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

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10597-10597
Author(s):  
Stefan Gluck ◽  
Femke De Snoo ◽  
Justine Peeters ◽  
George Somlo ◽  
Laura Van T Veer
Keyword(s):  
Breast Cancer ◽  
Biomarker Discovery ◽  
Chemotherapy Response ◽  
Long Term Outcomes ◽  
Luminal A ◽  
Molecular Subtyping ◽  
Luminal B ◽  
Luminal Type ◽  
Basal Type

10597 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.

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.

Molecular subtyping to predict better clinical and pathologic tumor response in operable early-stage breast cancer treated with docetaxel-capecitabine with or without trastuzumab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11090-11090
Author(s):  
Stefan Gluck ◽  
Melanie Royce ◽  
Lisette Stork-Sloots ◽  
Femke De Snoo
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Complete Response ◽  
Early Stage Breast Cancer ◽  
Luminal A ◽  
Molecular Subtyping ◽  
Luminal B ◽  
Luminal Type ◽  
Basal Type ◽  
Selection Of

11090 Background: Classification into molecular subtypes is important for the selection of therapy for patients with early breast cancer. Here we determine rates of pathological complete response (pCR) in early stage breast cancer to neoadjuvant capecitabine plus docetaxel, +/- trastuzumab, and investigate MammaPrint together with the molecular subtyping profile BluePrint as markers of pathological response in comparison to other biomarkers. Methods: This analysis was carried out on data from 122 patients enrolled in a multicenter study (XeNA) of neoadjuvant therapy for four 21-day cycles with capecitabine 825 mg/m2 plus docetaxel 75 mg/m2if HER2-, and a standard trastuzumab dose if HER2+ (Glück , BCRT 2011). Clinical and pathological features, TP53 mutation analysis and PAM50 results were collected through GEO at NCBI (GSE22358). MammaPrint and BluePrint outcomes were determined from the available gene expression data and 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: In patients who completed 4 cycles of chemotherapy and surgery the overall pCR rate was 16%. Stratified by BluePrint pCR was observed in 1/15 (7%) of the Luminal A and 2/44 (5%) of Luminal B, in 10/22 (45%) of the HER2-type and in 7/41 (17%) of the Basal-type. The response rate among TP53 mutated patients was 6/61 (26%), which was significantly higher than TP53 wild-type patients (3/54 4%; p=0.012). Concordance of BluePrint/MammaPrint with PAM50 molecular subtyping was 61%. Conclusions: Molecular Subtyping with BluePrint and MammaPrint can identify better outcomes of patients in the neo-adjuvant setting. Patients with Luminal A breast cancer have a good baseline prognosis with excellent survival and may not benefit from chemotherapy (Glück, SABCS 2013). MammaPrint and BluePrint provide predictive information for patients treated with treated with docetaxel-capecitabine +/- trastuzumab.

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.

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.

Response to neoadjuvant chemotherapy and outcome based on breast cancer subtype

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11516-e11516
Author(s):  
A. Guerrero-Zotano ◽  
J. Gavila ◽  
M. A. Climent ◽  
M. J. Juan ◽  
V. Guillem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Breast Cancer Subtypes ◽  
Nuclear Staining ◽  
Luminal A ◽  
Long Term Outcome ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Her 2

e11516 Background: Gene expression profiling identifies several breast cancer subtypes with different chemosensitivity and outcome. We used immunohistochemistry surrogate markers to classify tumors according to known breast cancer subtypes and examined the relationship between neoadjuvant chemotherapy (NAC) response and long-term end points, including distant disease-free survival (DDFS) and overall survival (OS). Methods: Review of clinical and pathological data from 271 breast cancer patients treated in our institution with NAC between 1991–2008. Breast cancer subtypes were defined as follows: Luminal A: Estrogen receptor positive (ER+) and/or progesterone peceptor positive (PR+), human epidermal growth factor receptor 2-positive (Her-2+); Luminal B: ER+ and/or PR+,Her-2+; Basal: ER-,PR-,Her-2-;HER2: ER-,PR-,Her-2 +. ER and PR positive scored as positive if tumor cell nuclear staining was at least 2+. Her-2 scored as positive if test DAKO scored 3+ or FISH ratio Her-2/CEP-17>2.2. Results: 121 (45.8%) patients were classifed as Luminal A; 22 (8.1%) as Luminal B; 75 (27.7%) as Basal, and 50 (18.5%) as HER2. Most patients (63%) received NAC based on anthracyclines and taxanes. 36% Her-2+ patients were treated with NAC based on trastuzumab, and 43% received trastuzumab as adjuvant treatment. Response and outcome results are shown below (Table). Independently from subtype, only four patients out of 58 with pCR relapsed. Among patients who didn´t achieved pathologic complete response (pCR), basal and HER2 subtypes have the worst outcome (4 years SG 80% and 72% respectevely) compared with Luminal A (4 years SG: 94.7%), (log-rank p=0.009). Conclusions: Basal and HER2 tumor despite high chemosensitivity have worst long term outcome, particularly if pCR is not achieved after NAC. [Table: see text] No significant financial relationships to disclose.

First results of the prospective Neoadjuvant Breast Registry Symphony Trial (NBRST).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22117-e22117
Author(s):  
Pat W. Whitworth ◽  
Mark Gittleman ◽  
Stephanie Akbari ◽  
Lisette Stork ◽  
Femke De Snoo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Complete Response ◽  
Adjuvant Endocrine Therapy ◽  
Excision Biopsy ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Prior Therapy ◽  
Basal Type

e22117 Background: Classification into molecular subtypes may be important for the 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). The aim of the prospective NBRST study is to measure chemosensitivity as defined by pathological Complete Response (pCR), or endocrine sensitivity as defined by partial response (PR) and metastasis-free survival in molecular subgroups. Methods: The study includes women aged 18–90 with histologically proven breast cancer, who are scheduled to start neo-adjuvant chemotherapy (CT) or neo-adjuvant endocrine therapy (ET), and who provide written informed consent. Additional inclusion criteria include no excision biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for breast cancer. Treatment is at the discretion of the physician adhering to NCCN approved regimens. 500 Patients will be enrolled. Results: 128 Patients (median age 52, range 22-79), T1-4 N0-3, had definitive surgery and the overall pCR rate was 22%.14 (11%) patients are classified as Luminal A-type (BluePrint Luminal/MammaPrint Low Risk) of whom 11 received neo-adjuvant CT; none of these patients had a pCR. While 3 patients received neo-adjuvant ET and all 3 had a PR. 47 (37%) Patients are classified as Luminal B-type (BluePrint Luminal/MammaPrint High Risk). All but 1 patient received neo-adjuvant CT and 4 (9%) had a pCR. 20 (16%) Patients are classified as BluePrint HER2-type and received neo-adjuvant CT plus Trastuzumab; 8 (40%) had a pCR. 47 (37%) Patients are classified as BluePrint Basal-type and received neo-adjuvant CT; 15 (32%) had a pCR. Of the patients with IHC/FISH HER2+ cancer 13/39 (33%) had a pCR and 6/21 (29%) of the patients with IHC/FISH triple negative breast cancer. Conclusions: We observed differences in pCR to neo-adjuvant treatment in groups stratified by BluePrint and MammaPrint. Patients with Luminal A-type breast cancer have a high response to neo-adjuvant endocrine therapy (100% PR) and no pCR to neo-adjuvant CT. While patients with BluePrint HER2-type and Basal-type breast cancer have a high pCR rate to neo-adjuvant CT. Clinical trial information: NCT01479101.

Hormones as indicator of relapse-free period in breast cancer (BC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12550-e12550
Author(s):  
Natalia Yu. Samaneva ◽  
Elena M. Frantsiyants ◽  
Liubov Yu Vladimirova ◽  
Anna E. Storozhakova ◽  
Elena A. Sheiko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pituitary Hormones ◽  
Blood Levels ◽  
Test Results ◽  
Luminal A ◽  
Luminal B ◽  
Before And After ◽  
Student’S T ◽  
Student’S T Test

e12550 Background: BC is still one of the main causes of death in women due to the tumor recurrence and/or resistance to anticancer therapy. The criteria to assess the effectiveness of BC treatment are important. The purpose of the study was to analyze blood levels of steroid and pituitary hormones in BC patients after two chemotherapy cycles. Methods: The study included 42 patients with various biological BC subtypes: luminal A, luminal B and triple-negative BC (TNBC). Levels of estradiol, testosterone, progesterone, prolactin, LH, FSH and cortisol were measured by RIA in the blood of all patients before and after two neoadjuvant chemotherapy cycles. Significance of differences was evaluated by the Student’s t-test. Results: Levels of many hormones were high before the treatment in patients with all BC subtypes. After two chemotherapy cycles, unidirectional changes in the values were found in patients with subsequent remission for more than three years. Levels of estradiol decreased in luminal A BC by 1.7 times (p˂0.05), in luminal B BC – by 11.6 times (p˂0.05), cortisol decreased by 2.4 and 1.7 times (p˂0.05) respectively, and prolactin – on average by three times (p˂0.05). LH levels increased in luminal A and luminal B BC by 1.65 times (p˂0.05). In patients with TNBC, levels of estradiol decreased by 1.8 times, and cortisol – by two times (p˂0.05). Patients with subsequent remission regardless of BC subtypes had unchanged levels of testosterone, progesterone and FSH. Patients with luminal B and TNBC subtypes with progression in 6-12 months did not show significant changes in prolactin and cortisol levels after two chemotherapy cycles, compared with the values before treatment. Conclusions: A decrease in blood levels of prolactin and cortisol after two chemotherapy cycles is an indicator of a long-term remission in patients with breast cancer.

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.

scholarly journals Assessment of Long-term Distant Recurrence-Free Survival Associated With Tamoxifen Therapy in Postmenopausal Patients With Luminal A or Luminal B Breast Cancer

JAMA Oncology ◽  
2019 ◽  
Vol 5 (9) ◽  
pp. 1304 ◽  
Author(s):  
Nancy Y. Yu ◽  
Adina Iftimi ◽  
Christina Yau ◽  
Nicholas P. Tobin ◽  
Laura van ’t Veer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Recurrence ◽  
Tamoxifen Therapy ◽  
Recurrence Free Survival ◽  
Luminal A ◽  
Free Survival ◽  
Luminal B

scholarly journals Molecular subtyping of breast cancer intrinsic taxonomy with oligonucleotide microarray and NanoString nCounter

2021 ◽  
Author(s):  
Yen-Jen Chen ◽  
Ching-Shui Huang ◽  
Nam-Nhut Phan ◽  
Tzu-Pin Lu ◽  
Chih-Yi Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kappa Statistic ◽  
Normal Breast ◽  
Oligonucleotide Microarray ◽  
Breast Cancers ◽  
Luminal A ◽  
Molecular Subtyping ◽  
Luminal B ◽  
Cross Platform ◽  
Breast Tissues

Breast cancer intrinsic subtypes have been identified based on the transcription of a predefined gene expression (GE) profiles and algorithm (PAM50). This study compared molecular subtyping with oligonucleotide microarray and NanoString nCounter assay. A total of 109 Taiwanese breast cancers (24 with adjacent normal breast tissues) were assayed with Affymetrix Human Genome U133 plus 2.0 microarrays and 144 were assayed with the NanoString nCounter while 64 patients were assayed for both platforms. Subtyping with the nearest centroid (single sample prediction) was performed, and 16 out of 24 (67%) matched normal breasts were categorized as the normal breast-like subtype. For 64 breast cancers assayed for both platforms, 41 (65%, one unclassified by microarray) were predicted with an identical subtype, resulting in a fair Kappa statistic of 0.60. Taking nCounter subtyping as the gold standard, prediction accuracy was 43% (3/7), 81% (13/16), 25% (5/20), and 100% (20/20) for basal-like, HER2-enriched, luminal A and luminal B subtype predicted from microarray GE profiles. Microarray identified more luminal B cases from luminal A subtype predicted by nCounter. It’s not uncommon to use microarray for breast cancer molecular subtyping for research. Our study showed that fundamental discrepancy existed between distinct GE assays, and cross platform equivalence should be carefully appraised when molecular subtyping was conducted with oligonucleotide microarray.

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