Surviving Breast Cancer

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1 Surviving Breast Cancer What to expect after completing treatment Dexter T. Estrada, MD Hematology Oncology Medical Group of Fresno, Inc. November 3, 2012

2 Epidemiology & Survival Estimates Breast cancer is the most common cancer in women It is the second leading cause of cancer death It is also the main cause of death for women between 40 and 59 years of age Siegel R, Naishadham D, Jemal. Cancer statistics, CA Cancer J Clin. 2012;62(1):10.

3 Epidemiology & Survival Estimates Breast cancer deaths have been declining since 1975 o increased screening through mammography o advances in cancer therapy Younger women (<50) and ER/PR positive cases saw greater declines African Americans still have a higher mortality rate Kohler BA, Ward E, et al. Annual report to the nation on the status of cancer, , featuring tumors of the brain and other nervous system. J Natl Cancer Inst. 2011;103(9):714. American Cancer Society. Breast Cancer Facts & Figures , American Cancer Society, Inc, Atlanta. Jatoi I, et al. Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol. 2007;25(13):1683.

4 Epidemiology & Survival Estimates From 1975 to 1977, 75.1% of women with breast CA survived 5 years From 2001 to 2007, this had increased to 90% o 98.6% local disease o 83.8% regional disease o 23.3% distant metastasis Siegel R, Naishadham D, Jemal. Cancer statistics, CA Cancer J Clin. 2012;62(1):10.

5 Breast Cancer 5-year Survival

6 Cancer treatment and survivorship statistics, 2012 CA: A Cancer Journal for CliniciansVolume 62, Issue 4, pages , 14 JUN 2012 DOI: /caac.21149http://onlinelibrary.wiley.com/doi/ /caac.21149/full#fig1

7 Surveillance Guidelines

8 Surveillance Guidelines

9 Managing the adverse effects of treatment

10 Cardiotoxicity Vascular conditions o atherosclerosis o thrombosis o hypertension Cardiac structural problems o valvular degeneration o pericardial disease Cardiac dysfunction o heart failure

11 Cardiotoxicity - vascular Atherosclerosis and subsequent thrombotic complications occur esp with left chest wall irradiation. Optimal management includes: o Aspirin o statin-based lipid therapy o in select patients, additional antiplatelet therapy i.e. clopidogrel

12 Cardiotoxicity - vascular Hypertension can arise from antiangiogenic therapy i.e. bevacizumab o ACE-I, B-blockers, ARBs ideal for heart failure prevention Thrombosis may be prevented by removing unused catheters

13 Cardiotoxicity - structural Valvular degeneration and pericardial disease are not common in breast cancer survivors unless there is significant mediastinal or cardiac exposure to radiation

14 Cardiotoxicity - functional Classical offending agents are the anthracyclines: doxorubicin, epirubicin, mitoxantrone Trastuzumab also causes dysfunction

15 Cardiotoxicity - functional May occur at anthracycline doses <450 mg/msq, and possibly irreversible if not treated early Early detection with: o 2-d echocardiogram/muga o biomarkers: troponin, BNP, cytochrome C, micro RNAs

16 Cardiotoxicity - functional Early treatment for subclinical HF may improve LVEF o ACE-I o B-blocker o aspirin o statin therapy o sodium restriction o regular exercise o weight control

17 Bone health Bone remodelling is a dynamic process This is mediated by receptor activatorkappa B ligand (RANKL) and Osteoprotegerin. Other factors include: o parathyroid hormone o insulin-like growth factor 1 o proinflammatory cytokines

18 Bone health

19 Bone health

20 Bone health

21 Bone health Chemotherapy induced ovarian failure (CIOF) highest with the ff: o alkylating agents - cyclophosphamide o platinum agents o anthracyclines o taxanes CIOF also increases with age esp with diminished ovarian reserve, reduced number and quality of follicles

22 Bone health Tamoxifen causes a small amount of bone loss in premenopausal women, preserves bone in postmenopausal women All aromatase inhibitors (letrozole, anastrozole, exemestane) are associated with increased risk of bone loss and fractures.

23 Bone health

24 Bone health

25 Bone health FRAX = WHO Fracture Assessment Tool o clinical aid to assess 10-year individual osteoporotic fracture risk with or without BMD o optimized for postmenopausal women and man over 50 who have not been treated for bone loss o may underestimate risk in AI use

26 Bone health

27 Bone health Pharmacologic agents for osteoporosis: bisphosphonates PO or IV denosumab SERMS: tamoxifen, raloxifene teriparatide

28 Bone health PO bisphosphonate inhibits osteoclast-mediated bone resorption alendronate, risedronate, ibandronate causes esophagitis efficacy demonstrated in small trials but compliance low compared to IV forms

29 Bone health IV bisphosphonate inhibits osteoclast-mediated bone resorption zoledronic acid, pamidronate causes fevers, arthralgias, renal insufficiency, osteonecrosis screening dental exam and major dental work should be done before initiation

30 Bone health Denosumab human monoclonal antibody against RANKL blocking osteoclast formation and activation higher incidence of hypocalcemia but fewer infusion reaction and renal insufficiency, similar ONJ risk screening dental exam and major dental work should be done before initiation

31 Bone health Teriparatide recombinant parathyroid hormone approved for postmenopausal osteoporosis generally not used in the cancer population esp with some cancers having PTH receptors - theoretical risk of stimulating cancer growth

32 Preserving fertility chemotherapy induced ovarian failure increases with age strategies for fertility preservation include egg banking prior to start of cytotoxic chemotherapy

33 Secondary malignancies Hematologic malignancies including treatment related myelodysplastic syndrome, leukemia, or lymphoproliferative disease may develop Increased risk for second breast malignancy or other solid tumors

34 Survivorship care plans Advocated by the Institute of Medicine and professional organizations including the American Society for Clinical Oncology Survivorship clinic may be one way to address this

BREAST CANCER AND BONE HEALTH

BREAST CANCER AND BONE HEALTH Rowena Ridout, MD, FRCPC Toronto Western Hospital Osteoporosis Program University Health Network / Mount Sinai Hospital rowena.ridout@uhn.ca None to declare Conflicts of Interest