Effect of postmastectomy radiotherapy in patients <35 years old with stage II-III breast cancer treated with doxorubicin-based neoadjuvant chemotherapy and mastectomy

Authors: Garg AK, et al.
Source: Int J Radiat Oncol Biol Phys. 2007 Sep 12, epub.

Introduction

Young age is considered an independent poor prognostic factor in patients with breast cancer. In the past decade, several randomized trials and meta-analyses have displayed improvements in local control and overall survival with postmastectomy radiotherapy (PMRT) for locally advanced breast cancer, but have failed to report age-specific results. With increasing use of neoadjuvant chemotherapy in this population, a recent retrospective review has suggested continued improvement to local control and cancer specific survival over all age groups. This retrospective review of the experience of MD Anderson Cancer Center was conducted to evaluate the effect of PMRT after neoadjuvant chemotherapy in young patients.

Materials and Methods

• 107 patients
• Age <35 years
• Treated between 1975-2005 at MDACC
• Stage II-III (2003 AJCC) breast cancer treated on protocol with neoadjuvant doxorubicin-based chemotherapy and mastectomy
• 80 patients received PMRT
• 27 patients did not receive PMRT
• • 21 patients had 0-3 LN positive, not referred for PMRT
  • 6 patients had >3 LN positive, 1 refused PMRT, 5 others not referred for unknown reason

Results

• Median follow-up: 75 and 63 months (irradiated vs nonirradiated)
• Greater percentage of Stage III, lymphovascular invasion, and T4 disease in PMRT group (83% vs. 41%, 49% vs. 33%, and 50% vs. 26%)
• Improved 5-year locoregional recurrence rate (LRR) in PMRT group (12% vs. 37% p=0.001)
• Improved LRR in Stages IIB and IIIa-IIIc subsets (0% vs. 44%, p=0.003 and 15% vs. 36%, p=0.023)
• 5-year overall survival (OS) improved with PMRT for all patients, Stage IIB, Stage IIIa-IIIc, >= 4 positive nodes at surgery, and with lymphovascular invasion (67% vs. 48%, 92% vs. 56%, 60% vs. 27%, 67% vs. 48%, and 83% vs. 57%)

Author’s Conclusions

Addition of PMRT was associated with increased overall survival and locoregional control in patients <35 years old who received neoadjuvant chemotherapy and mastectomy for Stage IIb to III breast cancer. The clinical benefit was evident in patients with stage T3 disease or >3 positive lymph nodes. The benefit in smaller tumors with 1-3 positive lymph nodes remains unclear.

Clinical Implications

At present, recommendations regarding PMRT in patients receiving neoadjuvant chemotherapy for breast cancer are unclear. These data support the use of PMRT in young women with stage IIb-III breast cancer. Previous retrospective analysis of PMRT in the setting of neoadjuvant chemotherapy with patients of all ages did not reveal a benefit in Stage IIb disease. Given the modest numbers of Stage IIb patients (12 in each arm), and the retrospective nature of this study, further studies would benefit to clarify the role of PMRT in Stage IIb disease in young patients.

An additional limitation of this study is the length of follow-up. Given a 6-year median follow-up, it is not clear that late locoregional recurrences or late toxicities would be accounted for in these data.

This study provides useful data on a high-risk population to aid in treatment decisions, but the limitations of a retrospective study of this nature prohibit clear conclusions that might change previous clinical standards.