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Cancer Survivorship Challenges and Opportunities
1. Learning Objectives
1. Define cancer survivorship goals.
2. Learn the general biomarkers cancer patients should have
monitored
3. How do cancer survivors become active participants in
maintaining wellness?
4. What are the major nutritional goals for survivors of cancer?
3. Cancer Survivor Facts
• 60% of survivors are currently over the age 65
years.
• Breast, Prostate, and colorectal, are the 3 most
prevalent cancer sites.
• Approximately 14% of the 11.1 million
estimated cancer survivors were diagnosed over
20 years ago.
• Average age of male and female cancer
survivors is 69 and 64 respectively.
4. Trends in Five-year Related Survival (%)* Rates, US, 1975-2003
Site 1975-1977 1984-1986 1996-2003
All sites 50 54 66
Breast (female) 75 79 89
Colon 51 59 65
Leukemia 35 42 50
Lung and bronchus 13 13 16
Melanoma 82 87 92
Non-Hodgkin lymphoma 48 53 64
Ovary 37 40 45
Pancreas 2 3 5
Prostate 69 76 99
Rectum 49 57 66
Urinary Bladder 74 58 81
*5-year relative survival rates based on follow up of patients through 2004.
Source: Surveillance, Epidemiology, and End Results Program, 1975-2004, Division of Cancer Control and
Population Sciences, National Cancer Institute, 2007
5. CURE VS. HEALING
• Cure: (curarae) – To set right on a physical level
• Healing: (haelen) – To restore to wholeness
“I will keep pure and holy both my life and my
art.”—Hippocratic oath
6. IOM Study:
Survivorship Care
• Survivorship care is a neglected phase of
cancer care
• Cancer recurrence, second cancers, and
treatment late effects concern survivors
• Few guidelines on follow-up care
• Primary care M.D.s lack survivorship
education and training
7. GAYNOR INTEGRATIVE ONCOLOGY:
Treatment + Healing=Care
• Patients given cancer therapeutic options as well as
late effects of cancer treatments, with expected time
course
• Plan for what needs to be done in the future
(screening, delayed Rx effects)
• Comprehensive plan for healthy lifestyle to prevent
recurrence and reduce the risk of other comorbid
conditions. Includes nutrition, exercise and
psychospiritual support
8. Burden of Illness in Cancer Survivors: Findings From a Population-
Based National Sample
K Robin Yabroff, William F. Lawrence, Steven Clauser, William W. Davis,
Martin L. Brown
• Comparison of cancer survivors and age-matched
individuals from the national Health Interview Survey
(NHIS) in 2000
• Health status significantly poorer in cancer survivors
• Required more help with activities of daily living.
JNCI 96:1322,2004
9. Stress and Cancer
Prostate Cancer and Distress
- 3 U.S. cancer centers
- 263 patient/spouse dyads
- Functional Assessment of Cancer Therapy (FACT)
- More advanced cancer – more distress
- Patients and spouses equally affected
- Recurrence = worse emotional QOL
Northouse,2007
Journal of Clinical Oncology, Vol 25, No 27 (September 20), 2007: pp.
4171-4177
10. Meditation and Cancer Patients
Meta-analysis
- 3RC trials, 7 uncontrolled trials
- Positive results
- Mood, sleep quality, subjective stress reduction
- Dose-response effect observed
Smith 2005
Smith, Joanna E. and Richardson, Janet and Hoffman, Caroline and Pilkington, Karen (2005)
Mindfulness-based stress reduction as supportive therapy in cancer care: systematic review.
Journal of Advanced Nursing, 52 (3). pp. 315-327.
11. Yoga and Stress
Study Evaluated:
- N = 39 lymphoma patients
- Tibetan yoga (TY) (7 wkly sessions)
- Wait list control
- Patients in TY group
- Better subjective sleep quality (P<0.02)
- Longer sleep duration (P<0.03)
- Less use of sleep medications (P<0.02)
Cohen 2004
Alternative and Complementary Therapies. August 2004, 10(4): 235-236.
12. Imagery
• A technique of using the imagine to visualize a
soothing, pleasant image.
• Benefits include: decreased physical tension,
anxiety, and the adverse effects of
chemotherapy.
13. Exercise
• Currently nearly 10 million cancer
survivors in the U.S.
• Numerous studies suggest that exercise
has a positive effect on quality of life
following a cancer disgnosis.
(Courneya & Friedenriech, 1999: Dimeo et al., 1999)
14. • Suffering occurs when there is a
resistance reaction to a perceived
threat to the integrity or existence of
the person.
• Pain is part of the human life.
SUFFERING VS. PAIN
16. Music in Oncology Patients
• Music alleviates anxiety in patients receiving
RT (Smith,et.al. Nurs Forum 28:855-862. 2001)
• Reduces anxiety mood disorders in pediatric
patients (Barrera<M. et.al. Psychooncology
11:379-388, 2002)
• QOL indices improved in terminal cancer
patients (Hilliard,R. J.Music Ther 40:113-
137,2003)
17. Sound Therapy
Sound therapy is the systematic, scientific, and creative
application of sound and chanting to achieve a sense of
harmony and inner peace. Sound therapy is an integrative
wellness practice similar to yoga and meditation. As a holistic
treatment approach, sound therapy focuses on the well being
of the entire person, not just the part which is diseased.
18. SPIRITUALITY AND DEPRESSION
• Most studies show that there is an inverse
relationship between religious observance and
severity of depression (85% of studies)
• Intrinsic religious faith is associated with lower
levels of depressive symptoms.
• Private religious behaviors (prayer and meditation)
inversely associated with depression. (Koenig, 1997)
19. K-ras, Oncotype DX, CYP2D6
By increasing efficacy and screening out
patients who likely will not respond to a
particular drug, biomarkers improve patient
care and the treatment of cancer, while
reducing costs associated with unnecessary
less effective therapies.
20.
21. OncotypeDx Predictive Biomarker
Therapeutically Relevant Gene Expression
Signature
• <10% of node negative ER+ breast cancer
patients require or benefit from the cytotoxic
chemotherapy that they receive
• Identify patients with node negative ER+
breast cancer who have low risk of recurrence
on tamoxifen alone
23. • Thiopurines – TPMT
• Irinotecan – UGT1A1
• Warfarin – CYP2C9 and VKORC1
• Tamoxifen – CYP2D6
Biomarkers of Drug Metabolism may also be
predictive of responders
25. Jin et al., J. Natl. Cancer Inst. 97:20-39, 2005.
Tamoxifen Biotransformation
26. Relapse–Free Survival, % Disease–Free Survival
Tamoxifen Pharmacogenomics
Goetz et al., Breast Cancer Res. Treat. 101:113-121, 2007.
Breast Cancer (190 Patients)
28. Fasting Insulin and Outcome in Early-Stage Breast
Cancer: Results of a Prospective Cohort Study
Purpose: Insulin, a member of a family of growth
factors that includes insulin-like growth factor (IGF)-I and
IGF-II, exerts mitogenic effects on normal and malignant
breast epithelial cells, acting via insulin and IGF-I receptors.
Because of this and because of its recognized association
with obesity, an adverse prognostic factor in breast cancer,
we examined the prognostic associations of insulin in early-
stage breast cancer.
J Clin Oncol 20(1):42-51, January 1, 2002
29. Fasting Insulin and Outcome in Early-Stage Breast
Cancer: Results of a Prospective Cohort Study
High levels of fasting insulin identify women
with poor outcomes in whom more effective
treatment strategies should be explored.
J Clin Oncol 20(1);42-51, January 1, 2002
30. I G F-1 Biomarkers
• similar in structure to insulin.
• regulated by growth hormone.
• Levels of growth hormone and IGF-1 decline as men and women age.
• this decrease is believed to be linked to health problems associated with
old age.
• 633 men, aged 50 and older.
• IGF-1 levels were measured between 1988 and 1991.
• 18 years of follow-up, men whose IGF-1levels were above 100 nanograms
per milliliter at the start of the study twice a likely to die of cancer as
those with lower levels.
• The increased risk of cancer death for older men with high
levels of IGF-1 was not explained by differences in age, body size,
lifestyle or cancer history.
March 2010, Journal of Clinical Endocrinology & Metabolism
31. FRENCH LILAC
Gallega officianalis
• Metformin—A new targeted therapy for
cancer treatment and prevention?
• Diabetics on metformin-40% less cancer
overall, 56% less breast cancer, 62% less
pancreatic cancer
• Suppresses EGFR 2 (her2neu)
• 3 fold increased path CR rate in neoadjuvant
chemo
• Induces apoptosis in pancreatic cancer
32. DETOXIFYING ENZYMES and BREAST
CANCER
• JOHNS HOPKINS UNIVERSITY STUDY
– Compared genetic detoxifying enzyme ability of
110 patients with breast cancer vs. 113 controls
– Abnormal glutathione-S-transferase genes causing
decreased enzyme activity resulted in a fourfold
increased risk of breast cancer
(Helzlsouer, K. et al., J. Nat. Can. Inst. 1998)
33. VITAMIN D AND BREAST CANCER
Garland,Cedric et al.(UCSD) AACR 2006
Meta-analysis 1,760 women- 25-OH Vit. D levels
Multiple regression analysis: D3 level>52ng/ml assoc
with 50% lower risk breast CA compared with
levels<12 ng/ml.
Previous study (Prev Med 1990:19:614-22):
Demonstrated women living closer to the equator,
had significantly lower risk of breast cancer death
34. Deficiency of Vitamin D, a Membrane Bound
Antioxidant, Linked to Poorer outcome in Breast
Cancer
• Vitamin D receptors found in breast cancer cell nuclei
• Effects: slow cell growth, induces apoptosois and
differentiation
• 37.5% had levels < 50 (deficient), 38% 50-
72(insufficient), 24%>72(sufficient)
• Median f/u 512 women 11.6 years-Deficient patents
94% >chance mets and 73%.chance of death than
patients with levels over 50.
• Goodwin,P. et. al ASCO 2008 abst. 511
36. Inherited Breast / Ovarian Cancer
BRCA1 or 2 Mutation
Future of Predictive Genomics
• Women have an 82% lifetime risk of breast or ovarian cancer
• Risk has increased since 1940
• Risk of breast cancer 24% if born before 1940 but
67% if born after 1940
• Risk of ovarian cancer was twice as high for BRCA1
carriers and 23% higher for BRCA2 carriers if born
after 1940
King et.al Science 24 October 2003 Vol.302 P 643-646
37. Soy and Breast Cancer
•
Soy Food Intake and Breast Cancer Survival Xiao Ou Shu, MD, PhD; Ying Zheng, MD, MSc; Hui
Cai, MD, PhD; Kai Gu, MD; Zhi Chen, MD, PhD; Wei Zheng, MD, PhD; Wei Lu, MD, PhD
• JAMA. 2009;302(22):2437-2443.
• Context Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of
breast cancer. However, the estrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concern
about soy food consumption among breast cancer patients.
• Objective To evaluate the association of soy food intake after diagnosis of breast cancer with total mortality and cancer recurrence.
• Design, Setting, and Participants The Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5042 female breast cancer
survivors in China. Women aged 20 to 75 years with diagnoses between March 2002 and April 2006 were recruited and followed up through June
2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected at
approximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews conducted at 18, 36, and 60 months after diagnosis.
Annual record linkage with the Shanghai Vital Statistics Registry database was carried out to obtain survival information for participants who were
lost to follow-up. Medical charts were reviewed to verify disease and treatment information.
• Results During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer–related deaths were
documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was
inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95%
confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The
multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in
the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor–positive or –
negative breast cancer and was present in both users and nonusers of tamoxifen.
• Conclusion Among women with breast cancer, soy food consumption was
significantly associated with decreased risk of death and recurrence
38. Nurses Health Study
• Women who take Aspirin regularly following a breast
cancer diagnosis cut their risk of death and metastasis
by nearly 50%.
• “aspirin has relatively benign adverse effects compared
with cancer chemotherapeutic drugs and may also
prevent colon cancer, cardiovascular disease, and
stroke”
• Appears to affect estrogen receptor–positive and –
negative tumors.
• (J. Clin. Oncol. October 2010)
39. SOY ISOFLAVONES AND BREAST
PROLIFERATION
• Palomares,M San Antonio Breast Cancer Symposium(2005)
(Poster)
• 23 postmenopausal breast cancer (Stage I, II, DCIS) patients at
City of Hope National Medical Center
• Randomized:Isoflavone tab 100mg/d vs.placebo for 1 year
• Bx contralat. breast at 0, 6, and 12 mo:Ki67 index decreased
from baseline in Rx group by 3.1% vs.0.9% control (6 mo.) and
4.9% vs.4.1% (12 mo.) “Our findings suggest no negative
effects of soy and perhaps even a beneficial effect”
40.
41. Obesity /Survival /Ovarian Cancer
-Pavelka et al., Cancer (Published Online): 28 August 2006
●Evaluated association of of excess body weight on
ovarian cancer survival
●For patients with advanced stage disease, obesity was
independently associated with both shorter time to
recurrence and shorter overall survival. Findings suggest
adverse effect of excess body weight on tumor biology.
42. HE4 for Recurrence of Ovarian Cancer
• FDA approved 2010
• Slightly higher sensitivity and specificity than
CA 125
• 75% PTS. W/NO CHANGE— CORRELATED
W/NO PROGRESSION OF DISEASE
• 60% W/+ CHANGE—CORRELATED WITH
DISEASE PROGRESSION
43. Green Tea and Prostate Cancer
• Bertuzzi,S AACR 2005(abstract)
• 30 men with high grade PIN
• Randomized Control vs 600 mg/d green tea catechins
• Bx done at 0 and 12 mo
• 9 cases prostate CA control and 1 in Rx group at 1
year
• The 30% incidence at 1 year is c/w literature
• No adverse effects in Rx group
