Molecular subtyping improves diagnostic stratification of patients with primary breast cancer into prognostically defined risk groups

Yao, Katharine; Goldschmidt, Robert; Turk, Mary; Wesseling, Jelle; Stork‐Sloots, Lisette; Snoo, Femke De; Cristofanilli, Massimo

doi:10.1007/s10549-015-3587-9

Cited by 18 publications

(24 citation statements)

References 16 publications

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“…Notably, 22% of over 400 breast cancer patients studied were reclassified into a different subgroup compared with conventional assessment and showed an improved distribution of response rates in the relevant treatment groups. Similar findings were reported by Yao et al 12 Previous studies have shown that mRNA reporting of ER, PR and HER2 using microarrays is highly comparable to IHC testing. [13][14][15] However, others have cautioned against the preferential use of hormone receptor reports using RNA-based reverse transcription polymerase chain reaction (RT-PCR) technology, highlighting discordance with the IHC results and the potential of denying patients who were ER or PR positive on IHC the benefit of endocrine therapy.…”

Section: Introductionsupporting

confidence: 90%

Reclassification of early stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis

Grant¹,

Myburgh²,

Murray³

et al. 2019

S. Afr. J. Sci.

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Immunohistochemistry (IHC) is routinely used to approximate breast cancer intrinsic subtypes, which were initially discovered by microarray analysis. However, IHC assessment of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status, is a poor surrogate of molecular subtype. Therefore, MammaPrint/BluePrint (MP/BP) microarray gene expression profiling is increasingly used to stratify breast cancer patients into different treatment groups. In this study, ER/PR status, as reported by standard IHC and single-gene mRNA analysis using TargetPrint, was compared with molecular subtyping to evaluate the combined use of MP/BP in South African breast cancer patients. Pathological information of 74 ER/PR positive, HER2 negative tumours from 73 patients who underwent microarray testing, were extracted from a central breast cancer genomics database. The IHC level was standardised by multiplying the intensity score (0–3) by the reported proportion of positively stained nuclei, giving a score of 0–300. Comparison between mRNA levels and IHC determination of ER/PR status demonstrated a significant correlation (pless than 0.001) for both receptors (ER: 0.34 and PR: 0.54). Concordance was shown in 61 (82%) cases and discordance in 13 (18%) of the 74 tumours tested. Further stratification by MP/BP identified 49 (66.2%) Luminal A, 21 (28.4%) Luminal B and 4 (5.4%) Basal-like tumours. Neither IHC nor TargetPrint could substitute BP subtyping, which measures the functional integrity of ER and can identify patients with false-positive tumours who are resistant to hormone therapy. These findings support the implementation of a pathology-supported genetic testing approach combining IHC and microarray gene profiling for definitive prognostic and predictive treatment decision-making in patients with early stage breast cancer. Significance: Single-gene genomic oestrogen and progesterone receptor reporting adds limited additional information to the molecular stratification of breast cancer tumours and does not supersede the immunohistochemistry results. Neither single-gene genomic mRNA nor immunohistochemistry reporting of oestrogen and progesterone receptor status can replace the combined use of MammaPrint/BluePrint genomic molecular subtyping. Reliable distinction between Luminal A and B type tumours is not possible using immunohistochemistry or single-gene genomic mRNA assessment of oestrogen/progesterone and HER2 receptor status. Combining immunohistochemistry and microarray gene profiling enables the identification of endocrine treatment resistant hormone-positive tumours lacking ERα function (Basal-like), despite positive expression at the protein and single-gene RNA level.

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Section: Introductionsupporting

confidence: 90%

Reclassification of early stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis

Grant¹,

Myburgh²,

Murray³

et al. 2019

S. Afr. J. Sci.

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“…Based on the expression of 80-genes, a molecular subtyping profile (“BluePrint”) has been developed for the stratification of breast cancer tumors into the three main molecular subtypes: luminal, HER2 and basal [ 13 ]. By adding the prognostic risk profile of the 70-gene signature (70-GS), a substratification of luminal-type tumors into low risk (luminal A) and high risk (luminal B) type cancers can be made [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Conventional Pathology Versus Gene Signatures for Assessing Luminal A and B Type Breast Cancers: Results of a Prospective Cohort Study

Steenhoven

Kuijer

Diest

et al. 2018

Genes

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In this study, in estrogen receptor positive (ER+) early stage breast cancer patients who were considered candidates for 70-gene signature (70-GS, “MammaPrint”) use, we compared molecular subtyping (MS) based on the previously validated 80-gene signature (80-GS, “BluePrint”) versus surrogate pathological subtyping (PS). Between 1 January 2013 and 31 December 2015, 595 clinical intermediate risk ER+ early stage breast cancer patients were enrolled. Hormone receptor (HR) and HER2 receptor status were determined by conventional pathology using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Ki67 was assessed in a subset of patients. The overall concordance between PS and MS for luminal type cancers (A and B together) was 98%. The concordance between PS and MS for luminal A and luminal B type cancers based on the Bloom Richardson histological grade (BR) (n = 586) or Ki67 (n = 185) was low: 64% (Kappa 0.20 [95% CI 0.11–0.28]) and 65% (Kappa 0.22 [95% CI 0.062–0.37]), respectively. In this prospective study (NCT02209857) of a selection of ER+ and predominantly HER2− early-stage breast cancer patients, the additional ability of the 80-GS to distinguish between luminal, HER2-type and basal-like cancers was inherently very limited. The distinction of luminal-type tumors into A and B according to Ki67 status or BR grade versus the 70-GS revealed poor concordance.

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“…Ten-year follow-up data in patients receiving systemic adjuvant therapy [ 28 ] and 5-year outcome data in the neoadjuvant setting [ 7 ] have shown that BluePrint classification is more strongly associated with CT response than IHC/FISH subtyping. In the MINDACT study, 16% of the patients were re-stratified to the low-risk luminal A group by BluePrint and had 95% 5y-DMFS [ 15 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Strong impact of MammaPrint and BluePrint on treatment decisions in luminal early breast cancer: results of the WSG-PRIMe study

Wuerstlein

Kates

Gluz

et al. 2019

Breast Cancer Res Treat

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Purpose The WSG-PRIMe Study prospectively evaluated the impact of the 70-gene signature MammaPrint® (MP) and the 80-gene molecular subtyping assay BluePrint® on clinical therapy decisions in luminal early breast cancer. Methods 452 hormone receptor (HR)-positive and HER2-negative patients were recruited (N0, N1). Physicians provided initial therapy recommendations based on clinicopathological factors. After prospective risk classification by MammaPrint/BluePrint was revealed, post-test treatment recommendations and actual treatment were recorded. Decisional Conflict and anxiety were measured by questionnaires. Results Post-test switch (in chemotherapy (CT) recommendation) occurred in 29.1% of cases. Overall, physician adherence to MP risk assessment was 92.3% for low-risk and 94.3% for high-risk MP scores. Adherence was remarkably high in “discordant” groups: 74.7% of physicians initially recommending CT switched to CT omission following low-risk MP scores; conversely, 88.9% of physicians initially recommending CT omission switched to CT recommendations following high-risk MP scores. Most patients (99.2%) recommended to forgo CT post-test and 21.3% of patients with post-test CT recommendations did not undergo CT; among MP low-risk patients with pre-test and post-test CT recommendations, 40% did not actually undergo CT. Luminal subtype assessment by BluePrint was discordant with IHC assessment in 34% of patients. Patients’ State Anxiety scores improved significantly overall, particularly in MP low-risk patients. Trait Anxiety scores increased slightly in MP high risk and decreased slightly in MP low-risk patients. Conclusions MammaPrint and BluePrint test results strongly impacted physicians’ therapy decisions in luminal EBC with up to three involved lymph nodes. The high adherence to genetically determined risk assessment represents a key prerequisite for achieving a personalized cost-effective approach to disease management of early breast cancer.

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Molecular subtyping improves diagnostic stratification of patients with primary breast cancer into prognostically defined risk groups

Cited by 18 publications

References 16 publications

Reclassification of early stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis

Reclassification of early stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis

Conventional Pathology Versus Gene Signatures for Assessing Luminal A and B Type Breast Cancers: Results of a Prospective Cohort Study

Strong impact of MammaPrint and BluePrint on treatment decisions in luminal early breast cancer: results of the WSG-PRIMe study

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