ASO Author Reflections: Prognostic and Therapeutic Implications of Nodal Burden in HER2-Positive Breast Cancer.

PAST
The landscape of axillary nodal management in breast cancer as well as systemic therapy for those with HER2+ disease has changed significantly over time. For many years, axillary lymph node dissection (ALND) was performed uniformly regardless of clinical nodal status. This was fraught with high rates of lymphedema often leading to decreased functional status for patients. Driven by the desire to decrease morbidity associated with ALND, novel techniques such as sentinel node biopsy (SLNB) and omission of ALND for those with low nodal burden have been established as oncologically safe options.1 Taking this a step further, guidelines evolved to recommend against routine surgical axillary nodal staging for older patients with early stage, low-risk disease. Notably, patients with HER2+ breast cancer have been excluded from omission practices given the aggressive nature of HER2+ tumor biology. Thus, the questions arise of whether these patients should be excluded from nodal surgery omission practices and whether nodal omission is being applied in patients with HER2+ disease. This study aimed to investigate surgical nodal management in patients ≥ 70 years with hormone-receptor negative (HR−)/HER2+ breast cancer and overall survival (OS) by nodal surgery type, as well as to identify factors associated with surgical nodal omission.2

PRESENT
Most recently, the SENOMAC and SOUND trials (whose results became available after this study’s timeframe) omitted surgical nodal staging for patients who had early stage breast cancer with a negative axillary ultrasound, regardless of tumor biology, and found equivocal outcomes compared with those who had conventional nodal surgery.3 Our results showed that a small proportion of patients were having omission of axillary surgery, and that omission led to inferior OS. More importantly, the omission of axillary staging in this population is a departure from guideline-concordant care and remains important in guiding adjuvant treatment options. The recent APT, ATEMPT, and APHINITY4 trials have demonstrated that axillary nodal staging has significant implications in the decision-making process of adjuvant systemic therapies for patients with HER2+ disease, and therefore axillary nodal staging should remain standard of care for those patients who are suitable candidates for HER2-directed systemic therapy, regardless of age.

FUTURE
There will likely be further efforts at surgical axillary deescalation across varied populations, including patients with HER2+ disease, as we learn more about the impact of axillary staging on survival and recurrence. Researchers and clinicians should be thoughtful about which patient populations are appropriate for deescalation and consider the potential downstream implications of omitting nodal staging. Ultimately long-term data from the recent SOUND and INSEMA trials will shed further insight into outcomes in those with HER2+ disease.5 The provision of guideline-concordant care within a multidisciplinary care model is paramount to successful treatment of older patients with HER2+ breast cancer.