Review question
In women with metastatic breast cancer (when the cancer has spread to other parts of the body), what is the effectiveness of breast surgery (mastectomy: removal of the whole breast including nipple and areola, or lumpectomy: removal of the tumour and breast tissue around it but preserving the nipple and areola) combined with medical treatment (such as chemotherapy and hormone therapy) compared to medical treatment alone?
Background
Metastatic breast cancer is considered an incurable disease with poor prognosis, although some women can live for many years. It is traditionally treated only with medical treatment. Breast surgery was believed to be palliative and performed only to relieve symptoms such as local bleeding, infection, or pain. With the development of new medications, women with metastatic breast cancer are living longer, and breast surgery could benefit this group of women. Retrospective data (i.e. data from types of studies other than randomised controlled trials that are more likely to suffer from bias) suggest that breast surgery could improve the survival of women with metastatic breast cancer.
Study characteristics
The evidence is current to February 2016. We included only randomised clinical trials, as they are considered to be the best type of scientific study to answer questions about treatment, that compared the survival of women undergoing breast surgery combined with medical treatment versus medical treatment alone. We identified and included two randomised controlled trials involving a total of 624 women: 311 women underwent breast surgery plus medical treatment, and 313 women only received medical treatment.
Key results
The review authors are uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low. The included studies did not report any information relating to quality of life. Breast surgery may improve the control of local disease but it probably worsened control at distant sites. The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy appeared to be the same in the group undergoing breast surgery combined with medical treatment and in the group receiving only medical treatment.
What does this mean?
It is not possible to make definitive conclusions about the benefits of breast surgery associated with medical treatment for women with metastatic breast cancer. The decision to perform surgery in such cases should be individualised and shared between the physician and the patient, considering the potential risks and benefits involved in this choice. The inclusion of results of ongoing trials involving women with these characteristics in the next update of this review will help to decrease existing uncertainties.
Based on existing evidence from two randomised clinical trials, it is not possible to make definitive conclusions on the benefits and risks of breast surgery associated with systemic treatment for women diagnosed with metastatic breast cancer. Until the ongoing clinical trials are finalised, the decision to perform breast surgery in these women should be individualised and shared between the physician and the patient considering the potential risks, benefits, and costs of each intervention.
Metastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an increased survival in other types of metastatic cancer. Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase the women's survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomised controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question.
To assess the effects of breast surgery in women with metastatic breast cancer.
We conducted searches using the MeSH terms 'breast neoplasms', 'mastectomy', and 'analysis, survival' in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 22 February 2016. We also searched ClinicalTrials.gov (22 February 2016) and the WHO International Clinical Trials Registry Platform (24 February 2016). We conducted an additional search in the American Society of Clinical Oncology (ASCO) conference proceedings in July 2016 that included reference checking, citation searching, and contacting study authors to identify additional studies.
The inclusion criteria were randomised controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy.
Two review authors independently conducted trial selection, data extraction, and 'Risk of bias' assessment (using Cochrane's 'Risk of bias' tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies.
We included two trials enrolling 624 women in the review. It is uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low (HR 0.83, 95% CI 0.53 to 1.31; 2 studies; 624 women). The two studies did not report quality of life. Breast surgery may improve local progression-free survival (HR 0.22, 95% CI 0.08 to 0.57; 2 studies; 607 women; low-quality evidence), while it probably worsened distant progression-free survival (HR 1.42, 95% CI 1.08 to 1.86; 1 study; 350 women; moderate-quality evidence). The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy was reported by 30-day mortality and did not appear to differ between the two groups (RR 0.99, 95% CI 0.14 to 6.90; 1 study; 274 women; low-quality evidence).