Characterization of germline and tumor genomic profile in unselected young black breast cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13090-e13090
Author(s):  
Tuya Pal ◽  
Deborah Cragun ◽  
Xuefeng Wang ◽  
Sean J. Yoder ◽  
Tania MESA ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Black Women ◽  
Predictive Value ◽  
Carrier Status ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Brca1 Carriers ◽  
Young Black Women ◽  
Associated Tumors

e13090 Background: Young black women bear a disproportionate burden of breast cancer (BC), yet there is limited characterization of these cancers based on BRCA1 and BRCA2 ( BRCA) status and tumor genomics. In this pilot study, we characterized: tumor and clinical characteristics based on BRCA carrier status and overlap of basal-like (BL) and triple negative (TN) BC. Methods: A population-based sample of 481 black women diagnosed with invasive BC < age 50 were recruited through the Florida Cancer Registry (FCR). BRCA status was determined based on germline testing. TN status was determined based on pathology reports and FCR data. Among a subset of 90 participants, gene expression profiling (GEP) was conducted on tumor samples through PAM50 analyses to classify intrinsic subtypes and risk of recurrence (ROR) scores. Results: Mean age at BC diagnosis was 41.9 (range: 25-50) and mean ROR score was 49.6 (range: 8.7-80.7). Participants included 7 BRCA1 carriers, 5 BRCA2 carriers, 67 non-carriers (NC), and 11 with no confirmed testing. Of 46 BL tumors, 33 were TN (71.7%) constituting 94.3% of TN tumors (the remaining 5.7% were Luminal A). All BRCA1 carriers had BL tumors, of which 5 were TN. Sensitivity, positive predictive value, and negative predictive value in identifying BRCA1 carrier was higher based on BL compared to TN status (Table 1). BRCA2-associated tumors included 3 Luminal A, 1 Luminal B, and 1 BL. Mean ROR score was highest among BRCA1 carriers (57.7), followed by NC (50.5) and BRCA2 carriers (41.5). Conclusions: Study findings suggest BL status predicted BRCA1 positivity better than TN status. BRCA2- (compared to BRCA1-) associated tumors were more heterogeneous with over half being Luminal A, which may explain the lower ROR among BRCA2 carriers. Additional follow-up and expansion of this cohort with collection of clinical outcomes will be useful in assessing the predictive utility of ROR scores among young black women with BC. [Table: see text]

The association between race and intrinsic subtype on hormone receptor-positive breast cancer among young black women.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12591-e12591
Author(s):  
Sonya Reid ◽  
Jaleesa Moore ◽  
Ann Tezak ◽  
Anne Weidner ◽  
Ingrid A. Mayer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Black Women ◽  
Hormone Receptor ◽  
White Women ◽  
Published Data ◽  
Intrinsic Subtypes ◽  
Luminal A ◽  
Hormone Receptor Positive ◽  
Incidence And Mortality ◽  
Young Black Women

e12591 Background: Hormone receptor-positive, HER2-negative breast cancer (HR+/HER2- BC) has the highest incidence and mortality rate across all racial/ethnic groups. HR+/HER2- BC is clinically and biologically heterogenous. Gene expression profiling assays can provide prognostic information and predict risk of late recurrence among women with HR+/HER2- BC. Prior studies have shown worse clinical outcomes among black women with HR+/HER2- BC. We sought to compare the distribution of intrinsic subtypes among young black women with HR+/HER2- BC, compared to published data from a young white cohort in the Carolina Breast Cancer Study (CBCS). Methods: Two population-based cohorts of black women diagnosed with BC between 2002 to 2012 at or below age 50 years were analyzed. Participants were recruited from twelve Southeastern states. All participants were asked to complete release of medical records and tissue/tumor forms to verify clinical information and to obtain primary tumor samples for future analyses. We compared the distribution of intrinsic subtypes and associations to clinical characteristics as compared to white female counterparts using Pearson chi-squared test. Results: Of 569 black participants, 124 women had HR+/HER2- BC and tumor samples available for analysis. There were 66 Luminal A (53%), 35 Luminal B (28%), 19 Basal (15%), and 4 HER2-enriched (3%) tumors. Black women with non-Luminal A tumors were younger ( < 40) with larger tumors ( > 2cm) and had higher risk of recurrence (ROR-T) scores as compared to black women with Luminal A tumors (p = 0.065, 0.006, and < 0.001, respectively). Compared to young white women in the CBCS, black women in our study had a significantly higher percentage of non-Luminal HR+/HER2- BC (p = 0.037). Conclusions: Our results suggest that among young women with HR+/HER2- BC, black women have a higher proportion of non-Luminal tumors compared to their white counterparts. Non-Luminal HR+/HER2- tumors (i.e., basal and HER2-enriched) are more aggressive and may be less sensitive to endocrine therapy. These results suggest that overrepresentation of aggressive HR+/HER2- BC subtypes may contribute to the racial survival disparity observed among black women.

The effect of molecular subtype on survival in a racially diverse cohort of patients with high-risk breast cancer receiving trimodality therapy.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 156-156
Author(s):  
J. L. Wright ◽  
C. Takita ◽  
J. E. Panoff ◽  
I. M. Reis ◽  
W. Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Black Women ◽  
Cancer Patients ◽  
Racial Differences ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Trimodality Therapy ◽  
Black Patients ◽  
Post Menopausal

156 Background: To understand the origins of racial disparities in breast cancer outcomes, the relative importance of race must be examined in the context of molecular subtype. We assessed racial differences in progression-free survival (PFS) and overall survival (OS) in relation to subtype in a cohort of uniformly treated stage II-III breast cancer patients. Methods: We reviewed records of 582 consecutive patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 and evaluated the effect of demographic, tumor, and treatment characteristics on PFS and OS. Results: Median follow-up 44.7 months. Patients: 24% black, 76% white, 55% pre/peri-menopausal. Disease: stage II 30%, stage III 70%. Treatment: all had mastectomy and PMRT; 98% had chemotherapy. All ER+ patients received endocrine therapy. Black and non-black patients were similar in age, menopause status, stage, and completion of trimodality therapy. Black patients were more likely to be ER- (56% vs 38%, p=0.0001), PR- (69% vs 54%, p=0.002), and triple negative (TN) (46% vs 24%, p<.0001). Among ER+, there were no differences in menopause or PR status by race. Black patients had worse PFS (60.6% vs 78.3%, p=.001) and OS (72.8% vs 87.7%, p<.0001). There was no racial difference in PFS (p=0.229 and 0.273 respectively) or OS (p=0.113 and 0.097 respectively) among ER- or TN. Among ER+, black patients had worse PFS (55% vs 81%, p<.001) and OS (73% vs 91%, p<.0001). The difference in PFS was seen in the ER+/PR+/HER2- (“luminal A”) subgroup (p=.002) but not ER+/PR-/HER2- (“luminal B”) (p=0.129), and in the post-menopausal ER+/HER2- subgroup (p=.004) but not pre/perimenopausal ER+/HER2- (p=.150). On multivariate analysis, racial differences in PFS (p=.055) and OS (p=.052) were maintained in the luminal A postmenopausal subgroup. Conclusions: In a cohort of breast cancer patients black women had worse survival. This disparity was driven by (1) a higher proportion of ER- and TN tumors in the black women and (2) worse outcome of similarly treated post-menopausal black women with luminal A breast cancer. The efficacy of various types of endocrine therapy must be examined in the setting of racial diversity.

scholarly journals Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3366
Author(s):  
Anna-Sophie Liegmann ◽  
Kerstin Heselmeyer-Haddad ◽  
Annette Lischka ◽  
Daniela Hirsch ◽  
Wei-Dong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Copy Number ◽  
Genome Instability ◽  
Single Cells ◽  
Gene Mutations ◽  
Intratumor Heterogeneity ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Pik3ca Mutations

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification. To further elucidate genomic instability and tumor heterogeneity in older patients, we analyzed the genetic aberration profiles of 39 breast cancer patients aged 50 years and older (median 67 years) with either short (median 2.4 years) or long survival (median 19 years). The analysis was based on copy number enumeration of eight breast cancer-associated genes using multiplex interphase fluorescence in situ hybridization (miFISH) of single cells, and by targeted next-generation sequencing of 563 cancer-related genes. Results: We detected enormous inter- and intratumor heterogeneity, yet maintenance of common cancer gene mutations and breast cancer specific chromosomal gains and losses. The gain of COX2 was most common (72%), followed by MYC (69%); losses were most prevalent for CDH1 (74%) and TP53 (69%). The degree of intratumor heterogeneity did not correlate with disease outcome. Comparing the miFISH results of diploid with aneuploid tumor samples significant differences were found: aneuploid tumors showed significantly higher average signal numbers, copy number alterations (CNAs) and instability indices. Mutations in PIKC3A were mostly restricted to luminal A tumors. Furthermore, a significant co-occurrence of CNAs of DBC2/MYC, HER2/DBC2 and HER2/TP53 and mutual exclusivity of CNAs of HER2 and PIK3CA mutations and CNAs of CCND1 and PIK3CA mutations were revealed. Conclusion: Our results provide a comprehensive picture of genome instability profiles with a large variety of inter- and intratumor heterogeneity in breast cancer patients aged 50 years and older. In most cases, the distribution of chromosomal aneuploidies was consistent with previous results; however, striking exceptions, such as tumors driven by exclusive loss of chromosomes, were identified.

scholarly journals Mapping of Genomic Vulnerabilities in the Post-Translational Ubiquitination, SUMOylation and Neddylation Machinery in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 833
Author(s):  
Jesús Fuentes-Antrás ◽  
Ana Lucía Alcaraz-Sanabria ◽  
Esther Cabañas Morafraile ◽  
María del Mar Noblejas-López ◽  
Eva María Galán-Moya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Gene Mutations ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Luminal A ◽  
Genomic Alterations ◽  
Cancer Hallmarks ◽  
Worse Prognosis

The dysregulation of post-translational modifications (PTM) transversally impacts cancer hallmarks and constitutes an appealing vulnerability for drug development. In breast cancer there is growing preclinical evidence of the role of ubiquitin and ubiquitin-like SUMO and Nedd8 peptide conjugation to the proteome in tumorigenesis and drug resistance, particularly through their interplay with estrogen receptor signaling and DNA repair. Herein we explored genomic alterations in these processes using RNA-seq and mutation data from TCGA and METABRIC datasets, and analyzed them using a bioinformatic pipeline in search of those with prognostic and predictive capability which could qualify as subjects of drug research. Amplification of UBE2T, UBE2C, and BIRC5 conferred a worse prognosis in luminal A/B and basal-like tumors, luminal A/B tumors, and luminal A tumors, respectively. Higher UBE2T expression levels were predictive of a lower rate of pathological complete response in triple negative breast cancer patients following neoadjuvant chemotherapy, whereas UBE2C and BIRC5 expression was higher in luminal A patients with tumor relapse within 5 years of endocrine therapy or chemotherapy. The transcriptomic signatures of USP9X and USP7 gene mutations also conferred worse prognosis in luminal A, HER2-enriched, and basal-like tumors, and in luminal A tumors, respectively. In conclusion, we identified and characterized the clinical value of a group of genomic alterations in ubiquitination, SUMOylation, and neddylation enzymes, with potential for drug development in breast cancer.

scholarly journals PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients

Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Predictive Value ◽  
Untreated Patient ◽  
Triple Negative ◽  
Statistical Significance ◽  
Breast Cancer Patients ◽  
The Impact

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

scholarly journals Abnormal Long Non-Coding RNAs Expression Patterns Have the Potential Ability for Predicting Survival and Treatment Response in Breast Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 996
Author(s):  
Ana Carolina Pavanelli ◽  
Flavia Rotea Mangone ◽  
Luciana R. C. Barros ◽  
Juliana Machado-Rugolo ◽  
Vera L. Capelozzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Predictive Value ◽  
Expression Patterns ◽  
Survival Rates ◽  
In Silico Analysis ◽  
Cancer Prognosis ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Non Coding Rnas

Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival rates in malignancies creates new scenarios for precision medicine and targeted therapy. Breast cancer (BRCA) is a heterogeneous malignancy. Despite advances in its molecular classification, there are still gaps to explain in its multifaceted presentations and a substantial lack of biomarkers that can better predict patients’ prognosis in response to different therapeutic strategies. Here, we performed a re-analysis of gene expression data generated using cDNA microarrays in a previous study of our group, aiming to identify differentially expressed lncRNAs (DELncRNAs) with a potential predictive value for response to treatment with taxanes in breast cancer patients. Results revealed 157 DELncRNAs (90 up- and 67 down-regulated). We validated these new biomarkers as having prognostic and predictive value for breast cancer using in silico analysis in public databases. Data from TCGA showed that compared to normal tissue, MIAT was up-regulated, while KCNQ1OT1, LOC100270804, and FLJ10038 were down-regulated in breast tumor tissues. KCNQ1OT1, LOC100270804, and FLJ10038 median levels were found to be significantly higher in the luminal subtype. The ROC plotter platform results showed that reduced expression of these three DElncRNAs was associated with breast cancer patients who did not respond to taxane treatment. Kaplan–Meier survival analysis revealed that a lower expression of the selected lncRNAs was significantly associated with worse relapse-free survival (RFS) in breast cancer patients. Further validation of the expression of these DELncRNAs might be helpful to better tailor breast cancer prognosis and treatment.

Prognostic subset of metastatic and non-metastatic luminal B breast cancer (LBBC) subtype based on Ki67 index.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12570-e12570
Author(s):  
Lalnun Puii ◽  
Lalram Sangi ◽  
Hrishi Varayathu ◽  
Samuel Luke Koramati ◽  
Beulah Elsa Thomas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Ki67 Index ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Ki 67 ◽  
Luminal B ◽  
Therapeutic Implications ◽  
Significant Difference

e12570 Background: Gene expression profiling for breast cancer has classified ER positive subtype into luminal A and luminal B. Luminal B breast cancer (LBBC) have a higher proliferation and poorer prognosis than luminal A tumors. Ki-67 index is the commonly used proliferation marker in breast cancer; however Ki67 expression can also be used to identify a subset of patients among LB with a favorable prognosis. This study attempts to verify this subset of LBBC patients based on DFS and PFS in non-metastatic and metastatic patients respectively. Methods: We retrospectively analyzed 80 IDC breast cancer patients diagnosed in 2013-2016 with complete follow-up till January-2021. We defined LBBC as ER+, PR+ or PR- , HER2+ or HER2- with a Ki67 index >20%. PFS was considered as the endpoint in patients presenting with metastatic disease whereas DFS was used in non-metastatic disease. The cut-off for ki67 was calculated using an X-tile plot (version 3.6.1, Yale University) by dividing Ki67 data into two populations: low and high, with randomized 1:1 “training” and “validation” cohorts. Results: Median age was 51.5 years. 18.7% (n=15) presented with metastasis at the time of diagnosis and their overall median PFS was found to be 25.8 months. The incidence of HER2 positive LBBC was found to be 15% (n=12) and none of them were found to be presented with metastasis. Survival and frequency of various sub groups in our study are enlisted in the given table. We estimated a Ki67 cut-off of 30% in patients with upfront metastatic disease and PFS was found to be higher in <30% compared to a Ki67 index >30% (38.9 months vs 19.7 months, p-0.002). Overall median DFS was not achieved in non-metastatic group (Mean DFS: 64.7 months) where as a statistically significant difference was observed in the survival of HER2 positive (median DFS: 53.5 months, mean DFS: 50.9) than HER2 negative patients (median DFS not achieved, mean: 66.97 months) ( p-0.021). We obtained a Ki67 cut-off of 32% in non- metastatic group and mean DFS was found to be higher in Ki67<32% (69 months) compared to Ki67>32% (61.4 months), however it failed to exhibit a statistically significant relationship ( p-0.373). Conclusions: Our study indicates that a subset of patients exists within metastatic and non-metastatic LBBC with differing prognosis based on Ki67. Larger studies are further required to confirm the findings and therapeutic implications.[Table: see text]

Geographical disparities of incidence and prevalence of triple-negative breast cancers: Multistate study data analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12599-e12599
Author(s):  
Hyein Jeon ◽  
Myeong Lee ◽  
Mohammed Jaloudi
Keyword(s):  
Breast Cancer ◽  
Black Women ◽  
Significant Relationship ◽  
White Women ◽  
Triple Negative ◽  
The State ◽  
Luminal A ◽  
Black Females ◽  
Black And White ◽  
State Effect

e12599 Background: Higher prevalence of triple negative breast cancer (TNBC) in black women with associated poor outcomes due to various disparities is well documented within a single state. We examine multiple states to better understand the state effect on such differences in incidence and prevalence of TNBC in black women. Methods: Female patients of ages 19 years old and above with breast cancer from the Surveillance, Epidemiology and End Results (SEER) Program across 13 states (608 counties) from 2015 (n = 66,444) and 2016 (n = 66,122) were examined. The relationships between the proportion of black and white women and the rate of patients with different tumor subtypes (luminal A, luminal B, HR-HER2+, and triple negative) were examined at the county level using ordinary least-square regression models. In parallel, due to consideration of various state-specific healthcare policies, socio-cultural norms, and socio-economic disparities, multi-level regression models were applied to examine the nested, random effect of each state on TNBC prevalence in each county. Bonferroni correction was applied to reduce the Type I error caused by repeated use of the same variables in multiple tests. Results: The baseline breast cancer rates between black and white women were similar in the population (0.171% for black and 0.168% for white). Consistent to previous studies, we demonstrate a significant positive correlation (p < 0.001) in TNBC in black females in both years. Surprisingly, when accounted for the random effects on states, 38.2% (2015) and 34.3% (2016) increase in incidence of TNBC in black females were seen, suggestive of state-specific disparity affecting race-specific health. In 2015, other subtypes of breast cancer in both black and white females did not result in significant relationship. Interestingly, in 2016, there was a significant relationship seen between the TNBC rate in white females and the white female population rate only after adjusting for the state effect (p = 0.026). This indicates the impact of non-biological factors such as state-wide health policies. Additionally, HR-HER2+ black females had a significant relationship against respective population rate only after adjusting for the state effect as well (p = 0.0394). For luminal A white females, a 15% decrease in incidence was seen after adjusting for state effect (p = 0.0424). Conclusions: This is the first known across-state examination of breast cancer subtypes by race with random effects on state. This study shows the role of state-specific factors affecting incidence in black and white females and potentially indicates the importance of state-level management for breast cancer on health disparities in addition to race-driven effects. Further studies are needed to elucidate comparable differences between states affecting the rates of various subtypes of breast cancer and thus health outcomes.

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