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Introduction
Fifty years ago, Hodgkin disease (HD, also known as Hodgkin's disease), a cancer
of the lymphatic system*, was nearly uniformly fatal. With the introduction of
effective treatment regimens, HD is now a potentially curable cancer, associated
with an 85 percent five-year relative survival rate. There are currently about
120,000 survivors of HD in the United States alone. However, the success of
these treatments is accompanied by an increased risk of second cancers, the
leading cause of death among long-term survivors of HD. Survivors have an
increased risk of leukemia, sarcoma (cancer that develops from connective tissue
such as bone, cartilage, or muscle), and breast, lung, and thyroid cancers.
Among female HD survivors, breast cancer is the most likely tumor to develop and
is a major concern for these women.
Background
Previous studies have shown that increased breast cancer risk begins to be
evident about 10 to15 years after radiation therapy for Hodgkin disease and
continues for at least 20 years. It has also been reported that women who are
age 30 years or less when treated with radiotherapy for Hodgkin disease are more
likely to develop breast cancer than those treated at older ages.
JAMA Report
In a study published in the July 23, 2003, issue of the Journal of the American
Medical Association, Lois B. Travis, M.D., from the National Cancer Institute in
Bethesda, Md., and her colleagues looked more closely at female Hodgkin disease
survivors in the United States, Canada, Denmark, Finland, Sweden, and the
Netherlands, in an effort to evaluate factors that contribute to breast cancer
development in young women. This large international case-control study was
conducted among women who were treated for Hodgkin disease at age 30 or younger.
The study included 105 women who developed breast cancer after treatment for HD
and 266 matched controls who did not develop breast cancer (JAMA 2003;290:465).
The investigators focused on the following risk factors:
• The radiation dose to the breast;
• The radiation dose to the ovaries;
• The number of cycles of alkylating agents, a particular type of chemotherapy;
and
• Treatment-related menopause.
In the course of their study, they estimated the radiation dose to the area of
the breast where each patient's tumor developed and to a comparable location in
the matched controls. They found that the higher the radiation dose to the
breast, the more likely the women were to develop breast cancer. Specifically,
compared with women receiving less than a 4 gray (Gy) dose to the breast, women
treated with a breast dose of 4 Gy or greater were 3.2 times more likely to
develop breast cancer, and those treated with a dose greater than 40 Gy were 8
times more likely to develop breast cancer. The increased risks associated with
radiotherapy were still present after 25 years of follow-up, and increased with
increasing dose of radiation to the breast.
They also found that treatment with alkylating agents reduced the breast cancer
risk associated with radiotherapy. Whereas treatment with 4 Gy or greater of
radiation resulted in a 3.2 times greater risk of breast cancer, adding
alkylating agents to the radiation reduced this relative risk to 1.4. Breast
cancer risk decreased with increasing number of cycles of alkylating agents.
Breast cancer risk also decreased with increasing radiation doses to the
ovaries. Compared with those who received ovarian doses of less than 5 Gy, women
who received ovarian doses of 5 Gy or greater had lower breast cancer risks,
regardless of whether alkylating agents were used. The decreased breast cancer
risk associated with both alkylating agent therapy and radiation dose to the
ovaries is probably caused by their damaging effect on ovarian function,
including the induction of premature menopause.
It is important to note that recent changes in the treatment of Hodgkin disease
are not reflected in the current, multi-center study. Lower radiation doses and
reduced fields (which result in a reduction of the amount of exposed breast
tissue) have been introduced for selected patients, and alkylating agent-based
chemotherapy regimens such as MOPP (mechlorethamine, vincristine [Oncovin],
procarbazine, and prednisone) have been largely replaced by more modern
regimens, including ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and
dacarbazine), as initial therapy. ABVD is at least as effective as MOPP against
most tumors, but has a negligible effect on fertility and is associated with a
lower risk of leukemia.
Thus, most of the women in the current report were treated with the more
aggressive radiotherapy regimens and alkylating agents of the past.
A recent study published in the Journal of the National Cancer Institute (JNCI
2003;95:971) included most of the Dutch patients in the current JAMA
publication, but extended the group to older ages (eight additional cases) (< 41
years). The results supported the conclusions reported by Travis et al. (JAMA
2003;290:465).
Conclusions and Public Health Implications
Travis and colleagues drew the following conclusions:
• The high radiation-related breast cancer risk in Hodgkin survivors, which did
not diminish at the highest doses or the longest follow-up, suggests the need
for lifetime surveillance and programs of patient and public awareness.
• Ovarian stimulation appears to be important for the development of
radiation-induced breast cancer, as evidenced by the reduced risk associated
with ovarian damage from alkylating agents or radiation.
• Although there are no consensus recommendations for women treated with
radiotherapy for Hodgkin disease, several investigators (cited by Travis and
colleagues in the JAMA paper) advocate yearly clinical breast exams and annual
mammography beginning five to eight years after irradiation.
• It is important to continue to minimize radiation doses and fields without
compromising the current excellent cure rates.
Overall, Travis and colleagues emphasize that the benefits of radiotherapy and
chemotherapy for Hodgkin disease patients far outweigh the treatment-related
risks, including the increased risk of breast cancer for women.
Future Research Recommendations
Based on the results of this international study, Travis and her colleagues made
the following recommendations:
• Although the lower radiation doses and reduced fields currently used for
Hodgkin disease patients are likely to result in lower breast cancer risks,
long-term follow-up of patients receiving reduced doses is needed to verify this
prediction.
• Additional studies evaluating the risk of breast cancer following HD should
include detailed information on hormonal and other established risk factors for
breast cancer in addition to information on treatment for HD.
* The lymphatic system is a part of the body's immune system that helps fight
disease and infection. It includes the bone marrow, spleen, thymus, and lymph
nodes, and a network of thin tubes that branch, like blood vessels, into
surrounding tissues. The network of vessels distributes lymph, a colorless
watery fluid containing infection-fighting cells, to the body's tissues.
Source :
http://www.cancerlinksusa.com/breast/article/breast_cancer_risk_hd.asp