Computational pathology improves risk stratification of a multi-gene assay for early stage ER+ breast cancer
Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN−) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inte...
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| Published in | NPJ breast cancer Vol. 9; no. 1; pp. 40 - 10 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
17.05.2023
Nature Publishing Group Nature Portfolio |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2374-4677 2374-4677 |
| DOI | 10.1038/s41523-023-00545-y |
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| Abstract | Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN−) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN− IBC. H&E images from a total of
n
= 321 patients with ER+ and LN− IBC from three cohorts were employed for this study (Training set: D1 (
n
= 116), Validation sets: D2 (
n
= 121) and D3 (
n
= 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02–5.32,
p
= 0.045) on D2 and a HR of 2.94 (95% CI = 1.18–7.35,
p
= 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20–89.18,
p
= 0.0106; D1:
p
= 0.0238; D2:
p
= 0.0389), potentially providing more granular risk stratification than offered by ODx alone. |
|---|---|
| AbstractList | Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN−) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN− IBC. H&E images from a total of
n
= 321 patients with ER+ and LN− IBC from three cohorts were employed for this study (Training set: D1 (
n
= 116), Validation sets: D2 (
n
= 121) and D3 (
n
= 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02–5.32,
p
= 0.045) on D2 and a HR of 2.94 (95% CI = 1.18–7.35,
p
= 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20–89.18,
p
= 0.0106; D1:
p
= 0.0238; D2:
p
= 0.0389), potentially providing more granular risk stratification than offered by ODx alone. Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN−) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN− IBC. H&E images from a total of n = 321 patients with ER+ and LN− IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02–5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18–7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20–89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone. Abstract Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN−) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN− IBC. H&E images from a total of n = 321 patients with ER+ and LN− IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02–5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18–7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20–89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone. Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN- IBC. H&E images from a total of n = 321 patients with ER+ and LN- IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02-5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18-7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20-89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone. Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN- IBC. H&E images from a total of n = 321 patients with ER+ and LN- IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02-5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18-7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20-89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone.Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN- IBC. H&E images from a total of n = 321 patients with ER+ and LN- IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02-5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18-7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20-89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone. |
| ArticleNumber | 40 |
| Author | Madabhushi, Anant Mokhtari, Mojgan Parmar, Vani Toro, Paula Feldman, Michael D. Davidson, Nancy E. Gilmore, Hannah Koyuncu, Can F. Ganesan, Shridar Fu, Pingfu Janowczyk, Andrew Lu, Cheng Chen, Yuli Corbin, Haley Whitney, Jon Corredor, Germán Harbhajanka, Aparna Goldstein, Lori J. Buzzy, Christina Desai, Sangeeta Li, Haojia |
| Author_xml | – sequence: 1 givenname: Yuli surname: Chen fullname: Chen, Yuli organization: Shaanxi Normal University, School of Computer Science, Department of Biomedical Engineering, Case Western Reserve University – sequence: 2 givenname: Haojia orcidid: 0000-0001-5000-5334 surname: Li fullname: Li, Haojia organization: Department of Biomedical Engineering, Case Western Reserve University – sequence: 3 givenname: Andrew surname: Janowczyk fullname: Janowczyk, Andrew organization: Department of Biomedical Engineering, Case Western Reserve University, Precision Oncology Center, University of Lausanne – sequence: 4 givenname: Paula surname: Toro fullname: Toro, Paula organization: Department of Biomedical Engineering, Case Western Reserve University – sequence: 5 givenname: Germán orcidid: 0000-0003-3002-0937 surname: Corredor fullname: Corredor, Germán organization: Department of Biomedical Engineering, Case Western Reserve University, Department of Biomedical Engineering, Georgia Institute of Technology and Emory University – sequence: 6 givenname: Jon surname: Whitney fullname: Whitney, Jon organization: Department of Biomedical Engineering, Case Western Reserve University – sequence: 7 givenname: Cheng surname: Lu fullname: Lu, Cheng organization: Shaanxi Normal University, School of Computer Science, Department of Biomedical Engineering, Case Western Reserve University – sequence: 8 givenname: Can F. surname: Koyuncu fullname: Koyuncu, Can F. organization: Department of Biomedical Engineering, Case Western Reserve University – sequence: 9 givenname: Mojgan surname: Mokhtari fullname: Mokhtari, Mojgan organization: Department of Biomedical Engineering, Case Western Reserve University – sequence: 10 givenname: Christina surname: Buzzy fullname: Buzzy, Christina organization: Department of Biomedical Engineering, Case Western Reserve University – sequence: 11 givenname: Shridar surname: Ganesan fullname: Ganesan, Shridar organization: Rutgers Cancer Institute of New Jersey – sequence: 12 givenname: Michael D. surname: Feldman fullname: Feldman, Michael D. organization: Perelman School of Medicine, University of Pennsylvania – sequence: 13 givenname: Pingfu orcidid: 0000-0002-2334-5218 surname: Fu fullname: Fu, Pingfu organization: Department of Population and Quantitative Health Sciences, Case Western Reserve University, School of Medicine – sequence: 14 givenname: Haley orcidid: 0000-0002-0079-4459 surname: Corbin fullname: Corbin, Haley organization: University Hospitals Cleveland Medical Center – sequence: 15 givenname: Aparna surname: Harbhajanka fullname: Harbhajanka, Aparna organization: University Hospitals Cleveland Medical Center – sequence: 16 givenname: Hannah surname: Gilmore fullname: Gilmore, Hannah organization: University Hospitals Cleveland Medical Center – sequence: 17 givenname: Lori J. surname: Goldstein fullname: Goldstein, Lori J. organization: Fox Chase Cancer Center – sequence: 18 givenname: Nancy E. surname: Davidson fullname: Davidson, Nancy E. organization: Fred Hutchinson Cancer Research Center, University of Washington, and Seattle Cancer Care Alliance – sequence: 19 givenname: Sangeeta orcidid: 0000-0002-3588-9888 surname: Desai fullname: Desai, Sangeeta organization: Tata Memorial Centre, Homi Bhabha National Institute – sequence: 20 givenname: Vani surname: Parmar fullname: Parmar, Vani organization: Tata Memorial Centre, Homi Bhabha National Institute – sequence: 21 givenname: Anant orcidid: 0000-0002-5741-0399 surname: Madabhushi fullname: Madabhushi, Anant email: anantm@emory.edu organization: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Louis Stokes VA Medical Center |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37198173$$D View this record in MEDLINE/PubMed |
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| GrantInformation_xml | – fundername: Research reported in this study was supported by the National Cancer Institute under award numbers R01CA249992-01A1, R01CA202752-01A1, R01CA208236-01A1, R01CA216579-01A1, R01CA220581-01A1, R01CA257612-01A1, 1U01CA239055-01, 1U01CA248226-01, 1U54CA254566-01, National Heart, Lung and Blood Institute 1R01HL15127701A1, R01HL15807101A1, National Institute of Biomedical Imaging and Bioengineering 1R43EB028736-01, National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program (W81XWH-19-1-0668), the Prostate Cancer Research Program (W81XWH-15-1-0558, W81XWH-20-1-0851), the Lung Cancer Research Program (W81XWH-18-1-0440, W81XWH-20-1-0595), the Peer Reviewed Cancer Research Program (W81XWH-18-1-0404, W81XWH-21-1-0345, W81XWH-21-1-0160), the Kidney Precision Medicine Project (KPMP) Glue Grant and sponsored research agreements from Bristol Myers-Squibb, Boehringer-Ingelheim, Eli-Lilly and Astrazeneca. – fundername: NCI NIH HHS grantid: U01 CA248226 – fundername: NIBIB NIH HHS grantid: R43 EB028736 – fundername: NCI NIH HHS grantid: R01 CA257612 – fundername: NCRR NIH HHS grantid: C06 RR012463 – fundername: NCI NIH HHS grantid: U01 CA239055 – fundername: NCI NIH HHS grantid: U54 CA254566 – fundername: NCI NIH HHS grantid: UG1 CA233328 – fundername: BLRD VA grantid: I01 BX004121 – fundername: NCI NIH HHS grantid: R01 CA208236 – fundername: NCI NIH HHS grantid: R01 CA216579 – fundername: ; |
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| PublicationDate | 2023-05-17 |
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| PublicationTitle | NPJ breast cancer |
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| PublicationYear | 2023 |
| Publisher | Nature Publishing Group UK Nature Publishing Group Nature Portfolio |
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| Snippet | Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN−) invasive breast cancer (IBC)... Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC)... Abstract Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN−) invasive breast cancer... |
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| SubjectTerms | 631/67/1347 692/53/2422 Biomedical and Life Sciences Biomedicine Breast cancer Cancer Research Cell Biology Human Genetics Oncology |
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| Title | Computational pathology improves risk stratification of a multi-gene assay for early stage ER+ breast cancer |
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