Case Study IV Tamoxifen and Breast Cancer

Breast cancer is the most common noncutaneous cancer among women in the United States.57 Although breast cancer mortality has declined in the United States over the past decade, it remains the second leading cause of cancer-related deaths in women, after lung cancer.58 Approximately 211,300 women in the United States were diagnosed with invasive breast cancer in 2004, and about 39,800 women will have died of the disease.57

Hormonal therapy has an important place in the treatment and prevention of breast cancer. Because the antiestro-gen drug tamoxifen decreased contralateral breast cancer incidence, in 1992, the National Surgical Adjuvant Breast Cancer and Bowel Project (NSABP) started the Breast Cancer Prevention Trial (NSABP P-1) to test the hypothesis that tamoxifen could be used for the prevention of breast cancer in a group of healthy women at high risk for the disease.59-63 Before the Breast Cancer Prevention Trial, anecdotal evidence suggested that primary breast cancer could be prevented by tamoxifen chemotherapy; however, there was no evidence from a randomized clinical trial to support this notion.59-63 In the NSABP P-1 trial, women considered at high risk for breast cancer were (1) more than 60 years of age; or (2) aged 35 to 59 years with a 5-year predicted risk for breast cancer of 1.66% or more based on the Gail model risk for breast cancer (this risk is equivalent to that of a 60-year old woman64); or (3) having a history of lobular carcinoma in situ. In this trial, 13,388 women were randomized to receive tamoxifen 20mg/day (n = 6,681) or placebo for 5 years (n = 6,707). The main objective of the trial was to determine whether tamox-ifen prevented invasive breast cancers; secondary aims were to determine whether tamoxifen would lower the incidence of fatal and nonfatal myocardial infarctions and the incidence of bone fractures. Results from this trial, summarized in Table 23.4, showed that tamoxifen reduced the risk of invasive breast cancer by 49% and the risk of noninvasive breast cancers by 50%. These effects were observed in estrogen receptor positive (ER+), not estrogen receptor negative (ER-), breast cancers. Women on the tamoxifen arm had 19% fewer bone fractures, but this reduction was not statistically differ ent from the placebo group. With respect to vascular events and endometrial cancer, tamoxifen increased the risk of endometrial cancer (risk ratio = 2.93; 95% CI = 1.35-4.97) and increased the rates of stroke, pulmonary embolism, and deep-vein thrombosis.

Overall, this trial showed that tamoxifen use was associated with fewer ER+ breast cancers in pre- and postmenopausal women with a high-risk profile.61 However, there is a cautionary note for sexually active premenopausal women taking tamoxifen, because tamoxifen was initially developed as a fertility drug.65 Also, results from the Breast Cancer Prevention Trial showed that tamoxifen does not increase the risk of other cancers (besides endometrial), but may increase the risk of cataracts. Similar findings to the Breast Cancer Prevention Trial have appeared in other trials (Table 23.4), such as the Italian Randomized Trial of Tamoxifen and The International Breast Cancer Intervention Study 1.66'67 Preliminary analysis of the Italian study revealed no difference between the tamoxifen and placebo groups68; however, by the end of the trial, women in the tamoxifen arm did have a lower risk of breast cancer.66 On the other hand, the Royal Marsden Hospital Tamoxifen Chemoprevention trial reported no differences in the tamoxifen and placebo groups.69 Women recruited for the latter trial had a strong family history of breast cancer; because of this, it is likely that carriers of familial breast cancer genes have an intrinsically different response to estrogen antagonism. For example, a subsequent study in the same population by the NSABP group found that tamoxifen reduced breast cancer incidence by 62% in BRCA2, not BRCA1, carriers.70 The reason why tamoxifen did not decrease breast cancer incidence among women with BRCA1 mutations may be that BRCA1 tumors are frequently ER negative.71 As the Royal Marsden Hospital Tamoxifen Chemoprevention Trial included women with a strong family history of breast cancer, it is possible that many of them could have been ER negative.

Because tamoxifen increases the incidence of stroke and endometrial cancers, and long-term tamoxifen treatment may eventually lead to tamoxifen-resistant breast cancers, a search for alternative agents for breast cancer prevention and therapy, such as aromatase inhibitors, is under way. Aro-

TABLE 23.4. Breast cancer prevention trials with tamoxifen and raloxifene.
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment