Patterns of Relapse and Modalities of Treatment of Breast Cancer: The ‘IRIS’ Project, a Multicenter Observational Study

Cazzaniga, M.; Pronzato, P.; Priolo, Simone; Matteis, A. De; Costanzo, F. Di; Passalacqua, Rodolfo; Rosso, R.; Torri, Valter

doi:10.1159/000078325

Cited by 10 publications

(13 citation statements)

References 18 publications

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“…Our findings confirm this hypothesis: in fact, despite international guidelines about follow-up in breast cancer patients [15], recommending not to use bone scan in routinely restaging when patients are free from disease, this technique is often applied, as confirmed in an Italian survey designed to investigate patterns of relapse and modalities of treatment in newly diagnosed metastatic breast cancer patients [16]. …”

Section: Discussionsupporting

confidence: 82%

Diagnosis, Management and Clinical Outcome of Bone Metastases in Breast Cancer Patients: Results from a Prospective, Multicenter Study

Cazzaniga

Dogliotti²,

Cascinu

et al. 2006

Oncology

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Background: Little information is available about the management and clinical outcome of bone metastases (BM) in breast cancer patients. Methods: We prospectively studied 459 breast cancer patients with first diagnosis of BM for at least 2 years to collect information about diagnosis, management and clinical outcome. Results: Two hundred and forty-eight patients (54%) had only BM, 86 (18.7%) had concomitant nonskeletal BM and 125 (27.2%) had previous nonskeletal BM. At enrolment, skeletal-related events were present in 132 patients (28.8%). Cancer treatments consisted of hormones (227/459, 49.5%) or chemotherapy (192/459, 41.8%). Age (≤70) and nonskeletal BM are inversely correlated with the use of chemotherapy or endocrine treatment (p < 0.0001). Bisphosphonates were used in 67.5% of the cases, alone (62.3%) or combined with other drugs. After a median follow-up of 28 months (range 2–43), 272 patients developed new metastases (59.2%), progression occurred mainly in nonskeletal sites (107/459, 23.3%), except for BM patients, who progressed prevalently at bone (69/248, 27.8%). New skeletal-related events were observed in 122 patients (26.6%). The 2-year probability for disease progression control and survival was 0.19 (95% CI 0.15–0.24) and 0.64 (95% CI 0.58–0.69), respectively. The 2-year probability for death according to the presence of nonskeletal metastases and the time of appearance (previous or concomitant to BM) was 0.74 (95% CI 0.67–0.79) for BM, 0.38 (95% CI 0.25–0.51) for previous nonskeletal BM and 0.56 (95% CI 0.46–0.66) for concomitant nonskeletal BM (p < 0.0001). Conclusions: Clinical outcome is significantly different according to the metastatic sites.

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Section: Discussionsupporting

confidence: 82%

Diagnosis, Management and Clinical Outcome of Bone Metastases in Breast Cancer Patients: Results from a Prospective, Multicenter Study

Cazzaniga

Dogliotti²,

Cascinu

et al. 2006

Oncology

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“…In multiple myeloma, 70-95 % of patients have tumour bone disease [7]. In breast cancer, bone is often the first site of distant metastases [5] with approximately one half of patients experiencing bone metastases as the site of first relapse [8]. In advanced breast or prostate cancer, metastatic bone disease is present in the vast majority of patients.…”

Section: Epidemiology Of Cancer-associated Bone Disease Bone Metastasismentioning

confidence: 99%

Cancer-associated bone disease

Rizzoli

Body²,

Brandi³

et al. 2013

Osteoporos Int

128

103

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Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancerassociated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidencebased care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations. Epidemiology of cancer-associated bone disease Bone metastasisCancer affects nearly 12.7 million people and is associated with over 7 million deaths in 2008 [1]. Cancer is a rising global health burden and it is estimated that in 2030, cancer deaths will be tallied at over 13 million (World Health Organization (WHO) 2010 Global Status Report [2]). Addressing the morbidity and mortality of cancer is an important public health concern. On purpose, we are limiting our analysis to cancer bone involvement in adults and do not discuss cancer in children.Metastases from cancer are associated with 90 % of cancer deaths [3]. It was estimated that one half of people who die from cancer in the USA have bone involvement [4][5][6]. Different tumou...

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“…Estrogen-dependent breast cancer cell lines model estrogen-dependent human tumors, which are likely to remain dormant for extended periods and are least likely to have distant metastatic recurrences [4–6]. In the clinical setting, recurrent estrogen receptor positive cells continue to be estrogen sensitive and susceptible to hormonal blockade [7, 8]. …”

Section: Introductionmentioning

confidence: 99%

Dual FGF-2 and Intergrin α5β1 Signaling Mediate GRAF-Induced RhoA Inactivation in a Model of Breast Cancer Dormancy

Barrios

Wieder

2009

Cancer Microenvironment

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Interactions with the bone marrow stroma regulate dormancy and survival of breast cancer micrometastases. In an in vitro model of dormancy in the bone marrow, we previously demonstrated that estrogen-dependent breast cancer cells are partially re-differentiated by FGF-2, re-express integrin α5β1 lost with malignant transformation and acquire an activated PI3K/Akt pathway. Ligation of integrin α5β1 by fibronectin and activation of the PI3K pathway both contribute to survival of these dormant cells. Here, we investigated mechanisms responsible for the dormant phenotype. Experiments demonstrate that integrin α5β1 controls de novo cytoskeletal rearrangements, cell spreading, focal adhesion kinase rearrangement to the cell perimeter and recruitment of a RhoA GAP known as GRAF. This results in the inactivation of RhoA, an effect which is necessary for the stabilization of cortical actin. Experiments also demonstrate that activation of the PI3K pathway by FGF-2 is independent of integrin α5β1 and is also required for cortical actin reorganization, GRAF membrane relocalization and RhoA inactivation. These data suggest that GRAF-mediated RhoA inactivation and consequent phenotypic changes of dormancy depend on dual signaling by FGF-2-initiated PI3K activation and through ligation of integrin α5β1 by fibronectin.

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Patterns of Relapse and Modalities of Treatment of Breast Cancer: The ‘IRIS’ Project, a Multicenter Observational Study

Cited by 10 publications

References 18 publications

Diagnosis, Management and Clinical Outcome of Bone Metastases in Breast Cancer Patients: Results from a Prospective, Multicenter Study

Diagnosis, Management and Clinical Outcome of Bone Metastases in Breast Cancer Patients: Results from a Prospective, Multicenter Study

Cancer-associated bone disease

Dual FGF-2 and Intergrin α5β1 Signaling Mediate GRAF-Induced RhoA Inactivation in a Model of Breast Cancer Dormancy

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