Background
A major empirical problem in the endocrine therapy (ET) for breast cancer (BrC) has been the uncertainty regarding the threshold for defining hormone-receptor positivity.  A cut-off of ≥10% nuclear staining derived from historical ligand-binding assay thresholds (≥10 fmol/mg) has been used traditionally to identify HR-positive or negative (<10% staining) BrC.  Nevertheless, since the 2010 ASCO/CAP guideline revision recommends≥1% nuclear staining, a new subgroup of tumours with low HR expression (1–9%) has emerged, raising concerns about their true endocrine responsiveness. The 2005 St. Gallen consensus depicted such tumours as "uncertain endocrine responders,". Recent molecular studies suggest that these tumours may resemble HR-negative breast cancer in both clinical and biological behaviours.

Objective:
To determine whether breast tumours with low-level hormone receptor expression (1–9% nuclear staining) exhibit clinical and molecular characteristics consistent with endocrine-responsive or endocrine-resistant disease when compared with tumours defined as HR-positive using the ≥10% threshold.

Methods:
We conducted a systematic review of published studies on hormone receptor expression and molecular subtypes of breast cancer in Kenya, comparing the use of the traditional ≥10% cut-off versus the ≥1% ASCO/CAP guideline. Data from 10 studies were pooled and analysed for PR, ER, and HER2 prevalence, with subgroup analysis by cut-off criteria.

Results:
The cut-off criterion for HR positivity was a significant source of heterogeneity in HR prevalence across the studies. Research work using the ≥10% threshold reported a pooled ER positivity of 30% and PR positivity of 35%. However, studies adopting the ≥1% guideline reported significantly higher pooled prevalence of ER (70%) and PR (62%) positivity. The findings indicated that under the updated criteria, approximately 20% more patients could be considered eligible for endocrine therapy (ET). The shift also influenced the molecular subtype distribution. The pooled prevalence of luminal tumours (A and B) was 62% in studies using the revised ≥1% guideline, compared to 42% in those using the traditional cut-off.

Conclusion:
The present study provides robust evidence to date that the adoption of the revised ASCO/CAP hormone receptor thresholds significantly alters breast cancer classification and treatment eligibility in Kenya. Whereas more women with BrC may now qualify for ET, the biological behaviour of the newly defined 1–9% HR-positive tumours remain undefined. Therefore, there is a critical need to validate these thresholds against clinical outcomes in the Kenyan population.