Issues in Cancer Survivorship. Larissa A. Korde, MD, MPH June 26, 2010

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1 Issues in Cancer Survivorship Larissa A. Korde, MD, MPH June 26, 2010

2 Estimated US Cancer Cases in Women: CA Cancer J Clin 2006; 56: ; CA Cancer J Clin 2008;58:71 96.

3 Relative Survival* (%) By Cancer Site US, Site All sites Breast (female) Colon Leukemia Lung and bronchus Melanoma of the skin Non-Hodgkin lymphoma Ovary Pancreas Prostate *5-year relative survival rates based on follow up of patients through Source: Surveillance, Epidemiology, and End Results Program, , Division of Cancer Control and Population Sciences, National Cancer Institute, 2007.

4 Overview Menopausal symptoms Chemotherapy induced menopause Hormonal therapy side effects Hot flashes Musculoskeletal pain (aromatase inhibitors) Bone health

5 Managing Menopausal Symptoms

6 Hot Flashes a feeling of intense heat with sweating and rapid heartbeat, may typically last from two to thirty minutes for each occurrence Affect ~65% of women with breast cancer Therapeutic options Pharmacologic SSRIs/SNRIs: venlafaxine Centrally active agents: clonidine, gapapentin Non Pharmacologic Mind-body approaches Lifestyle modification

7 Hot Flash Management: Pharmacologic SSRI/SNRI Numerous agents evaluated in RCTs Venlafaxine mg qd Sertraline 50 mg qd Caution: Cyp2D6 interaction in women on tamoxifen Centrally active agents Clonidine 0.1 mg qd As effective as venlafaxine in recent trial Gabapentin mg qd Lancet Dec 16;356(9247): Breast J Mar-Apr;12(2): Breast Cancer Res Treat Aug 1. [Epub ahead of print]

8 SSRIs and Tamoxifen Metabolism Jin, Y. et al. J. Natl. Cancer Inst :30-39

9 Hot Flash Management: Non- Pharmacologic Mind-body approaches Hypnosis (JCO published online September 22, 2008) Acupuncture (J Clin Oncol Dec 10;25(35): ) Yoga Promising results Lack of placebo control in many trials Supplements Vitamin E Black cohosh Soy products

10 Hot Flash Management: Lifestyle Modification Hot flash diary: identify triggers Keep body temperature cool: dress in layers use a fan choose cold food and drinks sleep in cool room Regular exercise Avoidance of smoking Avoidance of dietary triggers spicy/hot foods, Caffeine alcohol

11 AI Related Musculoskeletal Complaints Aromatase inhibitors are considered optimal treatment for postmenopausal women with HR+ disease Musculoskeletal symptoms are common in women taking aromatase inhibitors ~30% report myalgias/arthralgias/arthritis Increased risk of carpal tunnel syndrome Associated with obesity, chemotherapy use, prior HRT use Significant number discontinue therapy (~5%) Sestak, SABCS 2008 Abst 2071;Dent SABCS 2008, Abst 2079

12 AI Related Musculoskeletal Complaints Class effect? Comparable rates on different AIs Substantial number of women experience joint/muscle pain on one AI but not another Recommended management Symptomatic/supportive: Tylenol, NSAIDs Drug holiday to document relationship of drug to symptoms Switch from one AI to another? Switch to tamoxifen Renshaw, SABCS 2008, Abst 2072

13 Pilot Study of Acupuncture for AI Related Joint Symptoms 21 participants randomized to immediate or delayed acupuncture Significant reduction in pain scores with acupuncture Crew et al, J Cancer Surviv Dec;1(4):283-91

14 Cancer Therapy Induced Bone Loss Chemotherapy Aromatase inhibitors Oophorectomy Goserelin Estrogen depletion Bioavailable estradiol BMD

15 Estrogen levels 200 Bioavailable E2, pmol/m Premenopausal women Postmenopausal women Normal men Androgen deprivation therapy Khosla S, et al. J Clin Endocrinol Metab. 2001;86:

16 Bone Loss and Fracture Risk 16X Gradient risk for fragility fracture 8X 4X 0.5X 2X 1X Normal Osteopenia Osteoporosis +1.0T 0-1.0T -2.0T -3.0T -4.0T

17 Bone Loss and AIs No patient with normal bone at baseline became osteoporotic after 5 years' treatment with anastrozole Status at baseline Status at 5 years Anastrozole (n=81) Tamoxife n (n=86) Normal bone Normal bone Osteopenic Osteoporotic Not recorded 12 (15%) 14 (17%) 0 6 (7%) 16 (19%) 3 (3%) 0 13 (15%) Osteopenic Normal bone Osteopenic Osteoporotic Not recorded 1 (1%) 21 (26%) 4 (5%) 21 (26%) Annual 3 rates 4 (5%) (%)* (24%) 1 (1%) 2 22 (26%) No. at risk Years Anastrozole Tamoxifen Anastrozole Tamoxifen Time since randomization (years) *Calculated using Kaplan-Meier estimates

18 ABSCG-12 Accrual premenopausal breast cancer patients Endocrine-responsive (ER and/or PgR positive) Stage I and II, < 10 positive nodes No chemotherapy except neoadjuvant Treatment duration: 3 yrs Tamoxifen 20 mg/day Tamoxifen 20 mg/day + Zoledronic acid 4 mg Q6Mos Anastrozole 1 mg/day Surgery (+RT) Goserelin 3.6 mg Q28D Anastrozole 1 mg/day + Zoledronic acid 4 mg Q6Mos Gnant M, et al. ASCO Abstract LBA4.

19 Disease-Free Survival: ZA Vs No ZA No. of Events Hazard ratio (95% CI) events vs no ZA, P Value 30 ZA (0.46 to 0.91), P = No ZA Time since randomization, mos Number at risk No ZA ZA Disease-free survival, % Gnant M, et al. ASCO Abstract LBA4.

20 Summary/Conclusions Hot flashes Related to early menopause Treatable with both pharmacologic and lifestyle interventions AI related musculoskeletal symptoms Change in AI Alternative approaches Bone loss Bisphosphonates Possible favorable effects on disease recurrence

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