CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: A retrospective substudy of the HERA trial (BIG 1-01)

Bernhard C. Pestalozzi, Eileen Holmes, Evandro de Azambuja, Otto Metzger-Filho, Laurence Hogge, Matt Scullion, I. Láng, Andrew Wardley, Mikhail Lichinitser, Roberto I Lopez Sanchez, Volkmar Müller, David Dodwell, Richard D. Gelber, Martine J. Piccart-Gebhart, David Cameron

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Abstract

Background: Several randomised trials have confirmed the benefit of adjuvant trastuzumab for patients with HER2-positive early breast cancer. However, concern has been expressed that adjuvant trastuzumab might be associated with an increased frequency of CNS relapses. We assessed the frequency and course of CNS relapses, either as first event or at any time, using data from the HERA trial. Methods: We estimated the cumulative incidence of first disease-free survival (DFS) events in the CNS versus other sites by competing risks analysis in patients with HER2-positive early breast cancer who had been randomly assigned to receive 1 year of trastuzumab or to observation in the HERA trial after a median follow-up of 4 years (IQR 3·5-4·8). To obtain further information about CNS relapse at any time before death, we circulated a data collection form to investigators to obtain standardised information about CNS events that occurred in all patients who had died before July, 2009. We estimated the cumulative incidence of CNS relapse at any time with a competing risks analysis. Results: Of 3401 patients who had been assigned to receive 1 year of trastuzumab or to observation, 69 (2%) had a CNS relapse as first DFS event and 747 (22%) had a first DFS event not in the CNS. The frequency of CNS relapses as first DFS event did not differ between the group given 1 year of trastuzumab (37 [2%] of 1703 patients) and the observation group (32 [2%] of 1698; p=0·55 [Gray's test]). 481 data collection forms were distributed, of which 413 (86%) were returned. The proportion of patients who had died and experienced a CNS relapse was numerically higher in the observation group (129 [57%] of 227) than in the group given trastuzumab for 1 year (88 [47%] of 186; p=0·06 [Gray's test]). Most CNS relapses were symptomatic (189 [87%] of 217). Conclusion: Adjuvant trastuzumab does not increase the risk of CNS relapse in patients with HER2-positive early breast cancer. Funding: None.

Original languageEnglish
Pages (from-to)244-248
Number of pages5
JournalThe Lancet Oncology
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 2013

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Breast Neoplasms
Recurrence
Disease-Free Survival
Observation
Trastuzumab
Incidence
Research Personnel

ASJC Scopus subject areas

  • Oncology

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CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab : A retrospective substudy of the HERA trial (BIG 1-01). / Pestalozzi, Bernhard C.; Holmes, Eileen; de Azambuja, Evandro; Metzger-Filho, Otto; Hogge, Laurence; Scullion, Matt; Láng, I.; Wardley, Andrew; Lichinitser, Mikhail; Sanchez, Roberto I Lopez; Müller, Volkmar; Dodwell, David; Gelber, Richard D.; Piccart-Gebhart, Martine J.; Cameron, David.

In: The Lancet Oncology, Vol. 14, No. 3, 03.2013, p. 244-248.

Research output: Contribution to journalArticle

Pestalozzi, BC, Holmes, E, de Azambuja, E, Metzger-Filho, O, Hogge, L, Scullion, M, Láng, I, Wardley, A, Lichinitser, M, Sanchez, RIL, Müller, V, Dodwell, D, Gelber, RD, Piccart-Gebhart, MJ & Cameron, D 2013, 'CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: A retrospective substudy of the HERA trial (BIG 1-01)', The Lancet Oncology, vol. 14, no. 3, pp. 244-248. https://doi.org/10.1016/S1470-2045(13)70017-2
Pestalozzi, Bernhard C. ; Holmes, Eileen ; de Azambuja, Evandro ; Metzger-Filho, Otto ; Hogge, Laurence ; Scullion, Matt ; Láng, I. ; Wardley, Andrew ; Lichinitser, Mikhail ; Sanchez, Roberto I Lopez ; Müller, Volkmar ; Dodwell, David ; Gelber, Richard D. ; Piccart-Gebhart, Martine J. ; Cameron, David. / CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab : A retrospective substudy of the HERA trial (BIG 1-01). In: The Lancet Oncology. 2013 ; Vol. 14, No. 3. pp. 244-248.
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abstract = "Background: Several randomised trials have confirmed the benefit of adjuvant trastuzumab for patients with HER2-positive early breast cancer. However, concern has been expressed that adjuvant trastuzumab might be associated with an increased frequency of CNS relapses. We assessed the frequency and course of CNS relapses, either as first event or at any time, using data from the HERA trial. Methods: We estimated the cumulative incidence of first disease-free survival (DFS) events in the CNS versus other sites by competing risks analysis in patients with HER2-positive early breast cancer who had been randomly assigned to receive 1 year of trastuzumab or to observation in the HERA trial after a median follow-up of 4 years (IQR 3·5-4·8). To obtain further information about CNS relapse at any time before death, we circulated a data collection form to investigators to obtain standardised information about CNS events that occurred in all patients who had died before July, 2009. We estimated the cumulative incidence of CNS relapse at any time with a competing risks analysis. Results: Of 3401 patients who had been assigned to receive 1 year of trastuzumab or to observation, 69 (2{\%}) had a CNS relapse as first DFS event and 747 (22{\%}) had a first DFS event not in the CNS. The frequency of CNS relapses as first DFS event did not differ between the group given 1 year of trastuzumab (37 [2{\%}] of 1703 patients) and the observation group (32 [2{\%}] of 1698; p=0·55 [Gray's test]). 481 data collection forms were distributed, of which 413 (86{\%}) were returned. The proportion of patients who had died and experienced a CNS relapse was numerically higher in the observation group (129 [57{\%}] of 227) than in the group given trastuzumab for 1 year (88 [47{\%}] of 186; p=0·06 [Gray's test]). Most CNS relapses were symptomatic (189 [87{\%}] of 217). Conclusion: Adjuvant trastuzumab does not increase the risk of CNS relapse in patients with HER2-positive early breast cancer. Funding: None.",
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T1 - CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab

T2 - A retrospective substudy of the HERA trial (BIG 1-01)

AU - Pestalozzi, Bernhard C.

AU - Holmes, Eileen

AU - de Azambuja, Evandro

AU - Metzger-Filho, Otto

AU - Hogge, Laurence

AU - Scullion, Matt

AU - Láng, I.

AU - Wardley, Andrew

AU - Lichinitser, Mikhail

AU - Sanchez, Roberto I Lopez

AU - Müller, Volkmar

AU - Dodwell, David

AU - Gelber, Richard D.

AU - Piccart-Gebhart, Martine J.

AU - Cameron, David

PY - 2013/3

Y1 - 2013/3

N2 - Background: Several randomised trials have confirmed the benefit of adjuvant trastuzumab for patients with HER2-positive early breast cancer. However, concern has been expressed that adjuvant trastuzumab might be associated with an increased frequency of CNS relapses. We assessed the frequency and course of CNS relapses, either as first event or at any time, using data from the HERA trial. Methods: We estimated the cumulative incidence of first disease-free survival (DFS) events in the CNS versus other sites by competing risks analysis in patients with HER2-positive early breast cancer who had been randomly assigned to receive 1 year of trastuzumab or to observation in the HERA trial after a median follow-up of 4 years (IQR 3·5-4·8). To obtain further information about CNS relapse at any time before death, we circulated a data collection form to investigators to obtain standardised information about CNS events that occurred in all patients who had died before July, 2009. We estimated the cumulative incidence of CNS relapse at any time with a competing risks analysis. Results: Of 3401 patients who had been assigned to receive 1 year of trastuzumab or to observation, 69 (2%) had a CNS relapse as first DFS event and 747 (22%) had a first DFS event not in the CNS. The frequency of CNS relapses as first DFS event did not differ between the group given 1 year of trastuzumab (37 [2%] of 1703 patients) and the observation group (32 [2%] of 1698; p=0·55 [Gray's test]). 481 data collection forms were distributed, of which 413 (86%) were returned. The proportion of patients who had died and experienced a CNS relapse was numerically higher in the observation group (129 [57%] of 227) than in the group given trastuzumab for 1 year (88 [47%] of 186; p=0·06 [Gray's test]). Most CNS relapses were symptomatic (189 [87%] of 217). Conclusion: Adjuvant trastuzumab does not increase the risk of CNS relapse in patients with HER2-positive early breast cancer. Funding: None.

AB - Background: Several randomised trials have confirmed the benefit of adjuvant trastuzumab for patients with HER2-positive early breast cancer. However, concern has been expressed that adjuvant trastuzumab might be associated with an increased frequency of CNS relapses. We assessed the frequency and course of CNS relapses, either as first event or at any time, using data from the HERA trial. Methods: We estimated the cumulative incidence of first disease-free survival (DFS) events in the CNS versus other sites by competing risks analysis in patients with HER2-positive early breast cancer who had been randomly assigned to receive 1 year of trastuzumab or to observation in the HERA trial after a median follow-up of 4 years (IQR 3·5-4·8). To obtain further information about CNS relapse at any time before death, we circulated a data collection form to investigators to obtain standardised information about CNS events that occurred in all patients who had died before July, 2009. We estimated the cumulative incidence of CNS relapse at any time with a competing risks analysis. Results: Of 3401 patients who had been assigned to receive 1 year of trastuzumab or to observation, 69 (2%) had a CNS relapse as first DFS event and 747 (22%) had a first DFS event not in the CNS. The frequency of CNS relapses as first DFS event did not differ between the group given 1 year of trastuzumab (37 [2%] of 1703 patients) and the observation group (32 [2%] of 1698; p=0·55 [Gray's test]). 481 data collection forms were distributed, of which 413 (86%) were returned. The proportion of patients who had died and experienced a CNS relapse was numerically higher in the observation group (129 [57%] of 227) than in the group given trastuzumab for 1 year (88 [47%] of 186; p=0·06 [Gray's test]). Most CNS relapses were symptomatic (189 [87%] of 217). Conclusion: Adjuvant trastuzumab does not increase the risk of CNS relapse in patients with HER2-positive early breast cancer. Funding: None.

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