An association between postoperative radiotherapy for primary breast cancer in 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) studies and the subsequent appearance of pleural mesothelioma

Our plain-English summary of An association between postoperative radiotherapy for primary breast cancer in 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) studies and the subsequent appearance of pleural mesothelioma, by M. Deutsch, S.R. Land, M. Begovic, et al (American Journal of Clinical Oncology, 2007).

The study

• Authors: M. Deutsch, S.R. Land, M. Begovic, R. Cecchini, N. Wolmark
• Journal: American Journal of Clinical Oncology
• Published: 2007;30(3):294-6
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Among the minority of patients with pleural mesothelioma and no known exposure to asbestos, there have been case reports suggesting a possible association with previous radiotherapy. The association between radiotherapy for primary breast cancer and the subsequent occurrence of mesothelioma was investigated in women entered into 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) prospective clinical trials for breast cancer.

Methods: Follow-up information was obtained on 22,140 patients entered into 11 NSABP clinical trials for treatment of primary breast cancer between 1971 and 1994. Postoperative radiotherapy was administered to 9342 patients, mainly after lumpectomy. Postlumpectomy patients were treated with radiotherapy just to the ipsilateral breast and without regional nodal irradiation. There were 12,798 patients who did not have postoperative radiotherapy, and almost all had mastectomy.

Results: Three pleural mesotheliomas were identified, and all occurred in the ipsilateral thorax of the irradiated patients (P = 0.009). All had received postlumpectomy breast irradiation for ductal carcinoma in situ. None had a known previous exposure to asbestos.

Conclusions: There appears to be a small but statistically significant increased risk of developing mesothelioma following radiotherapy administered for primary breast cancer. However, in absolute numbers, the risk is too small to be considered a contraindication to administering radiotherapy when indicated.

In plain English

This study examined whether radiotherapy after surgery for primary breast cancer was associated with later mesothelioma. The authors used follow-up information on 22,140 patients entered into 11 National Surgical Adjuvant Breast and Bowel Project clinical trials between 1971 and 1994. Of these, 9342 received postoperative radiotherapy, mainly to the breast after lumpectomy, and 12,798 did not; almost all of those had mastectomy. Three pleural mesotheliomas were found, all on the treated side of the chest in irradiated women (P = 0.009). All three had breast irradiation after lumpectomy for ductal carcinoma in situ. None had a known previous asbestos exposure, and all three died after the mesothelioma diagnosis. Using national registry (SEER) rates, 0.80 cases were expected among irradiated women, a relative risk of 3.74 compared with the general population. Among non-irradiated women, 1.13 cases were expected and none occurred, a difference that was not statistically significant. The authors concluded that the increased risk appeared small but statistically significant, and too small in absolute numbers to be a reason not to give radiotherapy when indicated. They noted that some cases may have been missed because they were never biopsied.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Analysis of follow-up data from 11 prospective breast cancer clinical trials. Observed mesothelioma cases were compared, using binomial tests, with numbers expected from SEER registry rates.
• Who was studied: 22,140 patients with primary breast cancer entered into 11 NSABP clinical trials in the United States between 1971 and 1994. 9342 received postoperative radiotherapy and 12,798 did not.
• Exposure: Postoperative radiotherapy, mainly whole-breast irradiation after lumpectomy to 50 Gy at 2 Gy per day, without regional nodal irradiation. Some B-04 mastectomy patients had chest wall and nodal irradiation at 45 to 50 Gy. None of the mesothelioma cases had a known previous asbestos exposure.
• Main results:
  • Three pleural mesotheliomas were identified, all in the same side of the chest as the treated breast in irradiated patients (P = 0.009, one-sided binomial test).
  • All three cases had received breast irradiation after lumpectomy for ductal carcinoma in situ.
  • None of the three had a known previous exposure to asbestos.
  • The intervals from breast cancer diagnosis to mesothelioma diagnosis were 25, 115 and 191 months. All 3 patients died, at 31, 3 and 15 months respectively after the mesothelioma diagnosis.
  • Among irradiated patients, 0.80 mesotheliomas were expected from SEER rates for U.S. women of the same age and years. The observed number (3) was significantly higher (one-sided P value of 0.039). The relative risk compared with the general population was 3.74.
  • Among women who did not receive radiation, 1.13 mesotheliomas were expected and 0 were observed. This difference was not statistically significant (one-sided P 0.32; two-sided P 0.43).
• The authors' conclusion: The authors concluded that there appeared to be a small but statistically significant increased risk of mesothelioma following radiotherapy for primary breast cancer. They added that in absolute numbers the risk is too small to be considered a contraindication to radiotherapy when indicated.
• Limitations the authors state:
  • Only histologically verified cases were counted, so the true incidence may be underestimated. Some ipsilateral pleural effusions or pleural masses may have been taken for metastatic breast cancer and not biopsied.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Clinical Trial, Thorax, Carcinoma.

Related studies

• Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study — J.M. Madrigal, C.N. Pruitt, et al. (2024)
• Metastases to the breast: differential diagnosis from primary breast carcinoma — B. Vergier, M. Trojani, et al. (1991)
• Effect of postoperative radiotherapy on changes in pulmonary function in patients with stage II and IIIA lung carcinoma — N.C. Choi, D.J. Kanarek, et al. (1990)
• Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for patients after extrapleural pneumonectomy for malignant pleural mesothelioma — T. Ebara, H. Kawamura, et al. (2012)
• Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series — S. Tonoli, P. Vitali, et al. (2011)
• Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy's and St Thomas' hospitals — A. Bille, E. Belcher, et al. (2012)

Browse more research in American Journal of Clinical Oncology, or return to medical research.