Molecular profiles of genomically high risk ER+ HER2- breast cancer tumors classified as functionally basal or luminal B by the 80-gene signature.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 563-563
Author(s):  
Joyce O'Shaughnessy ◽  
Virginia G. Kaklamani ◽  
Yuan Yuan ◽  
Julie Barone ◽  
Sami Diab ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Breast Cancers ◽  
Luminal B ◽  
Estrogen Response ◽  
Luminal Type ◽  
Basal Type

563 Background: The 80-gene signature (BluePrint/BP) classifies early-stage breast cancers based on functional molecular pathways as luminal, HER2, or Basal-type. In the NBRST study, 13% of immunochemistry (IHC) defined ER+ HER2- cancers reclassified as Basal-type by the BP assay (ER+ Basal), and these had worse prognosis but responded better to neoadjuvant chemotherapy than ER+ HER2- cancers classified as genomically luminal-type. The 70-gene risk of recurrence signature (MammaPrint/MP) further stratifies luminal-type cancers into low risk luminal A or high risk (HR) luminal B. HR cancers can be further stratified into High 1 (H1) or High 2 (H2), and the I-SPY2 trial has shown higher pCR rates in ER+ cancers classified as H2. Here, we investigated biological differences among ER+ Basal, ER- Basal, H1 luminal B, and H2 luminal B cancers by full transcriptome analysis. Methods: From the FLEX Study (NCT03053193), 1501 breast cancers with known IHC ER status were classified by MP and BP: 103 ER+ Basal, 210 ER- Basal and 1188 luminal B (H1 n=1034, H2 n=154). Clinical factors were assessed by either the Chi-square or Fisher’s exact tests; ANOVA or t test were used to analyze age. Differentially expressed genes (DEGs) were detected using Limma and pathway analyses were performed with GSEA. DEGs with a fold change >2 and FDR < 0.05 were considered significant. Results: Basal-type cancers (ER+/ER-) were larger and higher grade than luminal B cancers. Clustering analysis showed similar transcriptional profiles between ER+ Basal and ER- Basal cancers, distinct from luminal B cancers. Few DEGs were detected between ER+ Basal and ER- Basal cancers, and significantly more DEGs were found between ER+ Basal and luminal B cancers. Only three upregulated genes were detected in ER+ Basal compared to ER- Basal cancers: ESR1 and two immune-related genes ( FDCSP and LTF). Enrichment analysis of DEGs indicated increased immune activation and cell proliferation in ER+ Basal and ER- Basal cancers, and decreased estrogen response between ER+ Basal and luminal B cancers. Enrichment analysis between luminal B H1 and H2 cancers showed H2 cancers had higher immune activation and cell proliferation and lower estrogen response. Conclusions: Reclassification by BP of IHC defined ER+ HER2- cancers identified a subgroup of ER+ cancers that are biologically closer to ER- Basal than luminal-type cancers. Significant differences in response to neoadjuvant chemotherapy that have been seen between ER+ Basal and luminal B breast cancers lend support to the clinical importance of these findings. These data explain the poor prognosis observed in patients with ER+ Basal cancers and suggest that optimized chemotherapy, such as that for triple negative cancer, might be of benefit. BP provides clinically actionable information beyond pathological subtyping, which may guide neoadjuvant treatment recommendations. Clinical trial information: NCT03053193.

Molecular subtyping using MammaPrint and BluePrint as an outcome predictor in U.S. breast cancer (BC) patients.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 9-9
Author(s):  
Katharine Yao ◽  
Mary Turk ◽  
Karen Kaul ◽  
JoEllen Weaver ◽  
Femke De Snoo ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Free Survival ◽  
Low Risk ◽  
Axillary Lymph ◽  
Luminal A ◽  
Molecular Subtyping ◽  
Long Term Outcome ◽  
Luminal B ◽  
Luminal Type ◽  
Basal Type

9 Background: Combined use of MammaPrint and a molecular subtyping profile (BluePrint) identifies disease subgroups with marked differences in long-term outcome and response to neo-adjuvant therapy (Glück SABCS2011). The aim of this study was to evaluate the prognostic value of Molecular Subtyping using MammaPrint and BluePrint in women with early stage BC treated at U.S. institutions following National Comprehensive Cancer Network (NCCN) standard guidelines. Methods: Frozen tumor samples from 180 BC patients (TI-III, N0-Ib) median age 57 years at diagnosis (range 28-89) were suitable for hybridization on full genome array. MammaPrint and BluePrint Molecular Subtypes were determined and survival for Luminal A (MammaPrint Low Risk), Luminal B (MammaPrint High Risk), HER2-type and Basal-type patients was assessed. Patients were treated either with breast conserving therapy or mastectomy with axillary lymph node dissection between 1992 and 2005. The median follow-up is 12.7 years. 71% was ER positive and 20% Her2 positive by IHC/FISH. 58% received adjuvant endocrine therapy (ET) (excluding 13 patients unknown treatment), 64% received adjuvant chemotherapy (CT) (excluding 12 patients unknown treatment) and 33% received both. Results: 61 (34%) Patients with MammaPrint Low Risk/Luminal-type (Luminal A) showed 5-year DFS of 97% (34% received CT and 69% ET) and 50 (28%) patients with MammaPrint High Risk/Luminal-type (Luminal B) had a 5-year DFS of 98% (60% received CT and 68% ET). Patients with BluePrint Basal-type tumors (46 (26%)) had a 5-year DFS of 80% (78% received CT); HER2-type (23 (13%)) had a 5-year DFS of 78% (87% received CT without HER2 targeted therapy). Conclusions: In this retrospective study evaluating 180 US patients with early BC treated according to standard guidelines we showed how combining BluePrint with MammaPrint can detect molecularly defined subgroups of patients who are at high risk of recurrence (HER2 and Basal-type). Furthermore, we confirmed that molecularly defined Luminal type disease is associated with excellent disease-free survival. MammaPrint and BluePrint molecular and prognostic stratification should be prospectively evaluated for therapeutic selection.

Combined use of MammaPrint and molecular subtyping profile (BluePrint) to identify subgroups with marked differences in response to neoadjuvant treatment.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 42-42
Author(s):  
L. Stork-Sloots ◽  
F. De Snoo ◽  
P. Roepman ◽  
O. Krijgsman ◽  
R. Bernards ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Molecular Subtype ◽  
Low Risk ◽  
Molecular Subtyping ◽  
Receptor Status ◽  
Patient Cohort ◽  
Luminal Type ◽  
Basal Type

42 Background: Concordance between the IHC receptor status and the molecular subtype suggests that molecular profiles represent oncogenic processes that are driven by pathways in which ER, PR and HER2 play pivotal roles. It is, therefore, likely that the use of gene expression arrays will enable the identification of previously unappreciated subtypes of breast cancer that differ in clinical outcomes. Methods: The cohort consists of 133 (T1-4, N0-3) breast cancer patients treated with T/FAC neoadjuvant chemotherapy. Genome wide expression data was publicly available and downloaded from bioinformatics.mdanderson.org/pubdata.html. The data was used to determine the response to T/FAC neoadjuvant chemotherapy for patients stratified by MammaPrint and molecular subtype (BluePrint). The MammaPrint and BluePrint result were used to subtype the patients into 4 groups: MammaPrint Low-risk/Luminal-type, MammaPrint High-risk/Luminal-type, Basal-type and ERBB2-type. Results: Within this patient cohort, 20% (n=27) were classified as Basal-type, 62% (n=82) as Luminal-type, and 18% (n=24) as ERBB2-type. The overall pCR of this patient cohort was 26% and differed substantially among the subgroups. pCR was observed in 9% of all Luminal-type samples (i.e. 3% of MammaPrint Low Risk/Luminal-type and 11% of MammaPrint High Risk/Luminal-type), in 50% of the ERBB2-type samples and in 56% of the Basal-type samples. The pCR rates observed for the ERBB2-type and Basal-type patient groups were higher compared to classification based on IHC/CISH assessed ER and HER2 receptor status: 50% for ERBB2-type versus 39% for HER2+ and 56% for Basal-type versus 47% for ER-/HER2- samples. Conclusions: We observed marked differences in response to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. These findings confirm differences in chemotherapy response among molecular subgroups and indicate that the BluePrint profile described here will help to further establish a clinical correlation between molecular subtyping and treatment response.

Molecular subtyping using MammaPrint and BluePrint as an outcome predictor in 180 U.S. breast cancer (BC) patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 577-577
Author(s):  
Lisette Stork-Sloots ◽  
Katharine Yao ◽  
Mary Turk ◽  
Karen Kaul ◽  
JoEllen Weaver ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Free Survival ◽  
Low Risk ◽  
Axillary Lymph ◽  
Luminal A ◽  
Molecular Subtyping ◽  
Long Term Outcome ◽  
Luminal B ◽  
Luminal Type ◽  
Basal Type

577 Background: Combined use of MammaPrint and a molecular subtyping profile (BluePrint) identifies disease subgroups with marked differences in long-term outcome and response to neo-adjuvant therapy (Glück SABCS2011). The aim of this study was to evaluate the prognostic value of Molecular Subtyping using MammaPrint and BluePrint in women with early stage BC treated at US Institutions following National Comprehensive Cancer Network (NCCN) standard guidelines. Methods: Frozen tumor samples from 180 BC patients (TI-III, N0-Ib) median age 57 years at diagnosis (range 28-89) were suitable for hybridization on full genome array. MammaPrint and BluePrint Molecular Subtypes were determined and survival for Luminal A (MammaPrint Low Risk), Luminal B (MammaPrint High Risk), HER2-type and Basal-type patients was assessed. Patients were treated either with breast conserving therapy or mastectomy with axillary lymph node dissection between 1992 and 2005. The median follow-up is 12.7 years. 71% was ER positive and 20% Her2 positive by IHC/FISH. 58% received adjuvant endocrine therapy (ET) (excluding 13 patients unknown treatment), 64% received adjuvant chemotherapy (CT) (excluding 12 patients unknown treatment) and 33% received both. Results: 61 (34%) Patients with MammaPrint Low Risk/Luminal-type (Luminal A) showed 5-year DFS of 97% (34% received CT and 69% ET) and 50 (28%) patients with MammaPrint High Risk/Luminal-type (Luminal B) had a 5-year DFS of 98% (60% received CT and 68% ET). Patients with BluePrint Basal-type tumors (46 (26%)) had a 5-year DFS of 80% (78% received CT); HER2-type (23 (13%)) had a 5-year DFS of 78% (87% received CT without HER-2 targeted therapy). Conclusions: In this retrospective study evaluating 180 US patients with early BC treated according to standard guidelines we showed how combining BluePrint with MammaPrint can detect molecularly defined subgroups of patients who are at high risk of recurrence (HER2 and Basal-type). Furthermore, we confirmed that molecularly defined Luminal type disease is associated with excellent disease-free survival. MammaPrint and BluePrint molecular and prognostic stratification should be prospectively evaluated for therapeutic selection.

High-risk breast cancer genes at 8q22-24 and their role in over 5,000 patients evaluated with the 70-gene risk of recurrence assay.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3569-3569
Author(s):  
Sami Diab ◽  
Matei P. Socoteanu ◽  
Carlos A. Encarnacion ◽  
Cynthia R. C. Osborne ◽  
Carolyn B. Hendricks ◽  
...  
Keyword(s):  
High Risk ◽  
Molecular Subtype ◽  
Early Stage ◽  
Chromosome Region ◽  
Expression Patterns ◽  
Low Risk ◽  
Cancer Genes ◽  
Luminal A ◽  
Luminal B ◽  
Basal Type

3569 Background: Previous studies have shown that CCNE2 expression is higher in patients’ cancers resistant to CDK4/6 inhibitors. Increased expression of CCNE2, MTDH, or TSPYL5, genes contained within the 70-gene risk of distant recurrence signature (70GS), has also been implicated in breast oncogenesis, poor prognosis, and chemoresistance. These genes are located on chromosome region 8q22.1, one of the most recurrently amplified regions out of all 70GS genes in breast tumors (Fatima et al. 2017). MYC, located on 8q24, is overexpressed in 40% of all breast cancers (BC). Here we examined the expression of CCNE2, MTDH, and TSPYL5 in relation to 70GS risk and the 80-gene molecular subtype signature (80GS), and their correlation with MYC expression in early stage BC patients. Methods: CCNE2, MTDH, TSPYL5, and MYC mRNA expression was measured in 5022 BC samples sent to Agendia (Irvine, CA) for 70GS and 80GS testing, which included FFPE microarray full-transcriptome data. 70GS was used to stratify patients into Ultra Low Risk (UL), Low Risk (LR), High Risk (HR), and Ultra High Risk (UH). Both 70GS and 80GS were used to classify patient samples into Luminal A, Luminal B, HER2, or Basal type. Wilcoxon rank sum test was used to assess expression differences. Results: The expression of CCNE2, MTDH, and TSPYL5 significantly correlated with each other and was higher in HR patients compared to LR patients (p < 0.001) and higher in UH patients compared to HR patients (p < 0.001). Expression of these genes was highest in Basal type tumors, 83% of which were UH, followed by Luminal B type tumors, and lowest in Luminal A type tumors. CCNE2 and MYC expression was elevated in LR compared to UL patients (p < 0.001 and p = 0.0043). There was no difference in MYC expression between HR vs. LR or UH vs. HR. Lastly, there was no association between the expression of 8q22.1 genes and MYC in any 70GS subgroup. Conclusions: Within the 70GS, CCNE2, MTDH, and TSPYL5 have similar expression patterns and when overexpressed may identify an UH cohort of BC. This observation, in addition to their physical proximity at 8q22.1 suggests a possible amplicon in this region. The highest expression of CCNE2, MTDH, and TSPYL5 associated with UH patients and is concordant with previous studies that support the role of these genes in BC metastasis. Furthermore, this analysis suggests MYC may not stratify patients based on metastatic potential. These data may be clinically relevant for stratifying patients in ongoing clinical trials evaluating response and resistance to targeted therapies in early stage BC.

Whole transcriptome analysis comparing HR+ HER2- breast cancer tumors from patients 50 years.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 565-565
Author(s):  
Cathy Graham ◽  
Douglas Kanter Marks ◽  
Nina D'Abreo ◽  
Sami Diab ◽  
Vijayakrishna K. Gadi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptome Analysis ◽  
Gene Signature ◽  
Low Risk ◽  
Chemotherapy Response ◽  
Luminal B ◽  
Whole Transcriptome Analysis ◽  
Post Menopausal ◽  
Whole Transcriptome ◽  
Basal Type

565 Background: Recent prospective clinical trials have demonstrated a differential chemotherapy effect based on age (≤ 50 vs. > 50 years) or menopausal status (pre- vs. post-) in a genomic low risk group. Whether this is a direct anti-tumor effect of chemotherapy or a secondary ovarian function suppression effect caused by chemotherapy is unclear. We aimed to compare the biological characteristics of breast cancer tumors from patients aged ≤ 50 years and from patients aged > 50 years using whole transcriptome analysis to provide insights into this differential chemotherapy response. Methods: The FLEX Registry (NCT03053193) enrolls stage I-III breast cancer patients who receive 70-gene signature (MammaPrint/MP) test with or without 80-gene signature (BluePrint/BP) test and consent to clinically annotated transcriptome data collection. 3868 patients with HR+HER2- tumors were evaluated, of whom 808 were aged ≤ 50 years and 3060 were aged > 50 years. Clinical risk was assessed based on the MINDACT algorithm. MP classified tumors as low risk (LR) or high risk (HR). HR was stratified to H1 or H2; H2 exhibits a greater chemotherapy response. BP and MP classified tumors as luminal A-, luminal B-, HER2-, or basal-type. Differences in MP, BP, and clinical features were assessed by chi-squared or t test. For gene expression analysis, older patients were randomly selected to obtain an equal sample size as younger patients. Differentially expressed genes (DEGs) were detected using limma and considered significant with FDR <0.05 and fold change ≥ 2. Results: Approximately 70% of patients aged ≤ 50 were pre or peri-menopausal, whereas 90% of patients aged > 50 were post-menopausal. A higher proportion of patients aged ≤ 50 had tumors of high clinical risk (54%) compared to patients aged > 50 (39%) (p < 0.001). Approximately 53% of patients aged ≤ 50 had a HR tumor, of whom 25% classified as H2, while patients aged > 50 had a lower frequency (44%) of HR tumors (p<0.001). Additionally, younger patients had more tumors that classified as BP Luminal B and Basal-type than older patients (p<0.001). Principal component analysis of the top 500 genes with the highest variance revealed no distinct clustering by age group. Accordingly, only 5 DEGs were detected in tumors from patients aged ≤ 50 compared to patients aged > 50, and even fewer DEGs were detected when adjusting for MP risk and BP subtype group. Conclusions: Whole transcriptome analysis identified no substantial differences in gene expression between tumors, including Low Risk Luminal-type tumors, from women aged ≤ 50 (mostly pre or peri-menopausal) and women aged > 50 (mostly post-menopausal). These data support the likely explanation that the observed age-dependent difference in chemotherapy benefit in women ≤ 50 or >50 years of age is not due to intrinsic biological differences in breast cancers due to age, but rather to differences in the effect of chemotherapy on the host. Clinical trial information: NCT03053193.

Subgroup of post-neoadjuvant luminal-B tumors assessed by HTG in PENELOPE-B investigating palbociclib in high risk HER2-/HR+ breast cancer with residual disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 519-519
Author(s):  
Carsten Denkert ◽  
Frederik Marmé ◽  
Miguel Martin ◽  
Michael Untch ◽  
Herve R. Bonnefoi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Primary Endpoint ◽  
Primary Breast Cancer ◽  
Significant Interaction ◽  
Invasive Disease ◽  
Ki 67 ◽  
Luminal B

519 Background: About one third of patients with hormone-receptor-positive (HR+), HER2‐ primary breast cancer with residual invasive disease after neoadjuvant chemotherapy will relapse despite adjuvant endocrine therapy. Therapeutic inhibition of cyclin-dependent kinase 4 and 6 (CDK 4/6) by palbociclib combined with endocrine therapy demonstrated highly relevant efficacy in metastatic breast cancer. The phase III PENELOPE-B (NCT01864746) study did not show a significant benefit from palbociclib in women with centrally confirmed HR+, HER2- primary breast cancer without a pathological complete response after taxane‐containing neoadjuvant chemotherapy and at high-risk of relapse (CPS‐EG score ≥3 or 2 and ypN+) for the primary endpoint (Loibl et al. JCO 2021). Methods: After completion of neoadjuvant chemotherapy and locoregional therapy, PENELOPE-B patients were randomized (1:1) to receive 13 cycles (1 year) of palbociclib 125mg daily or placebo on days 1-21 in a 28d cycle in addition to standard endocrine therapy. Analysis of the primary endpoint of invasive disease-free survival (iDFS) was planned after 290 events. Secondary objective included iDFS in luminal-B group by treatment. Gene expression in post-neoadjuvant surgical residual tumor tissue samples was profiled using the HTG EdgeSeq Oncology Biomarker Panel targeting 2559 genes (HTG Molecular Diagnostics Inc.). Based on 91 genes of this panel the AIMS subtype (Paquet & Hallett, JNCI 2014) was calculated. Results: Gene expressions were measured in tumors from 906 of 1250 (72%) PENELOPE-B patients; 663 had LumA subtype, 64 LumB, 135 NormL, 16 BasalL, and 28 HER2E. Compared to LumA the LumB patients were older, had higher post-neoadjuvant Ki-67, higher risk status (CPS-EG), and higher grade; no significant correlation was found for the region of participating sites, cT, ypT, and ypN. Patients with LumB tumors had an estimated 3-year iDFS of 71.9% with palbociclib vs 44.8% with placebo HR = 0.50 (0.24-1.05); outcome was similar in patients with LumA tumors (3-year iDFS 83.9% vs 79.5%, HR = 0.93 (0.68-1.28), interaction p = 0.132); this was confirmed in multivariable analyses. Ki-67 by IHC and proliferation biomarkers from the HTG panel also showed no significant interaction with treatment. Conclusions: PENELOPE-B did not show a benefit from the addition of 1 year palbociclib to endocrine therapy compared to placebo in the total enrolled high-risk primary breast cancer population. However, the small group of luminal-B tumors (n = 64) derived benefit from palbociclib, although without a statistically significant interaction. Further investigation is required in a larger cohort to validate a palbociclib benefit that might be confined to this group.

scholarly journals In silico screening for ERα downmodulators identifies thioridazine as an anti-proliferative agent in primary, 4OH-tamoxifen-resistant and Y537S ERα-expressing breast cancer cells

2018 ◽  
Author(s):  
Claudia Busonero ◽  
Stefano Leone ◽  
Fabrizio Bianchi ◽  
Filippo Acconcia
Keyword(s):  
Cell Proliferation ◽  
In Silico ◽  
Gene Signature ◽  
Estrogen Receptor Α ◽  
Normal Breast ◽  
Breast Cancers ◽  
Intracellular Content ◽  
High Fraction ◽  
Approved Drugs ◽  
Fda Approved Drugs

AbstractPurposeMost breast cancers (BCs) express estrogen receptor α (ERα) and are treated with the endocrine therapy (ET) drugs 4OH-tamoxifen (Tam) and fulvestrant (i.e., ICI182,780-ICI). Unfortunately, a high fraction of ET-treated women relapses and become resistant to ET. Therefore, additional anti-BC drugs are needed. Recently, we proposed that the identification of novel anti-BC drugs can be achieved using the modulation of the ERα intracellular content in BC cells as a pharmacological target. Here, we searched for Food and Drug Administration (FDA)-approved drugs that potentially modify the ERα content in BC cells.MethodsWe screened in silico more than 60,000 compounds to identify FDA-approved drugs with a gene signature similar to that of ICI. We identified mitoxantrone and thioridazine and tested them in primary, Tam-resistant and genome-edited Y537S ERα-expressing BC cells.ResultsMitoxantrone and thioridazine induced ERα downmodulation and prevented MCF-7 cell proliferation. Interestingly, while mitoxantrone was toxic for normal breast cells, thioridazine showed preferential activity toward BC cells. Thioridazine also reduced the ERα content and prevented cell proliferation in primary, Tam-resistant and genome-edited Y537S ERα-expressing BC cells.ConclusionsWe suggest that the modulation of the ERα intracellular concentration in BC cells can also be robustly exploited in in silico screenings to identify anti-BC drugs and further demonstrate a re-purposing opportunity for thioridazine in primary and metastatic ET-resistant BC treatment.

Comparison of MammaPrint, BluePrint, and TargetPrint with clinical parameters in patients with breast cancer: Findings from a prospective United States cohort.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 47-47
Author(s):  
B. Nguyen ◽  
K. B. Deck ◽  
R. Sinha ◽  
D. Kerlin ◽  
J. Barone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Stage ◽  
Specific Treatment ◽  
Gene Signature ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Molecular Subtyping ◽  
Surgical Specimen ◽  
Luminal Type

47 Background: MammaPrint (MP) is a powerful predictor of disease outcome in early stage breast cancer. In addition, TargetPrint (TP), a microarray-based test that measures the mRNA expression level of ER, PR and HER2 and an 80 gene expression Molecular Subtyping profile BluePrint (BP) were developed. In the present study, MP, BP and TP were measured in a prospective U.S. breast cancer patient cohort. Methods: MP results were evaluated in fresh tumor samples from 127 breast cancer patients (T1-4N0-2; median age 62 [39-97 yr]) collected by core needle biopsy or from a surgical specimen between July 2008 and January 2011. We compared treatment advice as recommended by NCCN guidelines and classification according to MP. In addition, we compared IHC/FISH ER, PR and HER2 assessments with TP. The MP and BP results were used to subtype the patients into molecular subgroups. Results: For the group of patients (n=59) for which NCCN recommends the use of a multi-gene signature for determining chemotherapy treatment recommendations, 42 patients were classified as High Risk and 17 as Low Risk by MP. Comparison of TP with IHC/FISH indicated a concordance of 98% for ER, 94% for PR, and 98% for HER2. For a subgroup of 53 patients combined MP and BP results were available; 18 patients were Luminal-type/MP Low Risk, 27 patients were Luminal-type/MP High risk, 1 patient was Her2-type/MP Low Risk, 1 patient was Her2-type/MP High Risk and 6 patients were Basal-type/MP High Risk. Conclusions: Adding the multi-gene signature MammaPrint, as well as BluePrint and TargetPrint provides additional information for treatment guidance. By combining MammaPrint with the BluePrint molecular subtyping profile, specific groups of patients can be recognized that are at high risk of recurrence and that would possibly benefit from specific treatment. This study shows that TargetPrint provides high quality second opinion for local IHC/FISH assessment.

Response and long-term outcomes after neoadjuvant chemotherapy: Pooled dataset of patients stratified by molecular subtyping by MammaPrint and BluePrint.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 10-10
Author(s):  
Stefan Gluck ◽  
Femke De Snoo ◽  
Justine Peeters ◽  
George Somlo ◽  
Lisette Stork-Sloots ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Biomarker Discovery ◽  
Chemotherapy Response ◽  
Long Term Outcomes ◽  
Luminal A ◽  
Molecular Subtyping ◽  
Luminal B ◽  
Luminal Type ◽  
Basal Type

10 Background: Classification of breast cancers into molecular subtypes may be important for the proper selection of therapy for patients with early breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome (Sorlie, PNAS, 2001; Esserman, BCRT, 2011). Herein, we analyze using MammaPrint together with an 80-gene molecular subtyping profile (BluePrint) the response to neo-adjuvant chemotherapy and long term outcomes. Methods: This study was carried out on data from 144 patients from the I-SPY I trial; 232 patients from biomarker discovery program at MD Anderson (133 and 99 respectively; Hess, 2006, JCO; Iwamoto, 2011, BCRT); and 68 patients from City of Hope (Somlo, ASCO, 2010). All patients were treated in the neo-adjuvant setting with standard chemotherapy. MammaPrint and BluePrint were determined on 44K Agilent arrays run at Agendia or available through the I-SPY 1 data portal, or from Affymetrix U133A arrays. MammaPrint and BluePrint resulted in 4 distinct molecular groups: Luminal A (MammaPrint Low-risk/Luminal-type), Luminal B (MammaPrint High-risk/Luminal-type), Basal-type and HER2-type. Results: The overall pCR of this patient cohort was 22% but differed substantially among the subgroups. pCR was observed in 5% of the Luminal-A samples and 10% of Luminal-B, in 39% of the HER2-type samples and in 33% of the Basal-type samples. Patients with Basal-type tumors had a 5-year DFS of 71%; HER2-type had a 5-year DFS of 67% (n=71); 69% in HER2-type subgroup not treated with HER2-targeted therapy (n=45); Luminal-B type had a 5-year DFS of 77% and Luminal-A type showed 5-year DFS of 95%. Conclusions: We observed marked differences in response and DFS to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. These findings confirm differences in chemotherapy response among molecular subgroups and indicate that the BluePrint and MP profile used for this analysis helps to further establish a clinical correlation between molecular subtyping and treatment outcomes.

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