MONALEESA-7 Used Aromatase Inhibitors in Premenopausal Women
Yes, the MONALEESA-7 trial used aromatase inhibitors (specifically letrozole or anastrozole) in premenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer, but only in combination with mandatory ovarian suppression using goserelin. 1
Trial Design and Endocrine Therapy Combinations
MONALEESA-7 randomized 672 premenopausal/perimenopausal women (aged 18-59 years) to receive ribociclib or placebo plus endocrine therapy consisting of either a nonsteroidal aromatase inhibitor (NSAI) (letrozole 2.5 mg or anastrozole 1 mg daily) or tamoxifen 20 mg daily, all with mandatory goserelin 3.6 mg subcutaneously on day 1 of every 28-day cycle. 1, 2
Of the 672 total patients, 495 patients (74%) received the NSAI plus goserelin combination, while the remainder received tamoxifen plus goserelin. 1
The trial explicitly required ovarian function suppression with goserelin in all patients, regardless of whether they received an AI or tamoxifen, because aromatase inhibitors are contraindicated in premenopausal women without adequate ovarian suppression. 3, 1
Efficacy Results in the AI Subgroup
In the pre-specified subgroup of 495 patients who received ribociclib + NSAI + goserelin, median progression-free survival was 27.5 months versus 13.8 months with placebo + NSAI + goserelin (hazard ratio 0.569; 95% CI 0.436-0.743). 1
Median overall survival in this NSAI subgroup was not reached in the ribociclib arm versus 40.7 months in the placebo arm (hazard ratio 0.699; 95% CI 0.501-0.976). 1
The overall response rate for patients with measurable disease was 50.5% with ribociclib + NSAI + goserelin versus 36.2% with placebo + NSAI + goserelin. 1
Critical Requirement: Ovarian Suppression
Aromatase inhibitors cannot be used as monotherapy in premenopausal women because the reduction in tissue estrogen leads to compensatory increases in gonadotropin secretion, causing ovarian estrogen production and potential ovulation. 3
MONALEESA-7 demonstrated that the combination of ovarian suppression (goserelin) plus an AI achieved a 98% reduction in median estradiol levels (from 574.5 pmol/L pre-treatment to 13.45 pmol/L at 6 months), confirming adequate suppression. 4
Guidelines emphasize that significant caution must be exercised when using AIs in premenopausal women, as ovarian suppression may be incomplete; clinicians should confirm suppression by measuring estradiol levels and remain alert to symptoms suggesting persistent ovarian function. 3
Guideline Context
The 2016 ASCO guideline for metastatic breast cancer recommends ovarian suppression plus an AI (nonsteroidal preferred) as a first-line option for premenopausal women with HR-positive disease, particularly those with early relapse (≤12 months since adjuvant therapy). 3
The 2017 NCCN guideline states that premenopausal patients should receive selective ER modulators (tamoxifen or toremifene) or ovarian ablation/suppression plus endocrine therapy as for postmenopausal women, explicitly including AIs as an option when combined with ovarian suppression. 3
Ribociclib + AI + ovarian suppression is designated a Category 1 first-line option by NCCN for premenopausal women with HR-positive, HER2-negative advanced breast cancer, based directly on the MONALEESA-7 results. 5
Common Pitfalls to Avoid
Never prescribe an aromatase inhibitor to a premenopausal woman without confirmed ovarian suppression, as this leads to ineffective treatment and potentially harmful effects including ovulation and increased estrogen exposure. 3, 6
Do not assume that chemotherapy-induced amenorrhea equals true menopause; many women retain ovarian function and require formal ovarian suppression when receiving an AI. 3
Confirm adequate ovarian suppression by measuring estradiol levels, as tests vary widely in sensitivity and incomplete suppression correlates with worse outcomes, particularly in obese women. 3