Long-term Survival Effect of the Interval Between Mastectomy and Radiotherapy in Locally Advanced Breast Cancer

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Locoregional recurrence (LRR) is a cause for concern among patients with breast cancer, particularly for those with stage III disease; approximately 30% of patients with advanced breast cancer experience LRR postmastectomy.

There is evidence demonstrating that postmastectomy radiotherapy (PMRT) improves LRR and survival in this patient population, but the optimal duration between surgery and PMRT is unclear. However, previous findings have suggested that an interval longer than 6 to 12 weeks for patients who did not receive chemotherapy and longer than 6 to 7 months for patients who received adjuvant chemotherapy may increase the risk of recurrence.

In this retrospective study, researchers present the long-term survival outcomes of women with locally advanced breast cancer who received PMRT 4 or fewer months vs more than 4 months, 5 or fewer months vs more than 5 months, or 6 or fewer months vs more than 6 months after undergoing mastectomy. Potential prognostic factors that may mediate long-term survival were also evaluated.

Cancer Management and Research
Cancer Management and Research

Introduction: The timing of postmastectomy radiotherapy (PMRT) may influence locoregional recurrence and survival outcomes. In this study, we assessed the long-term survival effect of the interval between surgery and PMRT in locally advanced breast cancer treated with mastectomy and adjuvant chemotherapy.

Methods: In this retrospective study, we included women with locally advanced breast cancer who underwent adjuvant chemotherapy and PMRT after mastectomy between 1999 and 2007. Based on the interval between surgery and PMRT, the patients were classified into three groups: Group 1 (≤4 vs >4 months), Group 2 (≤5 vs >5 months), and Group 3 (≤6 vs >6 months). Univariate and multivariate regression analyses were performed to determine the prognostic factors of survival outcomes.

Results: A total of 340 women were included in this study, and the median follow-up duration was 79.8 months. The median surgery–PMRT interval was 5 months. The surgery–PMRT interval including Group 1, Group 2, and Group 3 was not significantly associated with locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival. In addition, in the subgroup analysis of the effect of surgery–PMRT interval on survival outcomes according to various clinicopathologic factors, the surgery–PMRT interval was also not associated with survival outcomes in different age groups, tumor stage, and breast cancer subtypes.

Conclusion: Our findings suggest that the delay in the start of PMRT in locally advanced breast cancer does not increase the likelihood of locoregional recurrence, distant metastasis, and death.


Keywords: breast carcinoma, surgery, time, irradiation, delay 

INTRODUCTION

Patients with locally advanced breast cancer, which is defined as stage III disease, had a higher risk for locoregional recurrence (LRR). Approximately 30% of patients with high-risk breast cancer develop LRR after mastectomy, but the administration of postmastectomy radiotherapy (PMRT) may reduce LRR and improve survival outcomes.1–3 In these high-risk patients, the interval between PMRT administration and mastectomy may affect LRR and survival outcomes. However, the optimal time between surgery and PMRT remains unclear.

There are conflicting results regarding the optimal interval between surgery and radiotherapy. However, it has been reported that an interval >6–12 weeks in patients not receiving chemotherapy, and an interval >6–7 months in patients receiving adjuvant chemotherapy after surgery, may lead to a higher risk of recurrence.4–9 Several retrospective studies have yielded variable findings in women receiving breast-conserving surgery.5,10–14 Adjuvant chemotherapy and radiotherapy is the standard treatment for high-risk breast cancer after mastectomy.15 In this study, we retrospectively assessed the long-term survival effect of the surgery–PMRT interval in women with locally advanced breast cancer treated with mastectomy and adjuvant chemotherapy.

MATERIALS AND METHODS

Patients

We retrospectively analyzed the medical data of patients with breast cancer who underwent mastectomy between 1999 and 2009 at the Sun Yat-Sen University Cancer Center, Guangzhou, China. Patients were eligible for inclusion in this study if:

  • in accordance with the current tumor (T) node (N) metastasis (M) staging system, they had stage III breast cancer;
  • they underwent mastectomy, and at least 4 cycles adjuvant chemotherapy followed by PMRT;
  • PMRT was administrated to the chest wall and supraclavicular lymph nodes to a prescription dose of 50 Gy in 25 fractions; and
  • they had complete clinicopathologic and follow-up data.

All patients gave their written informed consent to use of their medical records, and the clinical ethics committee of the Sun Yat-sen University Cancer Center approved this study.

Clinicopathologic factors

The following clinicopathologic factors were included: age; menopausal status; tumor stage; hormone receptor (HoR) status; and human epidermal growth factor receptor-2 (HER2) status. The expressions of estrogen receptor (ER), progesterone receptor (PR), and HER2 were assessed in accordance with our previous study.16 ER and PR positivity were defined as immunohistochemistry findings of >1% positive cells. HER2 positivity was defined as an immunohistochemistry score of 3+ or 2+ with confirmation by fluorescence in situ hybridization. The breast cancer subtypes (BCS) were classified as four subtypes according to HoR and HER2 status: HoR+/HER2−, HoR+/HER2+, HoR−/HER2+, and HoR−/HER2− subtypes. Based on the interval between mastectomy and radiotherapy, the patients were classified into three groups: Group 1 (≤4 vs >4 months), Group 2 (≤5 vs >5 months), and Group 3 (≤6 vs >6 months). The primary endpoints of this study were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). LRR was defined as pathologically confirmed recurrence including ipsilateral chest wall, axillary lymph nodes, supraclavicular and subclavian lymph nodes, or internal mammary lymph nodes. Distant metastasis was defined as tumor recurrence at a site distal to the primary cancer. DFS referred to absence of LRR or distant metastasis. OS was defined as the time from initial diagnosis to the date of death or last follow-up. 

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