Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy
Reviewer: Neha Vapiwala, MD
Last Modified: May 31, 2003
Presenter: M. G. Le Arriagada
Presenter's Affiliation: Institut Gustave-Roussy
Type of Session: Scientific
Premenopausal women with early breast cancer receive a significant reduction in overall mortality from adjuvant ovarian suppression (AOS) following surgery, approximately 24% (+/- 7%). However, in the presence of adjuvant chemotherapy, the benefit of ovarian suppression was decreased to a mortality reduction of only about 8% (+/- 10%). The purpose of this study is to answer whether a survival benefit is still seen when AOS is added to adjuvant chemotherapy (ACT).
Materials and Methods
- 926 premenopausal pts treated between 1/1989-2/1998 at 12 centers
- Mean age was 43 yrs
- Hormone receptor positivity was 76%
- All underwent local surgery (including axillary dissection)
- Pts centrally randomized to ACT + AOS (n= 461) or ACT alone (n= 465) following surgery
- If primary tumor < or = 3 cm, protocol specified breast conservation surgery followed by breast radiation (45-50 Gy + 15 Gy boost)
- If primary tumor > 3 cm, protocol specified modified radical mastectomy
- Appropriate axillary dissection in all pts
- Supraclavicular/ internal mammary nodal irradiation if indicated
- AOS achieved via LHRH analogue (triptorelin)in 48% and ovarian irradiation (12 Gy in 4 fractions) in 45%; rarely surgical oopherectomy
- ACT consisted of FAC/FEC chemotherapy in ~70% of pts
- Intent-to-treat analysis, Cox regression models
- Primary endpoints of overall survival and disease-free survival
- Also looked at effects of treatment modality
- Median follow-up was 9.5 yrs
- 10-yr overall survival rates were 68% ACT + AOS vs. 66% ACT alone
- 10-yr disease-free survival rates were 49% ACT + AOS vs. 49% ACT alone
- No treatment effect difference based on age, receptor status, or type of OS used
- Mortality reduction benefit seen with AOS in absence of adjuvant chemotherapy
- This survival benefit is comparable to that seen from CMF-based chemotherapy regimens
- AOS not effective in presence of adjuvant chemotherapy, presumably because of similar mechanism of action in both chemotherapy and hormonal therapy, ie: estrogen depletion and induction of menopause in pts with an estrogen-dependent cancer. This is supported by the study finding of 73% incidence of menopause in the ACT alone group within 3 years of follow-up.
The role of adjuvant ovarian suppression in early breast cancer pts following appropriate local therapy is established through a documented mortality benefit comparable to that seen with typical chemotherapy regimens. However, even if AOS is an effective alternative to chemotherapy, this trial does not show any improvement in benefit when it is added to chemotherapy. No treatment effect difference was seen with regards to local, regional, contralateral or distant disease recurrence, nor overall and disease-free survival. Also, no treatment variation was seen with respect to pt age, receptor status, or AOS modality.
Chemotherapy and ovarian suppression appear to demonstrate similar antineoplastic mechanisms of activity. As most of these pts are given adjuvant anthracycline-based chemotherapy in current clinical practice, the role of added OS is lacking. In conclusion, the authors point out that quality of life measures have not been applied here, but might add a useful dimension to this issue.
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