Interactions between radiotherapy and endocrine therapy in breast cancer.

Abstract

Whenever radiation therapy is given with curative intent there is the risk of serious damage to normal tissue. This risk increases with the dose of radiation, as does the probability of local tumour control. In the attempt to cure, the doses reach a level that inevitably causes some undesirable adverse effects, ranging from undetectable, or minimal, to unacceptably severe. Over the last few years, a number of reports have suggested that the prediction of normal tissue response after radiotherapy may be achieved by assays on samples withdrawn from the patients prior to treatment, although recent reports have described mixed results. The ability to predict tumour response to anti-hormones in patients with breast cancer has important implications with regard to treatment. Recent discoveries promise to provide individualized treatment options. However, there are no data to support that, used jointly, the combination of radiotherapy and hormone therapy may achieve an enhancement of breast cancer tumour response. Nowadays, development in cancer therapy is increasingly arising out of studies in basic science; its implementation in the hands of clinicians is improving the management of patients with cancer. In addition, as the biological aspects of irradiation and hormonal therapy offer an explanation, at least in part, for the outcome observed in patients with breast cancer after therapy, we have focused this review on trying to analyse the most relevant experimental research about the relative roles of radiotherapy and hormonal therapy, the corresponding side-effects and, taking into account recent advances, future areas of research that we consider of major importance in the field.

Effects of estrogen deprivation due to breast cancer treatment

“…It has been indicated that a reversible castration over 2-3 years with a GnRH analogue is comparable in terms of disease-free and overall survival to treatment with six courses of cyclophosphamide, methotrexate and fluorouracil (CMF) chemotherapy (Boccardo et al 2000, Castiglione-Gertsch et al 2000 among premenopausal patients with hormone receptor-positive disease. Radiotherapy at the ovaries seems to produce a two-third reduction in local recurrence of breast cancer; however, the absolute benefit is diminished because of the disadvantage of permanent amenorrhea (Early Breast Cancer Trialists' Collaborative Group 2002, del Moral et al 2002.…”

Interaction Between Estrogen Receptor Alpha, Ionizing Radiation and (anti-) Estrogens in Breast Cancer Cells

“…Numerous prospective and retrospective trials demonstrated that a breast conserving surgery, consisting of segmental mastectomy with or without axillaryÕs lymph node dissection, is equivalent to mastectomy in terms of overall and disease free survivals for patients with early stage breast carcinoma. Radiotherapy prevents local recurrence of breast cancer after breast-conserving surgery [5][6][7]. Both hormone therapy and adjuvant radiotherapy remain major treatments to manage early breast cancer [4].…”

“…Cells were irradiated(3,5, 8 Gy) and subsequently maintained in culture for 96 h either in the absence or presence of estrogenic or/ and anti-estrogenic ligands (E 2 at 0.1 nM, 4-OH-Tam at 100 nM, ICI 182,780 at 100 nM). Non-irradiated cells were cultured in parallel.…”

Aromatase inhibitors decrease radiation-induced lung fibrosis: Results of an experimental study

“…The effects of Tamoxifen (TAM) on the lung fibrosis have been investigated in a considerable number of studies while it was the only known agent for hormonotherapy over a long period of time [8,14]. It is a wellestablished fact that, alongside its anti-estrogenic effects, TAM has non-hormonal activities such as the stimulation of TGF-B production which in turn triggers tissue fibrosis [15,16].…”