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


CONCLUSIONS
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.
Kaufmann
Manfred
M
Klinik für Gynäkologie und Geburtshilfe, J.W. Goethe-Universität Frankfurt am Main, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany. M.Kaufmann@em.uni-frankfurt.de
Rody
Achim
A
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000517:prevention & control*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004351:Drug Resistance; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009570:Nitriles / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D018570:Risk Assessment; D013629:Tamoxifen / Q000627:therapeutic use; D013997:Time Factors; D014230:Triazoles / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D020847:Estrogen Receptor Modulators; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole