is widely used as an adjuvant treatment after surgery for breast cancer.
It is primarily administered to prevent recurrences
and is quite effective at doing so. But a study published in the March
7, 2007 Journal of the National Cancer
Institute (JNCI) has shown that
radiation also increases the risk of heart disease in women who receive
it following surgery for breast cancer. Using modern radiation delivery
techniques shifts the pattern of harm, but does not remove it.
It has long been acknowledged that the type of radiation used in the
1960s and 1970s elevated women's risk of subsequent cardiovascular
disease. However, techniques have changed since then, and radiation
often stated that newer radiation delivery procedures have been deliberately
designed to minimize this sort of heart damage. The dangers of radiation to
the heart have therefore frequently been dismissed as a thing of the past,
and countless women have been told that the procedures performed on them were
For example, in Clinical Oncology, a textbook
published in 2001 by the American Cancer Society, the problem is downplayed.
In the course of two paragraphs,
its seriousness is minimized half-a-dozen times:
Cardiac toxicity due to irradiation
is rare...Effects on the endocardium are rare...Below a total dose of 4500
cGy, radiation-induced damage is uncommon...Tamponade
[a life-threatening compression of the heart resulting from a collection
of fluid in the pericardium (the sac surrounding the heart), ed.] occurs
In general, pericarditis is self-limited... Chronic pericarditis is uncommon.
Acute myocardial infarction [is] rare... (Lenhard 2001: 243-244).
similarly claim that modern radiation therapy is entirely safe. Here
is an example of such a statement from breastcancer.org:
therapy techniques have changed dramatically since then [the 1970s,
ed.]. New technology allows doctors to use the lowest
dose of radiation possible.
They can also more precisely target the radiation to the breast and away
from the heart - so the heart receives a minimal amount or none at all.
is what the orthodox medical profession believed – and wanted
us to believe. However, the facts now speak otherwise. The JNCI study
a major blow to the orthodox medical profession's insistent claims that
radiation has evolved into a safe modality for the post-operative treatment
of breast cancer.
In the JNCI study, researchers at the Netherlands Cancer Institute
in Amsterdam evaluated 4,414 breast cancer patients who survived for
least ten years
after receiving radiotherapy between the years 1970 and 1986. The patients
were followed for a median of 18 years. These patients' rates of cardiovascular
disease were then compared with those seen in the general population
(Hooning 2007). In other words, this was a very large and prolonged
There were a total of 942 "cardiovascular events" during the follow-up
period. The good news was that radiation therapy limited to the breast itself
did not increase the risk of cardiovascular disease. However, when either the
left or right internal mammary chain of lymph nodes was included in the radiation
field, as is common in post-operative radiotherapy, it did significantly increase
Internal mammary chain irradiation performed during the 1970s increased
the risk of a heart attack (myocardial infarction) by 2.55 times compared
no radiation. It also raised the risk of congestive heart failure 1.72-fold.
given in the 1980s was also associated with an increased risk of heart
disease: a 2.66-fold greater risk of heart failure and a 3.17-fold
greater risk of
dysfunctional heart valves. (This was one of the first studies to investigate
heart valve failure.)
In the 1980s, it became common to add adjuvant chemotherapy to radiotherapy.
The standard chemotherapy regimen used during the 1980s was CMF (which
stands for the three drug combination of cyclophosphamide, methotrexate,
However, this study found that the addition of CMF chemotherapy to
radiation conferred a 1.85-fold increased risk of congestive heart
finding has caused a great deal of surprise since this combination
was never thought
to be particularly cardiotoxic.
It is chilling to realize that nowadays CMF chemotherapy has been replaced
by regimens based around so-called anthracycline drugs, the most prominent
of which is Adriamycin (doxorubicin). This class of drugs is already
well-known to carry serious risks of cardiotoxicity, including life-threatening
heart failure. This risk increases exponentially the greater the lifetime
A recent review in Seminars of Oncology concluded that "10 percent to
26 percent of patients administered cumulative anthracycline doses above those
recommended... develop congestive heart failure, and that more than 50 percent
of patients administered these doses will experience measurable functional
impairment months to years after the end of therapy." Also, the susceptibility
of patients to anthracycline-induced cardiotoxicity varies widely, with a dramatic
increase with advancing age (Jensen 2006).
The risk is further augmented by the addition of Herceptin (trastuzumab),
another cardiotoxic drug that is increasingly used in the treatment
of breast cancer.
Herceptin can cause heart damage ranging from mild and transient to
life-threatening congestive heart failure. To quote the package insert
by the Food and Drug Administration, Herceptin "has been associated with
disabling cardiac failure, death, and mural thrombosis leading to stroke" (FDA
2003). (Mural thrombosis is the formation of a fibrinous clot on the endocardial
lining of the heart or on the wall of a large blood vessel). In view of these
ominous warnings, studies focusing on the cumulative cardiac risk of radiation
therapy in patients who have also been given Adriamycin and/or Herceptin-containing
chemotherapy regimens are urgently needed.
The JNCI study also found a disturbing threefold increase in the risk
of heart attacks among radiotherapy-treated patients who also smoked
properly caution that "irradiated breast cancer patients should be advised
to refrain from smoking to reduce their risk for cardiovascular disease." Easier
said than done! The more logical solution would surely be to refrain from giving
adjuvant radiation to patients who insist on smoking.
Medical Detective Work
The fact that breast irradiation increases the risk of heart disease is not
a new finding. Starting in the late 1960s, it became known that, after receiving
adjuvant radiation to prevent breast cancer recurrence, more women than expected
were dying of heart disease, sometimes decades after their initial surgery.
It took brilliant medical detective work to prove that this apparently successful
use of radiation therapy was also the cause of many cardiac deaths (Fajardo
2001). So many women were dying of the long-term adverse effects, in fact,
that it more or less counterbalanced any survival benefit from the treatment
There was great resistance to this discovery. Reports of heart damage from
radiation began emerging as early as 1927, but even so, for the first 60 years
of the twentieth century, the heart was routinely described a "radioresistant" organ
(i.e., resistant to the negative effects of radiation), and cardiac complications
of radiation therapy were often described as rare and insignificant (Desjardins
1932 and Leach 1943).
It took systematic studies, over several decades, by Prof. Luis Fajardo of
Stanford University to dispel this tenacious misperception (Cohn 1967 and Fajardo
1968). The sensitivity of the heart to radiation therapy was only really acknowledged
in the early 1970s (Bouyer-Dalloz 2003). Even then, a long time elapsed before
the complete picture of radiation-induced heart disease finally became accepted
in medical thinking (Hancock 1993).
Further evidence began to emerge in the 1970s. A Swedish team conducted a randomized,
controlled clinical trial (RCT) involving 960 breast cancer patients over the
period 1971 to 1976. These patients received either surgery alone or surgery
preceded or followed by radiation. A total of 58 patients had heart attacks
during the follow-up period, which averaged 20 years. Patients who received
high doses of radiation had twice the risk of those who did not. There was
also a 2.5-fold increased risk of ischemic heart disease (i.e., the kind caused
by a decrease in the blood supply to the heart). The difference between the
two groups began to appear after four to five years, and the heart attack incidence
rates continued to increase in the irradiated group for ten to 12 years. There
was some evidence that most of the deaths were due to radiation-induced damage
to the small blood vessels of the heart (Gyenes 1998).
In another study, the strength of the heart was measured 15 to 20 years after
treatment for breast cancer. It was found that 25% of patients treated with
radiation to the left breast had heart-related problems on standard stress
tests, compared to none in the control group. The authors' main conclusion
was that left-sided chest irradiation (which more frequently affects the heart)
might represent a risk factor for ischemic heart disease (Gyenes 1994).
Because of these studies, modifications were made in the 1980s to the way that
radiation was delivered after surgery for breast cancer. Radiation oncologists
have often claimed that with more precise equipment and techniques, heart damage
was no longer a clinically relevant problem. This seemed plausible. However,
the latest study shows that such complacency was ill-founded. The range of
cardiovascular problems that can follow intense irradiation of the heart is
in fact very broad. It includes six major categories and various subcategories:
• Acute pericarditis during irradiation
• Delayed acute pericarditis
• Pericardial effusion (delayed)
• Constrictive pericarditis
2. Myocardial dysfunction
3. Diffuse myocardial fibrosis (with or without pericardial disease)
4. Coronary artery disease (CAD)
5. Electrical conduction abnormalities
6. Valvular heart disease
What complicates the issue is that radiation affects the heart and
cardiovascular system unevenly: different parts of the system are affected
in different ways, and individuals differ in their responses. For the
sake of simplicity, I will not discuss the complicated mechanisms by
which radiation damages the heart and circulatory system. What is most
relevant is the experimental and clinical evidence of such damage.
Considerable Laboratory Data
There is a considerable body of laboratory data demonstrating the harmful effects
of radiation on the heart. Most of these experiments have been carried out
on the New Zealand white rabbit, because it has reactions to heart irradiation
that are similar to those of humans. In one such study, after a single 20
Gy dose of radiation, fully 94% of the rabbits developed some form of heart
disease (Fajardo 1970). First, there was an acute reaction, which disappeared
within 48 hours. But starting at the 50th day, a delayed reaction set in,
and this reached its full development by 90 days. By 150 days, half the experimental
animals had died. What is particularly striking about these experiments is
the degree to which radiation was shown to cause myocardial fibrosis (a thickening
of the heart muscle).
Similarly, in the human clinical situation, the heart's response to radiation
is also divided into an acute and a long-term response. As in the test animals,
the initial response vanishes rather quickly. But then, some months or even
years later, the patient may experience heart pain (angina), difficulty breathing,
or even a full-scale myocardial infarction (heart attack). The problem is that
since they occur a considerable time after treatment, these radiation-induced
effects are indistinguishable from "ordinary" (i.e., randomly occurring)
heart problems. There is nothing about such events that screams out "radiation-induced
heart disease." The cardiologist therefore may not make a connection
to the patient's prior exposure to radiation.
The latest findings should caution us against hubris in the medical field.
It took tremendous investigative work by Professor Fajardo and others to prove
that radiation damages the heart. As a result of their work, some changes were
indeed made – and radiation oncologists hailed these changes as proof
that radiation treatment was now safe. Although the accuracy of radiation delivery
and targeting has improved considerably, other problems, such as the cumulative
cardiotoxic effect of chemotherapy and radiation, remain largely unaddressed.
This is especially relevant now that Adriamycin-based chemotherapy has become
the standard of care for breast cancer.
Radiation is a classic two-edged sword. It does substantially reduce the risk
of recurrences of breast cancer in the irradiated field. But this comes at
the price of an increased risk of damage to the heart, especially when the
internal mammary lymph node chains are irradiated or when the patient is a
smoker. Patients and their physicians need to carefully weigh benefits and
risks before agreeing to this or any other potentially toxic treatment.
W. Moss, PhD
Breastcancer.org quote available at: http://www.breastcancer.org/research_radiation_042805.html.
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