Annals of Surgical Oncology

, Volume 24, Issue 2, pp 398–406 | Cite as

Poor Prognosis After Second Locoregional Recurrences in the CALOR Trial

  • Irene L. Wapnir
  • Shari Gelber
  • Stewart J. Anderson
  • Eleftherios P. Mamounas
  • André Robidoux
  • Miguel Martín
  • Johan W. R. Nortier
  • Charles E. GeyerJr
  • Alexander H. G. Paterson
  • István Láng
  • Karen N. Price
  • Alan S. Coates
  • Richard D. Gelber
  • Priya Rastogi
  • Meredith M. Regan
  • Norman Wolmark
  • Stefan Aebi
  • On behalf of CALOR trial investigators
Breast Oncology



Isolated locoregional recurrences (ILRRs) of breast cancer confer a significant risk for the development of distant metastasis. Management practices and second ILRR events in the Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial were investigated.


In this study, 162 patients with ILRR were randomly assigned to receive postoperative chemotherapy or no chemotherapy. Descriptive statistics characterize outcomes according to local therapy and the influence of hormone receptor status on subsequent recurrences. Competing risk regression models, Kaplan-Meier estimates, and Cox proportional hazards models were used to evaluate associations between treatment, site of second recurrence, and outcome.


The median follow-up period was 4.9 years. Of the 98 patients who received breast-conserving primary surgery 89 had an ipsilateral-breast tumor recurrence. Salvage mastectomy was performed for 73 patients and repeat lumpectomy for 16 patients. Another eight patients had nodal ILRR, and one patient had chest wall ILRR. Among 64 patients whose primary surgery was mastectomy, 52 had chest wall/skin ILRR, and 12 had nodal ILRR. For 15 patients, a second ILRR developed a median of 1.6 years (range 0.08–4.8 years) after ILRR. All second ILRRs occurred for patients with progesterone receptor-negative ILRR. Death occurred for 7 (47 %) of 15 patients with a second ILRR and 19 (51 %) of 37 patients with a distant recurrence. As shown in the multivariable analysis, the significant predictors of survival after either a second ILRR or distant recurrence were chemotherapy for the primary cancer (hazard ratio [HR], 3.55; 95 % confidence interval [CI], 1.15–10.9; p = 0.03) and the interval (continuous) from the primary surgery (HR, 0.87; 95 % CI, 0.75–1.00; p = 0.05).


Second ILRRs represented about one third of all recurrence events after ILRR, and all were PR-negative. These second ILRRs and distant metastases portend an unfavorable outcome.



The CALOR trial was supported in part by Public Service Grants U10-CA-180868, U10-CA-189867, U10-CA-180822, and U24-CA-75362 from the National Cancer Institute, Department of Health and Human Services. The International Breast Cancer Study Group is supported in part by the Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australia and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Cancer Research Switzerland/Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK). Spanish participation was funded by Grupo Español de Investigación en Cáncer de Mama (GEICAM), and Dutch participation by BOOG, the Dutch Breast Cancer Trialists’ Group.


None of the authors have any conflicts of interest to report.

Supplementary material

10434_2016_5571_MOESM1_ESM.docx (45 kb)
Supplementary material 1 (DOCX 46 kb)


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Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Irene L. Wapnir
    • 1
  • Shari Gelber
    • 2
  • Stewart J. Anderson
    • 3
  • Eleftherios P. Mamounas
    • 4
  • André Robidoux
    • 5
  • Miguel Martín
    • 6
  • Johan W. R. Nortier
    • 7
  • Charles E. GeyerJr
    • 8
  • Alexander H. G. Paterson
    • 9
  • István Láng
    • 10
  • Karen N. Price
    • 2
  • Alan S. Coates
    • 11
  • Richard D. Gelber
    • 12
  • Priya Rastogi
    • 13
  • Meredith M. Regan
    • 14
  • Norman Wolmark
    • 15
  • Stefan Aebi
    • 16
  • On behalf of CALOR trial investigators
  1. 1.NRG Oncology, Department of SurgeryStanford University School of MedicineStanfordUSA
  2. 2.IBCSG Statistical Center, Department of Biostatistics and Computational BiologyDana-Farber Cancer Institute, and Frontier Science and Technology Research FoundationBostonUSA
  3. 3.NRG Oncology and Department of BiostatisticsUniversity of Pittsburgh Graduate School of Public HealthPittsburghUSA
  4. 4.NRG Oncology and University of Florida Health Cancer Center at Orlando HealthOrlandoUSA
  5. 5.NRG Oncology and Centre Hospitalier de l’Universite de MontrealMontrealCanada
  6. 6.GEICAM, Instituto de Investigacion SanitariaGregorio MarañonUniversidad ComplutenseMadridSpain
  7. 7.BOOG, Dutch Breast Cancer Trialists’ GroupLeids Universitair Medisch CentrumLeidenNetherlands
  8. 8.NRG Oncology and Virginia Commonwealth University Massey Cancer CenterRichmondUSA
  9. 9.NRG Oncology and Tom Baker Cancer CentreCalgaryCanada
  10. 10.IBCSG and National Institute of OncologyBudapestHungary
  11. 11.IBCSG, Bern, Switzerland and University of SydneySydneyAustralia
  12. 12.IBCSG Statistical Center, Department of Biostatistics and Computational BiologyDana-Farber Cancer Institute, Harvard TH Chan School of Public Health, Harvard Medical School, and Frontier Science and Technology Research FoundationBostonUSA
  13. 13.NRG OncologyUniversity of Pittsburgh Cancer InstitutePittsburghUSA
  14. 14.IBCSG Statistical Center, Department of Biostatistics and Computational BiologyDana-Farber Cancer Institute, Harvard Medical SchoolBostonUSA
  15. 15.NRG Oncology and the Allegheny Health Network Cancer InstitutePittsburghUSA
  16. 16.IBCSG, Luzerner Kantonsspital, Lucerne and University of Berne, Switzerland and Swiss Group for Clinical Cancer Research (SAKK)BernSwitzerland

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