Older Breast Cancer Patients: Risk for Cognitive Decline

Cancer is the leading cause of death in the US and breast cancer is the second most common
cancer among women in our country. Older women (women 60 and older) presently account for
nearly half of all new cases of breast cancer. With the "graying of America" and advances in
treatment for breast cancer, the absolute number of older women undergoing breast cancer
treatment and surviving their disease will almost double by the year 2030. Systemic hormonal
and non-hormonal chemotherapy is credited with improvements in survival, and rates of use of
these modalities have increased substantially over the past two decades. Preliminary work has
found that older women are interested in chemotherapy even for small returns in survival
extension. However, cognitive impairment has been demonstrated in most studies of breast
cancer systemic treatments, but virtually all of this research has been conducted in younger
populations. Since aging itself is associated with cognitive declines, it seems very likely
that older women are particularly vulnerable to the adverse cognitive effects of systemic
therapy; our preliminary work strongly suggests that this is the case, but this has never
been empirically tested.

This study will be the first large-scale, prospective, controlled investigation to evaluate
cognitive changes in older cancer patients and it will provide the basis for the next
generation of mechanistic, treatment and intervention studies. These will be important since
data from younger patients cannot be directly translated into the older population.
Investigators will use the vulnerability model of cancer survivorship to prospectively
describe the magnitude of systemic therapy effects on cognition in older (age >60 years)
breast cancer patients over a 60 month period, test associations between cognition and
quality of life (QOL) and evaluate whether APOE and COMT polymorphisms, inflammatory
biomarkers and physical activity moderate cognitive outcomes.

To achieve these objectives, investigators have assembled a multi-disciplinary team of
oncologists, geriatricians, neurologists, neuro- and cognitive psychologists, behavioral
scientists and consumers from Lombardi Comprehensive Cancer Center (LCCC), Memorial
Sloan-Kettering Cancer Center (MSKCC), Moffitt Cancer Center, City of Hope National Medical
Center (COH), Hackensack University Medical Center (HUMC), Indiana University (IU), Boston
University (BU), University of California (UCLA), University of South Florida (USF) and their
satellites, will work together to prospectively enroll 425 newly diagnosed older breast
cancer cases from LCCC, MSKCC, Moffitt, COH, HUMC, IU and tertiary referral centers with high
volumes. An equal number of non-cancer friend controls will be recruited. Friend controls
were chosen since they will be similar to patients in most ways except for exposure to cancer
and its treatments and they should be motivated to participate. If friends are not available,
controls matched to cases on age, education, race, and area (DC/NY/FL/CA/NJ/IU) will be
recruited from the community.

Investigators will administer baseline neuropsychological testing prior to any systemic
treatment (or at enrollment for controls), survey women about subjective cognitive function,
psychosocial factors, QOL and activities of daily living (IADLS). Investigators will abstract
clinical data from medical records. Investigators will obtain blood or saliva to test for
APOE and COMT polymorphisms at enrollment; these results will not be provided to participants
since this is considered a research test). Subjects have the option to provide blood for
biomarker research and for biobanking. Subjects also have the option of participating in
physical activity monitoring for one week. Subjects will also have the option to participate
in neuroimaging. Investigators conduct follow-up interviews and repeat the neuropsychological
testing and optional neuroimaging 12 months after baseline assessment; this time point
corresponds to 3-6 months post-treatment among women who receive chemotherapy. Our primary
cognitive outcome will be change in summary score on tests in the Attention, Working Memory,
and Psychomotor Speed Domain. In secondary analyses, investigators examine changes in scores
on 4 additional domains to assess broader cognitive function and examine questions of
differential impact: Language; Executive Functioning; Learning and Memory; Visual-spatial.

Data from this study will guide future interventions to better select older women for whom
the benefits of systemic therapy outweigh the harms and to develop approaches to mitigate
negative consequences of systemic treatment when it is indicated, improving the quality of
care for the growing population of older breast cancer patients.

Inclusion Criteria:

For cancer patients, eligibility includes:

- being female

- Age 60+ at diagnosis of a new primary histological confirmed adenocarcinoma breast
cancer

- AJCC stages 0-3 or planning neoadjuvant therapy

- In the judgment of the consenting professional, able to communicate well enough in
English through verbal and written communication to complete the study assessments and
provide informed consent

- If currently taking psychoactive medications (including, but not limited to
anticonvulsants, antidepressants, and anxiolytics), dose must have been stable at
least two months prior to enrollment.

- Participant report of no previous or current chemotherapy or hormonal treatment use
(anastrazole, exemestane, etc.) This does not include hormonal replacement therapy,
synthetic thyroid hormones, etc.

For controls, eligibility includes:

- being female

- Age 60+

- In the judgment of the consenting professional, able to communicate well enough in
English through verbal and written communication to complete the study assessments and
provide informed consent

- If currently taking psychoactive medications (including, but not limited to
anticonvulsants, antidepressants, and anxiolytics), dose must have been stable at
least two months prior to enrollment.

Exclusion:

We apply the same exclusion criteria for patients and controls.

- Participant report of a history of formal diagnosis of neurological problems (i.e.
Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Dementia, Seizure
Disorders, brain tumors, etc.)

- Participant report of surgery on the brain for any reason (cancerous or non-cancerous
tumors, subdural hematomas, AV malformations, increased intracranial pressure, etc.)

- Participant report of a history of stroke (with the exception of TIA if ≥1 year ago)

- Participant report of HIV/AIDS

- Participant report of moderate to severe head trauma (loss of consciousness > 60 min
or with evidence of structural brain changes on imaging)

- History of major psychiatric disorder (DSM-IV Axis 1) (i.e. major depressive disorder
(untreated or poorly treated), bipolar disorders, schizophrenia, or substance abuse
disorders (self-reported and/or stated in medical record).

- Participant report of a history of prior breast or other cancer with the exception of
non-melanoma skin cancer. An exception for cases only: women who completed treatment
for a previous cancer at least 5 years ago and have not undergone any chemotherapy or
hormonal therapy. This previous cancer cannot be breast cancer.

- Participant report of previous or current chemotherapy or hormonal therapy use

- Participant use of methotrexate (Amethopterin, Rhematrex, Trexall) or rituximab
(Rituxin) for rheumatoid arthritis, psoriasis or Crohn's disease, or cyclophosphamide
(Cytoxan, Neosar) for Lupus.

- Visual or hearing impairment that would preclude ability to complete interviews or
neuropsychological testing, such as significant macular degeneration or being unable
to correct hearing with hearing aides

- Non-English speaking

- To participate in the optional neuroimaging portion of the study:

Participant cannot be claustrophobic Participant cannot have a pacemaker, aneurysm clip or
other implants that are not MRI safe Participant cannot have any type of implanted
electrical device