Abstract
Background
The aim of this study was to describe the implementation of integrated palliative care (PC) and the intensity of care in the last 3 months before death for patients with metastatic breast cancer.
Materials and Methods
We conducted a multicentric study of all adult patients with metastatic breast cancer who died over a 4-month period. Complete data were collected and checked from clinical records, including PC interventions and criteria regarding EOL care aggressiveness.
Results
A total of 340 decedent patients from 12 comprehensive cancer centres in France were included in the study. Sixty-five percent met the PC team with a median time of 39 days between the first intervention and death. In the last month before death, 11.5% received chemotherapy, the frequency of admission to intensive care unit was 2.4%, and 83% experienced acute hospitalization. The place of death was home for 16.7%, hospitalization for 63.3%, PC unit for 20%. Univariate and multivariate analyses showed factors independently associated with a higher frequency of chemotherapy in the last month before death: having a dependent person at home, meeting for the first time with a PC team < 30 days before death, and time between the first metastasis and death below the median.
Conclusion
PC team integration was frequent and late for patients with metastatic breast cancer. However, PC intervention > 30 days is associated with less chemotherapy in the last month before death. Further studies are needed to better understand how to implement a more effective mode of PC integration for patients with metastatic breast cancer.
Keywords: end-of-life care, metastatic breast cancer, palliative care
Little data are available to help clinicians to implement palliative care for metastatic breast cancer. This article analyzes the integration of palliative care teams for the benefit of patients with metastatic breast cancer and describes end-of-life care in the last 3 months in this population.
Implications for Practice.
Few data are available to guide clinicians implementing palliative care for metastatic breast cancer. This study analyzed the integration of palliative care teams for patients with metastatic breast cancer and the impact on the intensity of care during the last 3 months of life. Palliative care intervention > 30 days was associated with less chemotherapy in the last month before death. Better knowledge of effective ways of integrating palliative care is needed for this population.
Introduction
The incidence of breast cancer and the related mortality are among the highest in the world: in 2020, this involved 2.3 million new cases and 685 000 deaths worldwide.1 Ten years after the first diagnosis, 15%-20% of breast cancers lead to metastatic relapse, with the highest risk of relapse reaching 20%-30% for triple negative cancers.2 Median overall survival for metastatic triple-negative breast cancer is approximately 1 year, and approximately 5 years for advanced breast cancer with hormone receptor-positive tumours and those with overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2).3 Efforts to improve palliative care (PC) implementation and end-of-life (EOL) care for metastatic breast cancer care are therefore paramount.
Since the 2000s, numerous randomized clinical trials have confirmed that early palliative care improves quality of life and reduces symptom intensity.4–7 The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have published guidelines to recommend specialized palliative care for patients with advanced cancer early in the course of the disease, and concurrent with active treatment.8,9 Different models of palliative care integration have been described, but there is an expert consensus to support timely and targeted palliative care interventions by a multidisciplinary team, to comprehensively address the patients’ and their caregivers’ multidimensional care needs.10 Using a Delphi method, international experts reached consensus on the main criteria for outpatient palliative care referrals, including needs-based and time-based criteria.11 In a randomized study on women with metastatic breast cancer and visceral metastases treated with 3rd- or 4th-line chemotherapy, patients receiving systematic palliative care consultations tended to present less deterioration in physical functioning, and there was an improvement in information exchange and communication, with no impact on the prescription rate of additional chemotherapy.12
Patients with advanced cancer are exposed to aggressive end-of-life care that can decrease patient quality of life and satisfaction with care, prolong family bereavement, and increase health-care utilization and costs.13-15 Quality indicators for end-of-life (EOL) cancer care were described for the first time 20 years ago and designed to be easily accessible and measurable using administrative health-related data.16-18 These indicators describe high-intensity medical care delivered in the last month of life, such as chemotherapy administration in particular new regimen initiation rate, emergency admission to acute medical or intensive care units, emergency room visits, place of death, and hospice use.19 These criteria were analyzed in Ontario, Canada, between 1993 and 2004: among 227 161 patients, 22.4% experienced at least one incident of potentially aggressive EOL cancer care, increasing over time, although overall rates were lower than in the US.20 Aggressiveness in EOL care has also been described in subpopulations with specific types of cancer, such as lung, pancreatic, or liver cancers.21-23 Numerous randomized studies have clearly demonstrated that PC team intervention can reduce aggressiveness in EOL care24-26
Little data are available concerning early PC interventions and EOL care specifically in metastatic breast cancer populations. Many characteristics in the management of metastatic breast cancer are associated with the complexity of palliative care implementation: availability of numerous oncology treatments, mild or transient symptomatology, and long median survival. At constant means, PC teams are faced with a dilemma: late integration for more numerous inpatients with short-life expectancy, or early integration with a longer follow-up for fewer outpatients. Little data are available to help clinicians to implement PC team for metastatic breast cancer. This study aimed to analyze the integration of palliative care teams for the benefit of patients with metastatic breast cancer and to describe EOL care in the last 3 months in this specific population. In addition, analyses were conducted to understand how the timing and setting of palliative care (PC) referrals could affect EOL care.
Methods
Design and Setting
We conducted a retrospective multicentre analysis on a cohort of adult patients who died from metastatic breast cancer in the period from November 1, 2019 to February 29, 2020. The decedents were identified from hospital administrative data, and all consecutive patients were included, whatever the place of death.
Out of 17 comprehensive cancer centers in France, 13 agreed to participate, 4 declined, and one discontinued just after the start of recruitment because of the resignation of the principal investigator. The PC provision of the participating institution is homogenous. The PC teams belong to the cancer center with a clinical activity for inpatients or outpatients (consultation or day care hospital). No center has any PC unit. The PC teams are composed of doctors (mean 2.7, SD 1.3), specialized nurses (mean 2, SD 1.4), and work in daily practice with a multidisciplinary team including psychologists, social workers, and dieticians. PC intervention initiation is based on oncologist’s assessment according to usual referral criteria (severe symptoms, psychosocial distress, expressed wish of hasten death, demand from patients or family, ethical issues). The PC team interventions are provided by a nurse and a specialist physician working together.
The main objective was to report the integration modes of palliative care, to describe the intensity of EOL care in the last 3 months and the place of death. The secondary objective was to look for clinical factors that could be associated with palliative care interventions or with EOL care aggressiveness, such as the overuse of systemic anti-cancer treatments.
Data Collected
The data collected included psycho-socio-demographic information, cancer history, and treatments. Data collection also concerned the PC trajectory: date of the first intervention, frequency of PC visits, other supportive care interventions, multi-disciplinary meetings involving the palliative care team, decision-making processes for discontinuing specific treatments and end-of-life discussions. Finally, we collected data on the intensity of EOL care in the last 3 months: chemotherapy administration and new regimen, emergency admission to acute medical or intensive care units, emergency room visits, rehabilitation and PC unit admission and length of stay, and place of death.
The data were made anonymous and extracted for each individual patient from hospital clinical records. Data collection ran from June 2020 until December 2020, using REDCAP software. Monitoring took place in each cancer center.
Statistics
Demographic and clinical characteristics were summarized using counts and percentages for categorical variables and summary statistics (means, medians, standard deviation, and interquartile range) for quantitative variables.
The associations between outcomes and qualitative variables were explored using chi-square tests or Fisher’s test, while Student’s t tests or Wilcoxon’s non-parametric tests were used for quantitative variables, depending on the test application conditions. A logistic regression was performed to assess factors associated with place of death and those associated with receiving chemotherapy in the last month before death. All available demographic and clinical features were tested in a univariate logistic model. Factors considered useful according to clinical considerations or with a P-value <0.2 and not correlated were included in a stepwise top-down procedure, using the Akaike information criterion for variable selection. Thus, age ar death, family situation, presence of dependents, time between last chemotherapy administration and death, PC and multi-disciplinary meetings, were tested for the place of death endpoint. For the endpoint chemotherapy administration in the last month, the variables tested were age at death, the presence of dependents, psychological vulnerability, time between first metastasis diagnosis and death, and PC and multi-disciplinary meetings. All statistical tests were 2 sided and a P-value under 0.05 was considered statistically significant. All statistical analyses were performed using R software version 4.1.2.
Results
Patient Characteristics
A total of 340 patients with metastatic breast cancer were followed in the 12 centers died during a 4-month period from November 1, 2019 to March 1, 2020. The main population characteristics are presented in Table 1. Median age at diagnosis was 56 years (46-65) and 98.5% were female. At least one comorbidity was present for 138 (40.6%) patients: mainly arterial hypertension (10%), diabetes mellitus (5.3%), dyslipidaemia (3.3%), hypothyroidism (2.6%), and depression (6.2%). Severe comorbidities are listed in Table 1 as well as psychosocial frailties. The breast cancer was the triple negative histologic type in 65 cases (19.7%) and HER2 + for 33 (9.7%). At the time of death, 55 (16.4%) had no visceral metastasis. The median time between diagnosis and first metastasis was 35 (2-85) months for the overall population, and 15.6 (1-31), 47.4 (7-96), and 23.7 (0-63) months for women with triple negative, RH + and HER2 + tumors, respectively.
Table 1.
Characteristics of the study population (N = 340).
| Criteria | Value |
|---|---|
| Mean age (SD) | 56.6 (14) |
| Female gender | 335 (98.5) |
| Breast cancer type (NA = 10) | |
| RH + | 223 (67.6) |
| HER 2 + | 33 (10) |
| Triple negative | 65 (19.7) |
| Other | 9 (2.7) |
| Site of metastasis (NA = 5) | |
| Visceral | 280 (83.6) |
| Non visceral | 55 (16.4) |
| Time between diagnosis and 1st metastasis | 35 (2-85) |
| Median (Q1-Q3) in months | |
| Time between 1st metastasis and death | 28 (13-50) |
| Median (Q1-Q3) in months | |
| At least one comorbidity | 138 (40.6) |
| Others cancer | 19 (5.6%) |
| Hart disease | 12 (3.5%) |
| Cerebrovascular accident | 11 (3.2%) |
| Dementia | 5 (1.5%) |
| Marital status (NA = 3) | |
| With a partner | 190 (56.4) |
| Single | 147 (43.6) |
| Primary caregiver if single (n = 147, NA = 14) | 99 (74,4) |
| Psychosocial vulnerability | |
| Precariousness | 61 (17.9) |
| Transplanted (NA = 16) | 22 (6.8) |
| Far from social circles (NA = 16) | 25 (7.7) |
| Dependent person at home (NA = 3) | 59 (17.5) |
| Psychological vulnerability (NA = 5) | 65 (19.4) |
| Distance between home and cancer centre (NA = 6) | |
| <1 h | 222 (66.5) |
| 1-2 hs | 95 (28.4) |
| >2 hs | 17 (5.1) |
Abbreviation: COPD, chronic obstructive pulmonary disease.
The causes of death were cancer for 241(80.6%) patients, acute complication for 27(9%), iatrogenic complication for 14(4.7%), comorbidity for 10 (3.3%), other etiology for 7(2.3%), and not available for 41 patients.
Palliative Care Interventions
At least one intervention by the palliative care team was found for 204 (60%) patients, with a median time of 39 days between the PC team’s first intervention and death (0-1257 days). Initiation of PC team intervention increases dramatically in the period before death: 29% had the first intervention more than 3 months, 27% in the 1-3 months before and 44% in the last month before death. The mean number of the PC interventions was 3, combining in- and outpatient consultations (Table 2). Other supportive care interventions were mainly from psycho-oncologists for 106 patients (31.2%), dieticians for 123 (36.2%), social workers for 91 (26.8%), physiotherapists for 68 (20%), and pain specialists for 66 (19.4%).
Table 2.
Integrated palliative care pathway (N = 340).
| Criteria (n) | N (%) |
|---|---|
| Hospital PC team intervention (NA = 26) | 204 (65) |
| Time between 1st hospital PC team visit and death (N = 204) | |
| Median in days (Q1-Q3) | 39 (13-108) |
| Patients with first PC team visit per time period (N = 204, NA = 3) | |
| ≤1 week before death | 37 (18) |
| >1 week and ≤ 1 month before death | 52 (26) |
| >1 month and ≤ 3 months before death | 50 (25) |
| >3 months before death | 62 (31) |
| Number of PC intervention (N = 204) | |
| Median number of in/out-patient consultations (NA = 18) | 3 (2-6) |
| Number of patients with PC Day hospital (NA = 4) | 61 (30) |
| Supportive care interventions | |
| Onco-geriatric specialist | 15 (4.4) |
| Pain specialist | 66 (19.4) |
| Dietician | 123 (36.2) |
| Physiotherapist | 68 (20.0) |
| Psychiatrist | 13 (3.8) |
| Psychologist | 93 (27.4) |
| Social Worker | 91 (26.8) |
| Palliative care discussions* | |
| Designation of person of trust (NA = 14) | 221 (68) |
| End of life discussions (NA = 15) | 187 (58) |
| Written advance directives (NA = 13) | 26 (8.0) |
| Refusal anticancer treatment (NA = 21) | 37 (12) |
| Asking for terminal sedation | 14 (4.1) |
| Asking for euthanasia (NA = 22) | 6 (1.9) |
| Multi-disciplinary palliative care meetings | 143 (42) |
| Mode of decision to end chemotherapy (NA = 11) | |
| None | 145 (44) |
| Oncologists | 63 (19.5) |
| Multi-disciplinary palliative care meetings | 121 (37) |
| Home PC intervention | |
| PC network in the last 3 months (N = 340, NA = 33) | 35 (11.4) |
| PC network if patient died at home (N = 44, NA = 9) | 10 (28.6) |
| Home hospitalization in the last 3 months (N = 340, NA = 27) | 58 (19) |
| Home hospitalization if patient died at home (N = 44, NA = 9) | 25 (71.4) |
*The total can be > 100.
There was no difference in the median time of PC intervention before death with the characteristic of the study population (age, histological sub-type, comorbidity, or psychosocial frailty).
The main problems encountered by the PC team were the designation of a person of trust (65%), EOL discussions (55%), refusal of anticancer treatment (10.8%), advance directives (7.6%), the wish to receive deep and continuous sedation maintained until death according to the new 2016 French law (4.1%), the desire to hasten death or euthanasia (1.8%), and discussions during multi-disciplinary PC meetings were documented for 143 patients (42%).
Chemotherapy Use Near the Time of Death
In the last 3 months of their lives, 295 (86.8%) patients received at least one anticancer treatment, while 45 patients (13.2%) did not receive any specific treatment (Table 3). The median time and between the last chemotherapy administration and death was 34 (0 to 169) days. The last chemotherapy administration (including targeted therapy and immunotherapy) occurred for 14% in the last month, and among them 7.6% in the last 14 days before death.
Table 3.
End-of-life care trajectories (N = 340).
| Criteria | N (%) |
|---|---|
| Systemic anticancer treatment in the last 3 months | |
| None | 45 (13.2) |
| Hormonotherapy only | 41 (12.1) |
| Chemotherapy | 233 (68.5) |
| Oral chemotherapy | 78 (22.9) |
| IV chemotherapy | 165 (48.5) |
| Immunotherapy | 6 (1.8) |
| Clinical trial protocol | 6 (1.8) |
| Median time in days to death following: | |
| Initiation of last systemic anti-cancer treatment line (median (Q1-Q3)) | 97 (48-213) |
| Last administration of systemic anti-cancer treatment (median (Q1-Q3) | 34 (0-66) |
| Time to death from last chemotherapy (NA = 26) | |
| >60 days | 215 (68.5) |
| 60-31 days | 55 (17.5) |
| 30-16 days | 20 (6.4) |
| 15-0 days | 24 (7.6) |
| Radiotherapy in the last months (NA = 6) | |
| None | 280 (83.8) |
| Bone | 23 (6.9) |
| Cerebral | 18 (5.4) |
| Other | 13 (3.9) |
| Emergency consultation in the last month (NA = 38) | 91 (30.1) |
| Intensive care admission | |
| Third month before death | 2 (0.6) |
| Penultimate month | 4 (1.2) |
| Last month | 8 (2.4) |
| Acute hospitalization | |
| Third month before death | 77 (22.7) |
| Penultimate month | 123 (36.3) |
| Last month | 258 (75.9) |
| Rehabilitation hospitalization | |
| Third month before death | 12 (3.5) |
| Penultimate month | 21 (6.2) |
| Last month | 26 (7.6) |
| Palliative care unit admission | |
| Third month before death | 8 (2.4) |
| Penultimate month | 19 (5.6) |
| Last month | 61 (17.9) |
| Median length of stay (N = 194) | |
| ICU | 4 (1-24) |
| Acute Hospitalization oncology ward | 14 (1-71) |
| Acute hospitalization outside cancer center | 7 (1-75) |
| Rehabilitation | 22 (2-90) |
| Hospice | 15 (1-90) |
*The total can be > or < 100.
The median number of treatment lines was 4 (0 to 20). The median time between the initiation of the last chemotherapy line and death was 3.2 (0 to 7) months. The last chemotherapy line (including targeted therapy and immunotherapy) was initiated for 17.1% of the patients in the last month, among them 9.6% in the last 14 days before death.
A few patients were treated with radiotherapy in the last 3 months: 23 (6.7%) patients for bone metastases, 18 (5.3%) patients for brain metastases and 13 (3.8%) patients for metastases in other sites.
The decision to discontinue systemic anticancer treatment was documented in the medical file for 184 (54%) patients. This decision was made during multi-disciplinary PC meetings for 35.5% and by referent oncologists for 18.5%. A pause in specific treatments—but not discontinuation—was recorded in 23 (16%) of the files.
Other EOL Care Aggressiveness Criteria
The proportion of hospitalized patients increased rapidly in the last 3 months before death: from 25.6% (M-3) to 80.6% in the last month (Table 3). This concerned mainly oncology ward with 77 (22.7%), 123 (63.3%), and 258 (75.9%) patients admitted in the third, penultimate and last month before death, respectively. The median length of stay in oncology ward was 14 (1-71 days).
The number of patients with at least one emergency consultation in the last month before death was 91 (30.1%). Hospitalizations in intensive care units concerned 2 (0.6%), 4 (1.2%), and 8 (2.3%) patients in the third, penultimate, and last month before death, respectively, with a median length of stay of 4 (1-24) days.
Hospitalization in rehabilitation units concerned 13 (3.8%), 22 (6.8%), and 27 (7.9%) patients in the third, penultimate, and last month before death, respectively, with a median length of stay of 22 (2-90) days. PC unit hospitalizations concerned 8 (2.4%), 19 (5.6%), and 61 (17.9%) patients in the third, penultimate, and last month before death, respectively, with a median length of stay of 15 (1-90) days.
The place of death was home for 51 (16.7%) patients, hospital for 193 (63.3%), in PC unit in for 60 (20.0%).
Factors Associated with Chemotherapy Frequency in the Last Month Before Death
Univariate and multivariate logistic regression results for factors associated with chemotherapy frequency in the last month before death are shown in Table 4.
Table 4.
Associated factors with chemotherapy frequency in the last month before death.
| Characteristic | n | ORa,b | IC 95 | P-value |
|---|---|---|---|---|
| (a) Univariate regression logistic | ||||
| Age at death | ||||
| ≤ 55 years old | 83 | 1 | ||
| > 55 years old | 247 | 0.59 | [0.35; 0.98] | 0.041 |
| Histological type | ||||
| No triple negative | 265 | 1 | ||
| Triple negative | 65 | 1.14 | [0.64; 2.02] | 0.7 |
| Dependent person | ||||
| No | 278 | 1 | ||
| Yes | 59 | 2.39 | [1.31; 4.44] | 0.005 |
| Social precariousness | ||||
| No | 279 | 1 | ||
| Yes | 61 | 1.21 | [0.68; 2.16] | 0.5 |
| Psychological vulnerability | ||||
| No | 270 | 1 | ||
| Yes | 65 | 0.50 | [0.27; 0.91] | 0.025 |
| Breast cancer type | ||||
| Other type | 265 | 1 | ||
| Triple negative | 65 | 1.14 | [0.64; 2.02] | 0.7 |
| Time from 1st metastasis to death (median = 28 months) | ||||
| < 28 months | 161 | 1 | ||
| ≥ 28 months | 156 | 0.43 | [0.27; 0.68] | <0.001 |
| Time from 1st palliative care visit to death (days) | ||||
| < 30 days | 87 | 1 | ||
| ≥ 30 days | 114 | 0.32 | [0.17; 0.58] | <0.001 |
| Resort to palliative care (PC) | ||||
| No resort to PC or use of PC < 30 days before death | 196 | 1 | ||
| Use of PC ≥ 30 days before death | 114 | 0.37 | [0.23; 0.61] | <0.001 |
| End-of-life discussions and/ or written advance directives | ||||
| Yes | 189 | 1 | ||
| No | 135 | 1.07 | [0.67; 1.71] | 0.8 |
| Oncopalliative multidisciplinary meetings | ||||
| Yes | 145 | 1 | ||
| No | 181 | 1.73 | [1.09; 2.77] | 0.021 |
| (b) multivariate regression logistic | ||||
| Dependant person | ||||
| No | 233 | 1 | [1.20; 4.66] | 0.014 |
| Yes | 52 | 2.34 | ||
| Psychological vulnerability | ||||
| No | 227 | 1 | [0.31; 1.19] | 0.2 |
| Yes | 58 | 0.61 | ||
| Time between first metastasis and death | ||||
| < 28 months | 146 | 1 | [0.24; 0.68] | <0.001 |
| ≥ 28 months | 139 | 0.40 | ||
| Time between first intervention of PC team and death | ||||
| Never or < 30 days | 175 | 1 | [0.26; 0.77] | 0.004 |
| ≥ 30 deaths | 110 | 0.45 | ||
| Palliative care concertation | ||||
| Yes | 131 | 1 | [0.91; 2.63] | 0.11 |
| No | 154 | 1.54 | ||
aAn odds ratio (OR) > 1 indicates an increased likelihood of chemotherapy in the last month before death.
bAn odds ratio (OR) > 1 indicates an increased risk of chemotherapy during the last month before death.
Univariate logistic regression identified 2 variables increasing the risk of still being under treatment 30 days before death: having a dependent person at home (OR 2.39; CI95% 1.31; 4.44, P-value = .005); documented onco-palliative multi-disciplinary meetings (OR 1.73; CI 95% 1.09; 2.77, P-value = .021). Other factors were associated with a decreased risk: age over 55 years (OR 0.59; 0.35; 0.98, P-value = .041); time between the first metastasis and death over 28 months (OR 0.43; CI 95% 0.27; 0.68, P-value < .001); first PC team intervention over 30 days before death (OR 0.37; CI 95% 0.23; 0.61, P-value < .001); psychological vulnerability (OR 0.5; CI95% 0.27; 0.91, P value = .025; Table 4a).
Using multivariate logistic regression models, factors independently and significantly linked to the likelihood chemotherapy in the last month before death were: having a dependent person at home (OR 2.34; CI 95% 1.20; 4.66, P-value = .014); time between the first metastasis and death over 28 months (OR 0.40; CI 95% 0.24; 0.68, P-value < .001); first PC team intervention over 30 days before death or not (OR 0.42; CI 95% 0.26; 0.77, P-value = .004) (Table 4b).
Discussion
This large nationwide multicentric study is the first study assessing PC integration in the specific population of metastatic breast cancer. It showed that 60% of patients with metastatic breast cancer met PC teams, but PC team intervention was initiated with a median time of 39 days between first contact and death. Although ambulatory PC for patients undergoing chemotherapy was possible in each cancer center, we observed late referral to the PC team for this population of patients with metastatic breast cancer. This could be due to insufficient interactions between oncologists and PC teams, a parameter that was not analyzed. Another explanation could be that the usual referral criteria are mainly crisis-based and not relevant for metastatic breast cancer patients who decline slowly with lasting chemosentivity. Studies are needed to find new PC referral criteria, providing a more focused and flexible management according to the clinical course.
Similar results to ours were found in an earlier French previous study conducted in 2010, suggesting that has been no improvement in the integration of palliative care over the past 10 years. In this retrospective study among 997 decedent patients with cancers of all types, 53% of the patients met a PC team, with a median time of 41 days between first meeting and death.27 In another French cross-sectional study on 687 inpatients, 216 (53, 2.4%) patients were followed by a palliative care team.28 Other French studies have assessed PC integration via data from national registries, with a major bias due to the lack of a systematic link between the coding of the palliative situation and the intervention of a specialized team.29,30 In other published studies from other countries, the integration rate of palliative care teams varies widely, which could be explained by the variability of factors such as the type of cancer, the PC staff resources and PC skills of oncologists. In a retrospective Italian study on 229 patients who died from non-small cell lung cancer, 43% met a palliative care team at a median of 20 days before death.31 In a Spanish decedent series of 684 patients with cancer, 61.0% were followed by a PC team, and for 13% the first meeting occurred in the last 3 days of life.32 In a German series of 532 decedent patients, 80% of whom had hematologic malignancies, only 30% were offered PC interventions, and contact was initiated within the last week of the patients’ life for 54%.33 In an American study among 366 decedents, 120 (33%) had an early PC referral over 3 months before death, and 169 (46%) were first seen as outpatients.34
Our study is also the first one assessing the rate of EOL aggressiveness criteria of a specific population with metastatic breast cancer. Our results showed a rate of chemotherapy of respectively 14% and 7.6% in the last month and in the last 2 weeks before death. Oncologists recognize the need to avoid systemic anti-cancer treatment for EOL patients. But the diagnostic of EOL for patients with cancer is difficult, and one of the main reasons is the inability to predict the response to anti-cancer treatment.
In an American study among 274 patients with metastatic breast cancer, the rates of chemotherapy were 22.6% and 10.2%, respectively, in the 4 weeks and in the 2 weeks before death.35 In the Swedish cohort, 1571 patients were identified and 23.2% of patients were treated with chemotherapy in the final month of life.36 Previous studies involving patients with any type of cancer, report wide variation in chemotherapy use, ranging in the last month from approximately 15% to 55% and in the last 2 weeks from 5% to 30%.37-41 This lower chemotherapy use in the metastatic breast cancer population compared with all type of cancer population could be explained by the longer median of survival or by more gradual clinical deterioration, leaving time for EOL discussions and advance care planning.
Using a multivariate regression model, our study found that intervention of a PC team beginning more than 1 month before death was associated with less chemotherapy administration in the last month before death, and these results were reported for the first time in a specific population with metastatic breast cancer. However, similar results were found in population of advanced cancer patients with all type of cancer: Davis and colleagues found that palliative care consultation occurring more than 90 days prior to death reduced chemotherapy in the last month of life.42,43 Other authors found association between PC intervention and reduced aggressiveness of EOL care.24-27,29,34,40 Other factors associated with chemotherapy rate and EOL care aggressiveness criteria were younger age, time since diagnosis of metastatic cancer less than 2 months, greater tumor burden, the type and size of cancer centres, absence of PC units.42
This study presents numerous limitations. Firstly, the number of patients was small, fewer than the 500 patients initially planned, but insufficient availability of PC staff led 5 cancer centers to refrain from taking part in the study. Secondly, the methodology of the decedent series analysis implied that only data recorded in the medical charts could be collected, with no patient or relative related outcome available. This data would have been necessary to analyze the quality of EOL trajectories more efficiently. Thirdly, the lack of randomization of PC interventions makes impossible to prove the impact of PC teams in reducing the intensity of EOL care. Patients who attend PC, are primarily more spiritual and the results could reflect the patient attitude and not the influence of PC. Finally, the various modes of organization of the different cancer centers (size of the center, nature of the activity, modality of interaction with PC team and oncologist like shared multidisciplinary meeting) and the regional health organizations (medical density, home palliative care network) could also have biased the results.
In conclusion, this study allows to observe a late involvement of PC teams in the management of patients with breast cancer, which goes against international guidelines. Furthermore, this study shows that management by a PC team more than a month before death can reduce over-intensive treatment by reducing use of chemotherapy at the EOL. Indicators like rate of patients referred to the PC team and median time between first meeting and death could be monitored by the health authorities. This could help to drive a policy for early PC integration in oncology practice.44 Other studies are needed to describe the optimal modes of integration of PC teams, providing a more focused and flexible PC management according to the clinical course for patients with metastatic breast cancer.
Contributor Information
Elisabeth Lucchi, Supportive and Palliative Care Department, Institut Curie, Paris, France.
Frédérique Berger, Biostatistics Department, Institut Curie, Paris, France.
Maude Milder, Biostatistics Department, Institut Curie, Paris, France.
Jean-Marie Commer, Supportive and Palliative Care Department, Institut de Cancerologie de Loire, Anger, France.
Sophie Morin, Supportive and Palliative Care Department, Institut Bergonie, Paris, France.
Geraldine Capodano, Supportive and Palliative Care Department, Institut Paoli-Calmette, Marseille, France.
Muriel Thomaso, Supportive and Palliative Care Department, Institut de Cancerologie de Montpellier, Montpellier, France.
Anne Fogliarini, Supportive and Palliative Care Department, Centre Lacassagne, Nice, France.
Nathalie Bremaud, Supportive and Palliative Care Department, Centre Georges François Leclerc, Dijon, France.
Aline Henry, Supportive and Palliative Care Department, Centre Alexis Vautrin, Nancy, France.
Benedicte Mastroianni, Supportive and Palliative Care Department, Centre Léon Berard, Lyon, France.
Gisele Chvetzoff, Supportive and Palliative Care Department, Centre Léon Berard, Lyon, France.
Carole Bouleuc, Supportive and Palliative Care Department, Institut Curie, Paris, France.
Conflict of Interest
The authors indicated no financial relationships.
Author Contributions
Conception/design: E.L., C.B. Provision of study material or patients: J.M.C., S.M., G.C., M.T., A.F., N.B., A.H., G.C., C.B. Collection and/or assembly of data: J.M.C., S.M., G.C., M.T., A.F., N.B., A.H., G.C., C.B. Statistical analysis: F.B., M.M. Data analysis and interpretation: All authors. Manuscript writing: E.L., C.B. Final approval of manuscript: All authors.
Data Availability
Materials described in this article, including all relevant raw data, will be freely available to any scientist wishing to use them for non-commercial purposes, without breaching participant confidentiality, on request to the corresponding author.
Ethics Approval and Consent to Participate
The study conformed to the principles of the Declaration of Helsinki and French Good Clinical Practice. Ethical approval was not needed, according to French law (Article L1121-1, Law no. 2011-2012 29 December 2011—art. 5). We made sure that the patients had not objected to the use of their files (routinely ascertained at the beginning of treatment for every patient). The study received approval from the institutional research board of the study sponsor (Institut Curie) on 27/07/2019 (number 190223), and approval of legal provisions and registration MROO4 on 27 May 2020, INDS: MR3615280520.
References
- 1. WHO: https://www.who.int/fr/news-room/fact-sheets/detail/breast-cancer
- 2. Waks AG, Winer EP.. Breast cancer treatment: a review. JAMA. 2019;321(3):288-300. 10.1001/jama.2018.19323 [DOI] [PubMed] [Google Scholar]
- 3. Largillier R, Ferrero JM, Doyen J, et al. Prognostic factors in 1,038 women with metastatic breast cancer. Ann Oncol. 2008;19(12):2012-2019. 10.1093/annonc/mdn424 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Haun MW, Estel S, Rücker G, et al. Early palliative care for adults with advanced cancer. Cochrane Database Syst Rev. 2017;6(6):CD011129. 10.1002/14651858.CD011129.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Temel JS, Greer JA, El-Jawahri A, et al. Effects of early integrated palliative care in patients with lung and GI cancer: a randomized clinical trial. J Clin Oncol. 2017;35(8):834-841. 10.1200/JCO.2016.70.5046 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Zimmermann C, Swami N, Krzyzanowska M, et al. Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial. Lancet. 2014;383(9930):1721-1730. 10.1016/S0140-6736(13)62416-2 [DOI] [PubMed] [Google Scholar]
- 7. Vanbutsele G, Pardon K, Van Belle S, et al. Effect of early and systematic integration of palliative care in patients with advanced cancer: a randomised controlled trial. Lancet Oncol. 2018;19(3):394-404. 10.1016/S1470-2045(18)30060-3 [DOI] [PubMed] [Google Scholar]
- 8. Ferrell BR, Temel JS, Temin S, et al. Integration of palliative care into standard oncology care: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 2017;35(1):96-112. 10.1200/JCO.2016.70.1474 [DOI] [PubMed] [Google Scholar]
- 9. Kaasa S, Loge JH, Aapro M, et al. Integration of oncology and palliative care: a Lancet Oncology Commission. Lancet Oncol. 2018;19(11):e588-e653. [DOI] [PubMed] [Google Scholar]
- 10. Hui D, Hannon BL, Zimmermann C, Bruera E.. Improving patient and caregiver outcomes in oncology: team-based, timely, and targeted palliative care. CA Cancer J Clin. 2018;68(5):356-376. 10.3322/caac.21490 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Hui D, Mori M, Watanabe SM, et al. Referral criteria for outpatient specialty palliative cancer care: an international consensus. Lancet Oncol. 2016;17(12):e552-e559. 10.1016/S1470-2045(16)30577-0 [DOI] [PubMed] [Google Scholar]
- 12. Chvetzoff G, Bouleuc C, Lardy-Cléaud A, et al. Impact of early palliative care on additional line of chemotherapy in metastatic breast cancer patients: results from the randomized study OSS. Support Care Cancer. 2022;31(1):82. 10.1007/s00520-022-07561-x [DOI] [PubMed] [Google Scholar]
- 13. Wright AA, Zhang B, Ray A, et al. Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008;300(14):1665-1673. 10.1001/jama.300.14.1665 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Wright AA, Zhang B, Keating NL, Weeks JC, Prigerson HG.. Associations between palliative chemotherapy and adult cancer patients’ end of life care and place of death: prospective cohort study. BMJ. 2014;348:g1219. 10.1136/bmj.g1219 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Wu CC, Hsu TW, Chang CM, et al. Palliative chemotherapy affects aggressiveness of end-of-life care. Oncologist. 2016;21(6):771-777. 10.1634/theoncologist.2015-0445 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Earle CC, Park ER, Lai B, et al. Identifying potential indicators of the quality of end-of-life cancer care from administrative data. J Clin Oncol. 2003;21(6):1133-1138. 10.1200/JCO.2003.03.059 [DOI] [PubMed] [Google Scholar]
- 17. Earle CC, Neville BA, Landrum MB, et al. Evaluating claims-based indicators of the intensity of end-of-life cancer care. Int J Qual Health Care. 2005;17(6):505-509. 10.1093/intqhc/mzi061 [DOI] [PubMed] [Google Scholar]
- 18. Earle CC, Landrum MB, Souza JM, et al. Aggressiveness of cancer care near the end of life: is it a quality-of-care issue? Clin Oncol 2008;26(23):3860-3866. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Abedini NC, Hechtman RK, Singh AD, et al. Interventions to reduce aggressive care at end of life among patients with cancer: a systematic review. Lancet Oncol. 2019;20(11):e627-e636. 10.1016/S1470-2045(19)30496-6 [DOI] [PubMed] [Google Scholar]
- 20. Ho TH, Barbera L, Saskin R, et al. Trends in the aggressiveness of end-of-life cancer care in the universal health care system of Ontario, Canada. J Clin Oncol. 2011;29(12):1587-1591. 10.1200/JCO.2010.31.9897 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Jang RW, Krzyzanowska MK, Zimmermann C, Taback N, Alibhai SMH.. Palliative care and the aggressiveness of end-of-life care in patients with advanced pancreatic cancer. J Natl Cancer Inst. 2015;107(3):dju424. 10.1093/jnci/dju424 [DOI] [PubMed] [Google Scholar]
- 22. Kao Y-H, Chiang J-K.. Effect of hospice care on quality indicators of end-of-life care among patients with liver cancer: a national longitudinal population-based study in Taiwan 2000-2011. BMC Palliat Care. 2015;14(1):39. 10.1186/s12904-015-0036-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Nieder C, Tollåli T, Haukland E, et al. Impact of early palliative interventions on the outcomes of care for patients with non-small cell lung cancer. Support Care Cancer. 2016;24(10):4385-4391. 10.1007/s00520-016-3278-z [DOI] [PubMed] [Google Scholar]
- 24. Maltoni M, Scarpi E, Dall’Agata M, et al. ; Early Palliative Care Italian Study Group (EPCISG). Systematic versus on-demand early palliative care: a randomised clinical trial assessing quality of care and treatment aggressiveness near the end of life. Eur J Cancer. 2016;69:110-118. 10.1016/j.ejca.2016.10.004 [DOI] [PubMed] [Google Scholar]
- 25. Triplett DP, LeBrett WG, Bryant AK, et al. Effect of palliative care on aggressiveness of end-of-life care among patients with advanced cancer. J Oncol Pract. 2017;13(9):e760-e769. 10.1200/JOP.2017.020883 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Vanbutsele G, Van Belle S, Surmont V, et al. The effect of early and systematic integration of palliative care in oncology on quality of life and health care use near the end of life: a randomised controlled trial. Eur J Cancer. 2020;124:186-193. 10.1016/j.ejca.2019.11.009 [DOI] [PubMed] [Google Scholar]
- 27. Colombet I, Bouleuc C, Piolot A, et al. ; EFIQUAVIE study group. Multicentre analysis of intensity of care at the end-of-life in patients with advanced cancer, combining health administrative data with hospital records: variations in practice call for routine quality evaluation. BMC Palliat Care. 2019;18(1):35. 10.1186/s12904-019-0419-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Molin Y, Gallay C, Gautier J, et al. PALLIA-10, a screening tool to identify patients needing palliative care referral in comprehensive cancer centers: a prospective multicentric study (PREPA-10). Cancer Med. 2019;8(6):2950-2961. 10.1002/cam4.2118 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Rochigneux P, Raoul JL, Beaussant Y, et al. Use of chemotherapy near the end of life: what factors matter? Ann Oncol. 2017;28(4):809-817. 10.1093/annonc/mdw654 [DOI] [PubMed] [Google Scholar]
- 30. Frasca M, Sabathe C, Delaloge S, et al. Palliative care delivery according to age in 12,000 women with metastatic breast cancer: analysis in the multicentre ESME-MBC cohort 2008-2016. Eur J Cancer. 2020;137:240-249. 10.1016/j.ejca.2020.07.007 [DOI] [PubMed] [Google Scholar]
- 31. Caraceni A, Lo Dico S, Zecca E, et al. Outpatient palliative care and thoracic medical oncology: referral criteria and clinical care pathways. Lung Cancer. 2020;139:13-17. 10.1016/j.lungcan.2019.10.003 [DOI] [PubMed] [Google Scholar]
- 32. García-Martín E, Escudero-Vilaplana V, Fox B, et al. Aggressiveness of end-of-life cancer care: what happens in clinical practice? Support Care Cancer. 2021;29(6):3121-3127. [DOI] [PubMed] [Google Scholar]
- 33. Dasch B, Kalies H, Feddersen B, et al. Care of cancer patients at the end of life in a German University Hospital: a retrospective observational study from 2014. PLoS One. 2017;12(4):e0175124. 10.1371/journal.pone.0175124 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Hui D, Kim SH, Roquemore J, et al. Impact of timing and setting of palliative care referral on quality of end-of-life care in cancer patients. Cancer. 2014;120(11):1743-1749. 10.1002/cncr.28628 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Mathew A, Achkar T, Abberbock S, et al. Prevalence and determinants of end-of-life chemotherapy use in patients with metastatic breast cancer. Breast J. 2017;23(6):718-722. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Kessler LE, Sigfridsson J, Hatzidaki D, et al. Chemotherapy use near the end-of-life in patients with metastatic breast cancer. Breast Cancer Res Treat. 2020;181(3):645-651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Pacetti P, Paganini G, Orlandi M, et al. Chemotherapy in the last 30 days of life of advanced cancer patients. Support Care Cancer. 2015;23(11):3277-3280. 10.1007/s00520-015-2733-6 [DOI] [PubMed] [Google Scholar]
- 38. Assi T, El Rassy E, Tabchi S, et al. Treatment of cancer patients in their last month of life: aimless chemotherapy. Support Care Cancer. 2016;24(4):1603-1608. [DOI] [PubMed] [Google Scholar]
- 39. Urvay S, Civelek B, Özaslan E, Sürel AA.. Chemotherapy at the end of life. J Palliat Care. 2021;36(2):73-77. 10.1177/0825859720946505 [DOI] [PubMed] [Google Scholar]
- 40. Ledoux M, Rhondali W, Lafumas V, et al. Palliative care referral and associated outcomes among patients with cancer in the last 2 weeks of life. BMJ Support Palliat Care. 2019;9(1):e16. 10.1136/bmjspcare-2014-000791 [DOI] [PubMed] [Google Scholar]
- 41. Davis MP, Vanenkevort EA, Elder A, et al. The financial impact of palliative care and aggressive cancer care on end-of-life health care costs. Am J Hosp Palliat Care. 2023;40(1):52-60. 10.1177/10499091221098062 [DOI] [PubMed] [Google Scholar]
- 42. Davis MP, Vanenkevort EA, Elder A, et al. When does early palliative care influence aggressive care at the end of life? Support Care Cancer. 2022;30(6):5371-5379. 10.1007/s00520-022-06954-2 [DOI] [PubMed] [Google Scholar]
- 43. Melac AT, Lesuffleur T, Bousquet PJ, et al. Cancer and end of life: the management provided during the year and the month preceding death in 2015 and causes of death in France. Support Care Cancer. 2020;28(8):3877-3887. 10.1007/s00520-019-05188-z [DOI] [PubMed] [Google Scholar]
- 44. Hui D, Bansal S, Strasser F, et al. Indicators of integration of oncology and palliative care programs: an international consensus. Ann Oncol. 2015;26(9):1953-1959. 10.1093/annonc/mdv269 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Materials described in this article, including all relevant raw data, will be freely available to any scientist wishing to use them for non-commercial purposes, without breaching participant confidentiality, on request to the corresponding author.