title: Local-regional control of recurrent breast carcinoma after mastectomy: does hyperfractionated accelerated radiotherapy improve local control?
abstract: OBJECTIVE
  Hyperfractionated, accelerated radiotherapy (HART) has been advocated for patients with local-regionally recurrent breast cancer because it is believed to enhance treatment effects in rapidly proliferating or chemoresistant tumors. This report examines the value of HART in patients with local-regionally recurrent breast cancer treated with multimodality therapy.
  
  
  METHODS
  The study included 148 patients with local-regionally recurrent breast cancer after mastectomy, who were treated with definitive local irradiation and systemic therapy consisting of either tamoxifen, cytotoxic chemotherapy, or both, along with excision of the recurrent tumor when possible. Patients with distant metastases were excluded, except for two patients with ipsilateral supraclavicular nodal metastases. Patients received comprehensive irradiation to the chest wall and regional lymphatics to a median dose of 45 Gy, with a boost to 60 Gy to areas of recurrence. Sixty-eight patients (46%) were treated once daily at 2 Gy/fraction (fx), and 80 (54%) were treated twice daily at 1.5 Gy/fx. Forty-eight patients (32%), who had palpable gross disease that was unresponsive to systemic therapy and/or unresectable, were irradiated. The median follow-up time of surviving patients was 78 months.
  
  
  RESULTS
  Overall actuarial local-regional control (LRC) rates at 5 and 10 years were 68% and 55%, respectively. Five- and ten-year actuarial overall survival (OS) and disease-free survival (DFS) rates were 50% and 35%, 39% and 29%, respectively. Univariate analysis revealed that LRC was adversely affected by 1. advanced initial American Joint Committee on Cancer (AJCC) stage (p = 0.001), 2. clinically evident residual disease at time of treatment (p < 0.0001), 3. more than three positive nodes at initial mastectomy (p = 0.014), 4. short interval from mastectomy to recurrence (< 24 months, p = 0.0007), 5. nuclear grade (III vs. I or II, p = 0.045), and 6. number of recurrent nodules (1 vs. > 1, p = 0.02). Patient age at time of recurrence (< 40 vs. > or = 40 years), recurrence location on the chest wall, estrogen receptor status, progesterone receptor status or menopausal status did not adversely affect LRC. On multivariate analysis, only clinically evident residual disease at the time of treatment and short interval from mastectomy to recurrence remained significant. When once-a-day irradiation was compared to the twice-a-day schedule, no significant differences were seen in LRC (67% vs. 68%), OS (47% vs. 52%), or DFS (42% vs. 36%) for the entire group of patients at 5 years. Pairwise comparison of the two fractionation schedules in each of the adverse outcome subgroups identified above showed no clinically significant differences in LRC at 5 years. For the 48 patients who began radiotherapy with measurable gross local recurrence, the complete response rate to radiotherapy was 73%, with no difference seen between the two fractionation schedules. The incidence of acute and chronic radiation-related complications was similar in both treatment groups.
  
  
  CONCLUSIONS
  Hyperfractionated accelerated radiotherapy, although well tolerated by patients with local-regionally recurrent breast cancer, did not result in superior local-regional control rates when compared to daily fractionated regimens. Alternative strategies, such as dose escalation or chemoradiation, may be required to improve control.
authors.affiliation: Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Ballo
authors.forename: E A
authors.initials: EA
authors.lastname: Strom
authors.forename: H
authors.initials: H
authors.lastname: Prost
authors.forename: S E
authors.initials: SE
authors.lastname: Singletary
authors.forename: R L
authors.initials: RL
authors.lastname: Theriault
authors.forename: T A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: M D
authors.initials: MD
authors.lastname: McNeese
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000532:radiotherapy; D008408:Mastectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D018365:Neoplasm, Residual; D012189:Retrospective Studies; D016019:Survival Analysis