PROMENADE: pembrolizumab for early ER-low/HER2-negative breast cancer, real-world French cohort

In the phase III KEYNOTE-522 study (NCT03036488), which defined triple-negative breast cancers (TNBCs) as tumours with an estrogen receptor (ER) level ≤1% (ER-null) according to European Society for Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) guidelines, the rate of pathological complete response (pCR) was increased by pembrolizumab addition to neoadjuvant chemotherapy. This combination has become the standard of care for stage II or III TNBC. However, updated ASCO guidelines suggest that tumours with low ER levels should be treated as ER-null. In some European countries, tumours with 1%-9% ER expression, called 'ER-low', are considered and treated as ER-null despite a lack of data concerning this population.

We conducted a retrospective real-world study in 16 comprehensive cancer centres across France. All patients with ER-low (ER 1%-9%), human epidermal growth factor receptor 2 (HER2)-negative BC receiving KEYNOTE-522 regimen since its availability in early 2022 were collected. The primary objective was to report the locally assessed pCR (ypT0/isN0 or residual cancer burden 0) rate in this population.

We included 155 female patients. The median age was 47.6 years (range 19.5-80.1 years), and 89 (57.4%) were premenopausal. One hundred thirty-seven (88.4%) patients had a tumour size ≥T2, and 83 (53.5%) were lymph node negative. Most tumours (n = 143; 93.6%) were invasive carcinoma of no special type and had aggressive characteristics, with 131 (85.6%) grade 3 and a median Ki67 of 70% (range 10%-100%). Eighty (51.6%) patients had HER2-low BC. Ninety-eight patients (63.2%) completed the KEYNOTE 522 regimen without deviation. Surgery consisted of a lumpectomy for 86 (56.2%) patients and a sentinel lymph node biopsy for 79 (52.7%) patients. One hundred and eleven (71.9%) patients had a pCR. In multivariable analysis, Nottingham Histologic Score grade 3 and stage III was significantly associated with pCR.

ER-low/HER2-negative tumours had a high rate of pCR after the KEYNOTE-522 regimen. Our results suggest that patients with ER-low HER2-negative BC should be treated as ER-null/HER2-negative BC in the neoadjuvant setting to maximise pCR.