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Risk of Ipsilateral Lung Cancer After Postmastectomy Radiotherapy and Smoking: Does the Possible Triumph Over the Actual?

The University of Texas M. D. Anderson Cancer Center, Houston, TX

To the Editor:

We read with interest the article by Kaufman et al¹ on the risk of second primary lung cancer associated with postmastectomy radiotherapy (PMRT) and cigarette smoking. In their matched population–based case-control study among women diagnosed with nonmetastatic breast cancer between the years 1965 and 1989, the authors found that patients who received PMRT and had smoked cigarettes had a sharply elevated risk of ipsilateral lung cancer compared with women who did not receive PMRT and never smoked.¹

A doubling of the risk of subsequent lung cancer was reported in the ipsilateral lung only, but this risk appeared mainly limited to patients who smoked, resulting in significantly higher lung cancer rates even in smoking patients who did not receive PMRT at all.¹ Another larger hospital-based case-control study investigated the joint effects of cigarette smoking and PMRT on lung cancer risk among patients registered between the years 1960 and 1997.² Smoking resulted a significant and independent risk factor for lung cancer, but no interactive effect between smoking and PMRT was found. Results of both studies are conflicting and should be interpreted cautiously, due to several limitations that could have biased the analyses—mainly the reliance on retrospectively ascertaining smoking history, which is consistently underreported in the medical record.

The risks of early and late radiogenic sequelae are strongly related to the dose, volume, and fractionation of the tissue of interest.^3,4 Data reported by Kaufman et al on the risk of lung cancer due to PMRT derived from pilot studies in which the dose to the lung was not ascertained, and the volume of lung included in radiation fields, were most likely higher than risk of lung cancer due to PMRT from treatment with current techniques.¹ Moreover, the era of interest overlaps at least two substantive changes in radiation technique, one of which was the discontinuation of enface photons.

Specifically, changes in radiation technique over time impacted long-term outcome improving the balance among a decreased rate of breast cancer deaths, a decreased rate of cardiovascular events, and number of radiation-related lung sequelae.⁵ The recent analysis of the Danish PMRT trials demonstrated a survival benefit even patients with one to three positive nodes.⁶ There is also coalescing of data revealing at least a 66% relative reduction of locoregional recurrence risk with the utilization of PMRT. Data also conclude that for every 4% to 5% absolute locoregional recurrence risk reduction, an ensuing 1% survival benefit is obtainable. Another recent study using Surveillance, Epidemiology, and End Results data of the late 1970s and all of the 1980s documented a continual decrease in cardiovascular events.⁷ Lastly, two recent studies in patients predominantly treated in 1980s and 1990s estimated a decreasing risk of lung cancer after PMRT.^8,9 Data suggest that the incidence of PMRT toxicities will continue to decrease as modern radiotherapy techniques are developed.¹⁰

Kaufman et al also speculated that "breast cancer survivors who are or have been smokers and have received radiotherapy may be appropriate candidates for lung cancer screening with spiral computed tomography."¹ However, screening for lung cancer with computed tomography has not demonstrated a reduction in lung cancer mortality to date (even in high-risk populations),¹¹ and the most authoritative United States medical organizations currently state that the evidence is insufficient to recommend for or against lung cancer screening with computed tomography and/or other tests.^12-14

The authors concluded that "physicians of patients newly diagnosed with breast cancer, especially those for whom the survival benefits of PMRT are marginal, should consider smoking history when discussing treatment options."¹ We however, conclude that data from Kaufman et al cannot be analyzed in a vacuum. The current threshold for the use of PMRT is steadily decreasing as the data for survival benefit in carefully selected patients are steadily increasing. We believe that smoking history should be considered; it should be considered and used as an opportunity at the time of one cancer diagnosis to intervene with cessation techniques and, it is hoped, prevent a second diagnosis of lung cancer. Informed consent processes should include a discussion of potential radiation-induced second malignancy. But, a possible detriment should not be the absolute conqueror of an actual benefit. In our opinion, careful three-dimensional treatment planning to limit the volume of treated lung is warranted and is becoming the standard of care; research should continue, but we believe that the known risk of lung cancer secondary to PMRT using modern techniques is low, and considerations of smoking history should not restrict PMRT use when otherwise indicated.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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

REFERENCES

1. Kaufman EL, Jacobson JS, Hershman DL, et al: Effect of breast cancer radiotherapy and cigarette smoking on risk of second primary lung cancer. J Clin Oncol 26:392-398, 2008[Abstract/Free Full Text]

2. Ford BM, Sigurdson AJ, Petrulis ES, et al: Effects of smoking and radiotherapy on lung carcinoma in breast carcinoma survivors. Cancer 98:1457-1464, 2003[CrossRef][Medline]

3. Kahán Z, Csenki M, Varga Z, et al: The risk of early and late lung sequelae after conformal radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys 68:673-681, 2007[Medline]

4. De Giorgi U, Giannini M, Frassineti L, et al: Feasibility of radiotherapy after high-dose dense chemotherapy with epirubicin, preceded by dexrazoxane, and paclitaxel for patients with high-risk stage II-III breast cancer. Int J Radiat Oncol Biol Phys 65:1165-1169, 2006[Medline]

5. Clarke M, Collins R, Darby S, et al: Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials. Lancet 366:2087-2106, 2005[Medline]

6. Overgaard M, Nielsen HM, Overgaard J: Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in the international consensus reports? Radiother Oncol 82:247-253, 2007[CrossRef][Medline]

7. Giordano SH, Kuo YF, Freeman JL, et al: Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 97:419-424, 2005[Abstract/Free Full Text]

8. Schaapveld M, Visser O, Louwman MJ, et al: Risk of new primary nonbreast cancers after breast cancer treatment: A Dutch population-based study. J Clin Oncol 26:1239-1246, 2008[Abstract/Free Full Text]

9. Kirova YM, De Rycke Y, Gambotti L, et al: Second malignancies after breast cancer: The impact of different treatment modalities. Br J Cancer 98:870-874, 2008[CrossRef][Medline]

10. Recht A, Edge SB, Solin LJ, et al: Postmastectomy radiotherapy: Clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19:1539-1569, 2001[Abstract/Free Full Text]

11. Black WC: Computed tomography screening for lung cancer: Review of screening principles and update on current status. Cancer 110:2370-2384, 2007[CrossRef][Medline]

12. Bach PB, Silvestri GA, Hanger M, et al: Screening for lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 132:69S-77S, 2007[CrossRef][Medline]

13. National Cancer Institute: Physician Data Query, National Cancer Institute Common Scientific Outline partners. http://www.cancer.gov/cancertopics/pdq/screening/overview/healthprofessional

14. US Preventive Services Task Force: Screening for Lung Cancer. http://www.ahrq.gov/clinic/uspstf/uspslung.htm

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