Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): A randomised trial

Stefan Aebi, Shari Gelber, Stewart J. Anderson, I. Láng, André Robidoux, Miguel Martín, Johan W R Nortier, Alexander H G Paterson, Mothaffar F. Rimawi, José Manuel Baena Cañada, Beat Thürlimann, Elizabeth Murray, Eleftherios P. Mamounas, Charles E. Geyer, Karen N. Price, Alan S. Coates, Richard D. Gelber, Priya Rastogi, Norman Wolmark, Irene L. Wapnir

Research output: Contribution to journalArticle

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Abstract

Background: Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. Methods: The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-. HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. Findings: From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. Interpretation: Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. Funding: US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Español de Investigación en Cáncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

Original languageEnglish
Pages (from-to)156-163
Number of pages8
JournalThe Lancet Oncology
Volume15
Issue number2
DOIs
Publication statusPublished - Feb 2014

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Breast Neoplasms
Recurrence
Drug Therapy
Estrogen Receptors
Disease-Free Survival
Adjuvant Chemotherapy
Neoplasms
Research
United States Dept. of Health and Human Services
Febrile Neutropenia
Intention to Treat Analysis
Segmental Mastectomy
Mastectomy
Progesterone Receptors
South Africa
Neutropenia
Switzerland
New Zealand
Radiotherapy
Research Personnel

ASJC Scopus subject areas

  • Oncology

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Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR) : A randomised trial. / Aebi, Stefan; Gelber, Shari; Anderson, Stewart J.; Láng, I.; Robidoux, André; Martín, Miguel; Nortier, Johan W R; Paterson, Alexander H G; Rimawi, Mothaffar F.; Cañada, José Manuel Baena; Thürlimann, Beat; Murray, Elizabeth; Mamounas, Eleftherios P.; Geyer, Charles E.; Price, Karen N.; Coates, Alan S.; Gelber, Richard D.; Rastogi, Priya; Wolmark, Norman; Wapnir, Irene L.

In: The Lancet Oncology, Vol. 15, No. 2, 02.2014, p. 156-163.

Research output: Contribution to journalArticle

Aebi, S, Gelber, S, Anderson, SJ, Láng, I, Robidoux, A, Martín, M, Nortier, JWR, Paterson, AHG, Rimawi, MF, Cañada, JMB, Thürlimann, B, Murray, E, Mamounas, EP, Geyer, CE, Price, KN, Coates, AS, Gelber, RD, Rastogi, P, Wolmark, N & Wapnir, IL 2014, 'Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): A randomised trial', The Lancet Oncology, vol. 15, no. 2, pp. 156-163. https://doi.org/10.1016/S1470-2045(13)70589-8
Aebi, Stefan ; Gelber, Shari ; Anderson, Stewart J. ; Láng, I. ; Robidoux, André ; Martín, Miguel ; Nortier, Johan W R ; Paterson, Alexander H G ; Rimawi, Mothaffar F. ; Cañada, José Manuel Baena ; Thürlimann, Beat ; Murray, Elizabeth ; Mamounas, Eleftherios P. ; Geyer, Charles E. ; Price, Karen N. ; Coates, Alan S. ; Gelber, Richard D. ; Rastogi, Priya ; Wolmark, Norman ; Wapnir, Irene L. / Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR) : A randomised trial. In: The Lancet Oncology. 2014 ; Vol. 15, No. 2. pp. 156-163.
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abstract = "Background: Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. Methods: The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-. HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. Findings: From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28{\%}) patients had disease-free survival events in the chemotherapy group compared with 34 (44{\%}) in the no chemotherapy group. 5-year disease-free survival was 69{\%} (95{\%} CI 56-79) with chemotherapy versus 57{\%} (44-67) without chemotherapy (hazard ratio 0·59 [95{\%} CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15{\%}) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. Interpretation: Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. Funding: US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Espa{\~n}ol de Investigaci{\'o}n en C{\'a}ncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).",
author = "Stefan Aebi and Shari Gelber and Anderson, {Stewart J.} and I. L{\'a}ng and Andr{\'e} Robidoux and Miguel Mart{\'i}n and Nortier, {Johan W R} and Paterson, {Alexander H G} and Rimawi, {Mothaffar F.} and Ca{\~n}ada, {Jos{\'e} Manuel Baena} and Beat Th{\"u}rlimann and Elizabeth Murray and Mamounas, {Eleftherios P.} and Geyer, {Charles E.} and Price, {Karen N.} and Coates, {Alan S.} and Gelber, {Richard D.} and Priya Rastogi and Norman Wolmark and Wapnir, {Irene L.}",
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T1 - Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR)

T2 - A randomised trial

AU - Aebi, Stefan

AU - Gelber, Shari

AU - Anderson, Stewart J.

AU - Láng, I.

AU - Robidoux, André

AU - Martín, Miguel

AU - Nortier, Johan W R

AU - Paterson, Alexander H G

AU - Rimawi, Mothaffar F.

AU - Cañada, José Manuel Baena

AU - Thürlimann, Beat

AU - Murray, Elizabeth

AU - Mamounas, Eleftherios P.

AU - Geyer, Charles E.

AU - Price, Karen N.

AU - Coates, Alan S.

AU - Gelber, Richard D.

AU - Rastogi, Priya

AU - Wolmark, Norman

AU - Wapnir, Irene L.

PY - 2014/2

Y1 - 2014/2

N2 - Background: Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. Methods: The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-. HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. Findings: From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. Interpretation: Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. Funding: US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Español de Investigación en Cáncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

AB - Background: Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. Methods: The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-. HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. Findings: From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. Interpretation: Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. Funding: US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Español de Investigación en Cáncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

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