Elsevier

The Breast

Volume 45, June 2019, Pages 104-112
The Breast

Original article
Locoregional surgical treatment improves the prognosis in primary metastatic breast cancer patients with a single distant metastasis except for brain metastasis

https://doi.org/10.1016/j.breast.2019.03.006Get rights and content

Highlights

  • •

    Breast surgery is an independent prognostic factor for pMBC patients.

  • •

    Breast surgery reduces the risk of mortality in patients with MBC by more than 40%.

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    Breast surgery is of particular significance for patients with single distant organ (bone, liver, or lung) involved.

Abstract

Background

We aimed to validate the clinical significance of locoregional surgery in improving the prognosis of primary metastatic breast cancer (pMBC).

Methods

We conducted a population-based retrospective study by analyzing clinical data obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Stratification analysis was employed to assess the effect of breast surgery on breast cancer-specific survival and overall survival. Then propensity score matching and COX regression models were employed to evaluate the survival advantages of breast surgery, if any in patients with pMBC.

Results

The median BCSS and OS in the surgery group were almost twice of that in the group without surgery. Breast surgery provided a survival advantage for patients with a single metastasis in the bone, liver or lung, but not in the brain. We found that axillary lymph node dissection performed in combination with specific breast surgical procedures did not result in a significant improvement in survival. Additionally, when combined with radiotherapy and/or chemotherapy, surgery significantly improved the survival and was not influenced by the molecular subtype and tumor size. Finally, using COX regression models before and after propensity score matching, breast surgery was found to reduce the risk of mortality in patients with MBC by more than 40%.

Conclusions

The effect of locoregional surgery has been underestimated in pMBC patients. Surgical procedures should be seriously considered when planning combination treatments for pMBC patients with a single metastasis except for brain metastasis.

Introduction

Breast cancer is the most common malignancy all over the world and remains the leading cause of cancer-related deaths in women. Among patients with breast cancer, approximately 6% have stage IV disease with distant metastasis at their first diagnosis [1]. The most frequently involved distant organs are the bones, liver, lung, and brain.

For stage IV breast cancer, systemic therapies consisting of chemo, hormonal, targeted, and immune therapies are recommended. Nevertheless, whether to perform a local surgery for primary metastatic breast cancer (pMBC) remains debatable. Traditionally, surgical treatment for patients with distant metastasis is not recommended since stage IV breast cancer is considered incurable. Patients with MBC usually undergo local surgery as a palliative treatment to relieve symptoms such as pain, bleeding, and infection. In addition, it is reported that resection of the primary tumor may promote distant metastases [2], though this hypothesis has not been backed by clinical evidence. Several recent studies have demonstrated improved prognosis of metastatic diseases following aggressive local surgeries [3,4], which has prompted researchers to investigate the efficacy of breast surgery in improving the overall survival (OS) in pMBC patients.

Over the past two decades, multiple retrospective studies have demonstrated a longer survival in patients who underwent breast surgery compared to those who did not [[5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]]. On the other hand, although several studies have also reported that breast surgery does not improve the prognosis of pMBC patients, these studies have not been conclusive due to their small sample sizes [[19], [20], [21]]. Several prospective clinical trials were conducted to provide more credible evidence for the benefits of locoregional treatment in pMBC patients. Only two of these randomized controlled trials (RCTs) are completed with full-text available. Soran et al. pointed out that locoregional treatment in de novo MBC is not always recommended and should only serve as an optional therapy for these patients [22]. However, another RCT conducted by the Tata Memorial Centre in India, concluded that breast surgery does not increase the OS in pMBC patients [23]. A recent systemic review by the Cochrane Breast Cancer Group, which included these two completed RCTs, reported that it is not possible to make definitive conclusions on the benefits and risks of breast surgery along with systemic treatment in women diagnosed with pMBC [24]. They also indicated that the decision to perform the surgery should be individualized and made after evaluating the potential risks, benefits, and costs in each case.

To further investigate the benefits of primary tumor removal, we sought to explore the data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program database to conduct this population-based epidemiologic study. Sites of metastasis, specific surgical procedures, chemotherapy, radiotherapy, molecular subtypes, and tumor sizes were used as stratification factors to analyze the OS and breast cancer-specific survival (BCSS). Based on the results of the univariate and multivariate analysis, we concluded that locoregional treatment of primary breast tumors could provide a survival advantage for pMBC patients.

Section snippets

Data acquisition and processing

Data for this population-based retrospective study was downloaded from the SEER database using the official software SEERStat on May 23, 2018. Complete demographic information on 1,342,410 women with breast cancer was obtained. After screening the data based on the 7th AJCC staging system, patients staged M1 with at least one distant metastasis involving the bone, liver, lung, or brain were included in this study. Our final cohort included 20,870 pMBC patients diagnosed from 2010 to 2015.

Demographic characteristics of the patients

Of the 20,870 patients who were diagnosed with pMBC between 2010 and 2015, 5779 (27.7%) of them underwent breast surgery, while 15,091 (72.3%) did not. Table 1 summarizes the clinical information for these patients. The median age for the surgery group was 59 years, while it was 63 years for the non-surgery group, indicating that younger patients were more likely to choose aggressive breast surgery. Race did not appear to influence the decision to remove the primary breast tumor. Based on the

Discussion

Basically, the outcomes of treatments for stage IV breast cancer including pMBC depend on the patient's response to systemic therapy. Surgical treatments for primary breast tumors can have positive outcomes only in women who respond well to systemic treatment. In this study, however, we focused on the role of locoregional management in promoting the survival of patients with pMBC. In recent years, multiple retrospective studies have highlighted the effects of surgical procedures on improving

Conflicts of interest statement

No potential conflicts of interest were disclosed.

Acknowledgements

The authors would like to thank the Surveillance, Epidemiology, and End Results (SEER) Program which is an authoritative and open-access source for cancer statistics and gave the authors the opportunity to accomplish this reliable population-based study on primary metastatic breast cancer. And the authors would like to appreciate the language editing service provided by EditageOnline™.

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    XL. Li and R. Huang contributed equally to this article.

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