An increasing proportion of metastatic breast cancer is diagnosed de novo, not as a recurrence. This seemingly negative trend is actually a positive sign that adjuvant therapies are successfully curing more patients with early-stage disease.
When sequencing antibody-drug conjugates, clinical experience suggests that resistance to the chemotherapy payload is a primary driver of failure. Therefore, oncologists tend to avoid using another ADC with the same payload consecutively, preferring to switch both target and payload if possible.
High rates of interstitial lung disease (ILD) in TDXD trials for brain metastases might be partly attributable to opportunistic infections like PJP, not direct drug toxicity. This occurs in patients receiving steroids for brain edema, underscoring the need for PJP prophylaxis.
To mitigate long-term toxicity from TDXD, oncologists are proposing an "induction/maintenance" approach. Patients receive TDXD for an initial period to achieve maximal response, then switch to a less toxic maintenance regimen for a "chemotherapy holiday," improving quality of life.
Even within recent major clinical trials like HER2CLIMB-05, less than half of eligible hormone receptor-positive patients received endocrine therapy. This highlights a critical and widespread gap in clinical practice, as this treatment adds significant benefit.
For nausea associated with the ADC TDXD, clinicians find adding low-dose olanzapine (2.5mg at bedtime) is a highly effective strategy for both acute and delayed nausea. This practical tip improves tolerability beyond standard three-drug prophylaxis.
An expert oncologist intentionally does not discuss poor prognostic biomarkers like MYC amplification or p53 loss with patients. Since these factors cannot be targeted with current therapies, revealing them provides no clinical benefit and only causes patient distress.
The high efficacy of neoadjuvant TDXD in high-risk HER2+ breast cancer presents a compelling argument to avoid initial surgery for patients with reasonably sized tumors. There is currently no data to support using adjuvant TDXD for patients who undergo surgery first.
Contrary to initial fears, both clinical trial and real-world data show that patients experiencing asymptomatic, grade 1 interstitial lung disease (ILD) from TDXD can be safely retreated. This allows patients to continue benefiting from a highly effective therapy without undue risk.
In the ASCENT-07 trial, blinded central review showed no benefit for sacituzumab, while treating investigators saw a clear benefit. This discrepancy arose because clinicians acted on new lesions or effusions that central reviewers deemed "unclear," showing how rigid trial criteria can miss nuanced clinical signals.