Hormonal Therapies in Breast Cancer
Maureen Major , MS , RN from Memorial Sloan-Kettering Cancer Center started the morning by updating the group on the latest studies in hormonal therapies for the treatment of early stage breast cancer. There are approximately 215,900 cases of breast cancer annually, with 40,110 deaths. Although lung cancer now accounts for more deaths in women, breast cancer still accounts for the second highest number of cancer deaths. Tamoxifen has been the mainstay of treatment in hormone receptor-positive women for over 20 years. Despite the increased risk of DVT and endometrial cancer, along with the menopausal symptoms, the benefits often far outweigh the risks. With the success of aromatase inhibitors in metastatic disease, the natural progression was to conduct studies of these agents in early stage disease, either with or in comparison to tamoxifen. The following are the recent studies addressing aromatase inhibitors in early stage breast cancer.
The ATAC trial randomized post-menopausal women with early stage breast cancer, after primary treatment, to receive anastrozole (Arimidex) 1mg daily + placebo, placebo + tamoxifen 20mg daily, or anastrozole 1mg + tamoxifen 20mg daily. The study found anastrozole alone to be superior to tamoxifen alone by 3.3% at the 6 year follow up point (p=0.005). The combination arm did not show superiority to either drug alone. (Baum, Lancet, 2002(359) p.2131 and Howell, 2004 SABCS, Abstract 1)
The second study, NCIC CTG, compared letrozole (Femara) 2.5 mg daily to placebo, after completion of 5 years of adjuvant tamoxifen. The addition of therapy after tamoxifen is being called "extended adjuvant therapy". The study included over 5000 post-menopausal women with hormone receptor-positive disease. The study found that the addition of letrozole improved disease-free survival significantly (p=0.00004), although overall survival was similar in the two groups. (Goss, New England Journal of Medicine 2003(349))
The IES study randomized postmenopausal women who had received 2-3 years of tamoxifen to receive an additional 3-2 years of tamoxifen 20mg vs. 3-2 years of exemestane 25mg daily (Aromasin). At 3 years follow-up, disease-free survival in the exemestane arm was significantly better (p=0.00005). Coombes, New England Journal of Medicine 2004(350) p.1081)
The BIG 1-98 study included over 8000 postmenopausal women with early stage disease. The study has 4 arms: tamoxifen (tam) for 5 years; letrozole (let) for 5 yrs; tam (2 yrs) then let (3 yrs); let (2 yrs) then tam (3 yrs). The initial analysis only looked at the first 2 arms and found letrozole to be superior in disease-free survival (p=0.003). In addition, the letrozole arm had 3.4% fewer recurrences or ipsilateral disease occurrences (p=0.0002). (Thurliman, Journal of Clinical Oncology 23(16s), Abstract 511) Future results of the 3 rd & 4 th arms of this study will help clinicians determine sequencing for these therapies.
As far as side effects go, AIs were better tolerated with regards to hot flashes, vaginal bleeding, endometrial cancer, CVA, and DVT. Tamoxifen fared better with regards to musculoskeletal disorders and fractures. As far as pre- or peri-menopausal women, they can be re-evaluated after 2-3 years of tamoxifen. If they have ceased having menses, they can consider switching to exemestane or complete 5 years of tam followed by 5 years of letrozole.