Effect of adjuvant radiotherapy in elderly patients with breast cancer

Abstract

Background: Radiotherapy (RT) is of critical importance in the locoregional management of early breast cancer. Although RT is routinely used following breast conserving surgery (BCS), patients may occasionally be effectively treated with BCS alone. Currently, the selection of patients undergoing BCS who do not need breast irradiation is under investigation. With the advancement of personalized medicine, there is an increasing interest in reduction of aggressive treatments especially in older women. The primary objective of this study was to identify elderly patients who may forego breast irradiation after BCS without measurable consequences on local tumor growth and survival.

Methods: We analyzed 2384 early breast cancer patients aged 70 and older who were treated in 17 German certified breast cancer centers between 2001 and 2009. We compared RT versus no RT after guideline adherent (GA) BCS. The outcomes studied were breast cancer recurrence (RFS) and breast cancer-specific survival (BCSS). Low-risk patients were defined by luminal A, tumor size T1 or T2 and node-negative whereas higher-risk patients were defined by patients with G3 or T3/T4 or node-positive or other than Luminal A tumors. To test if there is a difference between two or more survival curves, we used the Gp family of tests of Harrington and Fleming.

Results: The median age was 77 yrs (mean 77.6±5.6 y) and the median observation time 46 mths (mean 48.9±24.8 mths). 950 (39.8%) patients were low-risk and 1434 (60.2%) were higher-risk. 1298 (54.4%) patients received GA BCS of which 85.0% (1103) received GA-RT and only 15% (195) did not. For low-risk patients with GA-BCS there were no significant differences in RFS (log rank p = 0.651) and in BCSS (p = 0.573) stratified by GA-RT. 5 years RFS in both groups were > 97%. For higher-risk patients with GA-BCS we found a significant difference (p<0.001) in RFS and tumor-associated OS stratified by GA-RT. The results remain the same after adjusting by adjuvant systemic treatment (AST) and comorbidity (ASA and NYHA).

Conclusions: Patients aged 70 years and older suffering from low-risk early breast cancer with GA-BCS can avoid breast irradiation with <3% chance of relapse. In the case of higher-risk, breast irradiation should be used routinely following GA-BCS. As a side effect of these results, removing the entire breast of elderly low risk patients to spare them from breast irradiation seems to be not necessary.

Fig 1. Recurrence free survival for early breast cancer patients aged ≥ 70 years.

Kaplan-Meier curves of recurrence free survival for early breast cancer patients aged 70 years and older, stratified by age.

Fig 2. Recurrence free survival for early breast cancer patients aged ≥ 70 years.

Kaplan-Meier curves of recurrence free survival for early breast cancer patients aged 70 years and older, stratified by guideline-adherent radiotherapy.

Fig 3. Recurrence free survival for early breast cancer patients aged ≥ 70 years.

Kaplan-Meier curves of recurrence free survival for early breast cancer patients aged 70 years and older, stratified by risk. Low risk: luminal A and T1/T2 and node-negative. Higher-risk: other than luminal A or G3 or T3/T4 or node-positive.

Fig 4. Recurrence free survival for early breast cancer patients aged ≥ 70 years.

Kaplan-Meier curves of recurrence free survival for low risk early breast cancer patients aged 70 years and older stratified by BCS vs. mastectomy. Low risk: luminal A and T1/T2 and node-negative.

Fig 5. Recurrence free and tumor-associated overall survival for early breast cancer patients aged ≥ 70 years stratified by guideline adherent radiotherapy.

(A) Kaplan-Meier curves of recurrence free survival for low risk early breast cancer patients aged 70 years and older with guideline adherent BCS stratified by guideline adherent RT. Low risk: luminal A and T1/T2 and node-negative. (B): Kaplan-Meier curves of tumor-associated overall survival for low-risk early breast cancer patients aged 70 years and older with guideline adherent BCS stratified by guideline adherent RT.

Fig 6. Recurrence free and tumor-associated overall survival for early breast cancer patients aged ≥ 70 years stratified by guideline adherent radiotherapy.

(A) Kaplan-Meier curves of recurrence free survival for higher-risk early breast cancer patients aged 70 years or older with guideline adherent BCS stratified by guideline adherent RT. Higher-risk: other than luminal A or G3 or T3/T4 or node-positive. (B) Kaplan-Meier curves of tumor-associated overall survival for higher-risk early breast cancer patients aged 70 years or older with guideline adherent BCS stratified by guideline adherent RT. Higher-risk: other than luminal A or G3 or T3/T4 or node-positive.

Fig 7. Cox regression of recurrence free survival for early breast cancer patients aged ≥ 70 years adjusted by adjuvant systemic therapy (AST) and physical status.

(A) Cox regression of recurrence free survival for low risk early breast cancer patients aged 70 years or older with guideline adherent BCS stratified by guideline adherent RT and adjusted by adjuvant systemic therapy (AST), ASA physical status classification system and the New York Heart Association (NYHA) functional classification. Low risk: luminal A and T1/T2 and node-negative. (B) Cox regression of recurrence free survival for higher-risk early breast cancer patients aged 70 years or older with guideline adherent BCS stratified by guideline adherent RT and adjusted by adjuvant systemic therapy (AST), ASA physical status classification system and the New York Heart Association (NYHA) functional classification. Higher-risk: other than luminal A or G3 or T3/T4 or node-positive.