Long-term risk of breast cancer recurrence: the need for extended adjuvant therapy

Abstract

Background: All women with early breast cancer, even those with small tumors and negative nodes, remain at appreciable risk of recurrence after surgery over the subsequent 10-15 years. In women with tumors expressing estrogen receptors and/or progesterone receptors, standard systemic adjuvant therapy is 5 years of tamoxifen, which substantially reduces the risk of recurrence and breast cancer-related death. Tamoxifen efficacy benefits are limited to 5 years of treatment, presumably a consequence of acquired tamoxifen resistance. The third-generation aromatase inhibitors, which are highly selective and potent in suppressing whole-body estrogen synthesis in postmenopausal women, are being investigated as alternative or complementary treatments to tamoxifen. For treatment beyond adjuvant tamoxifen for 5 years, letrozole is the only aromatase inhibitor for which clinical trial data were reported. That trial, MA.17, evaluated letrozole as extended adjuvant treatment following standard adjuvant tamoxifen in postmenopausal women with predominantly estrogen receptor--and/or progesterone receptor--positive early breast cancer.

Results: Compared with placebo, letrozole markedly reduced the residual risk of recurrence, by 42%, and the improvement in disease-free survival was irrespective of patient nodal status. A significant improvement in overall survival has already been seen in the patients at highest risk, those with positive nodes.

Conclusion: On the basis of these results, extended adjuvant letrozole is recommended for all patients completing 5 years of adjuvant tamoxifen, including women generally considered at minimal risk.

Fig. 1

Relapse-free survival 10 years and 15 years after diagnosis of early breast cancer (5 years and 10 years, respectively, after completion of standard adjuvant therapy), by tumor stage and hormone receptor status (Hortobagyi et al. 2004). RFS relapse-free survival, HR hormone receptor. (Adapted from Fig. 4 of Hortobagyi et al. Presentation at ASCO 2004, Abstract 585)

Fig. 2

Annual risk of recurrence in patients with early breast cancer, for 12 years following diagnosis, according to estrogen receptor status (Saphner et al. 1996). (Reprinted with permission, from Fig. 4 in Saphner et al. (1996) American Society of Clinical Oncology)

Fig. 3

MA.17 trial design

Fig. 4

MA.17: Kaplan–Meier estimates of disease-free survival, for all patients (Goss 2004). (Reprinted with permission from Goss. Presentation at ASCO 2004, American Society of Clinical Oncology)

Fig. 5

MA.17: total recurrences of breast cancer, with letrozole vs placebo, for all patients, node-positive patients (Node+), and node-negative patients (Node−) (Goss 2004). (Reprinted with permission, from Goss. Presentation at ASCO 2004, American Society of Clinical Oncology)

Fig. 6

MA.17: Kaplan–Meier estimates of overall survival, for node-positive patients (Goss 2004). (Reprinted with permission from Goss. Presentation at ASCO 2004, American Society of Clinical Oncology)