(ChemotherapyAdvisor) – Age, clinical tumor characteristics before neoadjuvant chemotherapy, and pathologic nodal status/breast tumor response following treatment can be used to predict risk of locoregional recurrence (LRR) in women with breast cancer to optimize the use of adjuvant radiotherapy, a study in the Journal of Clinical Oncology online October 1 has found.

To date, limited information on predictors of LRR after neoadjuvant chemotherapy has led to controversy about the optimal use of adjuvant radiotherapy and the timing of sentinel lymph node biopsy.

Describing “the largest prospectively collected cohort of patients with operable breast cancer treated with neoadjuvant chemotherapy for whom information on rates and patterns of LRR is available,” Eleftherios P. Mamounas, MD, of Aultman Health Foundation, Canton, OH, and colleagues “examined patterns and predictors of LRR as first event in combined analysis of two National Surgical Adjuvant Breast and Bowel Project (NSABP) neoadjuvant trials.”


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In the trials, neoadjuvant chemotherapy was either doxorubicin/cyclophosphamide (AC) alone or AC followed by neoadjuvant/adjuvant docetaxel. Patients who underwent lumpectomy received radiotherapy to the breast alone and those undergoing mastectomy received no radiotherapy.

After 10 years of follow-up, 335 LRR events had occurred in 3,088 patients. “The 10-year cumulative incidence of LRR was 12.3% for mastectomy patients (8.9% local; 3.4% regional) and 10.3% for lumpectomy plus breast radiotherapy patients (8.1% local; 2.2% regional),” they found.

Following lumpectomy, independent predictors of LRR were age, clinical nodal status before neoadjuvant chemotherapy, and pathologic nodal status/breast tumor response. After mastectomy, clinical tumor size and clinical nodal status prior to neoadjuvant chemotherapy and pathologic nodal status/breast tumor response were independent predictors of LRR.

“By using these independent predictors, groups at low, intermediate, and high risk of LRR could be identified,” Dr. Mamounas reported. A nomogram incorporating these independent predictors was created that, once independently validated, “could be a useful tool for predicting risk of LRR and the optimal use of radiation therapy in patients treated with neoadjuvant chemotherapy.” Hormone-receptor status, HER2 status, and the effect of adding trastuzumab would also need to be incorporated.

“Our results clearly demonstrate that, in addition to age and clinical tumor characteristics available before neoadjuvant chemotherapy, pathologic response in the breast and pathologic axillary nodal status have a major impact on the rates and patterns of LRR,” the authors concluded.

An accompanying editorial noted that “although the findings of the study by Mamounas et al will not clarify radiation indications in every clinical situation, they do help to set the agenda for the next generation of clinical trials, which will focus on strategic integration of radiation with neoadjuvant chemotherapy.”

Abstract