Trial Information

Radiation Induced Atherosclerosis in Breast Cancer Patients

Radiation induced atherosclerosis in Breast Cancer patients

Radiation induced accelerated atherosclerosis is a well known entity that occurs in
different regions, according to the therapy delivered. This process takes a couple of years
to develop. Therefore, the most affected populations are the long term survivors of
potentially curative cancers such as Hodgkins lymphoma 1, 2, head and neck cancers 3-6,
pelvic cancers (both prostate cancer and cervical cancer) 7, and breast cancer8-14. The
mechanism of damage is thought to be direct endothelial damage, which is most significant
about 6 months post XRT, followed by inflammation, cholesterol plaque formation and intimal
thickening. This cascade, as well as the pathological findings, are similar to what is seen
in natively occurring AS. However, in the post XRT setup, it is not limited to one part of
the artery and usually encompasses the entire circumference of the radiated segment15-17.

The accelerated atherosclerosis resulting from radiation usually begins to be clinically
evident several years after the radiation incident, as there is sufficient functional
reserve to these vessels. However, changes can be seen much sooner, and some studies have
shown significant changes as soon as one year after the initial insult 2, 18.

Literature reports suggest as high as 77.5% of symptomatic carotid stenosis (on risky
regions of common carotid and internal carotid arteries) as compared to 21.6% on the matched
control group (consisting of newly diagnosed patients with similar risk factors)18. A
retrospective review from Philadelphia on 413 treated patients found RR for stroke of 2, as
compared with the general population (matched for risk factors) from the Stockholm
database5. Data from the Netherlands suggested risk for stroke as high as 5 times as
compared to the matched group without cancer. The analysis was done on patients who received
the treatment before 60 yo (the comparison was not made to the general population as these
patient are usually smokers and drinkers and are usually at a higher risk to begin with,
however XRT increases this already high risk by 5).

A new emerging technique of Carotid Intima-Media Thickening (IMT) has demonstrated the
impact of radiation (2.2 Vs 0.7mm in controls)6.

Our proposal is aimed to better characterize this side effect. For that purpose, we have
chosen to study women who received radiation to the breast, in which part of the carotid in
the irradiated side was in the high energy radiation field. The contralateral artery, which
received only trace of scattered radiation, can serve as the internal control. This is not
the case in head and neck patients, who usually receive a high dose of radiation to both
sides of the neck. The number of early breast cancer patients who received adjuvant
radiation is relatively high, a factor which may help us reach the accrual goal much faster.
Subsequently we are planning to proceed in a consecutive study and to try to
pharmacologically interfere with progression of the AS, and perhaps even prevent it.

Intima Media Thickening US is a non-invasive US technique that is available at Hadassah
University Medical Center and will be performed in this study in order to detect the degree
of AS in affected and non affected arteries.

The suggested study will consist of two populations. Group 1 are women who received
radiation for breast cancer in the past at various time intervals and the Group 2 are women
with newly diagnosed breast cancer.

Markers and biochemistry tests that might elucidate predisposing and contributing factors
for developing AS will also be done and analyzed on all patients. The latter could be a
target for treatment and a surrogate to the treatment efficacy, side effects, and cancer
progression (i.e. cholesterol levels, hypertension, hypothyroidism, etc.)