Potential benefit of intra-operative administration of ketorolac on breast cancer recurrence according to the patient's body mass index

Christine Desmedt (Corresponding Author), Romano Demicheli, Marco Fornili, Imane Bachir, Mariana Duca, Giulia Viglietti, Martine Berlière, Martine Piccart, Christos Sotiriou, Maurice Sosnowski, Patrice Forget, Elia Biganzoli

Research output: Contribution to journalArticle

Abstract

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are currently used in some countries as analgesics in primary cancer surgery. Retrospective studies suggest that NSAIDs could reduce breast cancer recurrences. Because NSAIDs also act on biological mechanisms present in patients with increased adiposity, we aimed at assessing whether the intra-operative administration of ketorolac or diclofenac would be associated with a reduction of recurrence in patients with elevated body mass index (BMI).MethodsWe considered two institutional retrospective series of 827 and 1007 patients evaluating the administration of ketorolac (n = 529 with, n = 298 without) or diclofenac (n = 787 with, n = 220 without). The BMI subgroups were defined as less than 25 kg/m2 (lean) and 25 or more kg/m2 (overweight and obese). Cumulative incidence estimation of distant metastases as well as Fine-Gray and Dixon-Simon models was used. These analyses were adjusted for clinico-pathological variables. All statistical tests were two-sided.ResultsThe administration of ketorolac was statistically significantly associated with decreased incidence of distant recurrences (adjusted hazard ratio [aHR]= 0.59, 95% confidence interval [CI] = 0.37 to 0.96, P = .03). In particular, the association was evident in the high–body mass index (BMI) group of patients (aHR = 0.55, 95% CI = 0.31 to 0.96, P = .04). The administration of diclofenac was not statistically significantly associated with decreased incidence of distant recurrences, either in the global population or in the BMI subgroups.ConclusionsThese results show that the intra-operative administration of ketorolac, but not diclofenac, is statistically significantly associated with a reduction of distant recurrences in patients with increased BMI. Altogether, this study points to a potentially important repositioning of ketorolac in the intra-operative treatment of patients with elevated BMI that, if prospectively validated, might be as impactful as and cheaper than adjuvant systemic anticancer therapies.
Original languageEnglish
Pages (from-to)1115-1122
Number of pages8
JournalJournal of the National Cancer Institute
Volume110
Issue number10
Early online date30 Apr 2018
DOIs
Publication statusPublished - Oct 2018

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Ketorolac
Body Mass Index
Diclofenac
Breast Neoplasms
Recurrence
Non-Steroidal Anti-Inflammatory Agents
Incidence
Confidence Intervals
Adiposity
Analgesics
Anti-Inflammatory Agents
Retrospective Studies
Neoplasm Metastasis
Therapeutics
Pharmaceutical Preparations
Population
Neoplasms

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Potential benefit of intra-operative administration of ketorolac on breast cancer recurrence according to the patient's body mass index. / Desmedt, Christine (Corresponding Author); Demicheli, Romano; Fornili, Marco; Bachir, Imane; Duca, Mariana; Viglietti, Giulia; Berlière, Martine; Piccart, Martine; Sotiriou, Christos; Sosnowski, Maurice; Forget, Patrice; Biganzoli, Elia.

In: Journal of the National Cancer Institute, Vol. 110, No. 10, 10.2018, p. 1115-1122.

Research output: Contribution to journalArticle

Desmedt, C, Demicheli, R, Fornili, M, Bachir, I, Duca, M, Viglietti, G, Berlière, M, Piccart, M, Sotiriou, C, Sosnowski, M, Forget, P & Biganzoli, E 2018, 'Potential benefit of intra-operative administration of ketorolac on breast cancer recurrence according to the patient's body mass index' Journal of the National Cancer Institute, vol. 110, no. 10, pp. 1115-1122. https://doi.org/10.1093/jnci/djy042
Desmedt, Christine ; Demicheli, Romano ; Fornili, Marco ; Bachir, Imane ; Duca, Mariana ; Viglietti, Giulia ; Berlière, Martine ; Piccart, Martine ; Sotiriou, Christos ; Sosnowski, Maurice ; Forget, Patrice ; Biganzoli, Elia. / Potential benefit of intra-operative administration of ketorolac on breast cancer recurrence according to the patient's body mass index. In: Journal of the National Cancer Institute. 2018 ; Vol. 110, No. 10. pp. 1115-1122.
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abstract = "BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are currently used in some countries as analgesics in primary cancer surgery. Retrospective studies suggest that NSAIDs could reduce breast cancer recurrences. Because NSAIDs also act on biological mechanisms present in patients with increased adiposity, we aimed at assessing whether the intra-operative administration of ketorolac or diclofenac would be associated with a reduction of recurrence in patients with elevated body mass index (BMI).MethodsWe considered two institutional retrospective series of 827 and 1007 patients evaluating the administration of ketorolac (n = 529 with, n = 298 without) or diclofenac (n = 787 with, n = 220 without). The BMI subgroups were defined as less than 25 kg/m2 (lean) and 25 or more kg/m2 (overweight and obese). Cumulative incidence estimation of distant metastases as well as Fine-Gray and Dixon-Simon models was used. These analyses were adjusted for clinico-pathological variables. All statistical tests were two-sided.ResultsThe administration of ketorolac was statistically significantly associated with decreased incidence of distant recurrences (adjusted hazard ratio [aHR]= 0.59, 95{\%} confidence interval [CI] = 0.37 to 0.96, P = .03). In particular, the association was evident in the high–body mass index (BMI) group of patients (aHR = 0.55, 95{\%} CI = 0.31 to 0.96, P = .04). The administration of diclofenac was not statistically significantly associated with decreased incidence of distant recurrences, either in the global population or in the BMI subgroups.ConclusionsThese results show that the intra-operative administration of ketorolac, but not diclofenac, is statistically significantly associated with a reduction of distant recurrences in patients with increased BMI. Altogether, this study points to a potentially important repositioning of ketorolac in the intra-operative treatment of patients with elevated BMI that, if prospectively validated, might be as impactful as and cheaper than adjuvant systemic anticancer therapies.",
author = "Christine Desmedt and Romano Demicheli and Marco Fornili and Imane Bachir and Mariana Duca and Giulia Viglietti and Martine Berli{\`e}re and Martine Piccart and Christos Sotiriou and Maurice Sosnowski and Patrice Forget and Elia Biganzoli",
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T1 - Potential benefit of intra-operative administration of ketorolac on breast cancer recurrence according to the patient's body mass index

AU - Desmedt, Christine

AU - Demicheli, Romano

AU - Fornili, Marco

AU - Bachir, Imane

AU - Duca, Mariana

AU - Viglietti, Giulia

AU - Berlière, Martine

AU - Piccart, Martine

AU - Sotiriou, Christos

AU - Sosnowski, Maurice

AU - Forget, Patrice

AU - Biganzoli, Elia

PY - 2018/10

Y1 - 2018/10

N2 - BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are currently used in some countries as analgesics in primary cancer surgery. Retrospective studies suggest that NSAIDs could reduce breast cancer recurrences. Because NSAIDs also act on biological mechanisms present in patients with increased adiposity, we aimed at assessing whether the intra-operative administration of ketorolac or diclofenac would be associated with a reduction of recurrence in patients with elevated body mass index (BMI).MethodsWe considered two institutional retrospective series of 827 and 1007 patients evaluating the administration of ketorolac (n = 529 with, n = 298 without) or diclofenac (n = 787 with, n = 220 without). The BMI subgroups were defined as less than 25 kg/m2 (lean) and 25 or more kg/m2 (overweight and obese). Cumulative incidence estimation of distant metastases as well as Fine-Gray and Dixon-Simon models was used. These analyses were adjusted for clinico-pathological variables. All statistical tests were two-sided.ResultsThe administration of ketorolac was statistically significantly associated with decreased incidence of distant recurrences (adjusted hazard ratio [aHR]= 0.59, 95% confidence interval [CI] = 0.37 to 0.96, P = .03). In particular, the association was evident in the high–body mass index (BMI) group of patients (aHR = 0.55, 95% CI = 0.31 to 0.96, P = .04). The administration of diclofenac was not statistically significantly associated with decreased incidence of distant recurrences, either in the global population or in the BMI subgroups.ConclusionsThese results show that the intra-operative administration of ketorolac, but not diclofenac, is statistically significantly associated with a reduction of distant recurrences in patients with increased BMI. Altogether, this study points to a potentially important repositioning of ketorolac in the intra-operative treatment of patients with elevated BMI that, if prospectively validated, might be as impactful as and cheaper than adjuvant systemic anticancer therapies.

AB - BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are currently used in some countries as analgesics in primary cancer surgery. Retrospective studies suggest that NSAIDs could reduce breast cancer recurrences. Because NSAIDs also act on biological mechanisms present in patients with increased adiposity, we aimed at assessing whether the intra-operative administration of ketorolac or diclofenac would be associated with a reduction of recurrence in patients with elevated body mass index (BMI).MethodsWe considered two institutional retrospective series of 827 and 1007 patients evaluating the administration of ketorolac (n = 529 with, n = 298 without) or diclofenac (n = 787 with, n = 220 without). The BMI subgroups were defined as less than 25 kg/m2 (lean) and 25 or more kg/m2 (overweight and obese). Cumulative incidence estimation of distant metastases as well as Fine-Gray and Dixon-Simon models was used. These analyses were adjusted for clinico-pathological variables. All statistical tests were two-sided.ResultsThe administration of ketorolac was statistically significantly associated with decreased incidence of distant recurrences (adjusted hazard ratio [aHR]= 0.59, 95% confidence interval [CI] = 0.37 to 0.96, P = .03). In particular, the association was evident in the high–body mass index (BMI) group of patients (aHR = 0.55, 95% CI = 0.31 to 0.96, P = .04). The administration of diclofenac was not statistically significantly associated with decreased incidence of distant recurrences, either in the global population or in the BMI subgroups.ConclusionsThese results show that the intra-operative administration of ketorolac, but not diclofenac, is statistically significantly associated with a reduction of distant recurrences in patients with increased BMI. Altogether, this study points to a potentially important repositioning of ketorolac in the intra-operative treatment of patients with elevated BMI that, if prospectively validated, might be as impactful as and cheaper than adjuvant systemic anticancer therapies.

UR - http://www.mendeley.com/research/potential-benefit-intraoperative-administration-ketorolac-breast-cancer-recurrence-according-patient

U2 - 10.1093/jnci/djy042

DO - 10.1093/jnci/djy042

M3 - Article

VL - 110

SP - 1115

EP - 1122

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 10

ER -