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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Apr 19, 2010 - Despite a strong biologic rationale, there may be no association between concomitant usage of cytochrome P450 2D6 inhibitors such as selective serotonin reuptake inhibitors and breast cancer recurrence in patients with early-stage disease who are treated with adjuvant tamoxifen, though there is an association between poor tamoxifen adherence and increased risk of breast cancer events, according to a study published online April 12 in the Journal of Clinical Oncology.