Clinical Investigations
Local Recurrence After Breast-Conserving Therapy for Invasive Breast Cancer: High Incidence in Young Patients and Association with Poor Survival

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Abstract

Purpose: To study risk factors for local recurrence (LR) after breast-conserving therapy (BCT) for invasive breast cancer and, for patients with an LR, the mode of detection, location, treatment, influence of radiation therapy, and impact on survival.

Methods and Materials: 1360 patients (median age 52 years; range 24–88) with a total of 1393 pT1-2 N0-1 tumors treated with BCT between 1980–1994 were studied (median follow-up 52 months). The adequacy of radiation treatment of the patients developing LR was studied in a quality control study. The impact of LR on overall survival and distant metastasis was studied in a Cox regression model with LR as a time-dependent covariate.

Results: A total of 88 LR occurred with a 5- and 10-year LR risk of 8 and 12%. Age was the only significant risk factor. Compared to patients >65 years old, patients <45 years old and patients 45–65 years old had a relative risk (RR) of 4.09 and 2.41, respectively, of developing LR. Risk on LR was found to increase gradually with younger age. Radiation therapy was considered adequate and did not play a role in influencing the LR rate. Almost 65% of the LR were true or marginal recurrences. Of all LR, 80% appeared during the first 5 years and were detected with equal frequency by the patient herself, the physician, and annual mammography. LR was a major predictor for distant metastasis (RR: 4.90; 3.15–7.62) and death (RR: 4.29; 2.93–6.28).

Conclusion: Young age is a major risk factor for LR and there is a significant gradual increase in LR with decreasing age. LR is associated with a higher risk of distant metastasis and death. Whether LR is the cause of or a marker for distant metastasis remains unresolved.

Introduction

The successful treatment of early stage breast cancer with breast-conserving therapy (BCT) has been well established over the past decades.

Retrospective series, as well as a number of prospective randomized trials, have indicated BCT as an equally effective alternative treatment to mastectomy with respect to survival 1, 2, 3, 4, 5, 6. With respect to local control, radiotherapy applied after local excision appears to be of major importance. In the nonirradiated lumpectomy cohort in the National Surgical Adjuvant Breast Program (NSABP)-B06 trial, a local recurrence rate of 39% was found compared to 10% in the irradiated patients at 8 years of follow-up [2]. Several studies showed that, with the combined therapy, satisfactory cosmetic results are achieved with local relapse rates at 5 years varying from 4 to 10% 3, 4, 7, 8, 9, 10, 11. These rates are comparable to those after mastectomy 2, 4, 6.

Based on the above, it was concluded, in June 1990 at the Consensus Development Conference on the Treatment of Early Stage Breast Cancer convened by the National Cancer Institute, that breast-conserving therapy is an appropriate method of primary therapy for the majority of women with Stage I and II breast cancer [12].

Although local control rates at 5 years after BCT are satisfactory, it seems that, with longer follow-up, the local recurrence (LR) rate tends to rise slowly, but continuously 2, 9, 13, 14. So, in the long run, local relapse after BCT may occur more frequently than after mastectomy. It has been shown that LR after mastectomy is associated with an unfavorable prognosis, even in the absence of synchronous distant relapse 15, 16. After salvage surgery for LR after BCT, survival is stated to be more favorable. However, some questions remain to be answered with regard to the consequences of LR after BCT. First, the efficacy of salvage therapy. Most patients can be salvaged locally from their LR; in some cases, however, salvage therapy may fail and LR remains of clinical importance. Second, the influence of LR after BCT on the incidence of metastasis and survival is a subject of debate. Due to relatively small numbers of events in most studies, the influence on survival is difficult to study in cohorts. Only a few studies have a sufficiently high number of local recurrences to evaluate their effect on survival. Patients with a local relapse after BCT have been shown to have a worse prognosis compared to patients without LR in some studies 17, 18, 19, 20, 21, whereas other studies did not find a difference in outcome 2, 22, 23. Even if the influence on survival is limited, it is important to keep the LR rate as low as possible, not in the least because of the impact of a relapse on cosmetics and the psychological stability of the patient.

This study was intended to evaluate results of breast-conserving therapy since the beginning of the 1980s in a cohort of 1481 tumors, especially with respect to the local recurrence rate. Because all patients were treated in the same radiotherapy department, the study refers to a single institution experience in this respect. However, the patients were operated on in different surgical departments in different hospitals. Clinical risk factors were studied for overall survival, distant metastasis, and local relapse. With respect to local relapse, the following points of interest were studied: (a) The influence of the surgery-radiotherapy interval on the LR rate; (b) the method of detection of LR; (c) the location of the relapse within the breast; (d) the adequacy of the radiation therapy; (e) the treatment of LR; (f) survival after LR; (g) the influence of LR on metastasis and survival.

Section snippets

Patients and Methods

The present patient cohort represents all breast cancer patients who received radiotherapy at Leiden University Hospital after breast-conserving surgery between 1980 and 1994. BCT was not routinely performed at our institution before 1980. Surgery was performed in Leiden University Hospital (n = 394), Elisabeth Hospital (n = 295), Bleuland Hospital (n = 208), Diaconessenhuis Hospital (n = 185), St. Jozef Hospital (n = 101), Rijnoord Hospital (n = 82), or other hospitals (n = 128). The same

Results

In total, 1360 patients were studied with 1393 tumors, with the tumor characteristics listed in Table 1. In the early years (1980–1984), fewer patients (15%) were operated with BCT than in later years, when BCT was more commonly used. Relatively many young women (< = 50 years old: 46%) and small tumors (70% pT1) with mostly negative lymph nodes (72% pN0) are included in this patient cohort. The median age of patients was 52 years (range 24–88). At time of analysis, 1176 patients were still

Discussion

Despite the general acceptance of BCT for early stage breast cancer, a number of questions regarding this treatment have remained. We studied risk factors in BCT in a large cohort of patients treated at one radiotherapy department. The three endpoints studied were overall survival, distant metastasis-free survival and local recurrence-free survival. Additional factors for LR were studied: the method and year of detection, the location within the breast, the choice of treatment, and survival

Acknowledgements

The authors thank Birgit van Leeuwen and Jan Molenaar from the Oncologische Documentatie University Hospital Leiden for supplying most of the data. This study was financially supported by the Dutch Cancer Society.

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