Breast Cancer Survivorship

Transcription

1 Breast Cancer Survivorship Melissa Accordino, MD Assistant Professor of Medicine Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

2 Who are the Cancer Survivors? More than 1 in 3 Americans will be diagnosed with cancer in their lifetime 15.5 million Americans have a personal history of cancer; >4% of the US population More than 28 million survivors worldwide

3 Cancer Survivorship Facts Prevalence will increase sharply during the next 25 years with aging of the population 60% of survivors are over the age of 65 Breast, Prostate, and Colorectal are the 3 most prevalent cancer sites Approximately 14% of survivors were diagnosed 20 years ago

4 Estimated and Projected # of Survivors by Year Since Diagnosis in the US Source: de Moor JS, et al. CEBP Annual Report 2013;22:

5 Estimated Number of Survivors by Cancer Site in the US (2012) Source: de Moor JS, et al. CEBP Annual Report 2013;22:

6 No Clear Consensus on Survivor Definition How do you define a cancer survivor (n=144) Disease-free after 5 years Disease-free after 2-3 years From the moment of diagnosis and for the balance of life Not sure Following completion of active treatment From diagnosis to recurrence Source: P De Fusco, et al. SABCS 2007, ASCO 2009

7 Definition of a Cancer Survivor From time of diagnosis, through the balance of his or her life NCCN Anyone with a history of cancer, from the time of diagnosis and for the remainder of life, whether that is days or decades. National Coalition for Cancer Survivorship

8 What Has Led to our Success? Earlier detection Novel treatments Combined modality therapy Prolonged adjuvant and/or maintenance therapies Prevention of second malignancies

9 For Many Patients, Cancer is now a Chronic Disease

10 The Effects of Cancer and Its Treatment Physical and/or psychosocial Effects Long-term effects Late effects Range in severity Some improve over time, while others progress or become permanent

11 Health Status Significantly Poorer in Cancer Survivors Cancer Survivors (n=1,817) Non-cancer Controls (n=1,817) Excellent Very Good Good Fair Poor Excellent Very Good Good Fair Poor 31% Fair & Poor 18% Fair & Poor Source: Yabroff KR, et al. JNCI 2004;96:

12 % of patients with lost productivity Loss of Productivity Significantly Poorer in Cancer Survivors Breast Cancer Survivors (n=301) Matched Controls (n=1,479) * * * * * p< Held job in past 12 months Unable to work due to health problems Limited in amount of work due to health Lost days from work in past 12 months (mean) Source: Yabroff KR, et al. JNCI 2004;96:

13 IOM Findings: Survivorship Care Survivorship care is a neglected phase of the cancer care trajectory Recurrence, second cancers, and treatment late effects concern survivors Few guidelines on follow-up care Providers lack education and training

14 IOM Findings: Survivorship Care Survivors may: Be unaware of risk Have no plan for follow-up Opportunities to intervene may be missed Care is often not coordinated Models of survivorship care not tested

15 Why is Cancer Different from other Chronic Diseases? Cancer treatment is Complex Multi-modal Multi-disciplinary Toxic Expensive Often poorly coordinated Cancer treatment usually occurs in isolation from primary health care delivery

16 Other Challenges Limited systematic study of the late effects of cancer therapy Follow-up care plans have been ad hoc, with focus on surveillance for recurrence When should health promotion and chronic disease prevention become the focus? Infertility?

17 What is Needed to Implement the Survivorship Care Plan? Acceptance of cancer as a chronic disease following an initial period of extraordinarily complex therapy Staff support for time required to prepare and communicate the plan Expand the evidence-base of knowledge re: late effects, follow-up needs, and survivorship care Train all health professions in the needs of the growing number of cancer survivors how to act on the care plan recommendations

18 Survivorship Care Plans: A model for Integration of QOL & QOC Quality of Life Quality of Care

19 Breast Cancer as a Model for Study of Late & Long-term Effects Most common cancer in women Occurs across the lifespan Complex treatments, high rates of cure Treatment affects menopausal status and endocrine milieu of the woman Potential for substantial impact on physical and emotional health

20 Surveillance Testing after Breast Cancer Breast cancer adjuvant clinical trials abandoned routine monitoring with chest, liver, and bone imaging in the 1990s recurrence detection rare before clinical symptoms Two randomized trials conducted in the 1990s did not find a difference in survival outcomes in women who had routine clinical visits and mammograms compared to women with more intensive surveillance including blood work, chest films, scans, and ultrasounds Sources: ASCO Guidelines 2006, 2013 Rojas et al. Cohrane Review 2005

21 Tumor Marker Surveillance after Breast Cancer No RCT data to support use of tumor markers for breast cancer monitoring (CEA, CA 15-3, CA 27.29) for effect on survival outcome, i.e. that detection of recurrence earlier makes a difference The rate of false negative or false findings for these markers are not known Normal or abnormal tumor marker results can contribute to false reassurance and/or increased anxiety for patients, as well as unnecessary medical evaluations

22 Source: Schnipper LE, et al. JCO 2012;30:

23 Surveillance Testing Utilization Women with early stage breast cancer diagnosed (n=258) at an academic medical center % of sample who received at least one % for pure surveillance testing 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Source: Han EE, et al. Cancer 2013;15:

24 % Increased Costs of Care Surveillance Testing Utilization Women 65 with locoregional breast cancer diagnosed (n=39,650) using SEER-Medicare Tumor Marker Use Costs of Care Increased in Patients who had TMs 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 35% * Months 3-12 after Diagnosis * 28% Months after diagnosis * p<0.001 Source: Ramsey SD, et al. JCO 2015;32:149-55

25 Common Survivorship Care Concerns Pain Fatigue Depression Physical limitations Cognitive changes Lymphedema Sexual dysfunction Menopause related symptoms Body Image / Weight Gain Secondary cancers Late effects of therapy Osteoporosis, cardiac, infertility

26 Cancer-related Fatigue Most common side effect of cancer and its treatment Occurs in 60-96% of patients during treatment (Wagner & Cella, 2004) Fatigue may persist for months or years after successful treatment completion 30% of breast cancer survivors report fatigue 1-5 years post-diagnosis (Bower et al.;2000) 63% of fatigued survivors continue to report fatigue 5-10 years post-diagnosis (Bower et al., 2006)

27 Cancer-related Fatigue Different than normal fatigue due to lack of sleep or overexertion More pervasive, debilitating, longer-lasting Involves physical, mental, and emotional components Not relieved by adequate sleep or rest Fatigue occurs across different types of cancer and different types of cancer treatment Mechanisms underlying cancer-related fatigue have not been determined

28 What Causes Fatigue? Comorbid medical conditions Cardiovascular disease BMI Comorbid symptoms Pain Menopausal sx Sleep disturbance Biological factors Anemia Inflammation Fatigue Health behaviors Physical activity Demographic factors Age Income Marital status Psychosocial factors Depression Catastrophizing coping style

29 Cognitive Complaints Self-reported complaints don t always match performance on neurophysiological (NP) testing Tests of memory, attention, reasoning, visual-spatial abilities Some studies document impairment on NP tests in cancer patients that pre-exist cancer treatment 20-30% of breast cancer patients Biology of cancer (e.g. inflammation related)? Common risk factors for both cancer and cognitive impairment (e.g. poor DNA repair mechanisms?) True incidence of cognitive decline is uncertain Estimates range from 15-25%; some percentages as high as 61%

30 Risk Factors Age Cognitive reserve or vulnerability Age and medication Genetic predisposition/ vulnerability to chemotherapy or cognitive impairment: APOE, COMPT Poor DNA repair Menopause Hormone therapy Anxiety/Depression Supportive Care meds Comorbid medical conditions Surgery and anesthesia Sleep disturbance

31 Candidate Mechanisms for Cognitive and Brain Changes Blood-brain barrier integrity Genetic susceptibility Changes in cognition, and brain structure and function DNA damage and telomere length Estrogen or testosterone reduction Cytokine deregulation Source: Ahles and Saykin Nature Reviews Cancer 2007;7:

32 The Effect of Modafinil on Cognitive Function in Breast Cancer Survivors Open label cancer survivors >30 days post chemo and/or RT with fatigue (n=76) those with improvement after 4 weeks (n=68) randomized to Modafinil vs. Placebo x 4 weeks Open label portion significant effect on: Speed of memory (p=0.007) Quality of episodic memory (p<0.0001) After randomization, relative to placebo, improvement of: Speed of memory (p=0.03) Quality of episodic memory (p=0.02) Mean continuity of attention (p=0.02) Source: Kohil S, et al. Cancer 2009;115:

33 Patient Factors and Interaction with Treatment & Survivorship Outcomes Effects of tobacco use on drug metabolism and treatment efficacy Weight and weight gain and its effect on treatment efficacy, comorbid conditions, and survivorship outcomes Physical activity influence on survival and other outcomes Concomitant medications and their effects on outcomes, e.g. metformin, aspirin, statins Comorbid conditions, e.g., hypertension or DM, and their effect on outcomes

34 Obesity at Diagnosis Associated with Inferior Outcomes in HR+ Breast Cancer (E1199) N=4,770 node positive & high risk node negative Br CA patients who received AC, taxanes, and hormonal treatment. Median age 49, 37% obese DFS for obesity (HR positive/her-2 negative/unknown Multivariable analysis HR 1.24 p=0.008 Source: Sparano JA, Cancer 2012;118:

35 Obesity at Diagnosis Associated with Inferior Outcomes in HR+ Breast Cancer (E1199) N=4,770 node positive & high risk node negative Br CA patients who received AC, taxanes, and hormonal treatment. Median age 49, 37% obese OS for obesity (HR positive/her-2 negative/unknown Multivariable analysis HR 1.37 p=0.002 Source: Sparano JA, Cancer 2012;118:

36 Lifestyle Modifications & Br CA Prognosis Observational studies suggest: Higher physical activity may improve survival High fruit/veg and low fat diet may improve survival Higher BMI is associated with poorer outcomes Clinical trials suggest: High fruit/veg and low fat diet may improve survival in ER- Br CA (WINS) Potential mechanisms include insulin-igf-1 axis, inflammatory pathways, and hormonal pathways Chlebowski JCO 2002, Holmes JAMA 2005, Pierce JCO 2007, Chlebowski JNCI 2006

37 Physical Activity & Mortality After BC Diagnosis Nurses Health Study (n=2,987) MET-hrs/wk RR (95% CI)* <3 Ref ( ) ( ) ( ) ( ) *Adjusted for age, time since diagnosis, smoking, BMI, menopausal status, HRT use, age at 1 st birth, parity, OC use, energy intake, stage, treatment Source: Holmes MD, et al. JAMA 2005;293:

38 Diet, Physical Activity and Survival Women s Healthy Eating and Living (WHEL) Study (n=1,490) Source: Pierce JP, et al. JCO 2007;25:

39 Women s Intervention Nutrition Study (WINS) (n=2,437) ER+ subjects ER- subjects Chlebowski JNCI 2006

40 HR Insulin and Breast Cancer Prognosis Death p=0.001 Distant Recurrence p= < > 51.9 Insulin Quartiles (pmol/l) Source: Goodwin PJ, et al. JCO 2002;20:42-51

41 SUMMARY Increasing number of cancer survivors Breast, Prostate, and Colon = 50% Successes in outcome have come at a cost: Financial Physical Functional Psychological Much research to be done!

42 THANK YOU