Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients

Abstract

Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day À1 ) with concomitant RT was prescribed in 90 hormone receptorpositive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2 -57.6%) vs 66% (95% CI 49.9 -78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40 -61%) vs 80% (95% CI 67 -89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10 -31.9%), 66% (95% CI 51.1 -77.6%), and 79% (95% CI 55 -90.9%) for CD8 p16, 16 -24, and 424%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients.

Zur Interaktion von Strahlentherapie und Tamoxifen beim Mammakarzinom

“…BET: brusterhaltende Operation; ChT: Chemotherapie; CI: Konfidenzintervall; ER: Östrogenrezeptor; F/U: Nachbeobachtungszeit; HR: Hazard-Ratio; ME: Mastektomie. duziertes kosmetisches Ergebnis) durch TAM wurde beschrieben [4,9,20,28,38,75].…”

“…Analoge klinische Untersuchungen für die Strahlentherapie fehlen. In den letzten Jahrzehnten gab es daher uneinheitliche Empfehlungen zur Therapiesequenz von TAM und Radiotherapie mit unterschiedlichen Begründungen: sequentielle Gabe von TAM wegen möglicher Radioprotektion am Tumor, simultane Gabe aufgrund einer möglichen Radiosensibilisierung des Tumors und sequentielle Gabe wegen möglicher Potenzierung radiogener pulmonaler Fibrose durch TAM [4,5,9,10,37,67].In dieser Arbeit sollen die derzeitigen Kenntnisse über Interaktionen beider Therapiemodalitäten in Bezug auf ihre Wirkung am Tumor und Normalgewebe anhand der aktuellen Literatur zusammengefasst werden. …”

Individualized treatment of early breast cancer

“…In accordance with these findings, aromatase inhibitor therapy in our analysis did not have any effect on the studied parameters. In contrast, the prospective study by Azria et al revealed that the concurrent administration of tamoxifen with radiotherapy doubled the risk of subcutaneous fibrosis [31].…”

“…The age, the menopausal status, the weight and the general health status of the patient, the stage of the tumour and the surgical intervention clearly influence the results [30]. The radiogenic changes of the breast depend on the irradiation's features and the individual radiosensitivity [30][31][32][33]. Adjuvant chemotherapy [41] and tamoxifen therapy [41,76] have been suggested to predict a poor cosmetic outcome [38].…”

“…The cosmetic and the functional outcome after postoperative breast radiotherapy depend on numerous patient-and therapyrelated factors. The radiogenic changes of the breast, such as dyspigmentation, teleangiectasia or breast oedema, fibrosis causing breast swelling and tenderness, depend on the dose, the irradiated volume and the individual radiosensitivity [30][31][32][33]. The impact of the systemic therapy on the cosmetic outcome has been the subject of numerous studies [34][35][36][37][38].…”