Original Study
Determinants of Last-line Treatment in Metastatic Breast Cancer

https://doi.org/10.1016/j.clbc.2017.07.008Get rights and content

Abstract

Background

In metastatic breast cancer (MBC) patients, the identification of factors helping clinicians in the choice between active therapy versus best supportive care is needed clinically. The aim of the present study was to identify the clinicopathologic factors that could improve the prognostic valuation of MBC patients and clinical decision-making at the end of life.

Patients and Methods

The present study analyzed data from a retrospective series of 522 MBC patients treated at the oncology department (University Hospital of Udine) from January 2004 to June 2014. The association between clinicopathologic features and death within 30 or 90 days since last-line treatment prescription was explored. Differences between lightly (≤ 3 lines) and heavily (> 3 lines) pretreated patients and the factors affecting treatment choice were investigated.

Results

The event “death” occurred in 410 patients. The median last-line survival was 100 days. The median number of therapeutic lines was 3. On multivariate analysis, worse Eastern Cooperative Oncology Group performance status was significantly associated with death within 90 and 30 days since last-line treatment prescription. Among the heavily pretreated patients, liver function impairment and evaluation by a breast cancer specialist were significantly associated with a greater and lower risk of death within 30 days, respectively. Among the lightly pretreated patients with luminal disease, age < 70 years, luminal B-like disease, and number of previous lines were associated with a greater chance of receiving chemotherapy.

Conclusion

In the present study, the Eastern Cooperative Oncology Group performance status was the most robust independent factor driving the last-line therapeutic choice for MBC patients. In addition, the molecular subtype and oncologist subspecialization also influenced the decision-making process.

Introduction

Currently, cancer is the second leading cause of morbidity and mortality,1 and breast cancer is the most common tumor in women worldwide.2 Moreover, a remarkable economic burden for end of life care in US metastatic breast cancer (MBC) patients, especially in the last 2 months of life, has been reported.3 Concurrently, the rate of MBC survival has increased owing to the availability of new, safe, and effective drugs. However, the treatment intent of MBC remains palliative and mainly focused on prolonging survival and improving quality of life (QoL). Thus, the identification of patients most likely to live long enough to derive a clinical benefit from anticancer treatments is crucial to avoid overly aggressive therapy.4, 5 In this scenario, oncologists should consider the appropriate balance between active therapy and best supportive care (BSC). However, the criteria driving clinical decision are still highly debated and no consensus has yet been reached regarding when to switch to BSC.6 The American Society of Clinical Oncology (ASCO) has suggested that n-th line chemotherapy (CT) without a definable benefit should be avoided.7 Also, discontinuation of active treatment in the last 2 weeks of life has been included in the Quality Oncology Practice Initiative as a driving parameter toward the improvement of clinical practice.8, 9 The inappropriate prescription of CT at the end of life has been reported to be the most wasteful and widespread oncologic practice.7 Moreover, the rate of death within 1 month after the last-line therapy prescription has been increasingly recognized as a QoL care indicator.10, 11, 12, 13 Physicians are constantly faced with the difficulty of providing an accurate estimate of life expectancy for metastatic cancer patients and avoiding aggressive treatment at the end of life owing to the lack of specific guidelines.8, 14 Additionally, the increasing number of new oncologic drugs with limited toxicity and potentially high efficacy have worsened this already complex scenario.15 Clinicians should consider that the choice of active treatment in the last weeks of life has been associated with poorer QoL, distress for patients and caregivers, decreased access to hospice care, aggressive medical interventions, and high health care costs.16, 17, 18, 19, 20

In addition to these factors, the importance of communication about death and discontinuation of active anticancer therapies should not be underestimated21, 22; early discussions with patients about their preferences for end of life care seems to be associated with less aggressive treatment.23, 24, 25 However, prescribing an additional therapeutic line is apparently easier than discussions about a patient's poor prognosis and death for both clinician- and patient-related factors.8 Several studies have shown that active treatment has been administered near the end of life, even up to the last 14 days, in a non-negligible proportion of patients (range, 3.4%-43%).21, 26, 27

The identification of factors that could drive the decision-making process and lead to the prescription of active treatments in this setting might be the first step toward decreasing the number of unnecessary therapies and improving palliative care. The performance status (PS) is one of the most studied prognostic factors for metastatic cancer patients and has been directly associated with survival. Other prognostic factors include anorexia, weight loss, dyspnea, and neurologic symptoms.28, 29 It has also been reported that some tumor types, including breast cancer, can be predictors of a more likely use of CT at the end of life.30 During the past decades, investigators have attempted to develop prognostic scores that would consider a series of signs and symptoms to allow for a rapid estimate of life expectancy, such as the palliative prognostic score,31 the palliative prognostic index,32 and the palliative performance scale.33, 34, 35

The symptoms reported in the end of life period can result from organ involvement or treatment toxicity, or both. Therefore, disease control and symptom palliation are the goals of therapy in the metastatic setting to improve QoL.36 MBC patients must manage a number of changes, including frequent medical procedures, toxicity, concerns about work and family, and emotional distress.37, 38 Thus, a better understanding of the timing of palliative care could help clinicians ensure the best possible quality of end of life care. In addition, the early integration of BSC in the first lines of anticancer therapies has seemed to improve QoL and survival rates.39, 40

We sought to identify the clinicopathologic factors that can better estimate the prognosis of MBC patients to improve the process of clinical decision-making at the end of life. We also tested the association between clinicopathologic variables and the interval from the last-line treatment prescription to death.

Section snippets

Patients and Methods

The present study was a retrospective analysis of the data from 593 consecutive patients with MBC treated at the oncology department (University Hospital of Udine) from January 2004 to June 2014. Patient data were extracted from the electronic medical records in accordance with strict privacy standards. The analysis focused on the subset of patients in which the event “death” had occurred. The patient characteristics were summarized using a descriptive analysis. Continuous variables are

Results

From the whole MBC cohort, we selected 410 patients for whom the event “death” had occurred because of disease progression. The median age at the last line of treatment was 67.15 years (range, 31-92 years), the median number of treatment lines was 3 (range, 1-13), and 183 patients were classified as heavily pretreated (> 3 lines). Last-line CT had been prescribed to 277 patients (67.6%), and 133 (32.4%) had received endocrine therapy (ET). The median LLS was 100 days. Of the 410 patients who

Discussion

In the present study, we retrospectively analyzed MBC patient prognosis at the last line of treatment, focusing on the association between clinicopathologic factors and decisions regarding therapy. In addition to common prognostic factors such as age and ECOG PS, we also investigated whether different symptoms could affect LLS to more accurately identify patients with greater frailty. The published data have confirmed the PS to be the most important prognostic factor, because it is

Conclusion

The presented data describe a real-life scenario in the end of life period and provide interesting insights regarding the clinicopathologic factors influencing QoL and the interval from the last-line prescription to death. To date, the evaluation of the risks and benefits of prescribing treatments in this setting is a major challenge and QoL represents an increasingly important goal. Our results have confirmed ECOG PS as the most robust independent factor driving both therapeutic choice and

Disclosure

The authors have stated that they have no conflicts of interest.

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