Breast cancer intrinsic subtypes by PAM50 in older women.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1524-1524
Author(s):  
Emily Oldham Jenkins ◽  
Allison Mary Deal ◽  
Carey K. Anders ◽  
Aleix Prat ◽  
Charles M. Perou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Biology ◽  
Continuous Variable ◽  
Intrinsic Subtype ◽  
Intrinsic Subtypes ◽  
Luminal A ◽  
Prognostic Information ◽  
Luminal B ◽  
Kaplan Meier ◽  
Treatment Data

1524 Background: Breast cancer (BC) incidence dramatically increases with age and the number of older BC patients (pts) in the U.S. is rising. Although immunohistochemical (IHC) data confirm that the incidence of luminal BC increases with age while the incidence of triple negative (TN) BC decreases, age-specific data on the frequency of BC subtypes defined by gene expression is limited. We characterized the incidence of BC intrinsic subtypes using gene microarrays according to age. Methods: Data from 2,150 pts were pooled from publicly available microarray datasets to determine the incidence of PAM50 breast cancer intrinsic subtypes (Luminal A [LumA], Luminal B [LumB], HER2-enriched [Her2E], Basal-like [Basal] and Normal-like [Norm]) by age. Adjuvant treatment data (none, chemotherapy, endocrine therapy or both) were available for 1,741 samples. Relapse-free (RFS) and overall survival (OS) differences were determined using the Kaplan-Meier method. Results: PAM50 intrinsic subtypes by age are tabulated below. The incidence of luminal (A, B, A+B) tumors increased with age (p<0.01, p<0.0001, p<0.0001, respectively), while the percentage of basal tumors decreased (p<0.0001). Basal tumors represented 13% of pts aged > 70 years (yrs); of the 70% with available IHC data, 74% were TNBC. Age as a continuous variable was not associated with RFS (p = 0.37). Subtype alone (n=2031), and after controlling for treatment (n=1645), was significantly associated with RFS (both p<0.0001). The addition of age to a multivariate analysis added no prognostic information. Conclusions: Though more favorable subtypes increase with age, older BC pts still have a substantial percentage of high-risk subtypes. Age alone was not a significant factor in outcome. Tumor biology as defined by intrinsic subtype is an important clinical predictor. [Table: see text]

scholarly journals Heterogeneity of Breast Cancer Associations with Common Genetic Variants inFGFR2according to the Intrinsic Subtypes in Southern Han Chinese Women

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Huiying Liang ◽  
Xuexi Yang ◽  
Lujia Chen ◽  
Hong Li ◽  
Anna Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Chinese Women ◽  
Intrinsic Subtype ◽  
Han Chinese ◽  
Dependent Manner ◽  
Intrinsic Subtypes ◽  
Luminal A ◽  
Luminal B ◽  
Common Genetic Variants

GWAS have identified variation in theFGFR2locus as risk factors for breast cancer. Validation studies, however, have shown inconsistent results by ethnics and pathological characteristics. To further explore this inconsistency and investigate the associations ofFGFR2variants with breast cancer according to intrinsic subtype (Luminal-A, Luminal-B, ER−&PR−&HER2+, and triple negative) among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582 polymorphisms in 609 patients and 882 controls. Significant associations with breast cancer risk were observed for rs2420946, rs2981579, and rs2981582 with OR (95% CI) per risk allele of 1.19 (1.03–1.39), 1.24 (1.07–1.43), and 1.17 (1.01–1.36), respectively. In subtype specific analysis, above three SNPs were significantly associated with increased Luminal-A risk in a dose-dependent mannerPtrend<0.01; however, only rs2981579 was associated with Luminal-B, and none were linked to ER−&PR− subtypes (ER−&PR−&HER2+ and triple negative). Haplotype analyses also identified common haplotypes significantly associated with luminal-like subtypes (Luminal-A and Luminal-B), but not with ER−&PR− subtypes. Our results suggest that associations ofFGFR2SNPs with breast cancer were heterogeneous according to intrinsic subtype. Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms underlying breast cancer.

scholarly journals Re-definition of claudin-low as a breast cancer phenotype

2019 ◽  
Author(s):  
Christian Fougner ◽  
Helga Bergholtz ◽  
Jens Henrik Norum ◽  
Therese Sørlie
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Subtype ◽  
Breast Tumors ◽  
Intrinsic Subtype ◽  
Intrinsic Subtypes ◽  
Luminal A ◽  
Diverse Range ◽  
Luminal B ◽  
Cancer Phenotype ◽  
Definition Of

The claudin-low breast cancer subtype is defined by gene expression characteristics and encompasses a remarkably diverse range of breast tumors. Here, we investigate genomic, transcriptomic, and clinical features of claudin-low breast tumors. We show that claudin-low is not simply a subtype analogous to the intrinsic subtypes (basal-like, HER2-enriched, luminal A, luminal B and normal-like) as previously portrayed, but is a complex additional phenotype which may permeate breast tumors of various intrinsic subtypes. Claudin-low tumors were distinguished by low genomic instability, mutational burden and proliferation levels, and high levels of immune and stromal cell infiltration. In other aspects, claudin-low tumors reflected characteristics of their intrinsic subtype. Finally, we have developed an alternative method for identifying claudin-low tumors and thereby uncovered potential weaknesses in the established claudin-low classifier. In sum, these findings elucidate the heterogeneity in claudin-low breast tumors, and substantiate a re-definition of claudin-low as a cancer phenotype.Contact informationC.F. [email protected]. [email protected]. [email protected]. [email protected]

scholarly journals Robust and interpretable PAM50 reclassification exhibits survival advantage for myoepithelial and immune phenotypes

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
James C. Mathews ◽  
Saad Nadeem ◽  
Arnold J. Levine ◽  
Maryam Pouryahya ◽  
Joseph O. Deasy ◽  
...  
Keyword(s):  
Survival Rates ◽  
Intrinsic Subtype ◽  
Cell Phenotype ◽  
Intrinsic Subtypes ◽  
Her2 Gene ◽  
Luminal A ◽  
Gene Group ◽  
Luminal B ◽  
Mammary Cell

Abstract We introduce a classification of breast tumors into seven classes which are more clearly defined by interpretable mRNA signatures along the PAM50 gene set than the five traditional PAM50 intrinsic subtypes. Each intrinsic subtype is partially concordant with one of our classes, and the two additional classes correspond to division of the classes concordant with the Luminal B and the Normal intrinsic subtypes along expression of the Her2 gene group. Our Normal class shows similarity with the myoepithelial mammary cell phenotype, including TP63 expression (specificity: 80.8% and sensitivity: 82.8%), and exhibits the best overall survival (89.6% at 5 years). Though Luminal A tumors are traditionally considered the least aggressive, our analysis shows that only the Luminal A tumors which are now classified as myoepithelial have this phenotype, while tumors in our luminal class (concordant with Luminal A) may be more aggressive than previously thought. We also find that patients with basal tumors surviving to 48 months exhibit favorable continued survival rates when certain markers for B lymphocytes are present and poor survival rates when they are absent, which is consistent with recent findings.

Stage, biology, and age.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11512-e11512
Author(s):  
Hee Jeong Kim ◽  
Beom Seok Ko ◽  
Jong Han Yu ◽  
jong Won Lee ◽  
Byung Ho Sohn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Triple Negative ◽  
Medical Center ◽  
Intrinsic Subtype ◽  
Young Age ◽  
Tnm Stage ◽  
Intrinsic Subtypes ◽  
Luminal A ◽  
Survival Difference

e11512 Background: Breast cancer subtypes are prognostic and predictive for patients. In this study, prognostic value of TNM stage, intrinsic subtype, and age were compared. Methods: We analyzed results from 7,626 breast cancer patients registered on the Asan medical center database between 1999 and 2009. We compared survival according to the TNM stage, intrinsic subtype using ER, PR, Her2- immunohistochemical staining, and age. Results: Luminal A subtype showed the best survival rates while triple negative subtype showed the worst survival rate amongst intrinsic subtypes. Survival analysis showed that Stage I triple negative breast cancer showed better survival compared to Stage III Luminal A subtype breast cancer (89.0% vs 76.6% P<0.001). Survival differences between intrinsic subtypes were more significant in lymph node positive breast cancer compared to lymph node negative breast cancer. Age did not affect survival between stages and intrinsic subtypes except for the young age subgroup (≤35), for whom there was no survival difference amongst intrinsic subtypes. Conclusions: Staging of breast cancer showed a more direct correlation to survival than known prognosis for intrinsic subtypes, as advanced, good prognostic intrinsic subtype breast cancer had worse survival than early, worse prognostic intrinsic subtype breast cancer. However for the young age group (≤35), the survival of all intrinsic subtypes were similar.

scholarly journals Performing Data Mining to Explain the Correlation between the BIRC5 Gene and Prognosis in Breast Cancer Patients

2020 ◽  
Author(s):  
Hong Dongsheng ◽  
Zhang YanFang ◽  
Ye Ziqi ◽  
Chen Jing ◽  
Lu Xiaoyang
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Cancer Cell Line ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Kaplan Meier ◽  
Er Positive

Abstract Background: Breast cancer is the most commonly malignant cancers in women, and BIRC5 has been found to be overexpressed in a variety of human tumors. Its expression is associated with the prognosis of many cancers. However, whether BIRC5 mRNA could be used as an independent prognostic factor for breast cancer remains inconsistent in previous studies.Methods: Altered BIRC5 expression in normal tissue relative to various tumor tissue and in breast cancer patients with different molecular subtypes, clinical outcomes and chemotherapy responses were examined using the Oncomine, GOBO and Kaplan-Meier plotter datasets.Results: We found that many breast cancers had increased BIRC5 mRNA expression, and GOBO analysis showed that triple-negative cell lines displayed highest BIRC5 mRNA expression levels in the breast cancer cell line panel. Moreover, BIRC5 high mRNA expression was significantly associated with longer relapse-free survival (RFS) in all breast cancer patients. In particular, sub analysis revealed that high mRNA expression of BIRC5 was significantly associated with better survival in ER positive (HR = 2.05, p = 1e-16), but not in ER negative breast cancer (HR = 1.24, p = 0.1), furthermore, the results also demonstrated that BIRC5 high expression was significantly associated with longer RFS in luminal A (HR = 1.51, p = 3.1e-06) and luminal B (HR = 1.28, p = 0.026).Conclusions: In conclusion, BIRC5 is involved in the development and progression of breast cancer and may be a suitable prognostic marker for human breast cancer.

The effect of margin status and molecular subtype on women with invasive breast cancer treated with breast-conservation therapy.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 83-83
Author(s):  
Jared Forrester ◽  
Adam D. Currey ◽  
Bonifride Tuyishimire ◽  
Jonathan Lin ◽  
Amanda L. Kong
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Molecular Subtype ◽  
Tumor Biology ◽  
Breast Conservation ◽  
Margin Status ◽  
Stage I ◽  
Luminal A ◽  
Luminal B ◽  
The Impact

83 Background: A consensus statement was recently published by SSO/ASTRO on margins for stage I and II invasive breast cancer treated with breast conserving surgery (BCS). We examined patients with invasive breast cancer who underwent BCS to determine if margin status and molecular subtype influence outcomes. Methods: We the reviewed charts of 754 Stage I-III breast cancer patients treated with BCS from 2003-2010. Margin status was defined as negative ≥ 2mm, close < 2mm and positive as tumor on ink. Conventional receptor analyses were used as markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal). Clinicopathologic variables were tested using the Fisher’s exact, Chi-square, ANOVA F-test, and Kruskal-Wallis tests. A Cox proportional - Hazards model was used to measure the impact of these variables on locoregional recurrence (LRR), breast cancer-specific (BCSS) and overall survival (OS). Results: The median age of the cohort was 58 (range 27-89 years). Most were white (88%), had T1 tumors (76%), luminal A tumors (66%), invasive ductal histology (80%), and were node negative (76%). Of the 754 patients, 26% had close margins, 2% positive margins, and 9% unknown margins. With a median follow-up of 5.2 years, OS was 92%. Twenty eight patients had a LRR with a median time to recurrence of 5.1 years. On multivariate analysis, molecular subtype, pathologic grade (p=0.01), and use of radiation (p<0.0001) were the only significant predictors of LRR. Unknown subtype, compared to Luminal A, was less likely to have a LRR (p=0.04). Basal (p=0.0002), Her2+ (p=0.03), Luminal B (p=0.002) and unknown subtype (p=0.04) had worse BCSS compared to Luminal A tumors. Margins had no impact on LRR or BCSS but those with close margins and unknown margins had worse OS compared to negative margins (p=0.01, p=0.007). Variables predictive of OS were margins, age, race, node status, chemotherapy, anti-endocrine therapy, and radiation. Conclusions: In this cohort treated with BCS, molecular subtype was a predictor of LRR and BCSS but not OS. Margin status did not impact LRR and BCSS. Although margin status was a predictor of OS, tumor biology remains the significant determinant of outcome.

scholarly journals Robust and Interpretable PAM50 Reclassification Exhibits Survival Advantage for Myoepithelial and Immune Phenotypes

2018 ◽  
Author(s):  
James C. Mathews ◽  
Saad Nadeem ◽  
Arnold J. Levine ◽  
Maryam Pouryahya ◽  
Joseph O. Deasy ◽  
...  
Keyword(s):  
Survival Rates ◽  
Intrinsic Subtype ◽  
Cell Phenotype ◽  
Intrinsic Subtypes ◽  
Her2 Gene ◽  
Luminal A ◽  
Gene Group ◽  
Luminal B ◽  
Mammary Cell

AbstractWe introduce a classification of breast tumors into 7 classes which are more clearly defined by interpretable mRNA signatures along the PAM50 gene set than the 5 traditional PAM50 intrinsic subtypes. Each intrinsic subtype is partially concordant with one of our classes, and the 2 additional classes correspond to division of the classes concordant with the Luminal B and the Normal intrinsic subtypes along expression of the Her2 gene group. Our Normal class shows similarity with the myoepithelial mammary cell phenotype, including TP63 expression (specificity: 80.8% and sensitivity: 82.8%), and exhibits the best overall survival (89.6% at 5 years). Though Luminal A tumors are traditionally considered the least aggressive, our analysis shows that only the Luminal A tumors which are now classified as myoepithelial have this phenotype, while tumors in our luminal class (concordant with Luminal A) may be more aggressive than previously thought. We also find that patients with Basal tumors surviving to 48 months exhibit favorable survival rates when certain markers for B-lymphocytes are present and poor survival rates when they are absent, which is consistent with recent findings.

Quantitative hormone receptors, triple-negative breast cancer (TNBC), and molecular subtypes: A collaborative effort of the BIG-NCI NABCG.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1008-1008 ◽  
Author(s):  
Maggie Chon U. Cheang ◽  
Miguel Martin ◽  
Torsten O. Nielsen ◽  
Aleix Prat ◽  
Alvaro Rodriguez-Lescure ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Tumor Biology ◽  
Intrinsic Subtype ◽  
Phase Iii ◽  
Her2 Status ◽  
Luminal A ◽  
Exact Test ◽  
Borderline Cases ◽  
Luminal B ◽  
Three Phase

1008 Background: Most TNBC trials focusing on biology of the basal-like subtype (BLBC) allow borderline (1-10% staining) estrogen receptor (ER) and progesterone receptor (PgR) expression by immunohistochemistry (IHC); however the optimal ER and PgR cut points to enrich for non-luminal subtypes has not been studied. In this study,we compared quantitative ER/PgR status with gene expression-based intrinsic subtype in order to determine if borderline cases should be included in TNBC trials. Methods: ER, PgR, and HER2 status was determined by central review of tumors collected from three phase III randomized trials: GEICAM 9906 (n=820), NCIC CTG MA.5 (n=476) and MA.12 (n=398). PAM50 intrinsic subtyping (BLBC, HER2-enriched, Luminal A, Luminal B and Normal-like) was performed using the qRT-PCR-based assay. Quantitative ER/PgR expression by IHC and subtype was tested using ANOVA and Fisher’s exact test. Results: Of 1,694 tumors, 15% were BLBC, 21% HER2-Enriched, 33% Luminal A, 25% Luminal B and 4% Normal-like. BLBC subtypes were significantly associated with low expression of ER and PgR (median = 0.05%) compared to other subtypes (p < 0.001). The vast majority of BLBC (96%) did not express any ER or PgR protein by IHC. BLBC represented 73% of TNBC (borderline cases not included) and significantly more than the additional TNBC with borderline ER/PgR (p < 0.001). Within borderline ER/PgR and HER2-negative cases only, 17% were BLBC and 46% were luminal subtypes (Table). Conclusions: BLBC rarely express ER or PgR by IHC. The majority of borderline TNBC (1-10% ER/PgR) are not BLBC; half of them are categorized as luminal categories that may be endocrine sensitive. TNBC trials seeking to target BLBC tumor biology should use the ASCO/CAP guidelines of 0% as the cutoffs for ER and PgR negativity. [Table: see text]

Pathological response and its effect on survival with neoadjuvant chemotherapy according to intrinsic subtype in locally advanced breast cancers in north India: Is it different from the West?

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 90-90
Author(s):  
Sushma Agrawal ◽  
Punita Lal ◽  
Shaleen Kumar ◽  
Gaurav Agarwal ◽  
Anjali Mishra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Intrinsic Subtypes ◽  
Luminal A ◽  
Luminal B ◽  
Basal Subtype ◽  
Her 2

90 Background: Breast cancer patients commonly present in locally advanced stage (LABC) in our country. We propose to correlate the pathological response to neoadjuvant chemotherapy (NACT) and its impact on survival based on the intrinsic subtypes. Methods: Consecutive patients of LABC who underwent NACT (taxane and or anthracyclines based )followed by definitive surgery and radiotherapy during the period January 2007 to December 2012 were grouped on the basis of intrinsic subtypes (Luminal A, Luminal B, Her-2 Type, Basal). The pathological response to NACT in tumour as well as axillary nodes [complete response (pCR), partial response (pPR)] was correlated with the disease free survival (DFS) and overall survival (OS) at 5 years in the intrinsic subtypes using Kaplan Meier Analysis. Results: Among 208 patients the median age was 46 years (range 24-81 years), 46% premenopausal,54% postmenopausal, presenting tumour and node stage was 15% T2, 40% T3, 45% T4,8% N0, 42% N1, 41% N2, 9% N3.The intrinsic subtypes at presentation were Luminal A (16%), Luminal B (23%), Her-2 Type (23%), Basal (37%).The pCR rate in node was significantly higher in Her-2 type and Basal subtype (Table ). At a median followup of 34 months (range 6-84 mo)the 5 year DFS and OS was significantly higher in patients achieving pCR tumour or node in Her-2 type and Basal subtype (Table ). Conclusions: The pCR rate to NACT in tumour or node seems to be considerably higher in our population than that reported in the western literature. pCR (tumour and node) is a surrogate for both DFS and OS at 5 years in Her-2 and basal subtypes of breast cancer. [Table: see text]

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