Poor Prognosis After Second Locoregional Recurrences in the CALOR Trial.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
NRG Oncology, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. wapnir@stanford.edu.
Irene L
IL
Wapnir
IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Frontier Science and Technology Research Foundation, Boston, MA, USA.
Shari
S
Gelber
NRG Oncology and Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
Stewart J
SJ
Anderson
NRG Oncology and University of Florida Health Cancer Center at Orlando Health, Orlando, FL, USA.
Eleftherios P
EP
Mamounas
NRG Oncology and Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada.
André
A
Robidoux
GEICAM, Instituto de Investigacion SanitariaGregorio Marañon, Universidad Complutense, Madrid, Spain.
Miguel
M
Martín
BOOG, Dutch Breast Cancer Trialists' Group, Leids Universitair Medisch Centrum, Leiden, Netherlands.
Johan W R
JW
Nortier
NRG Oncology and Virginia Commonwealth University Massey Cancer Center, Richmond, VA, USA.
Charles E
CE
Geyer
NRG Oncology and Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Alexander H G
AH
Paterson
IBCSG and National Institute of Oncology, Budapest, Hungary.
István
I
Láng
IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Frontier Science and Technology Research Foundation, Boston, MA, USA.
Karen N
KN
Price
IBCSG, Bern, Switzerland and University of Sydney, Sydney, Australia.
Alan S
AS
Coates
IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard TH Chan School of Public Health, Harvard Medical School, and Frontier Science and Technology Research Foundation, Boston, MA, USA.
Richard D
RD
Gelber
NRG Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Priya
P
Rastogi
IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Meredith M
MM
Regan
NRG Oncology and the Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA.
Norman
N
Wolmark
IBCSG, Luzerner Kantonsspital, Lucerne and University of Berne, Switzerland and Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland.
Stefan
S
Aebi
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008408:Mastectomy / Q000009:adverse effects*; D015412:Mastectomy, Segmental / Q000009:adverse effects*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
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