Ki-67 versus MammaPrint/BluePrint for assessing luminal type breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13673-e13673
Author(s):  
Chen Tian ◽  
Lili Fu ◽  
Jiyu Wei ◽  
Pengfei Yin ◽  
Henghui Zhang

e13673 Background: Ki-67 is widely used for risk stratification in patients with ER+/HER2- breast cancer. The multigene assay, MammaPrint/BluePrint (MP/BP) test, is validated as a good predictor of recurrence in patients with Luminal type breast cancer and a good tool of molecular subtyping classification. Previous study showed that MP/BP test was able to re-stratify 54% of patients with a Luminal-B pathological subtyping (PS) to a low-risk Luminal A-type group. But there is no study directly show the comparison between Ki67 and MP/BP test result. Here in this study, we compare Ki-67 with MP/BP test result in Chinese patients with luminal type breast cancer. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumour samples or fresh tumour samples from 1008 eligible breast cancer patients were collected from 122 hospitals in China. Tumor RNAs were isolated from samples and analyzed using RNA sequencing technology. Ki-67 protein expression were assessed in FFPE tissue blocks by IHC. The pathology subtyping of patient was categorized based on the 2013 St. Gallen. Comparison of MP/BP result with Ki-67 IHC was performed. Concordance between subtyping by the MP/BP and PS was also evaluated. Results: Of 1008 patients with ER+/HER2- breast cancer, 640 were MP Low-Risk and 368 were MP High-Risk. MammaPrint index was significantly associated with Ki-67 expression (p < 0.001). Among the patients with Ki-67 value lower than 15%, 81.11% were MP Low-Risk, while 65.12% of patients with Ki-67 value between 15%-20% and 46.67% of patients with Ki-67 value between 21%-30% were MP Low Risk. Of the patients with Ki-67 value higher than 30%, 77.24% were MP High-Risk. Among the 453 patients with PS Luminal-A tumours, 77 (17%) were categorized as Luminal-B by MP/BP test. While among the 555 patients with PS Luminal-B tumours, 265 (48%) were categorized as Luminal-A by MP/BP test. Conclusions: Our results show that for the patients with low Ki-67 value ( < 15%) or high Ki-67 value ( > 30%), the risk prediction by MP test are mostly agree with Ki-67 IHC, while for the patients with intermediate Ki-67 value (15-30%), MammaPrint test may provide more information. And compare with the traditional pathological factors, MP/BP test can help to identify a large group of patient with low risk of recurrence.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 9-9
Author(s):  
Katharine Yao ◽  
Mary Turk ◽  
Karen Kaul ◽  
JoEllen Weaver ◽  
Femke De Snoo ◽  
...  

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.


2015 ◽  
Vol 33 (18) ◽  
pp. 2035-2040 ◽  
Author(s):  
Fei-Fei Liu ◽  
Wei Shi ◽  
Susan J. Done ◽  
Naomi Miller ◽  
Melania Pintilie ◽  
...  

Purpose To determine the prognostic and predictive value of intrinsic subtyping by using immunohistochemical (IHC) biomarkers for ipsilateral breast relapse (IBR) in participants in an early breast cancer randomized trial of tamoxifen with or without breast radiotherapy (RT). Patients and Methods IHC analysis of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor, and Ki-67 was conducted on 501 of 769 available blocks. Patients were classified as luminal A (n = 265), luminal B (n = 165), or high-risk subtype (luminal HER2, n = 22; HER2 enriched, n = 13; basal like, n = 30; or triple-negative nonbasal, n = 6). Median follow-up was 10 years. Results Classification by subtype was prognostic for IBR (10-year estimates: luminal A, 5.2%; luminal B, 10.5%; high-risk subtypes, 21.3%; P < .001). Luminal subtypes seemed to derive less benefit from RT (luminal A hazard ratio [HR], 0.40; luminal B HR, 0.51) than high-risk subtypes (HR, 0.13); however, the overall subtype-treatment interaction term was not significant (P = .26). In an exploratory analysis of women with clinical low-risk (age older than 60 years, T1, grade 1 or 2) luminal A tumors (n = 151), 10-year IBR was 3.1% versus 11.8% for the high-risk cohort (n = 341; P = .0063). Clinical low-risk luminal A patients had a 10-year IBR of 1.3% with tamoxifen versus 5.0% with tamoxifen plus RT (P = .42). Multivariable analysis showed that RT (HR, 0.31; P < .001), clinical risk group (HR, 2.2; P = .025), and luminal A subtype (HR, 0.25; P < .001) were significantly associated with IBR. Conclusion IHC subtyping was prognostic for IBR but was not predictive of benefit from RT. Further studies may validate the exploratory finding of a low-risk luminal A group who may be spared breast RT.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 577-577
Author(s):  
Lisette Stork-Sloots ◽  
Katharine Yao ◽  
Mary Turk ◽  
Karen Kaul ◽  
JoEllen Weaver ◽  
...  

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.


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.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12570-e12570
Author(s):  
Lalnun Puii ◽  
Lalram Sangi ◽  
Hrishi Varayathu ◽  
Samuel Luke Koramati ◽  
Beulah Elsa Thomas ◽  
...  

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


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexey Surov ◽  
Yun-Woo Chang ◽  
Lihua Li ◽  
Laura Martincich ◽  
Savannah C. Partridge ◽  
...  

Abstract Background Radiological imaging plays a central role in the diagnosis of breast cancer (BC). Some studies suggest MRI techniques like diffusion weighted imaging (DWI) may provide further prognostic value by discriminating between tumors with different biologic characteristics including receptor status and molecular subtype. However, there is much contradictory reported data regarding such associations in the literature. The purpose of the present study was to provide evident data regarding relationships between quantitative apparent diffusion coefficient (ADC) values on DWI and pathologic prognostic factors in BC. Methods Data from 5 centers (661 female patients, mean age, 51.4 ± 10.5 years) were acquired. Invasive ductal carcinoma (IDC) was diagnosed in 625 patients (94.6%) and invasive lobular carcinoma in 36 cases (5.4%). Luminal A carcinomas were diagnosed in 177 patients (28.0%), luminal B carcinomas in 279 patients (44.1%), HER 2+ carcinomas in 66 cases (10.4%), and triple negative carcinomas in 111 patients (17.5%). The identified lesions were staged as T1 in 51.3%, T2 in 43.0%, T3 in 4.2%, and as T4 in 1.5% of the cases. N0 was found in 61.3%, N1 in 33.1%, N2 in 2.9%, and N3 in 2.7%. ADC values between different groups were compared using the Mann–Whitney U test and by the Kruskal-Wallis H test. The association between ADC and Ki 67 values was calculated by Spearman’s rank correlation coefficient. Results ADC values of different tumor subtypes overlapped significantly. Luminal B carcinomas had statistically significant lower ADC values compared with luminal A (p = 0.003) and HER 2+ (p = 0.007) lesions. No significant differences of ADC values were observed between luminal A, HER 2+ and triple negative tumors. There were no statistically significant differences of ADC values between different T or N stages of the tumors. Weak statistically significant correlation between ADC and Ki 67 was observed in luminal B carcinoma (r = − 0.130, p = 0.03). In luminal A, HER 2+ and triple negative tumors there were no significant correlations between ADC and Ki 67. Conclusion ADC was not able to discriminate molecular subtypes of BC, and cannot be used as a surrogate marker for disease stage or proliferation activity.


2019 ◽  
Vol 178 (2) ◽  
pp. 451-458 ◽  
Author(s):  
Giuseppe Viale ◽  
Amy E. Hanlon Newell ◽  
Espen Walker ◽  
Greg Harlow ◽  
Isaac Bai ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 642-642 ◽  
Author(s):  
Eva Maria Ciruelos Gil ◽  
Ismael Ghanem ◽  
Luis Manso ◽  
Sergio Hoyos ◽  
Carlos Castañeda ◽  
...  

642 Background: HER2+ breast cancer (BC) is a well characterized subtype of BC, due to the predictive value of HER2 overexpression for anti-HER2 targeted therapies. Nevertheless, around 50% of HER2+ BC are ER+ and clasiffied as luminal B/HER2+, but their biological and clinical behaviour may be different from HER2+/ER- tumors. Methods: We retrospectively reviewed 347 HER2+ (Herceptest +++ or FISH+) early BC patients (see Table) diagnosed at our institution in 1997-2007, and were divided into two study groups: HER2+/ER+ (group A) and HER2+/ER- (group B). ER+ was defined if expressed in > 10% tumor cells. Results: See table below. Mean age: 54.7 y (44.6 – 65). Mean Ki 67 was higher in B (37,2 vs 22,4%, p<0.0001). At the current FU, n¼ of events were insufficient to reach median DFS/OS. Mean DFS was 6.9 y (3.5 – 10.2); recurrent disease was higher (p 0.003) for B (54 pts, 43%) vs A (62 pts, 28%). 5-year DFS estimates: 78.4 % (95% CI 72.3 – 83.3) and 62.3 % (95% CI 53 – 70.27) for A and B, and 10-year DFS was 73.4% (95% CI 66.6 – 79) and 52.5% (95% CI 42.4 – 61.6) for A and B, respectively (p 0.0006). Most common recurrent sites were local (18) and bone (9) for HER2+/ER+ and liver (8) and lung (8) for HER2+/ER-. Mean OS was 8.03y (5.4 – 10.8); 28 (12,6%) pts died in A, vs 26 (21%) in B (p 0.043). 5-year OS estimates: 93.9 % (95% CI 89.7 – 96.4) and 87.6 % (95% CI 80.3 – 92.3) for A and B, and 10-year DFS was 84.2% (95% CI 77.5 – 89.0) and 74.1% (95% CI 63.4 – 82.2) for A and B, respectively (p 0.01). Conclusions: ER expression in HER2+ early BC defines two clinically distinct diseases with different long-term prognosis. These data may help to better individualize adjuvant therapies and future clinical trial designs. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 534-534
Author(s):  
Ivana Sestak ◽  
Yi Zhang ◽  
Catherine A. Schnabel ◽  
Jack M. Cuzick ◽  
Mitchell Dowsett

534 Background: The Breast Cancer Index (BCI) is a gene-expression based signature that provides prognostic information for overall (0-10 years) and late (5-10 years) distant recurrence (DR) and prediction of extended endocrine benefit in hormone receptor positive (HR+) early stage breast cancer. The current analysis aims to further characterize, correlate and compare the prognostic performance of BCI in luminal subtypes based on immunohistochemical classification. Methods: 670 postmenopausal women with HR+, LN- disease from the TransATAC cohort were included in this analysis. Luminal A-like tumors (LumA) were identified as those with ER+ and/or PR+ and HER2 -, and Ki67 < 20% by IHC. All other tumors were classified as Luminal B-like (LumB) for this analysis. Primary endpoint was DR. Cox regression models were used to examine BCI prognostic performance according to luminal subtype, adjusting for the clinicopathological model Clinical Treatment Score (CTS). Results: 452 (67.5%) patients were classified as LumA and 218 (32.5%) as LumB. BCI was highly prognostic in LumA cancers (adjusted HR = 1.57 (1.23-1.96), P < 0.001, ΔLR-χ2= 14.09), but not in LumB tumors (adjusted HR = 1.20 (0.94-1.52, P = 0.14, ΔLR-χ2= 2.23). In LumA, 10-year DR risks in BCI intermediate and high risk groups were very similar (25.6% (16.4-38.6) and 25.3% (13.5-44.3), respectively) and significantly different from BCI low (3.9% (2.1-7.0); HR = 7.47 (3.50-15.96) and HR = 8.13 (3.27-20.23), respectively). In LumB, 10-year DR risks in BCI low and BCI intermediate risk groups (13.8% (6.8-26.9) and 14.6% (8.3-24.9), respectively) were very similar and significantly lower than for the BCI high (29.1% (20.0-41.1)). Lum subtyping was only prognostic in the BCI low risk group (LumA vs. LumB: HR = 4.27 (1.65-11.02)) but not in the other two BCI risk groups. Conclusions: BCI provided significant prognostic information in Lum A subtype. These results show that BCI intermediate and high risk had similar risk of DR in LumA tumors, while shared similarly low risk of DR as BCI-low in LumB tumors. Further evaluation is needed to elucidate the distinct mechanisms underlying each classification system.


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