Bone health in breast cancer patients€¦ · sharing their slides on short notice. Years peak bone...

CAMPUS GROSSHADERN

CAMPUS INNENSTADT

KLINIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE

DIREKTOR: PROF. DR. MED. SVEN MAHNER

Brustzentrum der

Universität

München

Leitung:

Prof. Nadia Harbeck

Bone health in breast cancer patients

Nadia HarbeckBreast Center, University of Munich, Germany

Brustzentrum

Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe

KLINIKUM DER UNIVERSITÄT MÜNCHEN®

▪ Bone health and breast cancer therapy

▪ Adjuvant use of bone stabilizing agents

▪ Treatment guidelines in MBC

▪ Open questions

▪ YOUR Questions

11.11.20172

Bone health in breast cancer | Prof. Harbeck

Thanks to Prof. Peyman Hadji (Frankfurt) and Prof. Ralf Schmidmaier (Munich) for generously

sharing their slides on short notice.

peak bone mass

Puberty

0 10 20 30 40 50 60 70 80I I I I I I I I

Fracture risk

Age and Estrogen dependent Change of BMD and BT

Hadji P. et al. Ann Oncol (2012) 23(11):2782-2790; Adapted from Nicks KM, et al. Ann N Y Acad Sci. 2010;1192:153-160.

POSTMENOPAUSAL

Estradiol

Inh A, Inh B, FSH

Act, BMP tone

Turnover

Preosteoclast

Preosteoblast

Abbreviations: Act, activin; BMP, bone morphogenetic protein; FSH, follicle-stimulating hormone; Inh, Inhibin.

Breast Cancer Increases Fracture RiskResults of the WHI observational study

Hazard ratio

0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2

Decreased fractures Increased fractures

Risk increase

31%1.31

Breast cancer

WHI = Women’s Health Initiative.

1. Chen Z, et al. Arch Intern Med. 2005;165:552-558.

• Prospective cohort study with 5.1 years of follow-up1

• 5,298 breast cancer survivors in WHI study

• 80,848 reference population with no history of cancer

• Adjustment for age, weight, and ethnicity

• Women with history of BC had a 31% increased risk of fracture

Brustzentrum

Fracture incidence of postmenopausal healthy

and BC women on TAM and AI

Schmidt N., Kostev K, Coleman RE and Hadji P. et al. Breast Cancer Res Treat. 2016 Jan;155(1):151-7

ESMO clinical practice guideline:

Bone health in cancer patients

• Clinicians treating cancer patients need to be aware of:

• Treatments to reduce skeletal morbidity in metastatic disease

• Strategies to minimise cancer treatment-

induced skeletal damage

• ESMO guidelines “provide a framework for maintaining bone health in patients with cancer”

Coleman RE et al. Ann Oncol 2014;00:1–14.

Influence of Risedronate (OAW) on BMD in women

with ER/PR pos Breast Cancer on AI Treatment

Mean±SE percent change in bone mineral density in spine total hip ,

#p<0.05, ##p<0.01 for comparison between RIS (solid line) and placebo (dashed line) groups using linear mixed

*p<0.05, **p<0.01 change from baseline using paired t test. Greenspan S.L. et al. Osteoporos Int (2015) 26:1857–1864

Brustzentrum

Prevention of therapy-induced osteoporosis

▪ n=252, luminal EBC, adjuvant AI, -1.0 > T > -2.5

11.11.20179 Ellis et al, JCO 2008

Brustzentrum

Prevention of therapy-induced osteoporosis

▪ ABCSG-18: n=3420, luminal EBC, adjuvant AI

11.11.201710 Gnant et al, Lancet 2015

Brustzentrum

Prevention of therapy-induced bone loss

11.11.201711 Hadji et al, 2017

Brustzentrum

Prevention of therapy-induced bone loss

11.11.201712 Hadji et al, 2017

Brustzentrum

Bone-directed therapy in breast cancer patients

11.11.201713

Coleman et al, ESMO clinical practice guideline bone health in cancer patients (2014)

Brustzentrum

Bone metastases in animal models

✓CK+ HER2+ tumor cells could be detected in the bone

marrow already in the stage of atypical ductal hyperplasia.

This spread is thus not a late event in tumor progression.

11.11.201714 Hüsemann et al, Cancer Cell 2008

Brustzentrum

Disseminated tumor cells in the bone marrow of patients with EBC

▪ DTCs can already be detected in 30-40% of

patients at time of primary diagnosis

▪ Presence of DTCs is associated with poor outcome

▪ Systemic chemotherapy cannot eliminate all DTCs

11.11.201715

Domschke et al, Ann Surg Oncol 2013; Janni et al, Clin Cancer Res 2011; Braun et al. N Engl J Med 2005; Becker et al, Breast Cancer Res Treat 2007; Janni W et al. Cancer 2005.

Brustzentrum

Zoledronic acid in EBC patients with DTCs

11.11.201716 Banys et al, BMC Cancer 2013

Brustzentrum

Optimal time to start zoledronic acid in EBC: ZO-FAST

11.11.201717 Coleman et al. Ann Oncol. 2013;24(2):398-405

Brustzentrum

EBCTCG metaanalysis for adjuvant bisphosphonates

11.11.201718 EBCTCG, Lancet 2015

Brustzentrum

Recommendations of European Experts (2016): Bisphosphonates in EBC

11.11.201719 Hadji et al, Annals of Oncology, 2016

Brustzentrum

Bisphosphonates in EBC: Who benefits?

11.11.201720 Hadji et al, Annals of Oncology, 2016

Brustzentrum

Bone stabilizing agents in EBC: Denosumab

11.11.201721 Gnant et al, SABCS 2015

Brustzentrum

11.11.201722 Gnant et al, SABCS 2015

Brustzentrum

11.11.201723 Gnant et al, SABCS 2015

Brustzentrum

Bone health in cancer patients: ESMO guidelines

11.11.201724 Coleman et al, Annals of Oncology 2014

Brustzentrum

11.11.201725 Coleman et al, Annals of Oncology 2014

Zometa®

Xgeva®

Bondronat®

Prolia®

Brustzentrum

11.11.201726 Annals of Oncology 26 (supp 5), 2015

Brustzentrum

11.11.201727

Bone health in EBC: EMA approvals for denosumab

Brustzentrum

11.11.201728

HALT: hormone ablation therapy

Bone health in EBC: EMA approvals for denosumab

Brustzentrum

Bone modifying agents in breast cancer

11.11.201729 Sukhbinder et al, 2017

Brustzentrum

11.11.201730

Brustzentrum

✓ Bone health is an important issue in breast cancer patients due to natural changes and treatment induced bone loss (TIBL)

✓ Next to exercise, calcium and vitamin D, bone modifying agents (e.g. bisphosphonates, denosumab) are effective in reducing TIBL

✓ Adjuvant use of bone modifying agents (e.g. bisphosphonates, denosumab) is effective in reducing recurrences and thus prolonging DFS in postmenopausal patients.

✓ Body of evidence larger for adjuvant use of bisphosphonates with improvement of OS demonstrated in EBCTCG metaanalysis. Effective in postmenopausal patients irrespective of tumor biology, type of bisphosphonate. ABCSG 12 also demonstrated efficacy in premenopausal patients with ovarian suppression.

11.11.201731

Brustzentrum

11.11.201732

www.karger.com/brc

EVIDENCE-BASED, PATIENT-ORIENTED BREAST CANCER THERAPY

AGO (DKG, DGGG) www.ago-online.de

Annually revised, evidence-based

recommendations for diagnosis and treatment

www.cankado.comThe Digital Diary for Every Patient

Bone health in breast cancer patients€¦ · sharing their slides on short notice. Years peak bone...

Documents

Testosterone Effect on Lipids,Bone Density and Breast Cancer Incidence The “ABC Study”

Secondary breast cancer in the bone · for secondary breast cancer in the bone. Denosumab reduces bone loss, making complications of secondary breast cancer in the bone less likely

AR Expression in Breast Cancer CTCs Associates with Bone ...cancer bone metastasis, and suggests that therapeutic targeting of the AR may beneﬁt patients with metastatic breast cancer

miRNA-30 Family Members Inhibit Breast Cancer Invasion, … · Tumor Biology and Immunology miRNA-30 Family Members Inhibit Breast Cancer Invasion, Osteomimicry, and Bone Destruction

BONE HEALTH IN PATIENTS WITH BREAST CANCER PRACTICE GUIDELINE BR-010 Version 1 . BONE HEALTH . IN PATIENTS WITH BREAST CANCER . Effective Date: November 2012 . The recommendations

Cathepsin B Inhibition Limits Bone Metastasis in Breast Cancer › content › canres › ... · function of cathepsin B in breast cancer metastasis to bone. Molecular suppression

Management of Bone Metastasis in Breast Cancer · 2014-10-30 · Management of Bone Metastasis in Breast Cancer: Drugs, Dosing and Duration Kara Laing, MD, FRCPC Chair and Associate

Bone Health in Patients with Breast Cancer

Living Beyond Breast Cancer Bone Metastases Poznak_Bone... · 2019. 4. 24. · Is cancer a disease of self-seeding? Xray Imaging Bone Metastases CT MRI Bone Scan PET-CT scan . Personal

Bone Metastases in Breast Cancer Part 2 of a 5-Part … · bone metastases in patients with multiple myeloma, breast, prostate, lung, kidney, ... Thus, while strontium-89 may palliate

Disseminated Bone Metastasis from breast cancer. · PDF fileDisseminated Bone Metastasis from breast cancer. Lesions in the vertebral ... scan showing no definite evidence of acute

Bone scintigraphy in the monitoring of treatment effect of ...Bone scintigraphy in the monitoring of treatment effect of bisphosphonates in bone metastatic breast cancer L. Chavdarova,

Edinburgh Research Explorer · 2018. 2. 14. · Edinburgh Research Explorer Associations Between Serum Bone Biomarkers in Early Breast Cancer and Development of Bone Metastasis: Results

RESEARCH SYNTHESIS Induced Abortion and Breast Cancerbreast cancer is breast cancer that has metastasized “remote[ly]… ([to the] bone, brain, lung, etc).”4 This rise in breast

The Latest is the Greatest… Future Directions in the ...Background • Metastatic breast cancer • Bone metastases – incidence – consequences • Why does breast cancer go to

The role of IL-1B in breast cancer bone metastasis · REVIEW The role of IL-1B in breast cancer bone metastasis Claudia Tulotta and Penelope Ottewell Department of Oncology and Metabolism,

Bone health after breast cancer

Research Paper Rictor ablation in BMSCs inhibits bone ...Bone is the most common site for breast cancer metastasis [1, 2]. Breast cancers that detach from the primary tumor can enter

Marnie Marie Saunders cv current... · Breast cancer-induced bone metastasis ... of cytosolic calcium, prostaglandin E 2 ... The implant was designed using adaptive bone remodeling

Fresh Natural Bone-In Chicken Breast