February 24, 2014

Radiation Therapy for Breast Cancer Causes Long-Term Heart Toxicity

An analysis of long-term effects from radiation therapy in breast cancer treatment.
The use of adjuvant radiation therapy in women who have undergone a lumpectomy for breast cancer has become routine practice. The findings from the current study substantiate the body of evidence that has accumulated showing that radiation therapy does have long-term consequences to the heart muscle and vasculature.

Reference

Bouillon K, Haddy N, Delaloge S, et al. Long-term cardiovascular mortality after radiotherapy for breast cancer. J Am Coll Cardiol. 2011;57:445-452.

Design

Single institution (Institut Gustave Roussy) retrospective analysis.

Participants

4,456 women (mean age 55) who were treated for breast cancer between 1954 and 1984 and survived 5 years post treatment. Stage I–III disease was present in 98.5% of patients. Two-thirds underwent radiation therapy and 6% also had chemotherapy. Lymph nodes were removed in 88% of participants, and 90% of this group had radiation. Forty percent of those without nodal involvement underwent radiation.

Key Findings

During a median follow-up of 28 years, 2,637 deaths occurred. Of the 421 deaths from cardiovascular causes, 236 were due to ischemic heart disease, heart failure, dysrhythmias, and conduction disorders; 185 were due to vascular disease. Women who underwent radiation therapy to the left breast had a 1.77-fold (95% CI: 11.33–2.36) higher risk of cardiac disease than those who did not undergo radiation. Comparing those who received right-sided versus left-sided radiation, those receiving treatment on the left side had a 1.28-fold (95% CI: 0.92–1.78) higher risk of cardiac disease. Lastly, irradiation of the internal mammary chain increased risk of death from cardiac causes 1.3-fold (95% CI: 1.33–2.36) compared to those who received treatment limited to the chest wall.

Practice Implications

The use of adjuvant radiation therapy in women who have undergone a lumpectomy for breast cancer has become routine practice. Damage to the heart has been a concern, particularly for left-sided radiation therapy, for at least 2 decades. The findings from the current study substantiate the body of evidence that has accumulated showing that radiation therapy does have long-term consequences to the heart muscle and vasculature.

As the study above concludes, patients who have undergone radiation therapy long ago are at higher risk of cardiovascular disease, and we must keep this in mind when addressing their overall health.

This study looked at the long-term consequences to the heart from ionizing radiation received between 1954 and 1984. As the study above concludes, patients who have undergone radiation therapy long ago are at higher risk of cardiovascular disease, and we must keep this in mind when addressing their overall health. Advances in radiation planning (dosimetry), particularly the use of computer-guided planning, has greatly improved the precision of treatments. However, we should be concerned for our patients undergoing radiation to the chest wall for breast cancer, as the heart still receives significant doses of ionizing radiation, especially in women with left-sided breast cancer.1

So, how great is the risk to the heart? A 2000 meta-analysis of 40 studies in early breast cancer found that radiation significantly lessened local recurrence during the ensuing 10 years post-treatment (8.8% vs. 27.2%).2 Surprisingly, however, the authors also found that although mortality from breast cancer was reduced over a 20-year period, mortality from other causes, particularly cardiovascular causes, increased: “Overall 20-year survival was 37.1% with radiotherapy versus 35.9% control (P=0.06).” Advances in radiation therapy in the past decade are beginning to show a survival advantage to those who receive radiation therapy, but the amount of radiation the heart receives and can tolerate is still a matter for debate.3

Radiation therapy is generally given to women in the supine position, leaving the breast tissue to spread and fall to the side of the chest wall. This places the breast tissue very close to the chest wall and heart, particularly in women with large breasts. I could not find an adequate answer as to why the supine position predominates in radiation therapy, except to say that it has become convention, likely due to the size and design of original radiation therapy equipment.

Not surprisingly, using the prone position reduces the amount of radiation to the heart and lungs.4 In 2008, a poster presentation at the American Society of Clinical Oncology reported that the prone position, in which the breast is more pendulous, spared the vast majority of damage to women’s heart and lungs from ionizing radiation exposures.5

A 2011 poster presented by Dr. John Ng and colleagues from Columbia University at the annual meeting of the American Society for Radiation Oncology reported that using the prone position decreases the amount of radiation to which the lungs are exposed to 10% of that caused in the supine position.6 This is a striking reduction, since the risk of lung cancer in women with a history of radiation to the breast (in supine position) is 4.86% versus a background risk of 1.5% for those without radiation. Ng’s group reported the use of prone positioning is expected to result in a lifetime lung cancer risk of 1.99%, which is even less than the 2.92% increase in risk for those undergoing localized radiation such as balloon brachytherapy. While Ng et al did not assess the amount of radiation reaching the heart, it is safe to assume that radiation amounts to the heart were also lessened, since it is closer than lung tissue to the chest wall.

The use of prone positioning for breast cancer radiation therapy is an area of current research, with ongoing studies clarifying the fields of therapeutic coverage (ie, which nodes can be treated) and the type of radiation therapy that is best suited.7-9 It stands to reason that such a logical change should be implemented as more data verifies what appears to be a much more rational ergonomic design for radiation delivery. A few cancer centers in the United States currently offer radiation therapy in the prone position, but its widespread use has not been adopted.

Limitations of Study

This analysis used data that cannot be directly extrapolated due to the differences in technology and dosage of radiation therapy between 1954-1984 and today. All of the data were from one center in France, which may have varied protocol norms compared to other centers and other countries. There could also have been selection bias between the radiation and non-radiation groups.

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References

1. Taylor CW, Povall JM, McGale P, et al. Cardiac dose from tangential breast cancer radiotherapy in the year 2006. Int J Radiat Oncol Biol Phys. 2008;72(2):501-507.
2. Early Breast Cancer Trialists' Collaborative Group Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet. 2000;355(9217):1757-1770.
3. Lohr F, Heggemann F, Papavassiliu T, et al. [Is cardiotoxicity still an issue after breast-conserving surgery and could it be reduced by multifield IMRT?]. Strahlenther Onkol. 2009;185(4):222-230.
4. Varga Z, Hideghéty K, Mezo T, Nikolényi A, Thurzó L, Kahán Z. Individual positioning: a comparative study of adjuvant breast radiotherapy in the prone versus supine position. Int J Radiat Oncol Biol Phys. 2009;75(1):94-100.
5. Lymberis S, Parhar, Jozsef G, DeWyngaert J, Formenti SC. Results of prospective trial to determine optimal patient positioning prone versus supine for whole breast radiation. ASCO 2008 Breast Cancer Symposium. Available at http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=58&abstractID=40427. Accessed October 21, 2011.
6. Ng J, Shuryak I, Xu A, Deutsch I, Burri RJ, Brenner DJ. Modeling the risk of secondary lung malignancy in patients treated with breast radiation therapy. 2011 ASCO Annual Meeting. J Clin Oncol. 2011:29(suppl; abstr 1085). Available at http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=82570. Accessed October 22, 2011.
7. Alonso-Basanta M, Ko J, Babcock M, Dewyngaert JK, Formenti SC. Coverage of axillary lymph nodes in supine vs. prone breast radiotherapy. Int J Radiat Oncol Biol Phys. 2009;73(3):745-751.
8. Varga Z, Hideghéty K, Mezo T, Nikolényi A, Thurzó L, Kahán Z. Individual positioning: a comparative study of adjuvant breast radiotherapy in the prone versus supine position. Int J Radiat Oncol Biol Phys. 2009;75(1):94-100.
9. Alonso-Basanta M, Ko J, Babcock M, Dewyngaert JK, Formenti SC. Coverage of axillary lymph nodes in supine vs. prone breast radiotherapy. Int J Radiat Oncol Biol Phys. 2009;73(3):745-751.