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Breast Cancer and Bone Health. Tracy S. d’Entremont, MD Bryn Mawr Medical Specialists. Bone Homeostasis. Bone is a living tissue which is constantly renewing via a balance of resorption of old bone (via Osteoclasts ) and deposition of new bone (via Osteoblasts ). Osteoporosis.

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breast cancer and bone health

Breast Cancer and Bone Health

Tracy S. d’Entremont, MD

Bryn Mawr Medical Specialists

bone homeostasis
Bone Homeostasis
  • Bone is a living tissue which is constantly renewing via a balance of resorption of old bone (via Osteoclasts) and deposition of new bone (via Osteoblasts).
osteoporosis
Osteoporosis
  • Disruption to this balance can result in weak or brittle bones that are subject to fractures with little to no trauma or stress.
  • Fractures associated with postmenopausal osteoporosis have been associated with increased morbidity and mortality.
  • Aromatase Inhibitor associated bone loss has been demonstrated to occur at twice the rate of normal postmenopausal bone loss.
risk factors of osteoporosis
Risk Factors of Osteoporosis
  • Female
  • Advanced Age
  • White and Asian Ethnicity
  • Family History of Osteoporosis
  • Small Frame
  • Decreased Estrogen Levels
  • Decreased Testosterone Levels
  • Increased Thyroid Hormones
  • Increased Parathyroid Hormones
  • Increased Adrenal Hormones
  • Steroid Use
breast cancer specific risk factors
Breast Cancer Specific Risk Factors
  • Chemotherapy Induced Menopause
  • Aromatase Inhibitor associated decreased Estrogen Levels
  • Ovarian Suppression
    • GnRh Agonists
    • Oophorectomy
lifestyle risk factors
Lifestyle Risk Factors
  • Low Calcium Intake
  • Smoking
  • Sedentary Lifestyle
  • Excessive Alcohol
  • Eating Disorders or Poor Dietary Habits
interpretation of dexa scans
Interpretation of Dexa Scans
  • T-Score:the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as the patient
  • Normal Density: T-score > -1 SD
  • Osteopenia: T-score -2.5 to -1 SD
  • Osteoporosis: T-score < -2.5 SD
who should be scanned
Who Should Be Scanned?
  • All women aged 65 and older regardless of risk factors
  • Younger postmenopausal women with one or more risk factors.
  • Postmenopausal women who present with fractures (to confirm the diagnosis and determine disease severity).
  • Estrogen deficient women at clinical risk for osteoporosis.
  • Individuals receiving, or planning to receive, long-term glucocorticoid (steroid) therapy.
  • Individuals with primary hyperparathyroidism.
  • Individuals being monitored to assess the response or efficacy of an approved osteoporosis drug therapy.
  • Individuals with a history of eating disorders
which breast cancer patients should be scanned
Which Breast Cancer Patients Should be Scanned?
  • All Women Over the Age of 65
  • All Women with Medically Induced Menopause
  • Baseline Prior to Initiation of AI therapy
who fracture risk assessment frax tool
WHO Fracture Risk Assessment (FRAX) Tool
      • http://www.sheffield.ac.uk/FRAX/
  • Retrospective case-controlled study of 400 postmenopausal women with newly diagnosed breast cancer revealed that >28% of women were candidates for bone directed therapy when risk factors were taken into account in addition to BMD; where as BMD alone only identified < 10% at risk patients.

Br J Ca 2010; 102:645-650.

treatments to prevent bone loss
Treatments to Prevent Bone Loss
  • Exercise
    • Weight bearing and Resistence
  • Adequate Calcium Intake (at least 1300 mg/day)
  • Adequate Vitamin D Levels (at least 800 IU/day)
  • Low Caffeine
  • Quit Smoking
  • Maintain Healthy Weight
  • Tamoxifen
  • Raloxifene
  • Bisphosphonates
vitamin d
Vitamin D
  • The Women’s Health Initiative is the largest study looking at supplemental Calcium and Vitamin D use in order to decrease Bone Loss and decrease Fracture Risk.
  • Subgroup analysis has also looked at the incidence of certain cancers in those 36,000 postmenopausal women who took Ca + D supplements.
women s health initiative
Women’s Health Initiative
  • Initial data seemed to be negative:
    • 1306 cancers in the supplemental group
    • 1333 cancers in the placebo group
  • However reevaluation of the data taking into account the number of women who were already taking calcium and Vitamin D supplements at study entry soon revealed that Calcium and Vitamin D does decrease the risk of total, breast and colorectal cancers by roughly 14-20%.

Am J. Clin. Nutr. 2010 Jan; 95(1):258-9

tamoxifen
Tamoxifen
  • Although Tamoxifen has been shown to preserve BMD in postmenopausal women, it has not been shown to do the same in premenopausal women.
  • In at least one population based study in Canada, current use of Tamoxifen in post menopausal women was associated with a decreased incidence in osteoporotic fracture risk.

JCO Nov 10, 2008; 26(32):5227-5232.

raloxifene
Raloxifene
  • SERM approved for the treatment of osteoporosis in postmenopausal women
  • Approved for the prevention of Breast Cancer in High Risk Women or in Women with Osteoporosis
more trial
MORE Trial
  • Greater than 7700 postmenopausal women
  • Randomized to placebo, 60 mg, or 120 mg of Raloxifene for 3 years
  • Results demonstrate BMD of 2-3% increase compared with placebo
  • Decrease Rate of 1st vertebral fracture of 2.4%
  • Decrease Rate of subsequent fractures of 6%

JAMA. 1999; 282:637-645.

slide21

Trials of Antiresorptive Agents for Preventing AIBL in Postmenopausal Women with Breast Cancer

Antiresorptive agent N BMD Dosing Treatment Follow-Up, Mean BMD change from baseline

(trial) study, n duration, years months LS TH

Zoledronate (ZO-FAST) 1065 1065 4 mg i.v. q6mo 5 36 +4.39 +1.9

Zoledronate (Z-FAST) 602 602 4 mg i.v. q6mo 5 61 +6.19 +2.57

Zoledronate (E-ZO-FAST) 527 527 4 mg i.v. q6mo 5 36 +5.98 NR

Zoledronate (N03CC) 558 395 4 mg i.v. q6mo 5 24 +4.94 +1.22

Denosumab (HALT-BC) 252 252 60 mg s.c. q6mo 2 24 +6.2 +3.7

Risedronate (SABRE) 154 111 35 mg p.o./week 2 24 +2.2 +1.8

Risedronate 87 87 35 mg p.o./week 2 24 +0.4 +0.9

Clodronate 61 61 1600 mg p.o./day 3 60 -1.0 -0.1

Risedronate (ARBI) 213 70 35 mg p.o./week 2 24 +5.7 +1.6

Risedronate (IBIS-II) 613 59 35 mg p.o./week 5 12 +0.32 +0.67

Ibandronate (ARIBON) 131 5 150 mg p.o./mo 2 24 +2.98 +0.6

Risedronate 118 11 35 mg p.o./week 1 12 +4.1 +1.8

do bisphosphonates have anti tumor activity as well
Do Bisphosphonates Have Anti-Tumor Activity as Well?
  • European Study looked at 1800 premenopausal women taking goserelin + tamoxifen or goserelin + anastrazole and randomized them to zoledronatevs placebo.
  • The study demonstrated 3.2% absolute decrease in disease progression in the patients treated with bisphosphonate therapy.

NEJM 09; 360:679-691.

zo fast
ZO-FAST
  • ZoledronateFemara Adjuvant Synergy Trial
  • > 1000 Women treated with AI therapy randomized to immediate Bisphosphonate therapy vsbisphosphonates only after a fracture or when the BMD dropped to < -2.0
  • Demonstrated 41% relative risk reduction in disease recurrence in the group treated immediately with zoledronate

Ann Oncol 2010; 21:2188-2194.

long term risks of bisphosphonates
Long Term Risks of Bisphosphonates
  • There have been many case reports in the literature lately to suggest that long term bisphosphonate use is associated with atypical femoral fractures.
  • Fractures usually occur in the subtrochanteric region
  • The theory is that inhibition of osteoclasts may inhibit bone turnover and lead to increased bone deposition by osteoblasts, but is this bone sturdy bone or just dense, brittle bone?
  • Very little data exists to support the use of bisphosphonates beyond 5 yrs
  • The current recommendation is to discontinue use by 5 yrs.
denosumab
Denosumab
  • Monoclonal Antibody to RANK-ligand
  • HALT-BC
    • Hormone Ablation Bone Loss Trial in Breast Cancer
    • 52 Women
    • Denosumab vs. placebo was given prophylactically to prevent AIBL
    • Demonstrated effective increase in BMD by 7.6% in 2 yrs although no change in fracture risk in this small population
    • Larger ABCSGT-18 is Currently Accruing over 3400 women to confirm this data.

JCO 08;26(30): 4875-82