Experts are divided on switching to an oral SERD based on detecting an ESR1 mutation before radiologic progression. A key counterargument is that this is not the patient's only chance to receive the drug, and the strategy may offer less progression-free survival than waiting for clinical progression.
When using the AKT inhibitor capivasertib, preventing rash is more effective than treating it. A recommended strategy for physicians unfamiliar with the drug is to prescribe twice-daily non-drowsy antihistamines proactively for the first 6-8 weeks, as the rash is difficult to manage once it appears.
Contrary to the standard 150mg starting dose, many clinicians begin abemaciclib at 100mg BID. Data from the TRADE trial and retrospective MonarchE analyses show this improves tolerability, reduces early dropouts, and maintains efficacy, as patients who dose-reduced to 100mg performed just as well.
While the LADERA study showed a benefit for oral SERD gerodestrant over standard endocrine therapy, its applicability is questionable. In the metastatic setting, adding an oral SERD to a CDK inhibitor did not show a statistically significant benefit over an AI plus CDK, raising doubts about its added value in the adjuvant CDK era.
Final 15-year data from the SOFT/TEXT trials reveal that the survival advantage of adding ovarian function suppression (OFS) to an AI is not uniform. The benefit is most pronounced in the highest-risk premenopausal patients, particularly those under 35 or with grade 3 disease, for whom tamoxifen alone is considered inadequate.
For very high-risk premenopausal patients (e.g., 4+ positive nodes), clinicians may recommend continuing ovarian function suppression beyond the standard 5 years, sometimes advocating for permanent oophorectomy. This is based on clinical experience and data suggesting a more durable blunting of recurrence risk with permanent ovarian ablation.
Expert clinicians select genomic assays with nuance. For a patient where a low-risk result is desired to avoid chemotherapy, Oncotype DX may be chosen as it tends to yield more low-risk scores. Conversely, MammaPrint may be used for a chemo-hesitant patient, as it is more likely to return a high-risk result.
A practical approach for choosing between adjuvant CDK4/6 inhibitors is to use abemaciclib for patients meeting the high-risk MonarchE criteria, due to its longer follow-up and proven survival advantage. For all other eligible patients, including lower-risk node-positive and node-negative cases (NATALEE criteria), ribociclib is preferred.