Skip to main content
Erschienen in: Supportive Care in Cancer 3/2013

01.03.2013 | Original Article

Comparison of the effects of aromatase inhibitors and tamoxifen on radiation-induced lung toxicity: results of an experimental study

verfasst von: Guler Yavas, Cagdas Yavas, Hilal Acar, Hatice Toy, Deniz Yuce, Ozlem Ata

Erschienen in: Supportive Care in Cancer | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The purpose of this study is to compare the effects of anastrozole, letrozole and tamoxifen on radiation-induced pulmonary fibrosis.

Methods

Eighty female Wistar albino rats were divided into eight groups. Group (G) 1 was defined as control group. G2 was radiation therapy (RT) only group. Groups 3, 4 and 5 were tamoxifen, anastrozole and letrozole control groups respectively. Groups 6, 7 and 8 were RT plus tamoxifen, anastrozole and letrozole groups, respectively. A single dose of 12 Gy RT was given to both lungs. Tamoxifen, anastrozole and letrozole were started 1 week before the RT and continued until the animals were sacrificed 16 weeks after the RT. As an end point, the extent of pulmonary fibrosis for each rat was quantified with image analysis of histological sections of the lung. Kruskal–Wallis and Mann–Whitney U tests were used for statistical analyses.

Results

The congestion, inflammation and pulmonary fibrosis scores were significantly different between all the study groups (p values were <0.001 for each). When compared with RT only group, concomitant RT and tamoxifen group increased the radiation-induced pulmonary fibrosis (p = 0.005). However, using either anastrozole or letrozole with RT did not increase the radiation-induced pulmonary fibrosis (p values were 0.768 and 0.752, respectively).

Conclusion

Concomitant use of tamoxifen with RT seems to increase radiation-induced pulmonary toxicity. However, the use of both anastrozole and letrozole appears to be safe with concomitant RT, without increasing the risk of pulmonary fibrosis. This finding should be clarified with further clinical studies.
Literatur
1.
Zurück zum Zitat Graves PR, Siddiqui F, Anscher MS, Movsas B (2010) Radiation pulmonary toxicity: from mechanisms to management. Semin Radiat Oncol 20:201–207PubMedCrossRef Graves PR, Siddiqui F, Anscher MS, Movsas B (2010) Radiation pulmonary toxicity: from mechanisms to management. Semin Radiat Oncol 20:201–207PubMedCrossRef
2.
Zurück zum Zitat Kocak Z, Evans ES, Zhou SM (2005) Challenges in defining radiation pneumonitis in patients with lung cancer. Int J Radiat Oncol Biol Phys 62:635–638PubMedCrossRef Kocak Z, Evans ES, Zhou SM (2005) Challenges in defining radiation pneumonitis in patients with lung cancer. Int J Radiat Oncol Biol Phys 62:635–638PubMedCrossRef
3.
Zurück zum Zitat Trott KR, Herrmann T, Kasper M (2004) Target cells in radiation pneumopathy. Int J Radiat Oncol Biol Phys 58(2):463–469PubMedCrossRef Trott KR, Herrmann T, Kasper M (2004) Target cells in radiation pneumopathy. Int J Radiat Oncol Biol Phys 58(2):463–469PubMedCrossRef
4.
Zurück zum Zitat Kasper M, Haroske G (1996) Alterations in the alveolar epithelium after injury leading to pulmonary fibrosis. Histol Histopathol 11:463–483PubMed Kasper M, Haroske G (1996) Alterations in the alveolar epithelium after injury leading to pulmonary fibrosis. Histol Histopathol 11:463–483PubMed
5.
Zurück zum Zitat Fleckenstein K, Zgonjanin L, Chen L (2007) Temporal onset of hypoxia and oxidative stress after pulmonary irradiation. Int J Radiat Oncol Biol Phys 68:196–204PubMedCrossRef Fleckenstein K, Zgonjanin L, Chen L (2007) Temporal onset of hypoxia and oxidative stress after pulmonary irradiation. Int J Radiat Oncol Biol Phys 68:196–204PubMedCrossRef
6.
Zurück zum Zitat Chen Y, Williams J, Ding I et al (2002) Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol 12:26–33PubMedCrossRef Chen Y, Williams J, Ding I et al (2002) Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol 12:26–33PubMedCrossRef
7.
Zurück zum Zitat Jordan VC (2004) Selective estrogen receptor modulation: concept and consequences in cancer. Cancer Cell 5:207–213PubMedCrossRef Jordan VC (2004) Selective estrogen receptor modulation: concept and consequences in cancer. Cancer Cell 5:207–213PubMedCrossRef
8.
Zurück zum Zitat Bese NS, Umay C, Yildirim S, Ilvan S, Dirican A, Salar S et al (2006) The effects of tamoxifen on radiation-induced pulmonary fibrosis in Wistar albino rats: results of an experimental study. Breast 15:456–460PubMedCrossRef Bese NS, Umay C, Yildirim S, Ilvan S, Dirican A, Salar S et al (2006) The effects of tamoxifen on radiation-induced pulmonary fibrosis in Wistar albino rats: results of an experimental study. Breast 15:456–460PubMedCrossRef
9.
Zurück zum Zitat Koc M, Polat P, Suma S (2002) Effects of tamoxifen on pulmonary fibrosis after cobalt-60 radiotherapy in breast cancer patients. Radiother Oncol 64:171–175PubMedCrossRef Koc M, Polat P, Suma S (2002) Effects of tamoxifen on pulmonary fibrosis after cobalt-60 radiotherapy in breast cancer patients. Radiother Oncol 64:171–175PubMedCrossRef
10.
Zurück zum Zitat Huang E-Y, Wang C-J, Chen H-C et al (2000) Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lypmhatics: evidence for non-dosimetric factors. Radiother Oncol 57:91–96PubMedCrossRef Huang E-Y, Wang C-J, Chen H-C et al (2000) Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lypmhatics: evidence for non-dosimetric factors. Radiother Oncol 57:91–96PubMedCrossRef
11.
Zurück zum Zitat Bentzen SM, Skoczylas JZ, Overgaard M, Overgaard J (1996) Radiotherapy-related lung fibrosis enhanced by tamoxifen. J Natl Cancer Inst 88:918–922PubMedCrossRef Bentzen SM, Skoczylas JZ, Overgaard M, Overgaard J (1996) Radiotherapy-related lung fibrosis enhanced by tamoxifen. J Natl Cancer Inst 88:918–922PubMedCrossRef
12.
Zurück zum Zitat Ashcroft T, Simpson JM, Timbrelli V (1988) Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 41:467–470PubMedCrossRef Ashcroft T, Simpson JM, Timbrelli V (1988) Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 41:467–470PubMedCrossRef
13.
Zurück zum Zitat Osborne C, Boldt D, Clark G et al (1983) Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase. Cancer Res 43:3583–3585PubMed Osborne C, Boldt D, Clark G et al (1983) Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase. Cancer Res 43:3583–3585PubMed
14.
Zurück zum Zitat Wazer D, Tercilla O, Lin P et al (1989) Modulation in the radiosensitivity of MCF-7 human breast carcinoma cells by 17-estradiol and tamoxifen. Br J Radiol 62:1079–1083PubMedCrossRef Wazer D, Tercilla O, Lin P et al (1989) Modulation in the radiosensitivity of MCF-7 human breast carcinoma cells by 17-estradiol and tamoxifen. Br J Radiol 62:1079–1083PubMedCrossRef
15.
Zurück zum Zitat Paulsen G, Strickert T, Marthinsen A et al (1996) Changes in radiation sensitivity and steroid receptor content induced by hormonal agents and ionizing radiation in breast cancer cells in vitro. Acta Oncol 35:1011–1019PubMedCrossRef Paulsen G, Strickert T, Marthinsen A et al (1996) Changes in radiation sensitivity and steroid receptor content induced by hormonal agents and ionizing radiation in breast cancer cells in vitro. Acta Oncol 35:1011–1019PubMedCrossRef
16.
Zurück zum Zitat Sarkaria J, Miller E, Parker C et al (1994) 4-Hydroxytamoxifen, an active metabolite of tamoxifen, does not alter the radiation sensitivity of MCF-7 breast carcinoma cells irradiated in vitro. Breast Cancer Res Treat 30:159–165PubMedCrossRef Sarkaria J, Miller E, Parker C et al (1994) 4-Hydroxytamoxifen, an active metabolite of tamoxifen, does not alter the radiation sensitivity of MCF-7 breast carcinoma cells irradiated in vitro. Breast Cancer Res Treat 30:159–165PubMedCrossRef
17.
Zurück zum Zitat Ellis P, Saccani-Jotti G, Clarke R et al (1997) Introduction of apoptosis by tamoxifen and ICI 182780 in primary breast cancer. Int J Cancer 72:608–613PubMedCrossRef Ellis P, Saccani-Jotti G, Clarke R et al (1997) Introduction of apoptosis by tamoxifen and ICI 182780 in primary breast cancer. Int J Cancer 72:608–613PubMedCrossRef
18.
Zurück zum Zitat Whelan T, Levine M (2005) Radiation therapy and tamoxifen: concurrent or sequential? That is the question. J Clin Oncol 23(1):1–4PubMedCrossRef Whelan T, Levine M (2005) Radiation therapy and tamoxifen: concurrent or sequential? That is the question. J Clin Oncol 23(1):1–4PubMedCrossRef
19.
Zurück zum Zitat Azria D, Larbouret C, Cunat S et al (2005) Letrozole sensitizes breast cancer cells to ionizing radiation. Breast Cancer Res 7(1):R156–R163PubMedCrossRef Azria D, Larbouret C, Cunat S et al (2005) Letrozole sensitizes breast cancer cells to ionizing radiation. Breast Cancer Res 7(1):R156–R163PubMedCrossRef
20.
Zurück zum Zitat Brenner DJ (2008) The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction. Semin Radiat Oncol 18(4):234–239PubMedCrossRef Brenner DJ (2008) The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction. Semin Radiat Oncol 18(4):234–239PubMedCrossRef
21.
Zurück zum Zitat Baum M, Buzdar A, Cuzick J et al (2003) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 98:1802–1810PubMedCrossRef Baum M, Buzdar A, Cuzick J et al (2003) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 98:1802–1810PubMedCrossRef
22.
Zurück zum Zitat Howell A, Cuzick J, Baum M et al (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62PubMedCrossRef Howell A, Cuzick J, Baum M et al (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62PubMedCrossRef
23.
Zurück zum Zitat Forbes JF, Cuzick J, Buzdar A et al (2008) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 9:45–53PubMedCrossRef Forbes JF, Cuzick J, Buzdar A et al (2008) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 9:45–53PubMedCrossRef
24.
Zurück zum Zitat Buzdar A, Howell A, Cuzick J et al (2006) Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol 7:633–643PubMedCrossRef Buzdar A, Howell A, Cuzick J et al (2006) Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol 7:633–643PubMedCrossRef
25.
Zurück zum Zitat Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF, ATAC/LATTE investigators (2010) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 11(12):1135–1141PubMedCrossRef Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF, ATAC/LATTE investigators (2010) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 11(12):1135–1141PubMedCrossRef
26.
Zurück zum Zitat ATAC Trialists’ Group (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Lancet 359:2131–2139CrossRef ATAC Trialists’ Group (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Lancet 359:2131–2139CrossRef
27.
Zurück zum Zitat Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J et al (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350:1081–1092PubMedCrossRef Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J et al (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350:1081–1092PubMedCrossRef
28.
Zurück zum Zitat Goss PE, Hadji P, Subar M, Abreu P, Thomsen T, Banke-Bochita J (2007) Effects of steroidal and non-steroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women. Breast Cancer Res 9(4):R52PubMedCrossRef Goss PE, Hadji P, Subar M, Abreu P, Thomsen T, Banke-Bochita J (2007) Effects of steroidal and non-steroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women. Breast Cancer Res 9(4):R52PubMedCrossRef
29.
Zurück zum Zitat Love RR, Barden HS, Mazess RB, Epstein S, Chappell RJ (1994) Effect of tamoxifen on lumbar spine bone mineral density in postmenopausal women after 5 years. Arch Intern Med 154:2585–2588PubMedCrossRef Love RR, Barden HS, Mazess RB, Epstein S, Chappell RJ (1994) Effect of tamoxifen on lumbar spine bone mineral density in postmenopausal women after 5 years. Arch Intern Med 154:2585–2588PubMedCrossRef
30.
Zurück zum Zitat Bese NS, Umay C, Serdengecti S, Kepil N, Sut N, Altug T, Ober A (2010) The impact of trastuzumab on radiation-induced pulmonary fibrosis: results of an experimental study. Med Oncol 27(4):1415–1419PubMedCrossRef Bese NS, Umay C, Serdengecti S, Kepil N, Sut N, Altug T, Ober A (2010) The impact of trastuzumab on radiation-induced pulmonary fibrosis: results of an experimental study. Med Oncol 27(4):1415–1419PubMedCrossRef
Metadaten
Titel
Comparison of the effects of aromatase inhibitors and tamoxifen on radiation-induced lung toxicity: results of an experimental study
verfasst von
Guler Yavas
Cagdas Yavas
Hilal Acar
Hatice Toy
Deniz Yuce
Ozlem Ata
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
Supportive Care in Cancer / Ausgabe 3/2013
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-012-1584-7

Weitere Artikel der Ausgabe 3/2013

Supportive Care in Cancer 3/2013 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.