Short answer: Both treat hormone receptor-positive breast cancer.12 Femara, an aromatase inhibitor, is approved only for postmenopausal women, including after 5 years of tamoxifen; tamoxifen also covers metastatic disease in men, DCIS and risk reduction. In BIG 1-98, reported in the Femara label, high cholesterol, joint pain and fractures were more common on Femara, and hot flashes and vaginal bleeding on tamoxifen. Only tamoxifen has a boxed warning.
| Femara | Tamoxifen | |
|---|---|---|
| Approved for | Postmenopausal women: after surgery for hormone receptor-positive early breast cancer, after 5 years of tamoxifen, and first- or second-line treatment of advanced breast cancer1 | Metastatic breast cancer in women and men, treatment after surgery, lowering invasive cancer risk after DCIS, and lowering breast cancer incidence in high-risk women2 |
| Label dose | 2.5 mg once a day, with or without food; every other day with cirrhosis or severe liver impairment1 | 20 to 40 mg daily for breast cancer, doses above 20 mg split morning and evening; 20 mg daily for 5 years for DCIS and risk reduction2 |
| How long | After surgery: best length unknown, median 5 years in the trials; advanced cancer: until it progresses1 | Trial data support 5 years after surgery2 |
| BIG 1-98: high cholesterol | 52.3%1 | 28.6%1 |
| BIG 1-98: hot flashes | 33.5%1 | 38.0%1 |
| BIG 1-98: joint pain or arthritis | 25.4%1 | 20.6%1 |
| BIG 1-98: bone fractures (median 96 months) | 14.7%1 | 11.4%1 |
| BIG 1-98: vaginal bleeding | 5.3%1 | 13.1%1 |
| Boxed warning | None1 | Uterine cancers, stroke and pulmonary embolism in women using it after DCIS or to lower breast cancer risk2 |
BIG 1-98 compared Femara (2,448 women) with tamoxifen (2,447 women) after surgery for early breast cancer, with a median of 60 months of treatment and 96 months of follow-up.1 Beyond the table above, night sweats were 14.5% vs 17.4%, weight gain 12.9% vs 15.4% and osteoporosis 5.1% vs 2.7%. Total cholesterol reached 1.5 times the upper limit of normal or more in 8.4% vs 3.9%, and 29% vs 20% needed cholesterol-lowering medicine. In a separate 2-year study, lumbar spine bone density fell a median 4.1% on letrozole and rose 0.3% on tamoxifen.1
Tamoxifen has a boxed warning for women using it after DCIS or to lower breast cancer risk: in the P-1 trial, endometrial cancer was 2.20 vs 0.71 per 1,000 women-years on placebo, stroke 1.43 vs 1.00 and pulmonary embolism 0.75 vs 0.25. The label says the benefits outweigh these risks in women already diagnosed with breast cancer.2 The Femara label warns about bone loss, raised cholesterol, liver impairment, tiredness and dizziness, and harm to an unborn baby.1 Taking Femara with tamoxifen 20 mg a day lowered letrozole blood levels by 38% on average.1
The Femara label gives no missed-dose instruction; the tamoxifen Medication Guide does.12 Which, if either, fits is for your prescriber. More detail: Femara side effects, tamoxifen side effects, the Femara and tamoxifen dosing schedules, the Femara and tamoxifen missed-dose pages, and Arimidex vs tamoxifen: how do the two breast cancer tablets differ?.