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Correlation between clinical staging and skeletal alterations of bone metastases in breast cancer patients

Abstracts

Forty-eight breast cancer patients with bone metastases were studied aiming to evaluate the correlation between clinical staging of the primary tumor, according to the Cancer Staging American Committee protocol, and the skeletal manifestations of the bone metastases; the assessment parameters were the follow-up period, the number of metastases, the type of the lesions, their localization, and the affected bone region. A correlation was found between the primary lesion staging and the follow-up period, which was reduced when the staging degree increased; no correlation was observed between breast cancer clinical staging and the other parameters.

Bone metastasis; breast cancer


Foram estudadas 48 pacientes com câncer da mama e que apresentavam metástases ósseas, com o objetivo de avaliar-se a correlação entre o estadiamento clínico do tumor primário, de acordo com protocolo do Comitê Americano de Estadiamento do Câncer, e as manifestações esqueléticas das metástases ósseas, tendo sido utilizados como parâmetros para essa avaliação o período de seguimento, o número de metástases, o tipo de lesão, a sua localização e a região do osso acometida. Foi observado correlação entre o estadiamento da lesão primária e o tempo de seguimento, que diminuia à medida que o grau de estadiamento aumentava, não tendo sido observado correlação entre o estadiamento clínico do câncer de mama e os demais parâmetros estudados.

Metástase óssea; Câncer de mama


ARTIGO ORIGINAL

Correlation between clinical staging and skeletal alterations of bone metastases in breast cancer patients

Helton L.A. DefinoI; Flávio L. GarciaII; Leonardo C. SimionatoIII; Ângelo C.S. MatthesIV; Sérgio BighettiV

IProfessor Associado do Departamento de Cirurgia, Ortopedia e Traumatologia da FMRP- USP

IIMédico Residente da Área de Ortopedia e Traumatologia da FMRP-USP

IIIMédico Residente da Área de Ortopedia e Traumatologia da FMRP-USP

IVMédico Assistente do Departamento de Ginecologia e Obstetrícia da FMRP-USP

VProf. Associado do Departamento de Ginecologia e Obstetrícia da FMRP-USP

SUMMARY

Forty-eight breast cancer patients with bone metastases were studied aiming to evaluate the correlation between clinical staging of the primary tumor, according to the Cancer Staging American Committee protocol, and the skeletal manifestations of the bone metastases; the assessment parameters were the follow-up period, the number of metastases, the type of the lesions, their localization, and the affected bone region.

A correlation was found between the primary lesion staging and the follow-up period, which was reduced when the staging degree increased; no correlation was observed between breast cancer clinical staging and the other parameters.

Key-words: Bone metastasis; breast cancer

INTRODUCTION

The neoplasias are consequence of cell growth regulation disorders, resulting in abnormal proliferation associated to local lesions. The neoplastic cells spread on the surrounding tissues, and also detach from their original site, proliferating in tissues and locals distant from the primary site, forming metastases. 16

The susceptibility of different tissues to tumor metastases has still to be explained, and there are tissues, as the bone, with a high percentage of tumor metastases but rarely affected by primary tumors, in contrast with breast and colon which present high incidence of primary lesions and scarce metastatic lesions. The lungs evidence a distinct pattern, with high incidence of primary tumor lesions and also metastases. 16

Autopsies have shown that bone metastases are particularly frequent in patients which die due to breast, bronchi, prostate, kidney and thyroid neoplasms 5,6 and probably the breast, bronchi and prostate tumors are responsible for about 80% of the bone metastases. 7

Breast carcinoma is the most prevalent tumor in West European and North American women; in the United Kingdom, about 24000 new yearly cases are detected, responsible for 15000 annual deaths. 16 The breast carcinoma presents the highest frequency of bone metastases, reported as 38.6 to 49.6% (8,12,15) and this observation associated to the growing number of patients receiving orthopedic treatment due to breast carcinoma metastases led to this investigation, whose main objective was to determine a possible correlation between the clinical and radiological characteristics of the metastatic bone lesions with the staging of the breast primary lesion, and the influence of this staging on the elaboration of diagnostic or therapeutic approaches for bone lesions.

MATERIAL AND METHOD

Forty-eight 36 to 72 year-old (mean 53 years) female patients were retrospectively studied. They were attended from March, 1990 to February, 1997 in the Ginecology and Obstetrics and Orthopedics and Traumatology Areas of the Ribeirão Preto College of Medicine, University of São Paulo (FMRP-USP), presenting breast carcinoma with bone metastases.

Clinical staging was effected according to the Cancer Staging American Committee protocol (Table I), and 7 (14.5%) patients were Stage I, 14 (29.1%) stage II, 18 (37.5%) stage III and 9 (18.7%) stage IV. Tables II, III, IV, V and VI.

The histological types of the primary tumor were: ductal infiltrative, 44 patients (91.6%), lobular infiltrative, 2 (4.2%), medullary, 1 (2.1%), and papilliferous, 1 (2.1%). Fifteen patients had only one metastasis (31.2%), and 33 (68.8%) had multiple metastases (Fig. 1). The metastases were lithic, 35 patients (72.9%), blastic, 2 patients (4.2%), and mixed in 11 patients (22.9%) (Fig. 2). The most affected bones were the ribs, 22 patients (45.8%), the spinal column, 20 (41.6%) and the femur, 18 (37.5%). The bone localization of the metastases is in Table II; in the long bones 6 lesions were diaphyseal (20%), 20 (66.7%) metaphyseal and 4 (13.3%) epiphyseal.



In the spinal column, 9 patients (45%) had lesions at the thoracic, 9 (45%) at the lumbar, 1 (5%) at the sacral, and 1 (5%) at the cervical levels. The vertebral body was affected in 14 patients (70%), the pedicle in 5 (25%) and the posterior elements in 1 patient (5%).

The presence of bone lesions was detected by means of bone scintillography with technetium 99 and X-rays, and in 4 patients a complementary study with computerized tomography was carried out to confirm the bone lesion.

The parameters considered to evaluate the metastatic bone lesions were: number of bone metastases (single or multiple), type of lesion (lithic, blastic or mixed), localization and region involved; the parameters were evaluated and compared in 4 groups of patients, allocated according to their categorization in the primary lesion clinical staging (Cancer Staging American Committee Protocol).

RESULTS

The mean follow-up period of the studied patients was 3 years and 6 months; in the stage I patients the mean was 6 years and 4 months; in stage II, 3 years and 10 months; in stage III 3 years and 2 months; and in stage IV, 1 year and 3 months. (Fig. 3).


The infiltrative ductal carcinoma was the histological type which predominated (91.6%), and its predominance was also observed in the different clinical stages (stage I – 85.7%; stage II – 92.8%; stage III – 94.4% and stage IV – 88.8%).

The multiple metastases predominated in the group of study, and they were observed in 68.8% of the patients. The multiple metastases were also the most frequent in the different clinical stages; they were observed in 71.4% of the patients stage I; 57.1% of the patients stage II; 77.7% stage III; and 75% stage IV. (Fig. 1)

The rib was the most involved bone (45.8%), followed by the spinal column (41.6%) and femur (37.5%). The distribution of the metastases in the spinal column prevailed in the thoracic and lumbar segments. The metastases localization is presented in Tables III, IV, V and VI and no differences were observed between the clinical stages, the most frequent localization being the ribs and spinal column in all stages, with the exception of stage III where femoral metastases were more frequently observed.

The most frequent bone localization of the metastases was the long bones metaphyseal region (66.7%) and the vertebral body (70%); no differences were observed between the different clinical stages.

The kind of lesion (lithic or blastic) also had no correlation with the different clinical stages of the primary tumor, presenting a variable distribution in the different stages (Fig. 2).

The analysis of the parameters showed correlation between the clinical staging of the primary tumor and the follow-up period, which showed reduction when the clinical staging increased; no correlation was observed between the other parameters (histological type, number of metastases, kind of lesion, involved bone, and bone localization) and the clinical staging of the breast tumors.

DISCUSSION

The development of bone metastases is a complex and highly selective phenomenon, involving detachment of the malignant cells from the primary site of the lesion, their survival when in circulation, adhesion, vascular invasion and growth (3,17). These cells can also invade the contiguous bone.

The bone metastases are related to increased morbidity as pain, limitation of movement, pathological fractures, compression of nerve structures, hipercalcemia or supression of the bone marrow function. Pain frequently is the symptom of bone metastases, and it can be related to different mechanisms as: osteoclastic reabsortion mediated by cytokines, activation of the pain receptors by the prostaglandines, compression of the nervous structures or instability. 3,10.

Breast carcinoma is the tumor which presents the higher frequency of bone metastases and there are evidences that well differentiated tumors and those with positive estrogen receptors, present higher indices of bone metastases 16. The histological type of tumor observed in our series of patients is in agreement with the one described in the vast majority of breast carcinoma cases, and admittedly a highly metastazing tumor (4).

The characteristics of our group of patients agree with the literature approaching this subject, and a predominance of multiple metastatic lesions was observed; this emphasizes the need to carry out bone scintillography during the follow-up (7,11). The lithic pattern of the lesion predominates, evidencing the final result of the tumor cells interaction and the bone tissue (2,9). This interaction has been subject of several investigations, and several humoral factors secreted by the tumor cells, able to stimulate or inhibit osteoblasts or osteoclasts, have been described; thus, the final activity of these cells establishes the lithic or blastic pattern of the lesions (14). Concerning the frequency of the involved bones, we observed that the ribs were the main site of growth of the metastases, occurring in 22 patients (45.8%), immediately followed by the spinal column with 20 patients (41.6%), femur with 18 patients (37.5%), and hip with 16 patients (33.3%), in disagreement with the study of Lens and Freid (1931) (11) who described 81 cases of breast carcinoma, in which 63% of the patients presented hip lesions, 59% in the spinal column, 54% in the femur, 40% in the ribs, 36% in the cranium, and 27% in the umerus. Miller and Whitehill (1984)(12) also observed a high percentage of lesion distribution in the spinal column in 319 patients (74.6%), followed by the femur (42.6%), hip (40.1%), umerus (15.3%), tibia (2.1%), and radius (0.3%). Possibly the high index of lesions in the ribs, observed in our study, is related to the invasion by contiguity. Patients belonging to stage III were included in the analysis; by definition, these patients present fixation of the tumor in the musculature or in the thoracic wall. In spite of the variation found in these series, one must emphasize that the spinal column remains the most frequent skeletal site of malignant tumor metastases (6), due to the characteristics of the blood circulation and the existence of the Batson venous plexus. (1)

The preferred metaphyseal localization of the metastases is in the long bones, mainly femur and umerus due to the presence of red bone marrow and in the vertebral body was also observed in our series of patients, and agrees with the literature (3,4,13).

The mean follow-up period of our patients was 3 years and 6 months, according to Miller & Whitehill (1984) (12) and reduction in the follow-up period was observed when the grades of clinical staging increased; and that was the only correlation observed in our series of patients.

It was not possible to observe correlation between breast carcinoma clinical staging and alteration of bone metastases, so that the tumors which presented more advanced clinical stages did not present higher number of lesions, multiple lesions or preference for a certain localization in the skeleton or specific type of lesion.

The results observed in our investigation do not allow us to establish a correlation between the primary tumoral lesion staging and the metastatic manifestation of that pathology, and this must be considered in the assessment of the patients, in order that low staged lesions are not free from metastases and from possible complications due to bone tissue involvement.

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  • Publication Dates

    • Publication in this collection
      27 June 2006
    • Date of issue
      Mar 2001
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