Beyond 5 yearsBeyond 5 years

Francis F. Lopez, MDFrancis F. Lopez, MD

Medical OncologyMedical Oncology

Bakit 5 years????Bakit 5 years????

Risk of RecurrenceRisk of Recurrence

10 year over-all survival by stage10 year over-all survival by stage

OutlineOutline

Cancer treatment-induced bone loss Cancer treatment-induced bone loss (CTIBL)(CTIBL)

Overweight and obesityOverweight and obesity Contra-lateral breast cancerContra-lateral breast cancer Cardiac Complications from IrradiationCardiac Complications from Irradiation Neurologic complicationsNeurologic complications

Cancer treatment-Cancer treatment-induced bone lossinduced bone loss

Bone is a dynamic tissue undergoing resorption Bone is a dynamic tissue undergoing resorption and formation throughout life resulting in a net and formation throughout life resulting in a net bone balancebone balance

In osteoporosis, resorption usually exceeds In osteoporosis, resorption usually exceeds formation with the net effect of bone loss, formation with the net effect of bone loss, decreased strength, and an increased risk of decreased strength, and an increased risk of fracturefracture

Cause: hormone depletion promotes Cause: hormone depletion promotes osteoporosis and increases the risk of fractureosteoporosis and increases the risk of fracture

Hormone depletion (hypogonodal) state Hormone depletion (hypogonodal) state induced by cancer therapiesinduced by cancer therapies

Premature menopause resulting from Premature menopause resulting from chemotherapychemotherapy

Deliberate ovarian ablationDeliberate ovarian ablation Hypoestrogenemia secondary to Hypoestrogenemia secondary to

aromatase inhibitors (arimidex, femara aromatase inhibitors (arimidex, femara and aromasin)and aromasin)

Chemotherapy Chemotherapy

chemotherapychemotherapy

Bone loss with chemotherapy extends to Bone loss with chemotherapy extends to postmenopausal women, suggesting that postmenopausal women, suggesting that chemotherapy has a direct effect on bonechemotherapy has a direct effect on bone

• American Journal of medicine 114:653-659, 2003American Journal of medicine 114:653-659, 2003

Aromatase inhibitors (AI)Aromatase inhibitors (AI)

Women treated with AI were 2.5 times Women treated with AI were 2.5 times more likely to suffer a fracture compared more likely to suffer a fracture compared to women treated with tamoxifen to women treated with tamoxifen

Fracture RiskFracture Risk

Following end of treatment fracture rates were similar in both groups

(RR=0.98 (0.81-1.32), p=0.5

J. Cuzick on behalf of ATAC/LATTE Trialists’ Group. Poster presented at 12th Milan Breast Cancer Conference 2010

Major risk factors for osteoporosis Major risk factors for osteoporosis and fractureand fracture

Prior fragility fracture (>40 years of age)Prior fragility fracture (>40 years of age) Age (>65 years)Age (>65 years) Low bone mineral density (T-score < -2.5)Low bone mineral density (T-score < -2.5) Family history of osteoporotic fractureFamily history of osteoporotic fracture Vertebral compression fractureVertebral compression fracture Osteopenia apparent on x-ray filmOsteopenia apparent on x-ray film HypogonadismHypogonadism Early menopause (before age 45)Early menopause (before age 45)

Minor risk factors for osteoporosis Minor risk factors for osteoporosis and fractureand fracture

Rheumatoid arthritisRheumatoid arthritis Low dietary calcium intakeLow dietary calcium intake SmokerSmoker Excessive alcohol intakeExcessive alcohol intake Excessive caffeine intake (>4 cups/day)Excessive caffeine intake (>4 cups/day) Weight (<120 pounds)Weight (<120 pounds) Weight loss > 10% of weight at age 25Weight loss > 10% of weight at age 25

Diagnostic testsDiagnostic tests

Dual energy x-ray absoptiometry (DXA) Dual energy x-ray absoptiometry (DXA) scans at baseline (bone density)scans at baseline (bone density)

Thoracic and lumbar spine x-ray to rule Thoracic and lumbar spine x-ray to rule out vertebral fracture in patients with out vertebral fracture in patients with kyphosis, historical height loss kyphosis, historical height loss >> 6cm, 6cm, acute incapacitating back pain syndrome, acute incapacitating back pain syndrome, and in patients 65 years and olderand in patients 65 years and older

Follow-up: DXA scans every 1-2 yearsFollow-up: DXA scans every 1-2 years

TreatmentTreatment

““bone hygiene” measures: lifestyle bone hygiene” measures: lifestyle modification that promotes bone health:modification that promotes bone health:

Calcium 1000mg per dayCalcium 1000mg per day Vitamin D 800IU per dayVitamin D 800IU per day Smoking cessationSmoking cessation modest alcohol intake (<2 units per day)modest alcohol intake (<2 units per day) Increase exercise activityIncrease exercise activity

Overweight and ObesityOverweight and Obesity

Excuses for Weight GainExcuses for Weight Gain

Masarap kumainMasarap kumain

TamadTamad

BusyBusy

Ideal Body WeightIdeal Body Weight

45.5 kg + 2.3 x (height in inches – 60)45.5 kg + 2.3 x (height in inches – 60) Example: 45.5 + 2.3 x (62 inches – 60)Example: 45.5 + 2.3 x (62 inches – 60) 45.5 + 2.3 x 245.5 + 2.3 x 2 45.5 + 4.6 = 50kg or 110 pounds45.5 + 4.6 = 50kg or 110 pounds Overweight > 121 poundsOverweight > 121 pounds Obese > 132 poundsObese > 132 pounds

Obesity and breast cancerObesity and breast cancer

Poor prognostic characteristics on Poor prognostic characteristics on diagnosis: larger tumor, grade III and more diagnosis: larger tumor, grade III and more positive lymph nodespositive lymph nodes

Poor prognosis: affects over-all survival Poor prognosis: affects over-all survival and disease free survivaland disease free survival

Increased risk of contralateral breast Increased risk of contralateral breast cancer, loco-regional recurrence and other cancer, loco-regional recurrence and other primary cancersprimary cancers

Diet and ExerciseDiet and Exercise

Healthy Lifestyle:Healthy Lifestyle: Five or more servings (dakot o sandok) of Five or more servings (dakot o sandok) of

5 different kinds of fruits and vegetable 5 different kinds of fruits and vegetable (VF) per day(VF) per day

Physical activity (PA): Walking 30 minutes Physical activity (PA): Walking 30 minutes per day 6 days per weekper day 6 days per week

Healthy Lifestyle and MortalityHealthy Lifestyle and Mortality

High VF/high PA: 4.8%High VF/high PA: 4.8% Low VF/high PA: 10.4%Low VF/high PA: 10.4% High VF/low PA: 10.7%High VF/low PA: 10.7% Low VF/low PA: 11.5%Low VF/low PA: 11.5%

10 year survival10 year survival

High VF/high PA = 93%High VF/high PA = 93% Other groups: 86% to 87%Other groups: 86% to 87%

Therefore, gain 6% to 7% absolute risk Therefore, gain 6% to 7% absolute risk reduction in mortality at 10 years high reduction in mortality at 10 years high VF/high PAVF/high PA

Observed in both obese and non-obeseObserved in both obese and non-obese

Contra-lateral Breast Contra-lateral Breast cancercancer

IncidenceIncidence

From 1975 through 2006: From 1975 through 2006: 339,790 diagnosed with (first) breast 339,790 diagnosed with (first) breast

cancercancer 12,886 or 4% developed invasive breast 12,886 or 4% developed invasive breast

cancer in the contra-lateral breastcancer in the contra-lateral breast 40% occurred within the 140% occurred within the 1stst to 4 to 4thth year of the year of the

first breast cancer diagnosisfirst breast cancer diagnosis 30% between the 530% between the 5thth to 9 to 9thth year year 30% 10 years or later30% 10 years or later

Estrogen Receptor in 2Estrogen Receptor in 2ndnd breast breast cancercancer

First ER+ breast cancerFirst ER+ breast cancer 67% were still ER+67% were still ER+

First ER- breast cancerFirst ER- breast cancer 40% were ER+40% were ER+ 43% were ER-43% were ER-

Prophylactic mastectomy (PM)Prophylactic mastectomy (PM) Majority not high risk and 13% were high risk Majority not high risk and 13% were high risk

(gene mutation)(gene mutation)

Low risk group: Contralateral breast cancerLow risk group: Contralateral breast cancer No PM (0.5%)No PM (0.5%) PM 0%PM 0%

Low risk group: Distant metastasisLow risk group: Distant metastasis No PM 7% (2 to 3 years)No PM 7% (2 to 3 years) PM 4%PM 4%

Cardiac Complications from Cardiac Complications from IrradiationIrradiation

Neurologic ComplicationsNeurologic Complications

Irradiation to the left breast: not associated Irradiation to the left breast: not associated with higher risk of cardiac death up to 20 with higher risk of cardiac death up to 20 yearsyears

Cognitive and memory loss (chemo brain) Cognitive and memory loss (chemo brain) resolves a few years after treatmentresolves a few years after treatment

Thank you!