Impact of genetic ancestry on outcomes in ECOG-ACRIN-5103

Bryan P. Schneider, Fei Shen, Guanglong Jiang, Anne O'Neill, Milan Radovich, Lang Li, Laura Gardner, Dongbing Lai, Tatiana Foroud, Joseph A. Sparano, George W. Sledge, Kathy D. Miller

Research output: Contribution to journalArticle

Abstract

Purpose Racial disparity in breast cancer outcomes exists between African American and white womenin the United States.Wehave evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for patients with breast cancer in the context of a randomized, phase III adjuvant trial. Methods This study compared outcomes between 386 patients of African ancestry (AA) and 2,473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial, ECOGACRIN- 5103.Theprimary efficacy endpoint, invasive disease-free survival (DFS), and clinically significant toxicities were compared, including anthracycline-induced congestive heart failure, taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results Overall, AAs had significantly inferior DFS (P = .002; hazard ratio, 1.5) compared with EAs. This was significant in the estrogen receptor-positive subgroup (P = .03), with a similar, nonsignificant trend for those who had triple-negative breast cancer (P = .12). AAs also had significantly more grades 3 to 4 TIPN (odds ratio [OR], 2.9; P = 2.4 × 10-11) and grades 3 to 4 bevacizumab-induced hypertension (OR, 1.6; P = .02), with a trend for more congestive heart failure (OR,1.8;P=.08).A As had significantly more dose reductions in paclitaxel (P=6.6×10-6). In AAs, dose reductions in paclitaxelhada significant negative impactonDFS(P=.03), whereasin EAs, dose reductions did not have an impact on outcome (P = .35). Conclusion AAs had inferior DFS, with more clinically important toxicities, in ECOG-ACRIN- 5103. The altered risk-to-benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions in paclitaxel, especially as the result of TIPN, are warranted for this population.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJCO Precision Oncology
Volume2017
Issue number1
DOIs
StatePublished - Jan 1 2017

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Peripheral Nervous System Diseases
Breast Neoplasms
Disease-Free Survival
Odds Ratio
Paclitaxel
Heart Failure
Triple Negative Breast Neoplasms
Hypertension
Anthracyclines
Estrogen Receptors
African Americans
Outcome Assessment (Health Care)
Drug Therapy
Research
Population
taxane
Bevacizumab
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Impact of genetic ancestry on outcomes in ECOG-ACRIN-5103. / Schneider, Bryan P.; Shen, Fei; Jiang, Guanglong; O'Neill, Anne; Radovich, Milan; Li, Lang; Gardner, Laura; Lai, Dongbing; Foroud, Tatiana; Sparano, Joseph A.; Sledge, George W.; Miller, Kathy D.

In: JCO Precision Oncology, Vol. 2017, No. 1, 01.01.2017, p. 1-9.

Research output: Contribution to journalArticle

Schneider, BP, Shen, F, Jiang, G, O'Neill, A, Radovich, M, Li, L, Gardner, L, Lai, D, Foroud, T, Sparano, JA, Sledge, GW & Miller, KD 2017, 'Impact of genetic ancestry on outcomes in ECOG-ACRIN-5103', JCO Precision Oncology, vol. 2017, no. 1, pp. 1-9. https://doi.org/10.1200/PO.17.00059
Schneider, Bryan P. ; Shen, Fei ; Jiang, Guanglong ; O'Neill, Anne ; Radovich, Milan ; Li, Lang ; Gardner, Laura ; Lai, Dongbing ; Foroud, Tatiana ; Sparano, Joseph A. ; Sledge, George W. ; Miller, Kathy D. / Impact of genetic ancestry on outcomes in ECOG-ACRIN-5103. In: JCO Precision Oncology. 2017 ; Vol. 2017, No. 1. pp. 1-9.
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abstract = "Purpose Racial disparity in breast cancer outcomes exists between African American and white womenin the United States.Wehave evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for patients with breast cancer in the context of a randomized, phase III adjuvant trial. Methods This study compared outcomes between 386 patients of African ancestry (AA) and 2,473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial, ECOGACRIN- 5103.Theprimary efficacy endpoint, invasive disease-free survival (DFS), and clinically significant toxicities were compared, including anthracycline-induced congestive heart failure, taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results Overall, AAs had significantly inferior DFS (P = .002; hazard ratio, 1.5) compared with EAs. This was significant in the estrogen receptor-positive subgroup (P = .03), with a similar, nonsignificant trend for those who had triple-negative breast cancer (P = .12). AAs also had significantly more grades 3 to 4 TIPN (odds ratio [OR], 2.9; P = 2.4 × 10-11) and grades 3 to 4 bevacizumab-induced hypertension (OR, 1.6; P = .02), with a trend for more congestive heart failure (OR,1.8;P=.08).A As had significantly more dose reductions in paclitaxel (P=6.6×10-6). In AAs, dose reductions in paclitaxelhada significant negative impactonDFS(P=.03), whereasin EAs, dose reductions did not have an impact on outcome (P = .35). Conclusion AAs had inferior DFS, with more clinically important toxicities, in ECOG-ACRIN- 5103. The altered risk-to-benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions in paclitaxel, especially as the result of TIPN, are warranted for this population.",
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AU - Schneider, Bryan P.

AU - Shen, Fei

AU - Jiang, Guanglong

AU - O'Neill, Anne

AU - Radovich, Milan

AU - Li, Lang

AU - Gardner, Laura

AU - Lai, Dongbing

AU - Foroud, Tatiana

AU - Sparano, Joseph A.

AU - Sledge, George W.

AU - Miller, Kathy D.

PY - 2017/1/1

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N2 - Purpose Racial disparity in breast cancer outcomes exists between African American and white womenin the United States.Wehave evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for patients with breast cancer in the context of a randomized, phase III adjuvant trial. Methods This study compared outcomes between 386 patients of African ancestry (AA) and 2,473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial, ECOGACRIN- 5103.Theprimary efficacy endpoint, invasive disease-free survival (DFS), and clinically significant toxicities were compared, including anthracycline-induced congestive heart failure, taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results Overall, AAs had significantly inferior DFS (P = .002; hazard ratio, 1.5) compared with EAs. This was significant in the estrogen receptor-positive subgroup (P = .03), with a similar, nonsignificant trend for those who had triple-negative breast cancer (P = .12). AAs also had significantly more grades 3 to 4 TIPN (odds ratio [OR], 2.9; P = 2.4 × 10-11) and grades 3 to 4 bevacizumab-induced hypertension (OR, 1.6; P = .02), with a trend for more congestive heart failure (OR,1.8;P=.08).A As had significantly more dose reductions in paclitaxel (P=6.6×10-6). In AAs, dose reductions in paclitaxelhada significant negative impactonDFS(P=.03), whereasin EAs, dose reductions did not have an impact on outcome (P = .35). Conclusion AAs had inferior DFS, with more clinically important toxicities, in ECOG-ACRIN- 5103. The altered risk-to-benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions in paclitaxel, especially as the result of TIPN, are warranted for this population.

AB - Purpose Racial disparity in breast cancer outcomes exists between African American and white womenin the United States.Wehave evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for patients with breast cancer in the context of a randomized, phase III adjuvant trial. Methods This study compared outcomes between 386 patients of African ancestry (AA) and 2,473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial, ECOGACRIN- 5103.Theprimary efficacy endpoint, invasive disease-free survival (DFS), and clinically significant toxicities were compared, including anthracycline-induced congestive heart failure, taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results Overall, AAs had significantly inferior DFS (P = .002; hazard ratio, 1.5) compared with EAs. This was significant in the estrogen receptor-positive subgroup (P = .03), with a similar, nonsignificant trend for those who had triple-negative breast cancer (P = .12). AAs also had significantly more grades 3 to 4 TIPN (odds ratio [OR], 2.9; P = 2.4 × 10-11) and grades 3 to 4 bevacizumab-induced hypertension (OR, 1.6; P = .02), with a trend for more congestive heart failure (OR,1.8;P=.08).A As had significantly more dose reductions in paclitaxel (P=6.6×10-6). In AAs, dose reductions in paclitaxelhada significant negative impactonDFS(P=.03), whereasin EAs, dose reductions did not have an impact on outcome (P = .35). Conclusion AAs had inferior DFS, with more clinically important toxicities, in ECOG-ACRIN- 5103. The altered risk-to-benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions in paclitaxel, especially as the result of TIPN, are warranted for this population.

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