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


RESULTS
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.


CONCLUSIONS
Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative.


BACKGROUND
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).
Luzerner Kantonsspital, Lucerne, Switzerland; University of Berne, Berne, Switzerland; Swiss Group for Clinical Cancer Research (SAKK), Berne, Switzerland. Electronic address: stefan.aebi@onkologie.ch.
Stefan
S
Aebi
International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Frontier Science and Technology Research Foundation, Boston, MA, USA.
Shari
S
Gelber
National Surgical Adjuvant Breast and Bowel Project Biostatistical Center, Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Stewart J
SJ
Anderson
National Institute of Oncology, Budapest, Hungary.
István
I
Láng
Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
André
A
Robidoux
Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain.
Miguel
M
Martín
Leids Universitair Medisch Centrum, Leiden, Netherlands.
Johan W R
JW
Nortier
Tom Baker Cancer Centre, Calgary, AB, Canada.
Alexander H G
AH
Paterson
Baylor College of Medicine, Houston, TX, USA.
Mothaffar F
MF
Rimawi
Hospital Puerta Del Mar, Cádiz, Spain.
José Manuel Baena
JM
Cañada
Swiss Group for Clinical Cancer Research (SAKK), Berne, Switzerland; Breast Center, Kantonsspital, St Gallen, Switzerland.
Beat
B
Thürlimann
Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
Elizabeth
E
Murray
MD Anderson Cancer Center, Orlando, FL, USA.
Eleftherios P
EP
Mamounas
Virginia Commonwealth University Massey Cancer Center, Richmond, VA, USA.
Charles E
CE
Geyer
International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Frontier Science and Technology Research Foundation, Boston, MA, USA.
Karen N
KN
Price
International Breast Cancer Study Group, Bern, Switzerland; University of Sydney, Sydney, Australia.
Alan S
AS
Coates
International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Frontier Science and Technology Research Foundation, Boston, MA, USA.
Richard D
RD
Gelber
University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Priya
P
Rastogi
Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA, USA.
Norman
N
Wolmark
Stanford University School of Medicine, Stanford, CA, USA.
Irene L
IL
Wapnir
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008408:Mastectomy; D015412:Mastectomy, Segmental; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D009656:North America; D018579:Patient Selection; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D013019:South Africa; D013020:South America; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor