The Lancet. Oncology 2014-02
Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.
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).
Related Questions
Does neoadjuvant chemotherapy with complete response in the axilla alter your management preferences?
New comment by Radiation Oncologist at MedStar Georgetown University Hospital ( July 12, 2017)
If a patient has had prior whole breast only and now has axillary recurrence s/p ALND alone (not mastectomy), what would you treat? Just the SCV field that was previously unt...
Based on the CALOR trial (http://www.ncbi.nlm.nih.gov/pubmed/24439313), adjuvant chemotherapy should be considered, but what regimen is preferred?&nbs...
New answer by Medical Oncologist at Indiana University School of Medicine (August 7, 2016)
The CALOR trial took a pragmatic approach and randomized patients to systemic therapy or not. A specific regimen wasn't specified. If the patient has a known BRCA mutation, I ...
The CALOR study showed a benefit of adjuvant chemotherapy for local recurrence but the regimens given were "physicians choice".
New answer by Medical Oncologist at UT Southwestern Medical Center (November 8, 2016)
I agree with @Debu Tripathy. The CALOR study supports "physicians choice" chemotherapy in the setting of a local recurrence but unfortunately it doesn't guide specific chemoth...
Assume no history of radiation, no evidence of distant disease and no nodal disease on dissection. Would you treat the chest wall or the&nbs...
New answer by Radiation Oncologist at Duke University Medical Center (February 22, 2018)
Prognosis of local recurrence on the chest wall following mastectomy is dependent on several factors including time to recurrence, nodal status at diagnosis, ER status, prior ...
Assuming the patient was initially treated with surgical resection and adjuvant chemotherapy followed by radiation and appropriate endocrine therapy.
New answer by Medical Oncologist at University of North Carolina (December 21, 2017)
This one often depends on the nature of local relapse and whether relapse occurred on ET. The CALOR trial as flawed as it was suggested that chemotherapy helps in the "repeat ...
When would you sequence radiation?
New answer by Medical Oncologist at Warren Alpert Medical School of Brown University (July 23, 2018)
I agree with @Bora Lim. The CALOR trial supports administration of chemotherapy in TNBC patients with a locoregional recurrence. Assuming there is no evidence that the axillar...
< 4 lymph nodes involved, initial diagnosis was 11 years ago when she was treated with mastectomy and adjuvant tamoxifen for 5 years.
New answer by Medical Oncologist at NYU Winthrop Hospital (June 19, 2020)
Initially PET/CT to evaluate metastases.Then chemotherapy (CALOR trial), followed by local treatment.
And if the tumor is MSI-H, does that alter your thoughts?
New comment by at ProMedica Toledo Hospital ( September 9, 2022)
Great informative and well considered responses.
In view of the lack of any supportive data, would now and nearly always have recommended diligent observation.
No oncotype was sent on the original breast cancer.
New comment by Medical Oncologist at Mary Lanning Healthcare Morrison Cancer Center/University of Nebraska Medical Center Adjunct Faculty ( November 10, 2021)
Would you use Oncotype Dx to guide adjuvant therapy recommendations in the context of locally recurrent, node-negative, ER+ breast cancer previously treated with endocrine the...
At initial diagnosis she had T1cN0 disease treated with lumpectomy and SLNB followed by 12 weeks of paclitaxel with 1 year of trastuzumab.
New comment by Medical Oncologist at NYU Winthrop Hospital ( June 15, 2022)
T-DXd as second line therapy.