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 ◽  
...  

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]

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1524-1524
Author(s):  
Emily Oldham Jenkins ◽  
Allison Mary Deal ◽  
Carey K. Anders ◽  
Aleix Prat ◽  
Charles M. Perou ◽  
...  

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]


2020 ◽  
pp. 1-3
Author(s):  
Sara Khelf ◽  
◽  
Leila Guedjali ◽  
Souad Haddad ◽  
Dalila Satta ◽  
...  

Breast cancer (CS) is the most common female cancer worldwide, ranking first in Algeria for its frequency and mortality .Molecular classification has distinguished at least four molecular types: luminal A, luminal B, HER2 and basal-like. Our objective is to study the phenotypic profile of breast cancer in women with cancer as well as the different clinical, immunohistochemical and therapeutic aspects of different molecular groups.We undertook a retrospective study between October 2016 and December 2017. This study involved 121 files. The distribution of the population according to age showed that the most affected age group is [53-63] years old with 35%. Molecular classification results showed that the most common type was luminal A at 37.19%, followed by luminal type B at 27.27%, basal-like at 19.83%, and HER2 at 15.70%. Breast cancer of luminal type, expressing[ ER], accounts for 70 to 80% of all mammary carcinomas and that the luminal group A is the most common with proportions of 58 , 5% and 54.3% respectively while the distinction is observed in the other groups. Molecular classification plays a very important role in the treatment. This result shows that luminal type A is the most common, and that postmenopausal women are most likely to have breast cancer. This classification is very important in the orientation of the treatment. The resulting molecular classification is expected to better classify tumors to a personalized therapy. Breast cancer, molecular classification, immunohistochemistry, hormone receptors, HER2 status


2020 ◽  
Vol 17 (2) ◽  
pp. 187-192
Author(s):  
E.A. Novikova ◽  
◽  
O.V. Kostromina ◽  
D.V. Mikhailov ◽  
S.L. Leontiev ◽  
...  

Aim. The aim of the study was to determine the presence of peculiarities of the age structure in patients with various surrogate molecular biological subtypes of breast cancer. Materials and research methods. This work analyzes the age-related characteristics of the occurrence of molecular biological subtypes in 499 patients with invasive breast cancer. All cases were divided into 5 molecular biological subtypes based on immunohistochemical studies of hormone receptors, Her2, Ki-67. The average age of the patients was 53.4±0.39 years, the predominant group was patients from 50 to 60 years (37.2% of the total). Research results. In patients under 40 years old, the triple negative subtype prevailed (44.8%). Luminal A subtype prevailed in the groups 51-60 years old (more than 41.4%) and over 60 years old (39.7%). Luminal B (Her2-) subtype was equally found in all age groups.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3146
Author(s):  
Patricia Fernández-Nogueira ◽  
Gemma Fuster ◽  
Álvaro Gutierrez-Uzquiza ◽  
Pere Gascón ◽  
Neus Carbó ◽  
...  

Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs’ role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.


2019 ◽  
Vol 5 (1) ◽  
Author(s):  
James C. Mathews ◽  
Saad Nadeem ◽  
Arnold J. Levine ◽  
Maryam Pouryahya ◽  
Joseph O. Deasy ◽  
...  

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.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 516-516
Author(s):  
Volker Moebus ◽  
Hans-Joachim Lueck ◽  
Ekkehart Ladda ◽  
Peter Klare ◽  
Marcus Schmidt ◽  
...  

516 Background: GAIN-2 (NCT01690702) compared efficacy and safety of intense, dose-dense epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) vs dose-dense, dose-tailored epirubicin/ cyclophosphamide followed by dose-dense, dose-tailored docetaxel (dtEC-dtD) as adjuvant or neoadjuvant CT for node-positive or high risk node-negative EBC. Here, we report safety results and interim analysis (IA) of the primary endpoint iDFS. Methods: Pts (luminal A ≥N2; luminal B N+; HER2+ and TNBC) were randomized between iddEnPC (E 150 mg/m2, nP 330 mg/m2, C 2000 mg/m2, all q2w x 3) or dtEC-dtD (dtEC q2w x 4 followed after 1 week rest by dtD q2w x 4). Primary objective was to compare iDFS. 797 events are needed to detect a hazard ratio of 0.819 with a 2-sided log-rank-test with 80% power and α=0.05. The IA of iDFS was planned after 50% of the events have occurred. Safety and compliance were secondary objectives. Results: Between 10/2012 and 09/2018, 2887 pts were randomized and 2857 started treatment (iddEnPC 1429; dtEC-dtD 1428). Median age was 51 (range 18-75) years. Overall, 18.1% were luminal A, 31.5% luminal B/HER2-, 18.8% hormone-receptor (HR)+/HER2+, 8.5% HR-/HER2+ and 23.2% TNBC. Overall, 88.1% of pts completed all treatment in both arms. 66.8% with iddEnPC vs 58.8% with dtEC-dtD delayed CT dose (p<0.001). Grade 3-4 non-hematological adverse events (AEs) were more frequent with iddEnPC (iddEnPC 50.8% vs dtEC-dtD 45.1%, p=0.002). Grade 3-4 leukopenia, neutropenia, febrile neutropenia, arthralgia, and peripheral sensory neuropathy were significantly higher with iddEnPC. There were 1464 serious AEs (iddEnPC 870 vs dtEC-dtD 594) and 26 (9 vs 17) predefined AEs of special interest (anaphylaxis, any AE affecting cranial nerves, macula edema). Two deaths occurred during dtEC-dtD. After a median follow-up of 45.8 months, there was no difference in iDFS between arms (log-rank p=0.9102, hazard ratio iddEnPC vs dtEC-dtD 1.01, 95% CI 0.83-1.23). Conclusions: No new safety concerns were observed. Use of both iddEnPC and dtEC-dtD appears feasible in the (neo)adjuvant treatment of high risk EBC. Clinical trial information: NCT01690702 .


Author(s):  
Karen S Johnson ◽  
Emily F Conant ◽  
Mary Scott Soo

Abstract Gene expression profiling has reshaped our understanding of breast cancer by identifying four molecular subtypes: (1) luminal A, (2) luminal B, (3) human epidermal growth factor receptor 2 (HER2)-enriched, and (4) basal-like, which have critical differences in incidence, response to treatment, disease progression, survival, and imaging features. Luminal tumors are most common (60%–70%), characterized by estrogen receptor (ER) expression. Luminal A tumors have the best prognosis of all subtypes, whereas patients with luminal B tumors have significantly shorter overall and disease-free survival. Distinguishing between these tumors is important because luminal B tumors require more aggressive treatment. Both commonly present as irregular masses without associated calcifications at mammography; however, luminal B tumors more commonly demonstrate axillary involvement at diagnosis. HER2-enriched tumors are characterized by overexpression of the HER2 oncogene and low-to-absent ER expression. HER2+ disease carries a poor prognosis, but the development of anti-HER2 therapies has greatly improved outcomes for women with HER2+ breast cancer. HER2+ tumors most commonly present as spiculated masses with pleomorphic calcifications or as calcifications alone. Basal-like cancers (15% of all invasive breast cancers) predominate among “triple negative” cancers, which lack ER, progesterone receptor (PR), and HER2 expression. Basal-like cancers are frequently high-grade, large at diagnosis, with high rates of recurrence. Although imaging commonly reveals irregular masses with ill-defined or spiculated margins, some circumscribed basal-like tumors can be mistaken for benign lesions. Incorporating biomarker data (histologic grade, ER/PR/HER2 status, and multigene assays) into classic anatomic TNM staging can better inform clinical management of this heterogeneous disease.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13058-e13058
Author(s):  
Caterina Fontanella ◽  
Marta Bonotto ◽  
Pamela Driol ◽  
Francesca Valent ◽  
Lorenzo Gerratana ◽  
...  

e13058 Background: Widespread access to active agents against MBC has produced significant improvements in survival, even though few phase III trials are powered to detect overall survival (OS) effects. However, regulatory agencies hold OS as gold standard for approval of new drugs. OS can be portioned into the sum of progression-free survival (PFS) and survival post-progression (SPP). Recent data suggest that OS is a reasonable primary endpoint only when median SPP is short. On the other hand, patients enrolled in first-line trials could have a long life-expectancy. Aim of this study was to evaluate PFS, OS and SPP in a consecutive series of patients with MBC in order to obtain information as a basis for design of future clinical trials. Methods: Four hundred patients with MBC diagnosed from January 2004 to February 2011 at University Hospital of Udine, Italy, were included in the study. We examined the role of potential of disease and patients’ characteristics in influencing the different measures of outcome. Results: Median OS was 33.71 months (mo), in line with the best literature. Median PFS at first-line (PFS1) was 9.33 mo, with linear decrease at second (5.06), third (3.58), and fourth (3.19) line, respectively. Median SPP after first-line (SPP1) was 18.69 mo. Interestingly, differences in outcome were noticed according to immunophenotype. The best prognosis was observed in luminal A disease (OS= 46.72 mo, PFS1= 15.61 mo, SPP1= 25.43 mo). In luminal B disease, median OS was 27.66 mo, PFS1 8.94 mo, and SPP1 13.21 mo, respectively. In patients with HER2-positive disease, mainly treated with anti-HER2 therapy, outcome approached that of luminal A disease (OS= 41.10 mo, PFS= 9.89 mo, SPP1 18.69 mo). Patients with triple negative disease (TNBC) experienced the worst prognosis (OS= 8.54 mo, PFS1= 4.04 mo, SPP1= 2.83 mo). Conclusions: The study demonstrated different results in the measures of outcome according to the line of treatment and specific disease characteristics. As a consequence, endpoints of clinical trials should be tailored taking into consideration prognostic/predictive factors as well as the line of treatment.


2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 83-83
Author(s):  
Jared Forrester ◽  
Adam D. Currey ◽  
Bonifride Tuyishimire ◽  
Jonathan Lin ◽  
Amanda L. Kong

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.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12586-e12586
Author(s):  
Davit Zohrabyan ◽  
Samvel Bardakhchyan ◽  
Sergo Mkhitaryan ◽  
Liana Safaryan ◽  
Jemma Arakelyan ◽  
...  

e12586 Background: Breast cancer (BC) is the most common malignancy among the women in Armenia (AM). Currently there is a knowledge gap regarding the morphology distribution of the BC in AM. Methods: The data on patients with BC diagnosed in 2015-2016 in the pathology lab “Davidyants Labs” in AM were retrospectively reviewed. Pts with Her2+ results by IHC were excluded from the study, due to unavailability to perform FISH or CISH analyses. Overall 361 pathology reports were evaluated. Results: The median age was 54 years; range [19-82]. Histopathological subtypes were defined for 305 pts, from which lobular carcinoma 57.4% of cases (175/305), ductal carcinoma 26.9% (82/305), mucinous carcinoma 2.6% (8/305), mixed type carcinoma (lobular and ductal) 2.6% (8/305), DCIS 2% (n = 6/305), non specified carcinoma 2% (6/305), medullary carcinoma 1% (n = 3/305) and others 5.6% (17/305). Within the cohort 8.5% (23/270) were grade 1, 65.9% grade 2 (178/270); 25.6% grade 3 (n = 69/270). Vascular or lymphatic invasion was present in 59.5% (50/84) and 64.7% (55/85), respectively. Staging distribution, based on pT pN data for 92 pts who went to primary surgery, was: 0 stage 7.6% (7/92), I stage 22.8% (21/92), II stage 41.3% (38/92), III stage 28.3% (26/92). Staging distribution based on ypT ypN data for 27 pts who went to surgery after neoadjuvant chemo was 0 stage 25.9% (7/27), I stage 18.5% (5/27), II stage 29.6% (8/27), III stage 25.9% (7/27). ER and PR were defined for 244 patients. ER positive 89.8% (219/244) of cases, PR pos. 73% (178/244), ER/PR pos. 72.5% (177/244) cases. Her receptor was defined for 237 patients. Her3+ 16.9% (40/237); Her2+ 12.7% (30/237); Her1+ 38% (90/237); Her0 32.5% (n = 77/237). We could not evaluate Her2+ status by FISH or CISH, so these results were excluded from the analysis. Ki67 was low (≤20) in 42.1% (101/240) of cases and high ( > 20) in 57.9% (139/240). Within the group Luminal A type was 41.4% (84/203); Luminal B 32.5% (66/203); Her positive 19.7% (40/203) and triple negative 6.4% (13/203). p53 and perineural invasion (Pn) was present in 32% (16/50) and 52% (26/50), respectively. Tumor leukocyte infiltration was determined for 16 patients. Leukocyte infiltration was positive in 43.7% (7/16) cases, negative in 25% (4/16) cases, minimal in 31.3% cases (5/16). Conclusions: BC in Armenian women presents with different epidemiological characteristics in comparison with other ethnicities. Lobular type BC is the most frequent type among Armenian women, however, differential diagnosis between lobular/ductal carcinomas was done without IHC (E-Cadherin), which rises the need for further studies on that regard.


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