Clinical management of women with metastatic breast cancer: a descriptive study according to age group

Patients were retrieved from the population-based Eindhoven Cancer Registry (ECR). Since 1989, the ECR has recorded follow-up information on all patients with breast cancer, including the date and site of loco-regional and distant metastasis and the date of death. Information on date of death was obtained from the municipal registries in the area of the Eindhoven Cancer Registry and the Central Bureau for Genealogy. The latter is an institution that collects data on all deceased Dutch citizens via the municipal registries. In this way, information on patients who had moved outside the registry area was also obtained. Patients who died outside the Netherlands were wrongly listed as 'alive'. However, the estimated proportion of these patients was less then 0.3%. All 281 patients with a history of breast cancer who died after December 31, 1999 and had been treated at the Catharina Hospital in Eindhoven or the Máxima Medical Center in Veldhoven were selected for the study. These hospitals are both non-academic, teaching hospitals. According to the data of the ECR, 133 of these 281 patients developed distant metastases, including 11 patients with metastatic disease at the time of diagnosis of the primary tumor. It was assumed that the remaining 148 patients did not die from breast cancer; their mean age at death was 77 years. Five of the 133 patients with metastatic disease had to be excluded, because their medical records could not be traced. Another 12 patients were excluded because their metastases appeared to be related to another primary tumor or were redefined as a locoregional recurrence after review of their medical records. Thus, 116 patients remained available for the study. For each of these 116 patients, detailed information was collected on the site(s) of metastases, diagnostic procedures, treatment, hospitalization and clinical follow-up, starting from the time of diagnosis of distant disease. The first site of metastatic disease and all subsequent sites were recorded separately. For patients receiving systemic treatment, the type of drug and the reason for any postponement or dose reduction were recorded. Response to systemic treatment was measured clinically, biochemically or by radiological imaging. Assessment of treatment response was limited by the retrospective nature of the study. Thus, when evaluating the response to a new endocrine treatment or a new course of chemotherapy, patients with stable disease or partial or complete remission were taken together as one group and considered as responders. In all other cases patients were considered to have progressive disease. According to the information in the medical records, the response to radiotherapy was judged to be positive if the patient reported fewer complaints and negative if the severity of the complaints had not changed or increased. Data on the primary tumor and primary therapies were available from the database of the ECR.

Our study was based on a review of clinical charts only and hence needed no approval from our local ethics committee.

The date of first evidence of metastatic disease was defined as the date of diagnosis. The metastasis-free interval was defined as the interval between the date of diagnosis of the primary tumor and the date of diagnosis of metastastic disease, excluding the patients with metastatic disease at the time of diagnosis of the primary tumor.

To study age-related differences in treatment, response to treatment and survival patients were divided into three age groups: <50 years (n = 34), 50–69 years (n = 62) and 70+ years (n = 20), using the age at initial diagnosis of breast cancer.

The frequency distributions of the different variables between the three age groups were compared by means of the likelihood ratio Chi-square test or, when expected counts were less than five, Fisher's Exact test. The Kruskal Wallis test was used to compare continuous variables between the three age groups. The interval from diagnosis of the primary tumor until diagnosis of metastatic disease and the interval from diagnosis of metastatic disease until death found for the three age groups were compared by the logrank test. The significance level was set at 0.05 for all analyses.

Patient and disease characteristics are presented in Table 1. Of all 116 patients included in our study, 10 (9%) already had metastatic disease at diagnosis and 106 developed distant disease after a diagnosis of localized breast cancer with or without positive lymph nodes. The mean age of the patients was 58 years (range: 21–88) at the time of diagnosis of the primary tumor and 61.5 years (range: 23–93) at the time of diagnosis of metastatic disease (Figure). No significant differences were observed between age groups as far as the size of the primary tumor, axillary nodal status and the proportion of patients with metastatic disease at the time of diagnosis of the primary tumor were concerned. Also the proportion of patients undergoing surgery, radiotherapy or systemic treatment as part of their primary treatment did not differ between the three age groups.

Among the patients without metastatic disease at diagnosis, the length of the metastasis-free interval tended to be longer for patients 50–69 years than for younger and older patients (p = 0.07).

Before they died, 70% of the 116 patients developed metastases in the bone, 50% in the lung and/or pleura, 50% in the abdominal viscera, 23% in the central nervous system, and 19% in the skin (Table 1). Patients younger than 50 years were much more likely to develop metastases in the central nervous system than patients 50 years and older. The risk of developing bone or visceral metastases seemed to decrease with age (p = 0.16). The median survival after the diagnosis of metastatic disease was 12 months for patients 70 years and older and 21 months for patients younger than 70 years (p = 0.048).

Table 2 shows the differences in the management of the 116 patients with metastatic breast cancer according to age group. As far as diagnostic procedures are concerned, the median numbers of laboratory tests and imaging procedures were significantly lower among patients aged 70 years and older compared to the patients younger than 70 years of age. The proportion of patients visiting a medical oncologist and the number of visits decreased with increasing age. The large majority of the patients was admitted to hospital at least once after the diagnosis of metastatic disease. The median number of admissions was 3, being somewhat higher for patients younger than 50 years than for patients 70 years and older (p = 0.06). The mean duration of admission was significantly longer for patients 50 years and older than for younger patients (p = 0.02). Progression and treatment of metastatic disease were the main reasons for hospital admission in all age groups. Other important reasons for hospital admission were the treatment of co-morbid conditions and the management of treatment-related complications. Of the 116 patients, 53 (46%) died in the hospital.

The proportion of patients with metastatic disease receiving chemotherapy decreased with age (Table 2), as did the number of schemes (Table 3). Patients 20–49 and 50–69 years of age were treated mainly with combination chemotherapy (CAF, CMF or FEC), whereas patients 70 years and older were treated with (less aggressive) monotherapy, such as mitoxantrone and vinorelbine. Treatment delays occurred in about one-third of the cases, mainly due to myelosuppression. Dose reductions were relatively rare and in most cases they were a result of myelosuppression. Thirty-five of the 132 chemotherapy schemes (27%) resulted in partial remission or stabilization of the disease process. Complete remission was observed only once.

The proportion receiving hormonal treatment did not differ between the three age groups (Table 2). Tamoxifen and aromatase inhibitors were usually given as first or second line treatments and megestrol acetate was given to one-third of the patients, mainly as a third-line drug (Table 4). Thirty-eight of the 216 hormonal treatments (16%) resulted in partial remission or stabilization of the disease process.

Of the 116 patients, 79 received palliative radiotherapy. The proportion decreased with age (Table 2). Together, the 79 patients underwent 216 courses, of which 160 (70%) were less than 20 Gy and 176 (77%) resulted in a relief of the complaints of the patient (Table 5).