ASCO Update on Adjuvant Endocrine Therapy
 

Supplementary editorial provided by OncologySTAT

TAKE-HOME MESSAGE

Aromatase inhibitors were incorporated into the updated ASCO guideline on adjuvant endocrine therapy for hormone receptor–positive breast cancer.

STUDY IN CONTEXT

Recent publication of 12 landmark trials of endocrine therapy for women with hormone receptor–positive breast cancer spurred the American Society of Clinical Oncology (ASCO) to update its clinical practice guideline on this treatment. The Update Committee focused on the optimal adjuvant endocrine therapy strategy, using either tamoxifen or an aromatase inhibitor (AI), or both in sequence, that would lower the risk of recurrence. The committee also attempted to answer other clinical questions about endocrine therapy. The recent studies reviewed include three that tested AIs as primary adjuvant therapy, six that tested sequencing of tamoxifen and AIs, and three that tested extended adjuvant therapy.

Incorporating AI therapy

Studies have shown that incorporating an AI into adjuvant endocrine therapy improves disease-free survival in postmenopausal women with hormone receptor–positive breast cancer, compared with tamoxifen alone. Thus, the panel recommended that most postmenopausal women should consider taking an AI at some point during their adjuvant therapy, either as primary therapy for 5 years; sequential therapy for 2 to 3 years after receiving tamoxifen for 2 to 3 years; or extended therapy for 5 years after 5 years of tamoxifen. Two trials are currently evaluating whether longer duration of AI therapy improves outcomes.

If primary AI therapy is stopped before 5 years, consideration should be given to incorporating tamoxifen for a total of 5 years of endocrine therapy. If a patient starts therapy with tamoxifen, the best time to switch to an AI is not known (ie, after 2 to 3 years, or after 5 years?).

The panel noted that the absolute reduction in risk of recurrence with AI-based therapy, compared with tamoxifen, is modest. Further, an overall survival benefit for AIs versus tamoxifen has been reported in only two trials, both involving sequential therapy, and the improvement again was modest. However, the committee felt that the recommendation to consider AIs was warranted, since breast cancer recurrences are clinically important to patients.

No predictive markers

The clinical trials of endocrine therapy have not identified a specific marker that predicts whether tamoxifen or an AI would produce the best outcome for an individual patient, nor for any clinical subset of patients who would do better with one or the other.

The update panel recommended against using CYP2DG genotype to select adjuvant endocrine therapy, but it urged caution with the concurrent use of CYPD6 inhibitors, such as bupropion, paroxetine, or fluoxetine, and tamoxifen due to known drug-drug interactions. Adjuvant AI therapy has not been studied in male breast cancer patients. Tamoxifen remains the adjuvant endocrine therapy of choice for these patients.

Different toxicity profiles

The profile of adverse events for tamoxifen and AIs differs, and these differences should be considered, along with patient preferences and preexisting conditions, when deciding upon an adjuvant endocrine therapy strategy. The panel urged physicians to prepare patients for the anticipated adverse effects of endocrine therapy and to consider changing treatment if adverse effects are intolerable or patients are noncompliant.

Premenopausal women

The panel recommended that women who are pre- or perimenopausal at the time of diagnosis of their breast cancer, or who undergo ovarian suppression, should be treated with 5 years of tamoxifen. There have been no studies showing efficacy of AIs in women with residual ovarian function. However, patients who become postmenopausal in the years after diagnosis may incorporate AIs as either sequential or extended adjuvant endocrine therapy.

Are AIs interchangeable?

To date, studies have shown no meaningful clinical differences among the third-generation AIs, but direct comparisons are lacking. Based on clinical opinion rather than direct trial evidence, the panel recommended that postmenopausal patients who become intolerant of one AI may consider switching to tamoxifen or to a different AI. Two trials directly comparing different AIs as primary adjuvant therapy are currently underway.

In summary, the panel recommended the use of AIs during the course of adjuvant therapy, but the optimal timing and duration of AI therapy remains uncertain.

Hopeful