Breast cancer histopathology is predictive of low-risk Oncotype Dx recurrence score

Wilson, Parker C.; Chagpar, Anees B.; Çiçek, Ali Fuat; Bossuyt, Veerle; Buza, Natália; Mougalian, Sarah Schellhorn; Killelea, Brigid K.; Patel, Natalie; Harigopal, Malini

doi:10.1111/tbj.13117

Cited by 17 publications

(16 citation statements)

References 24 publications

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“…Far less patients within the ILC population have a high RS (only 6.6% vs 16.0% of those within the IDC population). These findings are concordant with those from earlier studies indicating that patients with ILC have a lower mean RS than those with IDC and a lower percentage with a high RS (range, 1%‐8%) 15‐19,28‐33 . We also observed that, among patients with ILC, those with a higher RS were more likely to be treated with CT.…”

Section: Discussionsupporting

confidence: 92%

“…These findings are concordant with those from earlier studies indicating that patients with ILC have a lower mean RS than those with IDC and a lower percentage with a high RS (range, 1%-8%). [15][16][17][18][19][28][29][30][31][32][33] We also observed that, among patients with ILC, those with a higher RS were more likely to be treated with CT. This finding is in agreement with the findings of Chen et al, who analyzed 6467 patients with ILC from the Surveillance, Epidemiology, and End Results (SEER) database.…”

Section: Discussionmentioning

confidence: 71%

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Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21‐gene recurrence score: A National Cancer Database analysis

Weiser

Polychronopoulou

Hatch

et al. 2022

Cancer

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BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients. METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy. RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease. CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 71%

Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21‐gene recurrence score: A National Cancer Database analysis

Weiser

Polychronopoulou

Hatch

et al. 2022

Cancer

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“…and proliferation genes assessed in the ODX assay. 32,34 Almost all low grade, LN-breast cancers are ER+/PR+/HER2-35 and consequently are eligible for ODX testing according to international guidelines. 11,12 "Classical" invasive lobular cancer (ILC)(ER+/PR+, low grade), in particular is molecularly identified as Luminal A intrinsic subtype of tumor and except for the pleomorphic variant, ILC has low to intermediate RS.…”

Section: Oncological Outcomesmentioning

confidence: 99%

Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre

et al. 2021

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“…HER2, luminal B), while OncotypeDx was not prognostic in this dataset. In fact, several papers have pointed to the limited value in ILC patients, with recent SEER dataset analyses showing that OncotypeDx offers little value above standard histopathology in ILC and other low-risk subtypes; 31,49 many recent studies concede that the relevance of OncotypeDx ILC requires further study. 28,29,50 Overall, LobSig appears to have increased value than existing signatures in the lobular context.…”

Section: Discussionmentioning

confidence: 99%

“…27 The clinical utility in ILC of the 21-gene signature, OncotypeDx®, remains unclear with two studies showing classification of 42% 28 and 35.5% 29 of patients as being as of intermediate risk (IR; managing the IR designated patient is clinically challenging 30 ) and further studies indicate limited additional value over histology. 31 Prosigna® is the commercial diagnostic test based on the PAM50 ‘intrinsic’ subtyping. It generates a Risk of Recurrence score (ROR) and has a better prognostic value than that of the OncotypeDx test, in ER+ node negative patients.…”

Section: Introductionmentioning

confidence: 99%

LobSig is a multigene predictor of outcome in invasive lobular carcinoma

et al. 2019

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Invasive lobular carcinoma (ILC) is the most common special type of breast cancer, and is characterized by functional loss of E-cadherin, resulting in cellular adhesion defects. ILC typically present as estrogen receptor positive, grade 2 breast cancers, with a good short-term prognosis. Several large-scale molecular profiling studies have now dissected the unique genomics of ILC. We have undertaken an integrative analysis of gene expression and DNA copy number to identify novel drivers and prognostic biomarkers, using in-house ( n = 25), METABRIC ( n = 125) and TCGA ( n = 146) samples. Using in silico integrative analyses, a 194-gene set was derived that is highly prognostic in ILC ( P = 1.20 × 10 −5 )—we named this metagene ‘LobSig’. Assessing a 10-year follow-up period, LobSig outperformed the Nottingham Prognostic Index, PAM50 risk-of-recurrence (Prosigna), OncotypeDx, and Genomic Grade Index (MapQuantDx) in a stepwise, multivariate Cox proportional hazards model, particularly in grade 2 ILC cases ( χ 2 , P = 9.0 × 10 −6 ), which are difficult to prognosticate clinically. Importantly, LobSig status predicted outcome with 94.6% accuracy amongst cases classified as ‘moderate-risk’ according to Nottingham Prognostic Index in the METABRIC cohort. Network analysis identified few candidate pathways, though genesets related to proliferation were identified, and a LobSig-high phenotype was associated with the TCGA proliferative subtype ( χ 2 , P < 8.86 × 10 −4 ). ILC with a poor outcome as predicted by LobSig were enriched with mutations in ERBB2 , ERBB3 , TP53 , AKT1 and ROS1 . LobSig has the potential to be a clinically relevant prognostic signature and warrants further development.

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Breast cancer histopathology is predictive of low-risk Oncotype Dx recurrence score

Cited by 17 publications

References 24 publications

Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21‐gene recurrence score: A National Cancer Database analysis

Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21‐gene recurrence score: A National Cancer Database analysis

Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre

LobSig is a multigene predictor of outcome in invasive lobular carcinoma

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