Editor’s pick of Hans Wildiers, MD, PhD, medical oncologist, University hospital Leuven
As treatment recommendations for breast cancer patients with low hormone receptor (HR) expression (1-9%) are ambiguous, a population-based 15-year cohort from the Munich Cancer Registry was used to compare patient characteristics and outcome of HR low positive tumours with HR negative and HR strongly positive tumours. Results from this analysis reveal that current definitions for HR positivity and its clinical relevance should be reconsidered.
Guideline recommendations for treatment of breast cancer with low hormone receptor (HR) expression (1-9%) are ambiguous and several studies showed more similarities with HR negative tumours than with HR strongly positive tumours (≥10%). Therefore, Schrodi et al. used population-based data of the Munich Cancer Registry (MCR) to evaluate the prognosis of the three HR subgroups in a large representative cohort comprising 15 years of primary diagnosis.
The Munich Cancer Registry has a catchment area of 4.9 million inhabitants. Pathology reports of solid tumours from all pathology laboratories in this catchment area are available and provide the total number of breast cancer cases in the region and the respective prognostic factors. In addition, patients’ demographics, prognostic factors, treatment and follow-up information are reported from clinicians and the life status of patients with a cancer diagnosis is maintained systematically trough death certificates. A total of 38,560 women diagnosed with early invasive breast cancer between 2004 and 2018 were included in the analysis. Endpoints were time to local recurrence (TTLR), time to lymph node recurrence (TTLNR), time to metastasis (TTM), overall survival (OS), and relative survival (RS). HR negative tumours were defined as 0% positive cells for both hormone receptors (ER and PR) or as immunoreactive score (IRS) zero. Low HR positivity was defined as between 1-9% positive cells for either ER or PR (or as IRS= 1) and not more than 9% positive cells (IRS= 0-1) for the other receptor. HR strongly positive tumours were defined as 10-100% positive cells for ER and/or PR or as IRS= 4-12. Cases with IRS= 2-3 and missing data on the percentage of positive cells were excluded from the evaluation, since they may contain cases with >10% of positive cells with weak staining.
Overall, 861 patients (2%) had HR low positive, 4,862 (13%) HR negative, and 32,837 (85%) had strongly HR positive tumours. Whereas the distribution of tumour characteristics was quite similar between the HR low positive and the HR negative subgroup, it should be noted that patients with HR strongly positive tumours were older, had smaller tumours, more Grade 1 tumours, less HER2 positive tumours, and a higher proportion of invasive lobular histology. In total, 87%, 45% and 5% of patients in the HR strongly positive group, low HR positive group and HR negative group received endocrine therapy, respectively. Regarding the treatment with chemotherapy, proportions were 34%, 77% and 79%, respectively.
Median follow-up time was 71 months (range 0-185 months). First, surrogate parameters for survival have been analysed. In the HER2 negative subgroup, the cumulative incidence curves of TTLR of HR low positive and HR negative tumours were almost identical, but the cumulative incidence of TTLR in the HR strongly positive group was significantly lower (10-year-CUI: HR 0% 14.0, HR 1-9% 13.2, HR ≥10% 6.9). In the subgroup of HER2 positive tumours, the difference between the HR low positive and the HR strongly positive group was observably smaller, and not statistically significant. The 10-year CUI was 10.8, 10.5, and 9.5, respectively. The same scheme was observable in TTLNR and TTM. Within the HER2 negative cohort (N= 33,366), survival of HR low positive tumours was significantly worse than that of HR strongly positive tumours (OS hazard ratio 0.66 [95%CI: 0.55-0.78]), whereas between HR low positive and HR negative tumours no significant survival difference could be detected (OS hazard ratio 0.93 [95%CI: 0.78-1.11]). Within the HER2 positive cohort (N= 5,194), no statistically significant differences between the three groups could be detected (HR 0.80[0.59-1.08] and 0.81[0.59-1.08], respectively). Overall, irrespective of HER2 status, patients with low HR positive tumours seem not to benefit from endocrine therapy.
“In conclusion, patients with HR low positive tumours, especially those who are HER2 negative, could be regarded and treated similarly to patients with triple-negative tumours.”
Schrodi S, Braun M, Andrulat A, et al. Outcome of breast cancer patients with low hormone receptor positivity: Analysis of a 15-year population-based cohort. Ann Oncol. 2021;S0923-7534(21)04218-6.