Population diversity in cancer treatment – differences matter

‘One size does not fit all’ is often used when talking about the need of personalising cancer treatments, but nowhere is it more apt than when considering population diversity in breast cancer, which may affect disease presentation and impact tolerability to treatment.

Ribociclib plus non-steroidal aromatase inhibition (NSAI) demonstrated consistent benefit in patients with stage II–III hormone receptor (HR)-positive/HER2-negative early breast cancer in the NATALEE trial (JAMA Oncol. 2025;11:1364–1372) and the combination therapy was approved by the U.S. Food and Drug Administration (FDA) in 2024 (J Clin Oncol. 2025;43:3312–3320). Marked differences in tumour presentation were reported in a subgroup analysis of the study presented at the ESMO Asia Congress 2025 (Singapore, 5–7 December) (LBA1): Asian patients were more commonly premenopausal (61.1% versus 41.6%) and younger at diagnosis (around 49 years versus 53 years) than non-Asian patients. In addition, Asian patients were nearly twice as likely to have advanced (N2/3) disease (31.0% versus 17.0%) and a greater proportion had received chemotherapy as treatment (96.2% versus 86.3%). Of note, Asian patients receiving ribociclib plus NSAI had higher rates of dose interruption (84.4% versus 64.4%) and dose reduction (34.1% versus 21.4%) due to adverse events compared with non-Asian patients. This very real variation may reflect not only pharmacogenetics but also cultural/national practices, for example in the way side-effects are managed.

Ethnicity differences – in disease presentation, tumour biology, tolerability, pharmacogenetics and cultural differences – must be taken into account in the selection of appropriate treatment. This applies both to the type of active agent as well as the dosing and type of supportive care required to manage side-effects. But for the oncology community to be able to implement this effectively, more data are needed. As highlighted for breast cancer (J Natl Cancer Inst. 2024;116:1992–2002), there is still a relative paucity of data for non-White populations. As an example, among more than 30,000 patients in a real-world database study on genomic alterations in breast cancer, the overwhelming majority (81%) were of European genetic ancestry, 12% were of African ancestry and only 7% were of East Asian (5%) or South Asian (2%) origin (Abstract 66MO).

Recognising diversity is pivotal to enabling equitable access to clinical trials, genomic testing and tailored treatment. Gaps in clinical, pathological and genetic data can result in national ethnicity-based disparities in cancer care (Br J Cancer. 2021;124:315–332), which can be exacerbated by socioeconomic factors. There is a danger that the management guidelines developed by cancer societies to direct optimum treatment may fail to represent different populations nationally and internationally. Moving forward, we need large genomic and pharmacogenomic studies to counterbalance the current underrepresentation of certain populations, including those of Asian and African descent, in the literature. We must also advocate for clinical trials that intentionally include diverse groups and that report ancestry-specific outcomes. Finally, it is essential that we get access to more real-world evidence from broader cross-sectional settings so that our global guidelines can truly reflect the patients we treat.