Elsevier

European Journal of Cancer

Volume 83, September 2017, Pages 116-124
European Journal of Cancer

Original Research
Primary metastatic breast cancer in the era of targeted therapy – Prognostic impact and the role of breast tumour surgery

https://doi.org/10.1016/j.ejca.2017.06.002Get rights and content

Highlights

  • 570 patients with primary metastatic breast cancer were analysed using data from two large observational studies.

  • Initial surgery of the primary was less frequently performed in patients with high local or distant tumour burden.

  • Multivariable analyses suggest no major advantage of surgery at presentation in the total population. However, removal of the primary may be beneficial in selected subgroups with limited metastatic extent.

Abstract

Background

Except for meeting the individual palliative need, the benefit of breast surgery in primary metastatic breast cancer (PMBC), also known as de novo metastatic breast cancer, on long-term outcomes remains controversial. Twenty-four hundred and one patients with metastatic breast cancer, enrolled between 2000 and 2011 in two prospective non-interventional studies on targeted therapy, were screened with respect to this question.

Methods

One study investigated trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in addition to mainly first-line chemotherapy. The other observed bevacizumab added to chemotherapy as first-line treatment for mostly HER2-negative disease.

Results

Five-hundred and seventy (24%) patients presented with PMBC, and valid information on resection of the primary tumour was available for 568 women. Out of these, 426 (75%) underwent local resection. The latter group was characterised by less overall metastatic burden and a lower proportion of T4 tumours. No major differences were observed with respect to age, hormone receptor and HER2 status, visceral disease and performance status. Numerically, the surgery group showed a slightly favourable progression-free survival (PFS, medians: 13.6 versus 11.8 months; P = 0.18) and overall survival (OS, 34.1 versus 31.7; P = 0.23). However, in multivariable analysis, including all other univariably significant parameters, no trend for better outcome after surgery remained detectable, neither for PFS (hazard ratio 0.99; P = 0.92) nor for OS (0.95; P = 0.71).

Conclusions

Our findings suggest no major survival benefit for local resection in the overall PMBC population treated with modern targeted therapies. However, further analyses are warranted to define specific risk groups, which may benefit from surgical removal of the primary.

Introduction

In the developed countries, about 25% of the total population of breast cancer patients cannot be cured due to advanced stage or recurrent disease. Approximately 6% suffer from primary metastatic breast cancer (PMBC, also termed de novo metastatic cancer), i.e. test positive for metastatic disease synchronously, at the time of their first diagnosis of a mammary carcinoma [1], [2], [3]. Hence, approximately one out of four patients entering a palliative stage has stage IV disease (M1) disease at presentation. This incidence has remained unchanged during the last 25 years [4], while the prognosis of PMBC seems to have improved slightly, but steadily over time [2], [4], [5].

Although survival differences between PMBC and secondary metastatic breast cancer (SMBC) have been shown in retrospective studies, the prognostic relevance might have changed in the era of antibody treatment. Moreover, the impact of primary breast surgery remains controversial, in spite of a large number of studies on this topic [3], [6], [7]. We reanalysed two large prospective non-interventional studies conducted in Germany between 2000 and 2011 for patients with advanced/metastatic breast cancer (ABC) whose treatment for primary stage IV disease included antibody treatment [8], [9], [10]. The data from both projects were pooled in order to obtain a sufficiently large cohort for prognostic and subgroup analysis.

The main objectives of this pooled analysis are as follows: First, to characterise patients with PMBC and analyse the impact of this initial stage on long-term prognosis, compared to patients with SMBC. Second, to further characterise subgroups of PMBC patients with respect to the chosen local therapy approach, and analyse the impact of initial breast surgery on the long-term prognosis.

Section snippets

Data sources and study design

All data were retrieved from two large prospective non-interventional studies, enrolling patients with ABC receiving antibody treatment:

  • ML16684 (started in 2000): Observational study on trastuzumab (Herceptin®) in HER2-positive ABC, predominantly without palliative cytotoxic pre-treatment. In the majority of patients, trastuzumab was combined with chemotherapy (mostly a taxane), but monotherapy or combination of trastuzumab with antihormonal therapy was permitted as well.

  • ML21165 (started in

Patient characteristics

Between 2000 and 2011, a total of 2401 evaluable patients were recruited and documented in both observational studies (Fig. 1). Five-hundred and seventy out of these (24%) presented with PMBC. Characteristics of the patients according to their initial cM0/cM1 status are shown in Table 1. Although there was no difference with respect to median age, we identified more patients aged over 70 years in the PMBC group. As expected, PMBC patients presented with distinctly more advanced T and N status

Discussion

The prognosis of PMBC has been subject to a variety of cohort studies during the last decades, suggesting a continuous improvement of long-term outcome over time [1], [3]. It remains unclear, whether this trend is mainly caused by improved therapy options, or a changing profile of disease characteristics. Especially, the growing insight on the molecular biology of breast cancer, influencing both diagnostic profiling and therapeutic options, may require additional studies on the PMBC population.

Role of the funding source

The data sources, non-interventional studies ML16684 and ML21165, had been sponsored by Roche Germany, which granted access to the database. Support for data analysis and third-party writing assistance by WiSP Research Institute, Langenfeld, Germany was provided by Roche Germany.

Conflict of interest statement

Marcus Schmidt: Honoraria Roche Pharma AG, Non-Financial Support Roche Pharma AG.

Marc Thill: Honoraria Roche Pharma AG.

Claus Richard Lattrich: Employee Roche Pharma.

Stella Keitel: Employee Roche Pharma.

Axel Hinke: Honoraria Roche Pharma AG.

Andreas Kutscheidt: Honoraria Roche Pharma AG.

All other authors declare no conflict of interest.

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