The SOFT and TEXT trials were designed to investigate the role of ovarian suppression and aromatase inhibitors in premenopausal women with hormone receptor-positive breast cancer. The SOFT trial found that tamoxifen plus ovarian suppression reduced the risk of breast cancer recurrence compared to tamoxifen alone. Exemestane plus ovarian suppression provided an additional benefit over tamoxifen-based therapy, especially in higher-risk patients who received chemotherapy. The TEXT trial showed exemestane plus ovarian suppression improved disease-free survival compared to tamoxifen plus ovarian suppression, with the largest benefits seen in younger, higher-risk patients and those with HER2-negative tumors. Long-term follow-up of both trials found continued benefits

1. SOFT
(Suppression of Ovarian Function Trial )
TEXT (Tamoxifen and Exemestane Trial)
Overview
Presented by: Dr.Noopur Priya

2. Introduction
5 years of TAM reduces the odds of recurrence by 40% when added to
adjuvant chemotherapy
GnRH agonists show similar efficacy to chemotherapy in the absence
of TAM in prememopausal women, but additional benefit from OFS for
women who receive 5 years of TAM + adjuvant chemotherapy is
uncertain
AIs are equi-efficacious to TAM for postmenopausal women with
endocrine-responsive breast cancer

3. The value of therapeutic suppression of ovarian Estrogen production in
premenopausal women who receive TAM is uncertain
In 2003 the International Breast Cancer Study Group (IBCSG) started
these trials
SOFT - Suppression of Ovarian Function Trial
TEXT - Tamoxifen and Exemestane Trial

4. Questions Answered
Is Tamoxifen alone or an Tamoxifen + Ovarian suppression an optimal
treatment?
Any role of Aromatase Inhibitors- Exmestane in premenopausal women?
Does AI improve outcome in comparison with Tamoxifen along with OS?

6. Study Type: Interventional, Phase 3 trial
Study Design:
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment

7. Criteria
Inclusion Criteria
Harmone positive >10% cells
Premenopausal
Within 8 months of CT
Within 3 months of surgery
Tz was allowed
Exclusion criteria
Prior CT/RT for any prior malignancy
BRCA1/2 Positive
Use of SERM/HRT within 1 year
Concurrent malignancy

8. The SOFT trial was:
o Designed to investigate the role of OFS and the role of the AI (Exemestane) in
premenopausal women
oRandomised, 3-arm, phase III RCT with 1:1:1 allocation --
The TEXT trial was:
o Designed to investigate the efficacy of AI (Exemestane)+OFS v/s TAM+OFS
in premenopausal women
o Randomised, 2-arm, phase III RCT with 1:1 allocation --

10. Treatments
Duration- 5 years
OS- TEXT- Triptorelin Gnrh agonist IM q28d
Ovarian radiation/Oopherectomy as concurrent to CT after 6
months to Triptorelin
SOFT- Any above method
Dose- Tamoxifen 20 mg od ,Exmestane 25 mg daily after meals

11. End Points
Primary end point – DFS
Secondary end point –
Interval without breast cancer
Time interval before recurrence of breast cancer at a
distant site
Overall survival

12. Patient Demographics- Majority
Age – 40 years
Negative Axillary Node
Tumor size less than equal to 2 cm
Grade 2
Her2 positive tumors- 236

13. SOFT Primary Analysis: Disease free survival
Her 2+ had greater benefit of
T+OS than T alone
At 5 years
DFS- T- 86.4%
T+OS- 88.4% HR-0.81

15. Important observations
T+ OS reduced hazard of breast cancer recurrence as compared to
Tamoxifen
P=0.02
Patient who did not receive CT , more than 95% remained disease free
More than 90% deaths occurred in patients who received CT

16. 949 premenopausal
women on adjuvant
T without CT
Characteristics
Age >40
Small tumor size
Node negative
Low to intermediate grade
Good outcome at 67 months
Did not inform relevance of
OS
1084
Premenopausal
after CT
Younger age
High risk of recurrence
Larger recurrence at 67
months
tamoxifen + OS resulted in
an absolute improvement
of 4.5 % points, as
compared with tamoxifen
alone
E + OS – Overall improvement was 7.7%

17. SOFT Conclusions
All premenopausal did not benefit with OFS
High risk group OS + T > T alone
reduced the risk of breast-cancer recurrence
 OS+ AI further reduced the risk of recurrence, as compared with
tamoxifen- based therapy, in this higher-risk premenopausal cohort.
Increase in side-effects

19. Nov 2003- April 2011
4690 premenopausal women
Randomization within 12weeks after surgery: E+ OS/ T+ OS
Triptorelin IM 3.75mg every 28 days
 8 year survival analysis of TEXT published in 2018

20. 2014 DFS 2018 DFS

21. 2014 2018

23. Important observations- 2014
E+OS improved DFS, lengthened time without breast cancer, and time
without distant recurrence.
28% decreased risk reduction of cancer
No significant improve in OS
When CT is indicated, E+OS further improves DFS
The 5-year median follow-up and the low event rate are insufficient to
assess whether the significant improvement in DFS with AI+OFS will
translate into an overall survival benefit

24. 2018 Results T + OS E+OS T
DFS 83.2 85.9 78.9 p=0.009 T vs
T+OS
OS 93.3 92.1 91.5 p=0.01 for t
vs t+os
Freedom from
recurrence
89.7 91.8
Her 2 neg 8 yr DFS 82.7 88.1
Her2 neg after ct
dfs
89.4 87.2 85.1
Grade 3 events 31 32.3 24.6
Tamoxifen- Thromboembolic events-DVT, PE Hot flushes, vaginal discharge,
endometrial ca
AIs- Osteoporosis, musculoskeletal symptoms

25. Important observations-2018
Higher rates of DFS and OS after addition of ovarian suppression to T
T+OS= 24% Lower risk of recurrence than T , P=0.009
E+OS resulted in -higher dfs with 7% benefit when compared with
T+OS
- Higher rate of freedom from distant recurrence
Side effects: Results did not apply to all premenopausal women

26. Treatment effects were similar in regards to receipt of CT or non
receipt
Absolute benefits more in patients who were premenopausal after CT
In age less than 40, risk group- DFS- T+OS was 5% more than T
-9% higher with E+ OS
 E+OS better in higher risk group receiving CT
 In HER2 neg tumors- E+OS better

27. Conclusion
1) In age less than 35 years , high grade, node positive tumors
Rate of freedom from BC
E+OS- 82.4%
T+OS-77.5%
T-73.8%
2)Further benefit in Her2 neg tumors with E+OS
3) Benefits must be weighted along with the side effects
E+OS > T+OS

28. Summary
Women who were deemed to receive adjuvant chemotherapy and
who retained premenopausal estradiol status after chemo, OS resulted
in significant increase in DFS.
Further improvement was seen with exemestane + OS, especially in
HER 2 negative patients.
Low risk premenopausal women Tamoxifen alone is sufficient

29. Guidelines for OS :ASCO
Stage I , Stage II Adjuvant CT- OS +HT
High risk stage I, Stage II CT- OS +HT
Stage I, node negative, not requiring CT Should not
receive OS
AI/T anyone is suitable
Side-effects should be considered
Incomplete ovarian suppression by Gnrh agonist should be
kept in mind

30. Guidelines for HT:ASCO
Node negative tumors- AI for 10 years based on prognostic
factors
Low risk tumors should not be offered extended therapy
Node positive- AI upto 10 years
Treatment not more than 10 years
Risk of second breast cancer should inform the decision to
continue adjuvant HT
Side-effects should be weighted against the side-effects

32. Thank You