TY - JOUR
T1 - Association between 21-Gene Assay Recurrence Score and Locoregional Recurrence Rates in Patients with Node-Positive Breast Cancer
AU - Woodward, Wendy A.
AU - Barlow, William E.
AU - Jagsi, Reshma
AU - Buchholz, Thomas A.
AU - Shak, Steven
AU - Baehner, Frederick
AU - Whelan, Timothy J.
AU - Davidson, Nancy E.
AU - Ingle, James N.
AU - King, Tari A.
AU - Ravdin, Peter M.
AU - Osborne, C. Kent
AU - Tripathy, Debasish
AU - Livingston, Robert B.
AU - Gralow, Julie R.
AU - Hortobagyi, Gabriel N.
AU - Hayes, Daniel F.
AU - Albain, Kathy S.
N1 - Funding Information:
Funding/Support: This study was funded in part by grant awards U10CA180888, U10CA180819, U10CA180821, U10CA180820, U10CA180863, U10CA180858, and U10CA180801 from the National Cancer Institute of Canada and Canadian Cancer Society and by Genomic Health Inc. Dr Woodward was supported by grant 1R01CA180061-01 from the National Institutes of Health and by the State of Texas Grant for Rare and Aggressive Breast Cancer.
Funding Information:
reported receiving personal fees from Genomic Health Inc outside the submitted work as well as a one-time advisory fee from Merck. Dr Barlow reported receiving grants from the National Cancer Institute, AstraZeneca, and Merck; and funding to the institution from Genomic Health. Dr Jagsi reported receiving stock options from Equity Quotient; grants and personal fees from Greenwall Foundation; grants from the Doris Duke Foundation, Susan Komen Foundation, and National Cancer Institute; personal fees from Vizient and Amgen; and grants from Genentech and Blue Cross Blue Shield of Michigan outside the submitted work. Dr Buchholz reported serving uncompensated on an advisory board for Genentech. Dr Shak reported receiving personal fees from Genomic Health during the conduct of the study; holding 21-gene assay patents; and being a stockholder at Genomic Health. Dr Baehner reported being a stockholder at Genomic Health. Dr Whelan reported research funding to his institution and receiving grants and nonfinancial support from Genomic Health outside the submitted work. Dr Ingle reported receiving grants from the National Cancer Institute during the conduct of the study. Dr King reported receiving speaker honoraria from Genomic Health Inc outside the submitted work. Dr Osborne reported receiving personal fees from Puma and Ventana and advisor fees from Pfizer, Genentech, Eli Lilly, AstraZeneca, and Novartis. Dr Tripathy reported receiving personal fees from Genomic Health during the conduct of the study, grants and personal fees from Novartis, and personal fees from Pfizer, GlaxoSmithKline, Sellas Life sciences, and Polyphor outside the submitted work. Dr Gralow reported receiving nonfinancial support from Roche/Genentech; personal fees from Genomic Health, Pfizer, Sandoz, and Puma outside the submitted work; one-time attendance at an advisory board meeting for AstraZeneca; and nonfinancial support from Novartis. Dr Hortobagyi reported receiving personal fees from Novartis, Halozyme, Peregrine Pharmaceuticals, F. Hoffman-La Roche Ltd, Agendia Inc, and Lilly as well as personal fees from Genomic Health Inc outside the submitted work. Dr Hayes reported holding stock options from Oncimmune LLC and Inbiomotion; receiving personal fees from Cepheid, Freenome, Cellworks, CVS Caremark Breast Cancer, and Agendia as well as grants from Merrimack, Eli Lilly, Menarini Silicon BioSystems, Puma Biotechnology, Pfizer, and AstraZeneca outside the submitted work; funding to the institution from Genomic Health; collaborating with Genomic Health on unfunded research; and being the inventor or co-inventor on 3 patents not related to the present work ([1] Title: A Method for Predicting Progression Free and Overall Survival at Each Follow-up Timepoint During Therapy of Metastatic Breast Cancer Patients Using Circulating Tumor Cells; filed March 14, 2005 with the European Patent Office, the Netherlands. Application no./ patent No: 05725638.0-1223-US2005008602; applicant/proprietor: Immunicon Corporation. [2] Title: Diagnosis and Treatment of Breast Cancer. Patent No: US 8,790,878 B2. Date of Patent: July 29, 2014. Applicant proprietor: University of Michigan. [3] Title: Circulating Tumor Cell Capturing Techniques and Devices. Patent no: US 8,951,484 B2. Date of patent: February 10, 2015. Applicant proprietor: University of Michigan.). Dr Albain reported receiving personal fees and nonfinancial support from Genomic Health outside the submitted work as well as one-time advisory board fees from Novartis, Pfizer, Myriad, Puma, and Seattle Genetics. No other disclosures were reported.
Publisher Copyright:
© 2020 American Medical Association. All rights reserved.
PY - 2020/4
Y1 - 2020/4
N2 - Importance: The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain. Objective: To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone. Design, Setting, and Participants: This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy. Patients at North American clinical centers were enrolled from June 1989 to July 1995. Medical records from patients with recurrence score information were reviewed for LRR and radiotherapy use. Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, 9 who received breast-conserving surgery without documented radiotherapy, and 5 with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019. Main Outcomes and Measures: The LRR was defined as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes. Time to LRR was tested with log-rank tests and Cox proportional hazards regression for multivariate models. Results: The final cohort of this study comprised 316 women with a mean (range) age of 60.4 (44-81) years. Median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10-year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score (P =.02). Among patients who had a mastectomy without radiotherapy (n = 252), the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group vs 16.8% for the intermediate or high recurrence score group (P =.03). A multivariable model controlling for randomized treatment, number of positive nodes, and surgical type showed that a higher recurrence score was prognostic for LRR (hazard ratio [HR], 2.36; 95% CI, 1.02-5.45; P =.04). In a subset analysis of patients with a mastectomy and 1 to 3 involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had a 11.1% LRR (P =.051). Conclusions and Relevance: This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision-making..
AB - Importance: The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain. Objective: To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone. Design, Setting, and Participants: This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy. Patients at North American clinical centers were enrolled from June 1989 to July 1995. Medical records from patients with recurrence score information were reviewed for LRR and radiotherapy use. Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, 9 who received breast-conserving surgery without documented radiotherapy, and 5 with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019. Main Outcomes and Measures: The LRR was defined as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes. Time to LRR was tested with log-rank tests and Cox proportional hazards regression for multivariate models. Results: The final cohort of this study comprised 316 women with a mean (range) age of 60.4 (44-81) years. Median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10-year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score (P =.02). Among patients who had a mastectomy without radiotherapy (n = 252), the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group vs 16.8% for the intermediate or high recurrence score group (P =.03). A multivariable model controlling for randomized treatment, number of positive nodes, and surgical type showed that a higher recurrence score was prognostic for LRR (hazard ratio [HR], 2.36; 95% CI, 1.02-5.45; P =.04). In a subset analysis of patients with a mastectomy and 1 to 3 involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had a 11.1% LRR (P =.051). Conclusions and Relevance: This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision-making..
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U2 - 10.1001/jamaoncol.2019.5559
DO - 10.1001/jamaoncol.2019.5559
M3 - Article
C2 - 31917424
AN - SCOPUS:85077999675
VL - 6
SP - 505
EP - 511
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
IS - 4
ER -