Age Bias in Cancer Care

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


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


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



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%)


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?


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


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


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!


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


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


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

Healthcare

Age Bias in Cancer Care