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Age Bias in Cancer Care:
Breast Cancer in Older Adults
Meghan Karuturi, MD, MSC
Assistant Professor, Breast Medical Oncology
MD Anderson Cancer Center
Objectives
Understanding the epidemiology of breast cancer and health care disparities in older adult patients
Recognizing issues and outcomes related to screening in older women
Learning about the effect of aging on patients with cancer
Evaluating the older patient with cancer
Understanding differences in treatment pertaining to older women: Lessons from the setting of Early Stage Breast Cancer
Breast Cancer in Older Adults
Understanding the epidemiology of breast
cancer and health care disparities in older
breast cancer patients
The U.S. Population is Aging
Presented By Rachel Freedman at 2017 ASCO Annual Meeting
Epidemiology of Breast Cancer in Older Adults
Age is a major risk
factor for breast cancer
63 y/o is average
age of dx in the US
Women age >/= 65
y/o constitute nearly
half of patients with
breast cancer
Epidemiology of
Breast Cancer in
Older Adults
Epidemiology of Breast Cancer in Older Adults
From 2010-2030, largest growth
in 65+ and 70++ age groups
In 2011, baby boomers started
turning 65
In 2030, largest growth in 80+
age group
Slide 5
Presented By Rachel Freedman at 2017 ASCO Annual Meeting
Epidemiology of Breast Cancer in Older Adults
SEER-Medicare Data 1992-2005, women 67+
Majority had favorable tumor characteristics
80% with stage 0-II disease
82-85% estrogen-receptor positive
70% grade I/II
73% of women 67-69 with ≤ 2 cm tumors (48% of women 90+)
Schonberg et al JCO 2010
Deaths for Women age ≥67 with
breast cancer: Stage Matters
Most common cause of death = cardiovascular disease (2% died from
breast cancer)
Most common cause of death = breast cancer (70%)
Schonberg et al JCO 2010
Tumor Distribution by Age: More HR+
Disease in Older Women
>86% of patients have ER+ disease
Howlander et al JNCI 2014
…Yet Breast Cancer Outcomes for Older
Women are Worse
Why are Outcomes Worse?
Reasons are multifactorial
Under-treatment
Omission of treatment: radiation, endocrine therapy, chemotherapy, targeted therapy
Sometimes appropriate (i.e RCT data support safe omission of RT in select cases)
Often inappropriate
Lower rates of treatment completion
Lower rates of adherence
Higher rates of lower intensity treatment
More toxicity with treatment
more non-guidelines treatment
Variable biology
? Over-treatment in some cases worse-treatment-related outcomes
Our Challenge as clinicians…
How can be optimally treat older patients so that we
maximize survival while accounting for life expectancy,
comorbidity and toxicity of treatments?
Breast Cancer in Older Adults
Recognizing issues and outcomes
related to screening in older women
Brief History of
Mammography
Medicare Covers Biennial
Mammograms
Data from 8 other RCTs
available (non include women
75+)
NIH conference screen 50+
ACS screen 40 in good health
Medicare Covers annual mammograms
USPSTF: screen
women 40+ every 1-2
years
1991 1990s 1997 1998 2002
In 2000, 51% of US women 80+ screened ≤ 2 years
By life expectancy:
10+ years: 62%
5 - <10 years: 53%
<5 years: 39%
2,011 women 80+ followed for a 5 year period
51% were screened (1,034 women)
Benefits: ~1 less women per 1,000 die from breast
cancer who are screened
Harms:
110 false-positive mammograms (19 benign breast
biopsies)
8 refused work-up
8 cases of DCIS
Schonberg et al JCO 2009
Current Guidelines
Breast Cancer Screening in
the Older Patient None of the RCTs included women 75+
For women with < 10 year life expectancy:
Recommend stopping mammography screening
Focus on how harms > benefits
For older women with ≥ 10 year life expectancy:
Elicit women’s values around screening outcomes
Assess whether the woman feels the benefits outweigh
the risks
Walter Schonberg et al JAMA 2014
How do we improve older women’s
decision making around breast cancer
screening?
Life Expectancy
Risk of Disease
Preferences
and Values
Personalized Breast Cancer Screening Decision
Breast Cancer in Older Adults
Learning about the effect of aging on
patients with cancer
Effects of Aging on Older
Adults
Comorbidity increases with Age
Decline in organ reserve with increasing Age
Change in Drug Pharmacokinetics/pharmacodynamics
with aging
Volume of distribution changes in aging as does ability of
liver to metabolize drugs
Renal function decreases with aging
At age 75, the average person,
compared to age 30:
92% of brain weight
84% of basal metabolism
70% kidney filtration rate
43% of maximal breathing capacity
We are not the people we once were!
Breast Cancer in Older Adults
Evaluating the older patient with cancer
The Older Patient: Key questions
Do we need to treat the cancer?
Who will die of their disease vs. with their disease?
If we treat, who is vulnerable to toxicity?
How do we modify therapy based on
Functional status
Cognitive status
Social situation
Treatment Preferences in the
Elderly
I would rather die than take a treatment that causes
Functional impairment = 74%
Cognitive impairment = 88%
Fried et al. NEJM 2002: 346 (14): 1061
Treatment Risk Assessment
Assessment
Fit
Treatment
Vulnerable
Assessment: Life
Expectantly? Toxicity?
Treatment Palliative
Frail
Palliative
Assessment Tools
CGA?
Karnofsky PFS?
ECOG PS?
Other?
Comprehensive Geriatric
Assessment
Who is the patient?
What are the
comorbidities?
What are the risk factors
for chemotherapy
toxicity?
Are the risk factors
modifiable
Perform a
Geriatric
Assessmen
t
Comprehensive Geriatric
Assessment
Functional Status
Comorbid Medical Conditions
Cognition
Nutritional Status
Psychological Status
Social Support
Medications (polypharmacy)
Factors other than chronologic age that predict
morbidity and mortality in older adults
Comprehensive
Geriatric Assessment
(CGA)
Geriatric Assessment in Older Adults
Cancer Patients
Consensus guidelines from both
NCCN and SIOG recommend
routine use of Comprehensive
Geriatric Assessment (CGA) for
the older patients with care
(defined as age 65+)
NCCN guidelines: recommend
routine use of geriatric
assessment of older adults with
cancer (65 y/o +)
Extermann et al Crit Rev Oncol Hematol 2005
Balducci et al. Crit Rev Oncol Hematol 2003
Factors Tools for
Assessment
Other Assessments
Functional
Status
-ADL
-IADL
-PS
Comorbidity -Charleson
Comorbidity Index
-Cumulative Illness
Rating Scale (CIRS-
G)
Socioeconomic
Status
-Living Conditions
-Caregiver presence and
competence
-Income
-Access to Transportation
Nutritional
Status
-Mini-Nutritional
Assessment (MNA)
Polypharmacy -# of Medications
-Drug-drug interaction
Geriatric
Syndromes
-Geriatric
Depression Scale
(GDS)
-Folstein Mini Mental
Status (MMSE)
-Delirium
-Falls
-Osteoporosis;
-Neglect and Abuse
- Failure to thrive
Comprehensive Geriatric Assessment
Evidence based benefits of
using CGA in Cancer patients
Predicting complications/side
effects
Estimating survival
Assisting in treatment
decisions
Diagnosing geriatric
syndromes
Better pain control
Improving pain control
Geriatric Assessment~ Functional Status:
Activities of Daily Living
Basic Self-Care Skills
Dressing
Bathing
Toileting
Transfer
Continence
Eating
Assistance in ADLs predictive of…
Prolonged hospital stay
Worsening of function in the hospital
Greater home care use
Nursing home placement
Death
Functional dependence assocaited with decreased survival—assistance with ≥1 ADLs: average life expectancy to <3 years
Narain et al, JAGS 1988
Geriatric Assessment~ Functional Status:
Instrumental Activities of Daily Living
Higher order function required to maintain independence in the community:
Shopping
Housekeeping
Transportation
Laundry
Telephone
Finances
Medications
Assistance in IADLs..
Understanding need for assistance with IADLs is critical for cancer treatment planning:
Transportation
Medications
Predicts survival in older patient with NSCLC
Balducci et al, The Oncologist 2000
Maione et al, JCO 2005
Breast Cancer in Older Adults
Understanding differences in treatment pertaining to
older women: Lessons from the setting of Early Stage
Breast Cancer
Treatment in Older Adults
with Breast Cancer
Breast cancer in older adults not always managed according to treatment guidelines (Hebert-Cronteau et al. JCO
2004)
Evidence supporting both under- and over-treatment
Women age 75+ receive less aggressive tx and have higher mortality from early-stage breast cancer (Bouchardy C et. Al. JCO 2003; 21: 3580-3587)
Older adults (65 years or older) with breast cancer enrolled in cooperative group trials of adjuvant chemotherapy derive similar benefits (DFS, OS) compared with younger patients, albeit with increased risk of side-effects and treatment–related mortality (Muss et al. N Engl J Med 2009; 360: 2055-2065)
Slide 15
Presented By Rachel Freedman at 2017 ASCO Annual Meeting
Under-representation of Older Adults in
Clinical Trials
Oxford Overview analysis of 15 year results
included too few pts >70 y/o to assess effect of
chemotherapy accurately (EBCTCG Lancet 2005; 365: 1687-
17).
Review of CALGB studies for node-positive
breast demonstrated that only 8% of pts
(542/6487) enrolled in cooperative group trials
were 65 yrs and older, and only 2% (159/6487)
70 yrs and older (Muss et al. N Engl J Med 2009; 360: 2055-2065)
Accrual of Older Patient in Clinical Trials is
Challenging
Hurria et al JCO 2014
Need for New Strategies for Accrual of Older
Patients to Breast Cancer Clinical Trials
Accrual to Alliance Systemic therapy Breast cancer
Trials Over Time by age 65+ and 75+
Surgical Considerations Omission of surgery in HR+ positive breast cancer who
decline surgery/unresectable tumors, short-life expectancy
Cochrane analysis showing endocrine therapy controlled primary lesion in a majority of pts for about 2 yrsConsideration of primary radiation in pts too frail for surgery—treatment assc w/reasonable tumor control, especially in pts w/smaller tumors
Role of sentinel node surgery in clinically negative axillary nodes
Older patients w/early breast cancer and clinically clear axilla treated with conservative surgery, post-op RT and adjuvant tamoxifen do not benefit from axillary dissection
Hind et al., Cochrane Database Syst Rev 1: CD004272, 2006
Van Limbergen E et al Eur J Cancer 1990; Arriagada R et al, Int J Radiol Oncol Biol Phys
1985).
Martelli G et al. Ann Surg 2012 Dec; 256(6): 920-4.
Role of Radiation
In select cases, can omit
radiation in older adults!
Adjuvant Chemotherapy Eligible women achieve reduction in DFS and breast
cancer-related mortality similar to younger women
(Muss et al. JAMA 293: 1073-1081 2005
CALGB 49907 trial (Muss et al J Clin Oncol 25: 3699-
3704, 2007 )
tested for non-inferiority of capecitabine as compared
with standard chemotherapy in women with breast cancer
who were 65 yrs or older
Adjuvant Chemotherapy in
Older Adults
Benefits of Hormonal
therapy in Older Patients Prevents Recurrence
Ipsilateral breast events
Contralateral breast events
Systemic events
Lower Mortality
Except (possibly) in grade 1 tumors ≤10 mm and in those age
60-74 (Christansen et al JNCI 2011)
Provides ability to safely omit local therapy with lower-risk disease
Surgery
Radiation
Trial data shows us that older women benefit as much as their
younger counterparts
Bone Health on Aromatase
Inhibitors
Meta-analysis demonstrated higher odds for fracture
(OR 1.47) for AI vs. tam
Another meta-analysis focused on bone health across
11 RCTs
Fracture rates of 0.9-11%
AI with 1.5 x risk for fracture than tamoxifen or placebo
However, Fracture data and BMD data are not
systemically collected across trials and not stratified by
pre-existing BMD or age
Amer et al JNCI 2011;
Becker T et al JAGS 2012
Poor Adherence to Hormonal therapy
Worse Survival
Survival for those with Stage I-III hormone-receptor
positive breast cancer
Hershman DL et al Breast Cancer Res Treat 2011
MA-17 Discontinuation of
Treatment
Summary for Endocrine Therapy in Early-
Stage Breast Cancer
Almost all older patients with hormone-receptor-positive breast
cancer will benefit from hormonal therapy
And they benefit as much a younger women
Five years of therapy (an not more) is sufficient for most women
with lower-risk tumors.
Optimizing adherence and minimizing toxicity on an individual
basis are critical improvement in disease outcomes
…this means we have to address adherence and treatment
discontinuation in clinic
Address costs, toxicity and barriers to adherence
Interventions to address adherence will be important for this
patient population and will take creativity
Will have to engange Primary care providers so that we can co-
manage these patients and addres toxicity together
Conclusion
Conclusion Assessing an older adult for cancer
Understanding the benefit
Quantifying the risks
A geriatric assessment can help to obtain key information
Decision to take therapy is an individual decision
Supporting the patient through the decision process is
essential
Conclusion
Thanks