The Austrian Breast and Colorectal Cancer Study Group (ABCSG), formerly known as "Cooperative Studiengruppe Mammakarzinom," was established in 1984 as a cooperative institution conducting multicenter clinical trials in breast and colorectal cancer. Since its inception, more than 20,000 patients have been enrolled in some 30 prospective randomized phase III studies. The key scientific treatment issues studied until now in major clinical programs have been (1) adjuvant endocrine therapy for pre- and postmenopausal women, as well as the role of bisphosphonates, and (2) chemotherapy in the neoadjuvant setting. The goal of this chapter is to provide a brief synopsis of the high-impact trials carried out by the ABCSG with respect to breast surgical oncology and to examine their study results in a broader context.
ABCSG Trial 5 (ABCSG-5) and Trial 12 (ABCSG-12) were clinical investigations exploring the efficacy of adjuvant endocrine treatment in premenopausal patients with early-stage breast cancer.
When ABCSG-5 was initiated in 1990, the adjuvant treatment of premenopausal breast cancer patients was considered to be a domain of adjuvant chemotherapy. Yet the fact that premenopausal women responded significantly better to adjuvant chemotherapy than older patients raised the hypothesis that this effect could mainly be mediated through endocrine manipulation rather than being a direct effect of cytostatic action.1 Supported by initial reports on 2 other modalities tamoxifen (TAM) and ovarian ablation2,3—ABCSG-5 was designed to compare the efficacy of combination endocrine treatment with standard chemotherapy.
ABCSG-5 randomized patients to receive either 3 years of the luteinizing hormone-releasing hormone analog goserelin (GOS) plus 5 years of TAM or 6 cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF; Table 47-1). The trial subjects were stratified according to their hormone receptor status, tumor stage and grading, number of involved nodes, and type of surgery.
Table 47-1 ABCSG Trials of Endocrine Treatment in Hormone Receptor–Positive Premenopausal Patients with Stage I and II Breast Cancer ||Download (.pdf)
Table 47-1 ABCSG Trials of Endocrine Treatment in Hormone Receptor–Positive Premenopausal Patients with Stage I and II Breast Cancer
|Criteria||ABCSG-5||ABCSG-12 (BMD Substudy)|
|Reference||Jakesz et al4 (2002)||Gnant et al9 (2008)|
|Regimen||TAM 20 mg/d, 5a + GOS 3.6 mg every 28 days, 3a vs CMF 600/40/600 × 6 every 4 weeks||TAM 20 mg/d, 3a + GOS 3.6 mg every 28 days, 3a ± ZA 4 mg every 6 months, 3a vs ANA 1 mg/d, 3a + GOS 3.6 mg every 28 days, 3a ± ZA 4 mg every 6 months, 3a|
|No. of assessable patients||1034||404|
|Characteristics||pT1–3, N±, G1–3,x||T1a–T4d, N±, G1–3,x|
|Primary end points||OS, RFS||Change in BMD|
|Recruitment period||December 1990 to June 1999||June 1999 to May 2006|
|Median follow-up (months)||60||48|