Wednesday, November 17, 2010

Tamoxifen

This is going to be a tome, and if so, this will be a chapter *separate from* hormone therapy, including estrogen reduction / anti-estrogen, PROGESTERONE / anti-progesterone.

Internet Drug Index has this warning on Nolvadex, brand-name Tamoxifen.

WARNING

For Women with Ductal Carcinoma in Situ (DCIS) and Women at High Risk for Breast Cancer: Serious and life-threatening events associated with NOLVADEX in the risk reduction setting (women at high risk for cancer and women with DCIS) include uterine malignancies, stroke and pulmonary embolism. Incidence rates for these events were estimated from the NSABP P-1 trial (see CLINICAL PHARMACOLOGY-Clinical Studies - Reduction in Breast Cancer Incidence In High Risk Women). Uterine malignancies consist of both endometrial adenocarcinoma (incidence rate per 1,000 women-years of 2.20 for NOLVADEX vs 0.71 for placebo) and uterine sarcoma (incidence rate per 1,000 women-years of 0.17 for NOLVADEX vs 0.4 for placebo)*. For stroke, the incidence rate per 1,000 women-years was 1.43 for NOLVADEX vs 1.00 for placebo**. For pulmonary embolism, the incidence rate per 1,000 women-years was 0.75 for NOLVADEX versus 0.25 for placebo**.
Some of the strokes, pulmonary emboli, and uterine malignancies were fatal.

Here's more from the Lancet:

Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed ...

For ER-positive disease only (common in cancers in premenopausal women), allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50—69, ≥70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0·00001 for recurrence, 2p=0·01 for breast cancer mortality) more effective than just 1—2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0—4 and 5—14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.

The big question is 31% of what. For example, if after radiation, the risk of recurrence is 2-10%, a 31% reduction is actually a reduction of 3%-to-.66% -- definitely outweighed by side effects, if you are in a serious side effect risk group.

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