Tamoxifen

The EBCTCG performed a meta-analysis of systemic treatment of early breast cancer by hormone, cytotoxic, or biological therapy methods in randomized trials involving 144,939 women with stage I or stage II breast cancer. An analysis published in 2005 included information on 80,273 women in 71 trials of adjuvant tamoxifen.[21][Level of evidence A1]

The EBCTCG performed a meta-analysis of systemic treatment of early breast cancer by hormone, cytotoxic, or biological therapy methods in randomized trials involving 144,939 women with stage I or stage II breast cancer. An analysis published in 2005 included information on 80,273 women in 71 trials of adjuvant tamoxifen.[21][Level of evidence A1]

In this analysis, the benefit of tamoxifen was found to be restricted to women with hormone receptor–positive or hormone receptor–unknown breast tumors. In these women, the 15-year absolute reduction associated with 5 years of use was 12% for recurrence and 9% for mortality.

The EBCTCG performed a meta-analysis of systemic treatment of early breast cancer by hormone, cytotoxic, or biological therapy methods in randomized trials involving 144,939 women with stage I or stage II breast cancer. An analysis published in 2005 included information on 80,273 women in 71 trials of adjuvant tamoxifen.[21][Level of evidence A1]

Allocation to approximately 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31%, largely irrespective of the use of chemotherapy, age (<50 years, 50–69 years, ≥70 years), progesterone receptor (PR) status, or other tumor characteristics.

The EBCTCG performed a meta-analysis of systemic treatment of early breast cancer by hormone, cytotoxic, or biological therapy methods in randomized trials involving 144,939 women with stage I or stage II breast cancer. An analysis published in 2005 included information on 80,273 women in 71 trials of adjuvant tamoxifen.[21][Level of evidence A1]

The meta-analysis also confirmed the benefit of adjuvant tamoxifen in hormone receptor–positive premenopausal women. Women younger than 50 years obtained a degree of benefit from 5 years of tamoxifen similar to that obtained by older women. In addition, the proportional reductions in both recurrence and mortality associated with tamoxifen use were similar in women with either node-negative or node-positive breast cancer, but the absolute improvement in survival at 10 years was greater in the node-positive breast cancer group (5.3% vs. 12.5% with 5 years of use).

Similar results were found in the IBCSG-13-93 trial.[39] Of 1,246 women with stage II disease, only the women with hormone receptor–positive disease benefited from tamoxifen.

The EBCTCG meta-analysis demonstrated that 5 years of tamoxifen was superior to shorter durations. The following results were reported:[21]

The EBCTCG meta-analysis demonstrated that 5 years of tamoxifen was superior to shorter durations. The following results were reported:[21]

A highly significant advantage of 5 years versus 1 to 2 years of tamoxifen with respect to the risk of recurrence (proportionate reduction, 15.2%; P < .001) and a less significant advantage with respect to mortality (proportionate reduction, 7.9%; P = .01) was observed.

Long-term follow-up of the Adjuvant Tamoxifen Longer Against Shorter (ATLAS [NCT00003016]) trial demonstrated that 10 years of tamoxifen therapy was superior to 5 years of tamoxifen therapy. Between 1996 and 2005, 12,894 women with early breast cancer were randomly assigned to receive 10 years or 5 years of tamoxifen therapy. The following results were reported:[43][Level of evidence A1]The results of the ATLAS trial indicated that for women who remained premenopausal after 5 years of adjuvant tamoxifen, continued tamoxifen for 5 more years was beneficial.[43] Women who have become menopausal after 5 years of tamoxifen may also be treated with AIs. For more information, see the Aromatase inhibitors section.

Long-term follow-up of the Adjuvant Tamoxifen Longer Against Shorter (ATLAS [NCT00003016]) trial demonstrated that 10 years of tamoxifen therapy was superior to 5 years of tamoxifen therapy. Between 1996 and 2005, 12,894 women with early breast cancer were randomly assigned to receive 10 years or 5 years of tamoxifen therapy. The following results were reported:[43][Level of evidence A1]The results of the ATLAS trial indicated that for women who remained premenopausal after 5 years of adjuvant tamoxifen, continued tamoxifen for 5 more years was beneficial.[43] Women who have become menopausal after 5 years of tamoxifen may also be treated with AIs. For more information, see the Aromatase inhibitors section.

Study results revealed that 10 years of tamoxifen reduced the risk of breast cancer recurrence (617 recurrences for 10 years of tamoxifen vs. 711 recurrences for 5 years of tamoxifen; P = .002), reduced breast cancer mortality (331 deaths for 10 years of tamoxifen vs. 397 deaths for 5 years of tamoxifen; P = .01), and reduced overall mortality (639 deaths for 10 years of tamoxifen vs. 722 deaths for 5 years of tamoxifen; P = .01).

Long-term follow-up of the Adjuvant Tamoxifen Longer Against Shorter (ATLAS [NCT00003016]) trial demonstrated that 10 years of tamoxifen therapy was superior to 5 years of tamoxifen therapy. Between 1996 and 2005, 12,894 women with early breast cancer were randomly assigned to receive 10 years or 5 years of tamoxifen therapy. The following results were reported:[43][Level of evidence A1]The results of the ATLAS trial indicated that for women who remained premenopausal after 5 years of adjuvant tamoxifen, continued tamoxifen for 5 more years was beneficial.[43] Women who have become menopausal after 5 years of tamoxifen may also be treated with AIs. For more information, see the Aromatase inhibitors section.

Of note, from the time of the original breast cancer diagnosis, the benefits of 10 years of therapy were less extreme before than after year 10. At 15 years from the time of diagnosis, breast cancer mortality was 15% at 10 years and 12.2% at 5 years.

Long-term follow-up of the Adjuvant Tamoxifen Longer Against Shorter (ATLAS [NCT00003016]) trial demonstrated that 10 years of tamoxifen therapy was superior to 5 years of tamoxifen therapy. Between 1996 and 2005, 12,894 women with early breast cancer were randomly assigned to receive 10 years or 5 years of tamoxifen therapy. The following results were reported:[43][Level of evidence A1]The results of the ATLAS trial indicated that for women who remained premenopausal after 5 years of adjuvant tamoxifen, continued tamoxifen for 5 more years was beneficial.[43] Women who have become menopausal after 5 years of tamoxifen may also be treated with AIs. For more information, see the Aromatase inhibitors section.

Compared with 5 years, 10 years of tamoxifen therapy increased the risk of the following:

Long-term follow-up of the Adjuvant Tamoxifen Longer Against Shorter (ATLAS [NCT00003016]) trial demonstrated that 10 years of tamoxifen therapy was superior to 5 years of tamoxifen therapy. Between 1996 and 2005, 12,894 women with early breast cancer were randomly assigned to receive 10 years or 5 years of tamoxifen therapy. The following results were reported:[43][Level of evidence A1]The results of the ATLAS trial indicated that for women who remained premenopausal after 5 years of adjuvant tamoxifen, continued tamoxifen for 5 more years was beneficial.[43] Women who have become menopausal after 5 years of tamoxifen may also be treated with AIs. For more information, see the Aromatase inhibitors section. › Compared with 5 years, 10 years of tamoxifen therapy increased the risk of the following:

Pulmonary embolus: RR, 1.87 (95% CI, 1.13–3.07; P = .01).

Long-term follow-up of the Adjuvant Tamoxifen Longer Against Shorter (ATLAS [NCT00003016]) trial demonstrated that 10 years of tamoxifen therapy was superior to 5 years of tamoxifen therapy. Between 1996 and 2005, 12,894 women with early breast cancer were randomly assigned to receive 10 years or 5 years of tamoxifen therapy. The following results were reported:[43][Level of evidence A1]The results of the ATLAS trial indicated that for women who remained premenopausal after 5 years of adjuvant tamoxifen, continued tamoxifen for 5 more years was beneficial.[43] Women who have become menopausal after 5 years of tamoxifen may also be treated with AIs. For more information, see the Aromatase inhibitors section. › Compared with 5 years, 10 years of tamoxifen therapy increased the risk of the following:

Stroke: RR, 1.06 (95% CI, 0.83–1.36).

Long-term follow-up of the Adjuvant Tamoxifen Longer Against Shorter (ATLAS [NCT00003016]) trial demonstrated that 10 years of tamoxifen therapy was superior to 5 years of tamoxifen therapy. Between 1996 and 2005, 12,894 women with early breast cancer were randomly assigned to receive 10 years or 5 years of tamoxifen therapy. The following results were reported:[43][Level of evidence A1]The results of the ATLAS trial indicated that for women who remained premenopausal after 5 years of adjuvant tamoxifen, continued tamoxifen for 5 more years was beneficial.[43] Women who have become menopausal after 5 years of tamoxifen may also be treated with AIs. For more information, see the Aromatase inhibitors section. › Compared with 5 years, 10 years of tamoxifen therapy increased the risk of the following:

Ischemic heart disease: RR, 0.76 (95% CI, 0.6–0.95; P = .02).

Long-term follow-up of the Adjuvant Tamoxifen Longer Against Shorter (ATLAS [NCT00003016]) trial demonstrated that 10 years of tamoxifen therapy was superior to 5 years of tamoxifen therapy. Between 1996 and 2005, 12,894 women with early breast cancer were randomly assigned to receive 10 years or 5 years of tamoxifen therapy. The following results were reported:[43][Level of evidence A1]The results of the ATLAS trial indicated that for women who remained premenopausal after 5 years of adjuvant tamoxifen, continued tamoxifen for 5 more years was beneficial.[43] Women who have become menopausal after 5 years of tamoxifen may also be treated with AIs. For more information, see the Aromatase inhibitors section. › Compared with 5 years, 10 years of tamoxifen therapy increased the risk of the following:

Endometrial cancer: RR, 1.74 (95% CI, 1.30–2.34; P = .0002). Notably, the cumulative risk of endometrial cancer during years 5 to 14 from breast cancer diagnosis was 3.1% for women who received 10 years of tamoxifen versus 1.6% for women who received 5 years of tamoxifen. The mortality for years 5 to 14 was 12.2 versus 15 for an absolute mortality reduction of 2.8%.