HICCC Breast
Program
Prevention & Survivorship Studies
Breast Cancer
Studies at Columbia
Late-Effects of Cancer Therapies
Most cancer therapies are known to carry a substantial risk of adverse long-term treatment-related effects. Because the number of women diagnosed with invasive and non-invasive breast cancer is increasing and the number of women who die each year from breast cancer has decreased modestly, the number of breast cancer survivors is likely to increase. Despite the known survival benefits of early breast cancer treatment, these treatments are often avoided, reduced or delayed due to toxicities. Dose reductions, treatment delays, or stopping treatment early due to toxicity can affect survival, and therefore it is critical to understand and predict which patients may be more susceptible to either the acute or late effects of cancer therapy. Furthermore, because some of the effects of cancer therapy may appear late in long-term survivors of breast cancer, it is critical to define which subgroups may be at risk due to increased susceptibility.
Using
large-databases to understand late-effects
of treatment. use large administrative
databases such as that from the linked
Surveillance, Epidemiology and End-Results
(SEER) program – Medicare database,
sponsored by NCI, and HMO’s such as Kaiser
Permanente and the Henry Ford Health Care
System, to evaluate patterns of care, early
termination, and late toxicities of
chemotherapy, radiation therapy and
supportive care medications on subsequent
end-organ function and risk of secondary
malignancies.
Defining
populations at risk for early and late
effects of treatment.
use prospective cohort and
case-control study designs to investigate
the impact of therapy on cognition,
dentition, pain, and bone health.
Interventions
to reduce treatment related toxicity.
phase II and III studies to evaluate
interventions to reduce complications from
premature menopause, depression, medication
induced joint pain, and neurotoxicity using
both traditional and non-traditional
interventions.
Interventional
studies to improve the quality-of-life of
minority cancer survivors.,
randomized interventions aimed at lifestyle
modification to improve outcomes, and
understanding barriers to recommended
treatment.
Ongoing
Peer-Reviewed Funded Trials that are open
and accruing
a. Effects of Physical Activity and Dietary Change in Minority Breast Cancer Survivors This study will test the effects of exercise and dietary change on weight reduction and biological markers associated with breast cancer risk in Hispanic and black breast cancer survivors. This is a randomized, crossover pilot and feasibility study of 50 women to test the effects of a 30-minute circuit-based exercise program that combines resistance training with aerobic exercise in conjunction with a low-fat calorie reduced diet. A wait-listed control group will be used for comparison. Participants in both groups will exercise at a neighborhood Curves® facility at least 5 times per week for six months and will participate in a series of nutrition classes.
b. Using Physiological Age to Predict Chemotherapy Toxicity This study is in collaboration with investigators at Georgetown and Kaiser Perminente to to develop and validate an index of physiological age that can be used to predict chemotherapy toxicity outcomes. The study was fostered by the DOD COE award, and includes many of the same investigators.
c. Posttreatment care of Latina breast cancer survivors This is a randomized prospective evaluation of a Survivorship Intervention in improving the quality of care, treatment satisfaction and understanding of care in Latina and Caucasian breast cancer survivors treated in an urban academic medical center. Over 120 women will be randomized to receiving written information for follow-up care of cancer survivors published by the National Cancer Institute (Facing Forward) in English or Spanish, or to a Survivorship Intervention. The intervention will consist of a review of written information for follow-up care of cancer survivors (Facing Forward) and will undergo a consultation in a survivorship clinic.
d. Study on the effect of acupuncture on joint pain induced by aromatase inhibitors in breast cancer patients This is a randomized placebo controlled trial of acupuncture. Based on the results of their initial investigation, this randomized trial will be the first attempt to control this side effect. This randomized trial of 45 women is currently ¾ completed.
e. Randomized Placebo Controlled Trial of
Acetyl-L-Carnitine For Taxane Induced Neuropathy The aims of this clinical trial are to determine if acetyl
L-carnitine (ALCAR) prevents symptoms of neuropathy as measured by the taxane subscale of the FACT-TAX in patients treated with adjuvant taxanes for breast cancer. This is a randomized placebo controlled trial of 250 women that will be run through
SWOG, and is currently approved for activation, with additional funding to evaluate the biomarker nerve growth factor as a predictor of response and outcome to this therapy.
g. The effects of chemotherapy and estrogen on cognitive function in premenopausal women with breast cancer. The primary aim of this proposed longitudinal study of 120 women with newly diagnosed breast cancer is to investigate whether chemotherapy and chemotherapy-induced estrogen depletion affect cognitive impairment in pre-menopausal women with early stage, localized breast cancer, and whether any observed impairment persists until six months after completing chemotherapy. (See below for details)
Studies
to open:
1. Prospective evalution of joint symptoms in patients on aromatase inhibitors
2. Prospective/cross sectional evaluation of taxane neuropathy
3. Phase II study of glucosamin/chondroitin for AI induced joint pain
4. Epigenetic changes associated with chemotherapy in breast cancer survivors.
Prevention Studies
Despite significant advances in the early
detection and treatment of breast cancer, it
is still the most common cancer and the second
leading cause of cancer death among women in
the U.S. Therefore, more attention has focused
on the potential of chemoprevention for
decreasing breast cancer incidence and
mortality. Currently, tamoxifen, which reduces
breast cancer incidence by 30 to 40% in
at-risk women, is the only FDA-approved drug
for breast cancer risk reduction. It is
estimated that over 10 million women in the
U.S. are at high risk for the development of
breast cancer and are eligible for primary
prevention with tamoxifen. However,
tamoxifen’s adverse effects, namely
endometrial cancer and thromboembolism, have
affected its wide acceptance and application.
In addition, tamoxifen has no effect on the
incidence of hormone receptor (HR)-negative
cancers, that account for about a third of all
breast carcinomas. Thus, novel prevention
strategies are being pursued in particular for
HR-negative tumors to The high costs of large
chemoprevention studies have prompted the
search for intermediate markers of cancer
development. A greater emphasis has been
placed on developing clinical breast models
which use surrogate endpoint biomarkers in
lieu of cancer occurrence in order to improve
the efficiency and reduce the cost of
chemoprevention trials. Identification of risk
biomarkers that correlate with cancer
incidence would also provide insight into drug
mechanisms and critical pathways associated
with carcinogenesis.
a. Phase I Dose
Escalation Study of Poly E for
Secondary Chemoprevention in Women
with Hormone Receptor-Negative Breast
Cancer. It is a phase Ib randomized,
placebo-controlled, double-blinded,
dose escalation study of oral
Polyphenon E (Poly E) 600 mg, 800 mg,
or 1000 mg daily for six months in 40
women with a history of early stage
hormone receptor (HR)-negative breast
cancer. Poly E is a green tea
polyphenol mixture containing
epigallocatechin gallate (EGCG), the
most pharmacologically active
component of green tea, other
catechins, and minimal amounts of
caffeine. The primary objective of
this study is to demonstrate the
safety and maximum tolerated dose (MTD)
of Poly E over a six-month period in
the management of patients with a
history of hormone receptor-negative
breast cancer. The secondary
objectives of this study are to
investigate the dose-related biologic
effects of Poly E in this patient
population: (1) To determine the
efficacy of Poly E in modulating
histologic changes (nonproliferative,
proliferative without atypia, atypical
hyperplasia) on random core biopsy of
the contralateral breast. (2) To
determine the efficacy of Poly E in
modulating immunohistochemical
expression of Ki-67 (proliferation
index), p53, EGFR, HER2/neu, cleaved
caspase-3 (apoptosis marker), and
estrogen receptor on random core
biopsy tissue of the contralateral
breast. (3)To determine the efficacy
of Poly E in modulating mammographic
breast density of the contralateral
breast. (4) To determine the efficacy
of Poly E in modulating hormone
metabolites (serum estradiol,
testosterone, IGF-1, IGFBP-3, SHBG).
(5)To determine the efficacy of Poly E
in modulating biomarkers of
inflammation (urine PGE-M and serum
CRP). (6)To determine the efficacy of
Poly E in modulating biomarkers of
oxidative damage (urine 8-OHdG,
isoprostane). (7) To determine Poly E
activity in relation to COMT genotype.
(8) To assess quality of life (QOL)
and attitudes toward complementary and
alternative medicine (CAM) in breast
cancer patients receiving Poly E.
b. Biomarker Modulation
Study of Vitamin D in Premenopausal
Women at High Risk for Breast Cancer.
Epidemiological, preclinical, and
clinical data suggest that vitamin D
may influence breast cancer
development, which has resulted in
increased interest in the use of
vitamin D for the treatment and
prevention of breast cancer. The trial
tests the hypothesis that high dose
vitamin D3 (cholecalciferol) causes
significant modulation of surrogate
endpoint biomarkers of breast cancer
risk, including radiographic, tissue-
and serum-based biomarkers. The
purpose of this trial is to test
feasibility, to assess toxicity and
tolerability of the high dose of
Vitamin D3, and to obtain preliminary
data on the effect of vitamin D on
mammographic density and the
expression of biomarkers in breast
tissue and blood in high-risk
premenopausal women. The active arm of
cholecalciferol (vitamin D3) 30,000 IU
weekly was chosen according to the
estimated dose needed to achieve
adequate levels of serum 25(OH)D and
due to its safety profile. The control
arm of ergocalciferol (vitamin D2) 400
IU daily was chosen according to the
RDA and due to the high prevalence of
vitamin D deficiency (>40-50%) in
the general population. We will also
evaluate the safety of high dose and
low dose vitamin D in this population
of healthy women at high risk for
breast cancer. The results of this
study will inform future phase III
breast cancer prevention trials of
high dose vitamin D that is currently
approved for development through SWOG.
