Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer

Abstract

BackgroundThe development of metastases is a negative prognostic parameter for the clinical outcome of breast cancer. Bone constitutes the first site of distant metastases for many affected women. The purpose of this retrospective multicentre study was to evaluate if and how different variables such as primary tumour stage, biological and histological subtype, age at primary diagnosis, tumour size, the number of affected lymph nodes as well as grading influence the development of bone-only metastases.MethodsThis retrospective German multicentre study is based on the BRENDA collective and included 9625 patients with primary breast cancer recruited from 1992 to 2008. In this analysis, we investigated a subgroup of 226 patients with bone-only metastases. Association between bone-only relapse and clinico-pathological risk factors was assessed in multivariate models using the tree-building algorithms “exhausted CHAID (Chi-square Automatic Interaction Detectors)” and CART(Classification and Regression Tree), as well as radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression.ResultsMultivariate analysis demonstrated that breast cancer subtypes have the strongest influence on the development of bone-only metastases (χ2 = 28). 29.9 % of patients with luminal A or luminal B (ABC-patients) and 11.4 % with triple negative BC (TNBC) or HER2-overexpressing tumours had bone-only metastases (p < 0.001). Five different mathematical models confirmed this correlation. The second important risk factor is the age at primary diagnosis. Moreover, BC subcategories influence the overall survival from date of metastatic disease of patients with bone-only metastases. Patients with bone-only metastases and TNBC (p < 0.001; HR = 7.47 (95 % CI: 3.52–15.87) or HER2 overexpressing BC (p = 0.007; HR = 3.04 (95 % CI: 1.36–6.80) have the worst outcome compared to patients with luminal A or luminal B tumours and bone-only metastases.ConclusionThe bottom line of different mathematical models is the prior importance of subcategories of breast cancer and the age at primary diagnosis for the appearance of osseous metastases. The primary tumour stage, histological subtype, tumour size, the number of affected lymph nodes, grading and NPI seem to have only a minor influence on the development of bone-only metastases.

Incidence proportions and prognosis of breast cancer patients with bone metastases at initial diagnosis

“…Compared with HR‐positive HER2‐negative patients, HR‐positive HER2‐positive patients experienced a 25.1% reduction in the hazards of overall mortality while triple‐negative patients experienced a 153.0% increase in the hazards of overall mortality. Our data are consistent with some previous retrospective studies 22, 23, 38, 39. We found that HR status in patients who are HER2‐positive is an important prognostic factor.…”

“…Patients with HR‐positive breast cancer are at increased risk for the development of bone metastases, whereas bone metastases are less frequent in cases of triple‐negative tumors 15, 16, 17, 18, 19, 20, 21. Previous studies also indicated that tumor subtype is an important prognostic factor for the survival of patients with bone metastases, where worse survival was seen in patients with triple‐negative breast cancer 22, 23…”

Bone-Induced Expression of Integrin β3 Enables Targeted Nanotherapy of Breast Cancer Metastases

“…Across nearly all patients, tumor-associated β3 expression was significantly higher on bone metastases. Furthermore, we show for the first time that β3 is highly expressed on breast cancer bone metastases of all subtypes, including those with the worst overall survival that have proven difficult to target (44), supporting the translational potential of targeting β3 in bone metastatic breast cancer patients.…”

Metastatic breast cancer: clinicopathological features and survival according to the site of metastasis

“…A proporção de pacientes que desenvolveram metástase óssea isolada foi 26,6%, semelhante a estudos conduzidos com grandes coortes, cujos resultados situam-se em torno de 24,0 a 28,0%. 11,12,32 Entre as mulheres com cân-cer de mama e metástase óssea, espera-se que entre 40 e 60% também desenvolvam metástase extraóssea durante o curso da doença, 18 o que foi observado em 46,8% das pacientes avaliadas.…”

“…12,20 O tempo médio de sobrevida das pacientes com câncer de mama que apresentam metástase óssea varia de 18 a 36 meses. 11,12,32,45 Em nosso estudo, esse valor foi 19,6 (IC95% 36,9). Já o tempo de sobrevida após o acometimento extraósseo (12,1 meses) também foi semelhante aos valores observados em estudos internacionais com grandes populações, os quais variam entre 11 e 16 meses.…”