Efficacy of an RNA-based multigene assay with core needle biopsy samples for risk evaluation in hormone-positive early breast cancer

Lee, Jeeyeon; Lee, Eun Hye; Park, Ho Yong; Kim, Wan Wook; Lee, Ryu Kyung; Chae, Yee Soo; Lee, Soo Jung; Kim, Jee‐Eun; Kang, Byeong-Il; Park, Jee Young; Park, Jiyoung; Jung, Jin Hyang

doi:10.1186/s12885-019-5608-2

Cited by 6 publications

(11 citation statements)

References 35 publications

(36 reference statements)

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“…Previous studies showing that intertumoral metabolic heterogeneity is more pronounced than intratumoral metabolic heterogeneity (32) and that core biopsy samples can be used to reliably assess intertumoral differences (33)(34)(35)(36)(37) provided us with a rationale for comparing global imaging-based metrics (mean LAC/PYR and mean summed SNR LAC ) with the results from IHC and RNA sequencing of single tumor biopsies. The strong correlation between the LAC/PYR with tumor volume, which is known to correlate with hypoxia (38), led us to investigate the contribution of hypoxia to the measured lactate signal.…”

Section: Discussionmentioning

confidence: 99%

Imaging breast cancer using hyperpolarized carbon-13 MRI

Gallagher

Woitek

McLean

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

156

204

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Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

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Section: Discussionmentioning

confidence: 99%

Imaging breast cancer using hyperpolarized carbon-13 MRI

Gallagher

Woitek

McLean

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

156

204

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“…Most studies focus on the use of clinically available FFPE specimens as starting material to perform downstream GEP [ 31 ]. Exceptionally, FF CNB are available and used for molecular profiling.…”

Section: Resultsmentioning

confidence: 99%

“…Formalin-fixed paraffin-embedded (FFPE) tumor samples are routinely prepared for diagnostic purposes and long-term storage. Protocols to extract nucleic acids from FFPE samples have been described as well, and core needle biopsies (CNB) have already been proven to serve as an adequate and suitable sample type for downstream GEP [ 27 , 28 , 29 , 30 , 31 ]. However, RNA can be easily degraded prior to and during the process of formalin fixation [ 26 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Overcoming the Challenges of High Quality RNA Extraction from Core Needle Biopsy

et al. 2021

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The use of gene expression profiling (GEP) in cancer management is rising, as GEP can be used for disease classification and diagnosis, tailoring treatment to underlying genetic determinants of pharmacological response, monitoring of therapy response, and prognosis. However, the reliability of GEP heavily depends on the input of RNA in sufficient quantity and quality. This highlights the need for standard procedures to ensure best practices for RNA extraction from often small tumor biopsies with variable tissue handling. We optimized an RNA extraction protocol from fresh-frozen (FF) core needle biopsies (CNB) from breast cancer patients and from formalin-fixed paraffin-embedded (FFPE) tissue when FF CNB did not yield sufficient RNA. Methods to avoid ribonucleases andto homogenize or to deparaffinize tissues and the impact of tissue composition on RNA extraction were studied. Additionally, RNA’s compatibility with the nanoString nCounter® technology was studied. This technology platform enables GEP using small RNA fragments. After optimization of the protocol, RNA of high quality and sufficient quantity was obtained from FF CNB in 92% of samples. For the remaining 8% of cases, FFPE material prepared by the pathology department was used for RNA extraction. Both resulting RNA end products are compatible with the nanoString nCounter® technology.

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“…Samples collected from the same breast cancer on different days are anticipated to show some variability in gene expression due to extrinsic factors such as the precise part of the tumour biopsied as well as differences in tumour fixation and processing [26,27]. This variability is expected to be similar between premenopausal and postmenopausal women.…”

Section: Correlation In the 21-gene Signature And Experimental Recurrmentioning

confidence: 99%

Discordance in 21-gene recurrence scores between paired breast cancer samples is inversely associated with patient age

et al. 2020

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Background: The Oncotype DX 21-gene Recurrence Score is a genomic-based algorithm that guides adjuvant chemotherapy treatment decisions for women with early-stage, oestrogen receptor (ER)-positive breast cancer. However, there are age-related differences in chemotherapy benefit for women with intermediate Oncotype DX Recurrence Scores that are not well understood. Menstrual cycling in younger women is associated with hormonal fluctuations that might affect the expression of genomic predictive biomarkers and alter Recurrence Scores. Here, we use paired human breast cancer samples to demonstrate that the clinically employed Oncotype DX algorithm is critically affected by patient age. Methods: RNA was extracted from 25 pairs of formalin-fixed paraffin-embedded, invasive ER-positive breast cancer samples that had been collected approximately 2 weeks apart. A 21-gene signature analogous to the Oncotype DX platform was assessed through quantitative real-time PCR, and experimental recurrence scores were calculated using the Oncotype DX algorithm. Results: There was a significant inverse association between patient age and discordance in the recurrence score. For every 1-year decrease in age, discordance in recurrence scores between paired samples increased by 0.08 units (95% CI − 0.14, − 0.01; p = 0.017). Discordance in recurrence scores for women under the age of 50 was driven primarily by proliferation-and HER2-associated genes. Conclusion: The Oncotype DX 21-gene Recurrence Score algorithm is critically affected by patient age. These findings emphasise the need for the consideration of patient age, particularly for women younger than 50, in the development and application of genomic-based algorithms for breast cancer care.

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Efficacy of an RNA-based multigene assay with core needle biopsy samples for risk evaluation in hormone-positive early breast cancer

Cited by 6 publications

References 35 publications

Imaging breast cancer using hyperpolarized carbon-13 MRI

Imaging breast cancer using hyperpolarized carbon-13 MRI

Overcoming the Challenges of High Quality RNA Extraction from Core Needle Biopsy

Discordance in 21-gene recurrence scores between paired breast cancer samples is inversely associated with patient age

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