Stage IV breast cancer in the era of targeted therapy

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Cancer (Impact Factor: 4.89). 03/2010; 116(5):1226-33. DOI: 10.1002/cncr.24873
Source: PubMed


Multiple studies have suggested that resection of the primary tumor improves survival in patients with stage IV breast cancer, yet in the era of targeted therapy, the relation between surgery and tumor molecular subtype is unknown. The objective of the current study was to identify subsets of patients who may benefit from primary tumor treatment and assess the frequency of local disease progression.
Patients presenting with stage IV breast cancer and intact primary tumors (n = 186) were identified from a prospectively maintained clinical database (2000-2004) and clinical data were abstracted (grading determined according to the American Joint Committee on Cancer staging system).
Surgery was performed in 69 (37%) patients: 34 (49%) patients with unknown metastatic disease at the time of surgery, 15 (22%) patients for local control, 14 (20%) patients for palliation, and in 6 (9%) patients to obtain tissue. Surgical patients were more likely to be HER-2/neu negative (P = .001), and to have smaller tumors (P = .05) and solitary metastasis (P <.001). Local therapy included axillary lymph node clearance in 33 (48%) patients and postoperative radiotherapy in 9 (13%) patients. The median survival was 35 months. Cox regression analysis identified estrogen receptor (ER) positivity (hazard ratio [HR], 0.47; 95% confidence interval [95% CI], 0.29-0.76), progesterone receptor (PR) positivity (HR, 0.57; 95% CI, 0.36-0.90), and HER-2/neu amplification (HR, 0.51; 95% CI, 0.34-0.77) as being predictive of improved survival. There was a trend toward improved survival with surgery (HR, 0.71; 95% CI, 0.47-1.06). On exploratory analyses, surgery was found to be associated with improved survival in patients with ER/PR positive or HER-2/neu-amplified disease (P = .004). No survival benefit was observed in patients with triple-negative disease.
Although a trend toward improved survival with surgery was observed, it was noted most strongly in patients with ER/PR positive and/or HER-2/neu-amplified disease. This suggests that the impact of local control is greatest in the presence of effective targeted therapy, and supports the need for further study to define patient subsets that will benefit most.

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Available from: Tari King, Jun 10, 2015
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    • "However, several retrospective studies indicated that patients who have primary DMD might benefit from the resection of the primary breast lesion in terms of prolonging survival [13-25]. These studies did not systematically consider the role of radiation in improving local control as a therapy concept; some authors did not even report on the rate of radiotherapy in their study cohorts [13,16,19,21-23], and the ones who did reported radiotherapy rates between 0%-67% [14,15,17,18,20,24,25]. Le Scodan et al. reviewed the clinical outcome of 581 patients with metastatic BC and focused more on the role of radiotherapy. "
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    ABSTRACT: Background The study evaluates frequency of and indications for disease-related radiotherapy in the palliative breast cancer (BC) situation and analyzes in which phase of the palliative disease course radiotherapy was applied. Patients & methods 340 patients who developed distant metastatic disease (DMD) and died (i.e. patients with completed disease courses) were analyzed. Results 165 patients (48.5%) received palliative radiotherapy (255 series, 337 planning target volumes) as a part of palliative care. The most common sites for radiotherapy were the bone (217 volumes, 64.4% of all radiated volumes) and the brain (57 volumes, 16.9%). 127 series (49.8%) were performed in the first third of the metastatic disease survival (MDS) period; 84 series (32.8%) were performed in the last third. The median survival after radiotherapy was 10 months. Patients who had received radiation were younger compared to those who had no radiation (61 vs. 68 years, p < 0.001) and had an improved MDS (26 vs. 14 months, p < 0.001). Compared to rapidly progressive disease courses with short survival times, in cases where effective systemic therapy achieved a longer MDS (≥24 months), radiotherapy was significantly more often a part of the multimodal palliative therapy (52.1% vs. 37.1%, p = 0.006). Conclusions In a cohort of BC patients with DMD, nearly one half of the patients received radiotherapy during the palliative disease course. In a palliative therapy approach, which increasingly allows for treatment according to the principles of a chronic disease, radiotherapy has a clearly established role in the therapy concept.
    Radiation Oncology 05/2014; 9(1):126. DOI:10.1186/1748-717X-9-126 · 2.55 Impact Factor
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    • "Recent studies on surgery of the breast tumor in patients with primary distant metastatic disease are inconclusive regarding the effect of surgery on overall survival. Most indicate that surgical treatment is associated with a significantly improved overall survival [5-12], but some state that this benefit is caused by confounding, induced by the retrospective study designs [15-18]. In order to provide a definite answer with respect to the role of surgery in primary metastatic breast cancer, a prospective randomized controlled trial, the SUBMIT study, is about to be initiated within The Netherlands. "
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    ABSTRACT: Five percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis. Randomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated.Patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints.Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint. The SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival. NCT01392586.
    BMC Surgery 04/2012; 12(1):5. DOI:10.1186/1471-2482-12-5 · 1.40 Impact Factor
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    ABSTRACT: Surgical removal of the intact primary breast tumor for patients who present with stage IV disease remains controversial. The classical view is that resection of the intact primary will have no survival benefit in stage IV disease; however, resection may prevent the development of uncontrolled chest wall disease. Multiple retrospective reviews have compared survival in stage IV patients who do or do not undergo resection of the intact primary, and have demonstrated longer survival with the use of primary site surgery. These are all compromised by the selection of women with favorable characteristics for surgical therapy and the inability to confirm important disease and treatment parameters in registry and retrospective data. Additionally, there are no data that allow examination of the value of radiotherapy in addition to surgery. These important questions cannot be addressed without Level 1 evidence, and randomized trials comparing primary site therapy versus none are ongoing.
    Current Breast Cancer Reports 06/2012; 4(2). DOI:10.1007/s12609-012-0076-6
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