = 2.98, 95 % CI = 1.33-6.66); in contrast, its association with BC-specific mortality was explained by the aforementioned patient-level covariates, particularly sociodemographic factors (HR = 1.15, 95 % CI = 0.71-1.87). TNBC subtype was independently associated with non-BC-specific mortality (HR = 2.15; 95 % CI = 1.20-3.84), while the association between TNBC and BC-specific mortality approached significance (HR = 1.42; 95 % CI = 0.99-2.03, P = 0.057). Non-metastatic invasive BC patients who lived in more socioeconomically deprived neighborhoods were more likely to die as a result of causes other than BC compared with those living in the least socioeconomically deprived neighborhoods. TNBC was associated with non-BC-specific mortality but not BC-specific mortality.

Outcome disparities in African American women with triple negative breast cancer: a comparison of epidemiological and molecular factors between African American and Caucasian women with triple negative breast cancer.

BACKGROUND: Although diagnosed less often, breast cancer in African American women (AAW) displays different characteristics compared to breast cancer in Caucasian women (CW), including earlier onset, less favorable clinical outcome, and an aggressive tumor phenotype. These disparities may be attributed to differences in socioeconomic factors such as access to health care, lifestyle, including increased frequency of obesity in AAW, and tumor biology, especially the higher frequency of triple negative breast cancer (TNBC) in young AAW. Improved understanding of the etiology and molecular characteristics of TNBC in AAW is critical to determining whether and how TNBC contributes to survival disparities in AAW. METHODS: Demographic, pathological and survival data from AAW (n = 62) and CW (n = 98) with TNBC were analyzed using chi-square analysis, Student's t-tests, and log-rank tests. Frozen tumor specimens were available from 57 of the TNBC patients (n = 23 AAW; n = 34 CW); RNA was isolated after laser microdissection of tumor cells and was hybridized to HG U133A 2.0 microarrays. Data were analyzed using ANOVA with FDR <0.05, >2-fold difference defining significance. RESULTS: The frequency of TNBC compared to all BC was significantly higher in AAW (28%) compared to CW (12%), however, significant survival and pathological differences were not detected between populations. Gene expression analysis revealed the tumors were more similar than different at the molecular level, with only CRYBB2P1, a pseudogene, differentially expressed between populations. Among demographic characteristics, AAW consumed significantly lower amounts of caffeine and alcohol, were less likely to breastfeed and more likely to be obese. CONCLUSIONS: These data suggest that TNBC in AAW is not a unique disease compared to TNBC in CW. Rather, higher frequency of TNBC in AAW may, in part, be attributable to the effects of lifestyle choices. Because these risk factors are modifiable, they provide new opportunities for the development of risk reduction strategies that may decrease mortality by preventing the development of TNBC in AAW.

The joint contribution of tumor phenotype and education to breast cancer survival disparity between Hispanic and non-Hispanic white women.

Some studies suggest that Hispanic women are more likely to have ER- and triple-negative (ER-/PR-/HER2-) tumors and subsequently poorer prognosis than non-Hispanic white (NHW) women. In addition, only a handful of studies have examined period-specific effects of tumor phenotype and ethnicity on breast cancer survival, leaving the time-varying effects of hormonal status and ethnicity on breast cancer survival poorly defined. This study describes short and long-term breast cancer survival by ethnicity at 0-5 years and 5+ years post-diagnosis using data from the New Mexico Health, Eating, Activity, and Lifestyle cohort of Hispanic and NHW women ages 29-88 years newly diagnosed with stages I-IIIA breast cancer. The survival rate for Hispanics at 0-5 years was 82.2 % versus 94.3 % for NHW. Hispanics were more likely to have larger tumors, more advanced stage, and ER- phenotypes compared to NHW women. There was a significantly higher risk of breast cancer mortality in Hispanics over 5 years of follow-up compared to NHW (HR = 2.78, 95 % CI 1.39-5.56), adjusting for age, tumor phenotype, stage, and tumor size. This ethnic difference in survival, however, was attenuated and no longer statistically significant when additional adjustment was made for education, although a >1.5-fold increase in mortality was observed. In contrast, there was no difference between ethnic groups for survival after 5 years (HR = 1.08, 95 % CI 0.36-3.24). Our results indicate that the difference in survival between Hispanic and NHW women with breast cancer occurs in the first few years following diagnosis and is jointly associated with tumor phenotype and socio-demographic factors related to education.