The New England journal of medicine 2018-07-12
Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer.
Abstract
Background
In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials.
Methods
Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy.
Results
In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group.
Conclusions
Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).
Related Questions
What factors would you consider when deciding between tamoxifen vs OFS/AI in premenopausal women with early stage HR+ breast cancer?
I think the question is asking when would I recommend tamoxifen alone versus aromatase inhibitor plus medical ovarian suppression with agents like goserelin or leuprolide in a premenopausal breast cancer patient. There are multiple factors to consider. If she has a history of active endometriosis or...
What risk factors would favor the addition of ovarian function suppression to endocrine therapy in triple-positive breast cancer?
Young age less than 40, node positive, high-grade, bulky tumor, or any patient at high risk of recurrence (requiring chemo) or residual tumor, I would favor giving ovarian suppression as per the SOFT and TEXT trial.
What is the goal of estradiol levels on ovarian suppression and AI for breast cancer?
This is a sneaky difficult question. We've known since George Beatson that estrogen was important for breast cancer, and the Early Breast Cancer Trialists Collaborative Group helped get Tamoxifen approved in 1978. I've heard it said that we've had more trials looking at estrogen therapy for breast c...
How does age factor into your planning whether to give a high risk pre-menopausal patient with breast cancer ovarian function suppression?
Generally, my age cutoff is 50, but it depends on the patient’s documented menopausal status prior to chemotherapy. If the patient is perimenopausal, then I initiate ovarian suppression plus aromatase inhibitor and check estradiol and FSH every 12 months. When she is clearly post-menopausal, then I ...
What is your approach for adjuvant endocrine therapy in a female with HR+ breast cancer with history of provoked DVT while on OCPs?
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How do you approach adjuvant endocrine therapy in a pre-menopausal patient with node negative HR+HER2- breast cancer with a high Oncotype RS who received adjuvant chemotherapy?
The SOFT/TEXT study can be used to answer this question. SOFT was a phase III study in premenopausal women with ER+ disease comparing ovarian function suppression (OFS)+ an aromatase inhibitor (AI) to OFS + tamoxifen vs tamoxifen alone; TEXT compared OFS+AI vs OFS+tamoxifen. The vast majority of wom...
How would you approach diagnosis of residual ovarian tissue in a patient with ER positive breast cancer, history of BSO, and a rising estradiol level on tamoxifen?
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Will you use ovarian function suppression in lieu of chemotherapy in premenopausal patients with pN1 ER+ HER2- breast CA with OncoType RS <25?
Most certainly. The difference between chemotherapy effect in postmenopausal vs. premenopausal women with ER+ breast cancer is not primarily due to a difference in disease biology. It is due to the endocrine effect of chemotherapy in premenopausal women and the lack of that effect in postmenopausal ...
How do you manage ovarian suppression for premenopausal patients with HR+/HER2 positive breast cancer?
Oophorectomy and GnRH agonist are two options for ovarian suppressive therapy. There are two fundamental differences between these options. First, GnRH monthly, and especially the 3-month depot preparations, will incompletely suppress estradiol levels in some women. 17% to 25% of women on monthly Gn...
Would you offer adjuvant chemotherapy for 1-3 node positive HR+, HER2 negative breast cancer with Mammaprint low risk to a young, pre-menopausal patient?
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Would you consider OFS in a young patient (<35) with ER+ breast cancer who required chemotherapy and menses resumed years later while on tamoxifen?
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Which adjuvant chemotherapy regimen would you recommend for a peri-menopausal woman with synchronous stage IA primary breast tumors, one that is ER+HER2+ and the second ER+HER2-?
I would treat the patient with paclitaxel 80mg/m2 x 12 weeks plus trastuzumab for a year (Tolaney et al., Clin Oncol 2019). The more difficult question is the optimal anti-estrogen therapy: tamoxifen (TAM), TAM + ovarian suppression (OS), or aromatase inhibitor (AI) + OS. This is because the SOFT an...
Is there a subset of breast cancer patients who may benefit more from GnRH analogs for fertility preservation compared to others?
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Based on TAILORx, what will be your approach to a pre-menopausal woman with a recurrence score 16-25?
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