Diagnosis and Treatment of Bone Metastases in Breast Cancer: Radiotherapy, Local Approach and Systemic Therapy in a Guide for Clinicians

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common—paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyze available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

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Actualities on Diagnosis, Targeting and Treating Bone Metastases in Breast Cancer with Radiotherapy and New Drugs

10.20944/preprints202005.0010.v1 ◽

2020 ◽

Author(s):

Fabio Marazzi ◽

Armando Orlandi ◽

Stefania Manfrida ◽

Valeria Masiello ◽

Alba Di Leone ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Bone Metastasis ◽

Metastatic Breast ◽

Standard Of Care ◽

New Drugs ◽

Focal Treatment ◽

Target Therapies ◽

Potential Impact ◽

Systemic Therapies

The standard of care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment in case of symptomatology onset. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive disease presentations are even more common, leading to a change of paradigm of focal treatments. In fact, acknowledgement of behaviour of disease in these setting of patients is carrying aim of radiotherapy towards modalities with radical intent. The aim of this literature review is to analyse available clinical data regarding disease behaviour, imaging, radiotherapy and chemo-radiotherapy integration outcomes for understanding bone metastasis from breast cancer and the potential impact of targeting it.

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Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Cells ◽

10.3390/cells10061377 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1377

Author(s):

Konstantinos Venetis ◽

Roberto Piciotti ◽

Elham Sajjadi ◽

Marco Invernizzi ◽

Stefania Morganti ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Clinical Management ◽

Bone Destruction ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Incurable Condition ◽

Skeletal Related Events ◽

Relevant Topic ◽

Systemic Therapies

Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient’s survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients’ survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic.

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Two may be better than one: PD-1/PD-L1 blockade combination approaches in metastatic breast cancer

npj Breast Cancer ◽

10.1038/s41523-019-0130-x ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 5

Author(s):

David B. Page ◽

Harry Bear ◽

Sangeetha Prabhakaran ◽

Margaret E. Gatti-Mays ◽

Alexandra Thomas ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Clinical Practice ◽

Clinical Data ◽

Targeted Therapies ◽

Metastatic Breast ◽

Programmed Death ◽

Programmed Death 1 ◽

Better Than ◽

Systemic Therapies

Abstract Antibodies blocking programmed death 1 (anti-PD-1) or its ligand (anti-PD-L1) are associated with modest response rates as monotherapy in metastatic breast cancer, but are generally well tolerated and capable of generating dramatic and durable benefit in a minority of patients. Anti-PD-1/L1 antibodies are also safe when administered in combination with a variety of systemic therapies (chemotherapy, targeted therapies), as well as with radiotherapy. We summarize preclinical, translational, and preliminary clinical data in support of combination approaches with anti-PD-1/L1 in metastatic breast cancer, focusing on potential mechanisms of synergy, and considerations for clinical practice and future investigation.

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What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

Cancers ◽

10.3390/cancers11122018 ◽

2019 ◽

Vol 11 (12) ◽

pp. 2018 ◽

Cited By ~ 5

Author(s):

Francesca Salamanna ◽

Veronica Borsari ◽

Deyanira Contartese ◽

Viviana Costa ◽

Gianluca Giavaresi ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Bone Metastases ◽

Metastatic Breast ◽

World Health ◽

Therapeutic Effects ◽

Preclinical Studies ◽

Functional Roles ◽

Novel Strategy ◽

Health Organization

Breast cancer cells produce stimulators of bone resorption known as interleukins (ILs). However, data on the functional roles of ILs in the homing of metastatic breast cancer to bone are still fragmented. A systematic search was carried out in three databases (PubMed, Scopus, Web of Science Core Collection) to identify preclinical reports, and in three clinical registers (ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register) to identify clinical trials, from 2008 to 2019. Sixty-seven preclinical studies and 11 clinical trials were recognized as eligible. Although preclinical studies identified specific key ILs which promote breast cancer bone metastases, which have pro-metastatic effects (e.g., IL-6, IL-8, IL-1β, IL-11), and whose inhibition also shows potential preclinical therapeutic effects, the clinical trials focused principally on ILs (IL-2 and IL-12), which have an anti-metastatic effect and a potential to generate a localized and systemic antitumor response. However, these clinical trials are yet to post any results or conclusions. This inconsistency indicates that further studies are necessary to further develop the understanding of cellular and molecular relations, as well as signaling pathways, both up- and downstream of ILs, which could represent a novel strategy to treat tumors that are resistant to standard care therapies for patients affected by breast cancer bone disease.

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Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.1.59 ◽

1993 ◽

Vol 11 (1) ◽

pp. 59-65 ◽

Cited By ~ 399

Author(s):

A H Paterson ◽

T J Powles ◽

J A Kanis ◽

E McCloskey ◽

J Hanson ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastases ◽

Bone Pain ◽

Controlled Trial ◽

Metastatic Breast ◽

Spinal Pain ◽

Recurrent Breast Cancer ◽

Nonvertebral Fracture ◽

Double Blind ◽

Oral Clodronate

PURPOSE Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer. PATIENTS AND METHODS We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients). RESULTS The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P < .01), in the number of terminal hypercalcemic episodes (seven v 17; P < .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P < .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P < .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P < .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups. CONCLUSIONS These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases.

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