Originally published as JCO Early Release 10.1200/JCO.2009.22.3578 on June 29 2009

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Reply to J.L. Oh et al

Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham & Women's Hospital, Boston, MA

We thank Drs Oh and Buchholz¹ for their letter regarding our review article,² emphasizing several important issues on the treatment of internal mammary nodes (IMNs) in breast cancer. As the letter suggests and as we summarized in the article, multiple studies consistently show that a significant minority of patients with breast cancer have pathologic IMN involvement, and the risk of IMN involvement increases in patients with medial tumors and/or positive axillary nodes. While it seems reasonable based on these data to consider IMN irradiation for patients with medial tumors and/or positive axillary nodes, evidence directly linking IMN treatment to a survival benefit is not currently available. Randomized trials evaluating IMN dissection did not show a survival benefit,^3–5 although they were largely underpowered, and retrospective studies evaluating patients with versus without IMN treatment have shown mixed results.^6–9 We eagerly await results from more recent randomized trials assessing the potential benefit of IMN irradiation to help shed light on this question.

Before these data become available, considerations regarding IMN treatment must include its potential therapeutic benefits balanced against a possible risk of increased morbidity. Drs Oh and Buchholz¹ highlight modern radiation treatment techniques for the IMN, including their elegant split-electron beam technique. Indeed, while the older radiation techniques using an anterior photon field or "Hockey Stick" technique to treat the IMN exposed a significant portion of the heart to radiation treatment,¹⁰ modern computed tomography–based planning have allowed the development of multiple techniques that cover the IMN but minimize radiation dose to the heart. As the letter correctly points out, the Danish Breast Cancer Cooperative Group trials 82b and 82c, which used an electron technique to treat the IMN, showed no increase in the rate of deaths from ischemic heart disease (0.9%) in patients randomly assigned to the radiation therapy arm.¹¹ We agree that current concerns about potential cardiac morbidity and mortality risk from IMN irradiation should not be completely based on outcomes of outdated radiation techniques from 20 to 30 years ago. More studies are needed to evaluate the long-term cardiac effects of modern radiation techniques. Specifically, an especially important area of research is studies that help clarify the relationship between dose/volume of heart-irradiated and long-term cardiac morbidity/mortality, which is not currently well understood. In addition, how radiation treatment to specific portions of the heart changes cardiac physiology also needs to be defined. Such information could allow IMN irradiation to be administered even more safely.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Oh JL, Buchholz TA: Internal mammary node radiation: A proposed technique to spare cardiac toxicity. J Clin Oncol 27:e172–e173, 2009.[Free Full Text]

2. Chen RC, Lin NU, Golshan M, et al: Internal mammary nodes in breast cancer: Diagnosis and implications for patient management—A systematic review. J Clin Oncol 26:4981–4989, 2008.[Abstract/Free Full Text]

3. Lacour J, Lê M, Caceres E, et al: Radical mastectomy versus radical mastectomy plus internal mammary dissection: 10-year results of an international cooperative trial in breast cancer. Cancer 51:1941–1943, 1983.[CrossRef][Medline]

4. Meier P, Ferguson DJ, Karrison T: A controlled trial of extended radical versus radical mastectomy: 10-year results. Cancer 63:188–195, 1989.[CrossRef][Medline]

5. Morimoto T, Monden Y, Takashima S, et al: Five-year results of a randomized clinical trial comparing modified radical mastectomy and extended radical mastectomy for stage II breast cancer. Surg Today 24:210–214, 1994.[CrossRef][Medline]

6. Arriagada R, Le MG, Mouriesse H, et al: Long-term effect of internal mammary chain treatment: Results of a multivariate analysis of 1,195 patients with operable breast cancer and positive axillary nodes. Radiother Oncol 11:213–222, 1988.[CrossRef][Medline]

7. Fowble B, Glick J, Goodman R: Radiotherapy for the prevention of local-regional recurrence in high-risk patients postmastectomy receiving adjuvant chemotherapy. Int J Radiat Oncol Biol Phys 15:627–631, 1988.[Medline]

8. Obedian E, Haffty BG: Internal mammary nodal irradiation in conservatively-managed breast cancer patients: Is there a benefit? Int J Radiat Oncol Biol Phys 44:997–1003, 1999.[CrossRef][Medline]

9. Stemmer SM, Rizel S, Hardan I, et al: The role of irradiation of the internal mammary lymph nodes in high-risk stage II to IIIA breast cancer patients after high-dose chemotherapy: A prospective sequential nonrandomized study. J Clin Oncol 21:2713–2718, 2003.[Abstract/Free Full Text]

10. Harris JR, Hellman S: Put the "hockey stick" on ice. Int J Radiat Oncol Biol Phys 15:497–499, 1988.[CrossRef][Medline]

11. Højris I, Overgaard M, Christensen JJ, et al: Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: Analysis of DBCG 82b and 82c randomised trials—Radiotherapy Committee of the Danish Breast Cancer Cooperative Group. Lancet 354:1425–1430, 1999.[CrossRef][Medline]

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Related Article

• Internal Mammary Node Radiation: A Proposed Technique to Spare Cardiac Toxicity
  Julia L. Oh and Thomas A. Buchholz
  JCO 2009 27: 172-173 [Full Text]

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