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.

Years

peak bone mass

Puberty

1,2

1,1

1,0

0,9

0,8

0

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

-

-

-

-

-

LS

-BM

D (

g/m

2)

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

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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

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Prevention of therapy-induced osteoporosis

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

11.11.20179 Ellis et al, JCO 2008


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Prevention of therapy-induced osteoporosis

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

11.11.201710 Gnant et al, Lancet 2015


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Prevention of therapy-induced bone loss

11.11.201711 Hadji et al, 2017


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Prevention of therapy-induced bone loss

11.11.201712 Hadji et al, 2017


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Bone-directed therapy in breast cancer patients

11.11.201713

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


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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


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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.


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Zoledronic acid in EBC patients with DTCs

11.11.201716 Banys et al, BMC Cancer 2013


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

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


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EBCTCG metaanalysis for adjuvant bisphosphonates

11.11.201718 EBCTCG, Lancet 2015


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Recommendations of European Experts (2016): Bisphosphonates in EBC

11.11.201719 Hadji et al, Annals of Oncology, 2016


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Bisphosphonates in EBC: Who benefits?

11.11.201720 Hadji et al, Annals of Oncology, 2016


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Bone stabilizing agents in EBC: Denosumab

11.11.201721 Gnant et al, SABCS 2015


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11.11.201722 Gnant et al, SABCS 2015


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11.11.201723 Gnant et al, SABCS 2015


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Bone health in cancer patients: ESMO guidelines

11.11.201724 Coleman et al, Annals of Oncology 2014


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11.11.201725 Coleman et al, Annals of Oncology 2014

Zometa®

Xgeva®

Bondronat®

Prolia®


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11.11.201726 Annals of Oncology 26 (supp 5), 2015


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11.11.201727

Bone health in EBC: EMA approvals for denosumab


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11.11.201728

HALT: hormone ablation therapy

Bone health in EBC: EMA approvals for denosumab


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Bone modifying agents in breast cancer

11.11.201729 Sukhbinder et al, 2017


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11.11.201730


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✓ 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



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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...

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