Study population

Patient characteristics are summarized in Table 1. Treatment and evaluations received in the EoL period are summarized in Table 2.

Table 1 Characteristics of the enrolled patientsTable 2 Antineoplastic treatment received in the last six months of lifeDiagnosis of breast cancer and metastasis

Among the 121 patients with advanced breast cancer included, all were female and the median age at primary disease diagnosis was 57 years (range 31–81); 28.1% of the patients were diagnosed with luminal A breast cancer (n = 34), 43.8% with luminal B (n = 53), 14.1% with HER2 + (n = 17) and 14% with TNBC (n = 17). Median age at initial diagnosis of metastasis was 64 years (range 31 – 88), and median age at death was 68 years (range 32—88). Patients younger than 60 years old at death were 37 (30.6%). The year of initial diagnosis of metastasis was between 2002 and 2021; 20.7% had visceral involvement at the initial diagnosis of metastasis (n = 25) and 2.5% had brain metastasis (n = 3).

Active cancer treatments

In terms of active treatments, we considered the last line of therapy received in the last six months of life. Fifty-four patients (44.6%) received combination treatment, more specifically: chemotherapy associated with hormonal therapy for 30 luminal patients (24.8%); chemotherapy associated with anti-HER2 agents for 13 HER2-positive patients (10.7%); hormonal therapy and biological therapy for 11 patients (9.1%). In detail, 75.2% of the patients (n = 91) received chemotherapy during the last six months of their life, 45.4% hormonal therapy (n = 55), and 10.7% anti-HER2 therapy (n = 13). Among the patients who received chemotherapy, for 13.2% (n = 12) it was the 1st line of treatment, for 59.4% (n = 54) it was the 2nd to 4th (for 17.6% the 2nd, for 23.1% the 3rd, for 18.7% the 4th), and for 27.4% (n = 25) it was the 5th to the 10th.

Among the receptor-positive patients, 55 received hormonal therapy during the last six months of life; for 29.1% (n = 16) it was the 1st line of treatment, for 60% (n = 33) the 2nd to 4th, and for 10.9% (n = 6) it was the 5th to the 7th.

Among the 17 HER2-positive patients, 13 received targeted HER2 treatment in the last six months of life; for eight of these 13 patients (61.5%) it was the 1st line of treatment, for five (38.5%) it was the 2nd or later line.

Overall, 119 out of 121 patients (98.3%) received at least one line of active treatment in the last six months of life. Among the patients who did not receive any active treatment in the last six months of life, one patient refused treatment due to personal reasons while the family refused treatment for the other patient, who was frail and no longer competent owing to cognitive deterioration.

Radiotherapy

Radiotherapy was administered to 32 patients (26.4%); bone and brain were the most common sites of irradiation (50%, n = 16, and 40.6% n = 13, respectively).

Comorbidities

We defined comorbidities as any distinct additional medical condition that had existed or occurred during the clinical course of our patients [20]. Overall, cardiovascular comorbidities were the most common (57.8%, n = 70), followed by endocrine and psychiatric comorbidities (both 23.1%, n = 28). In total, 94 patients had at least one comorbidity; 21/94 of these patients (22.3%) were younger than 60 years old.

Concomitant medications

We defined concomitant medications as any other prescription medications or drugs that the study participant took in the evaluated period of time, in addition to the anti-cancer therapy. Almost all of the patients (95.9%, n = 116) used non-cancer medication. This included steroids (62%, n = 75), cardiovascular drugs (59.5%, n = 72), psychiatric drugs (32.2%, n = 39), endocrine drugs (22.3%, n = 27), and neurological drugs (16.5%, n = 20). These patient groups were heterogeneous in terms of both age and breast cancer subtype.

Imaging

Most of the patients (81.8%, n = 99) had at least one computed tomography scan (CT) during the last six months of their life, with a median interval from the last CT scan to death of 46 days (range 1–182 days); among these, 26 patients had a CT scan in the last month, while eight patients had at least one CT scan in the last week. Twenty-two patients had no CT scans at EoL. However, eight of these had a different type of imaging test (four had at least one Positron Emission Tomography (PET) scan and one ultrasound, one had one PET scan, and three had at least one ultrasound). The 14 patients who had no imaging were heterogeneous in terms of both age and breast cancer subtype. Details about imaging are reported in Table 3.

Table 3 Radiological evaluations received in the last 6 months of lifeSpecialist evaluations (other than palliative)

Most of the patients (83.4%, n = 101) had at least one oncological evaluation during the observed period, with a median interval from the last oncological evaluation to death of about two months (59 days). Among other specialized evaluations, the most common were those with a physical medicine specialist (17.3%, n = 21), a cardiologist (16.5%, n = 20), or a neurologist (15.7%, n = 19). Nutritional and psychological evaluations were performed in 7.4% and 8.2% of patients, respectively (n = 9 and n = 10). Four of the nine nutritional evaluations were performed in young patients (age < 60 yrs.), as were six of the ten psychological evaluations. Details about evaluations are shown in Tables 4 and 5.

Table 4 Specialist evaluations received in the last 6 months of lifeTable 5 Supportive care evaluations received in the last six months of lifeHospitalizations

Roughly half of the patients (52.8%, n = 64) were hospitalized during the last six months of life, mostly at the Medical Oncology Unit (40.4%, n = 49) and approximately a month before death (median 32.7 days before death, range 1–157 days).

Emergency department admissions

Fifty-two patients (43%) were admitted to the emergency department during the last six months of life. The median interval between the last admission and death was 35.5 days (range 0–181 days), without significant differences by age or breast cancer subtype (Table 6).

Table 6 Hospital and emergency department admissions in the last six months of lifePalliative care interventions and palliative home care

Palliative care interventions were performed in 13.9% of the patients (n = 17). Among these, 11 (64.7%) were younger than 60 years old. Palliative home care was provided to 63/121 patients (52%), without significant differences by age or breast cancer subtype.

Site of death

Most of the patients died at home (66.1%, n = 80); among these patients, a substantial proportion (27.3%, n = 33) had no palliative support. Thirteen patients (10.7%) died in hospice, twenty-two died at the hospital (18.2%): 14 (11.6%) at the Medical Oncology Unit, 6 (5%) at the emergency department, and 2 (1.6%) at the Internal Medicine Unit. Six patients died elsewhere (e.g., at a nursing home).

The group of patients who died at the hospital showed no significant difference from patients who died elsewhere in terms of age or breast cancer subtype.

Most of the patients who received palliative home care died at home (47 out of 63, 74.6%), five died in Hospice (7.9%), seven at the Hospital (11.1%), and four at various other locations (6.3%). Sites of death are shown in Fig. 2.

Fig. 2Predictors of healthcare use

Comorbidities and concomitant medications were the factors most closely associated with the number of CT scans received (OR 4.02, 95% CI 1.5–10.8; p = 0.006; OR 7.66 1.2–49 p = 0.03, respectively).

Cardiovascular comorbidities (OR 3.00, 95% CI 1.32–6.5; p = 0.005), endocrine comorbidities (OR 4.14, 1.33–12.91; p = 0.006), concomitant steroids (OR 2.52, 95% CI 1.16–5.45; p = 0.018) and visceral involvement at metastatic diagnosis (OR 0.26, 95% CI 0.10–0.65; p = 0.035) were associated with a higher number of specialist evaluations.

Hospitalization was most frequently associated with comorbidities (OR 2.29, 95% CI 0.95–5.54; p = 0.06), specifically cardiovascular (OR 1.98, 95% CI 0.95–4.11; p = 0.06) and endocrine comorbidities (OR 2.78, 95% CI 1.11–6.95; p = 0.023). Association with concomitant steroids was also observed (OR 3.33, 95% CI 1.55–7.19; p = 0.002).

Emergency department admission was most frequently associated with comorbidities, particularly cardiovascular (OR 2.32, 95% CI 1.09–4.93; p = 0.027) and endocrine (OR 3.12, 95% CI 1.29–7.54; p = 0.009).

Hospitalization, emergency admissions, and specialist evaluations were not associated with the age of the patient nor with a specific breast cancer subtype. The same was true for CT scans. Palliative care interventions and nutritional and psychological evaluations were more common among younger patients but not associated with any specific breast cancer subtype.

Overall, comorbidities seemed to be the most relevant factor in terms of predicting healthcare use.