Discussion
endometrial cancer, breast cancer death, breast cancer, reduction of breast cancer, endometrial cancers, lung cancer, lung cancers, tumors
ENDOMETRIAL CANCER, RECURRENCE, BREAST CANCER, CONTRALATERAL BREAST CANCER, DISEASE, LUNG CANCER, LUNG CANCERS, EVENTS, TUMORS, METASTASES
In the present study with extended follow-up data, overall mortality, cumulative breast cancer mortality, incidence of contralateral breast cancer and incidence of lung cancer were delayed in the five year-group as compared to the two year-group. It is well known that the effect of tamoxifen remains beyond the duration of therapy. This continued reduction of breast cancer events after discontinuation of treatment is referred to as the tamoxifen carry over effect. In the ATLAS trial, comparing 5 vs. 10 years of tamoxifen, the benefit of extended therapy was not evident until after year 10; 5–9 years: RR = 0.90 (95% CI 0.79–1.02) and ≥10 years: RR = 0.75 (0.62–0.90) and the aTTom trial provided similar results [In this study, the difference in breast cancer mortality rates between the five year and two-year groups of patients with ER + disease increased until 15 years after surgery but not beyond 15 years. It is possible that for endocrine sensitive tumors inducing late recurrence, most of the tamoxifen effect was achieved after only two years. Furthermore, late recurring tumors may have been effectively controlled by aromatase inhibitors, reintroduction of tamoxifen or other types of systemic treatment controlling metastases and decreasing the risk of breast cancer death. Moreover, there are patients identified with molecular tools that have excellent long-term survival without endocrine treatment [With contralateral breast cancer as endpoint, our data do support a prolonged carry over effect. For endometrial cancers beyond 15 years there were 18 cases both in the five-year and the two-year group. Thus, there was no clear evidence for a prolonged carry over effect for the induction of endometrial cancer, but postmenopausal patients should be informed about the increased risk during and shortly after tamoxifen medication.We used two different non-randomized tamoxifen doses 20 or 40 mg daily and found no difference in incidence of contralateral breast cancers between the patients receiving 20 or 40 mg. However, the incidence of endometrial cancer tended to be increased among patients receiving 40 mg daily. The optimal dose for tamoxifen as adjuvant therapy has not been established but our data do not support an increase to 40 mg daily for postmenopausal patients.The results in this report could be compared to those comparing two years of tamoxifen with a control group [In accordance with the ATAC trial where 51 lung cancers were reported in the anastrozole group as compared with 34 in the tamoxifen group, we found fewer lung cancers in the five-year group [The trial described above contributed to the change of clinical practice to five rather than two years of adjuvant endocrine therapy. Three extra years of tamoxifen therapy gradually reduced the risk of breast cancer mortality. In our current studies of the trial we aim to identify the subgroups of patients that do need five years of therapy as well as those for which a reduction to two years is enough to control the disease and reduce side effects.