Table 2 Steps conducted in the systematic review

Research question

In Asian breast cancer patients, how does personalised and precision medicine (in terms of breast cancer molecular subtypes diagnosis, presence or absence of biomarkers and genetic variants affect breast cancer treatment response and outcome?

Inclusion criteria

Randomised trials, observational studies, case-control studies, and cohort studies of Asian breast cancer aged ≥18 years, who underwent systemic neoadjuvant chemotherapy treatment reporting the involvement of somatic genetic polymorphisms or biomarkers or molecular subtype classification on breast cancer treatment response.

The studies are written in the English language.

Participants

Asian breast cancer patients

Outcome

Outcome 1: Treatment response

Outcome 2: Survival

Search strategy

Databases: MEDLINE (PubMed), Science Direct, Scopus, and Cochrane Library.

Date range: 01.01.2000 to 31.03.2021.

Search terms: The search term strategies can be found in Additional file 2. The terms were adapted for different databases utilising a combination of Medical Subject Heading (MeSH) and keywords that are relevant which can be found in the titles and abstract.

Critical appraisal

The authors extracted data from the published reports independently. Disagreements were resolved by a third person. The Newcastle-Ottawa Scale (NOS) was used.

Data collection and synthesis

For each study, the extracted parameters include the article information (article title, first author, year published, journal published, country, and year of recruitment), study design, study population and sample size, characteristics of patients in three variables (molecular subtypes, biomarkers, and genetic variations), and the pCR data in selected variables. Notably, in the absence of molecular subtype classification in the included studies, whenever possible, they were approximated through the available biomarkers detected through IHC data.

Data analysis was done using Review Manager Software (RevMan version 5.4.1) [30]. The odds ratio (OR), hazards ratio (HR), and their corresponding 95% confidence interval (95% CI) were assessed to evaluate the association between treatment response (pCR) and NAC treatment provided to breast cancer patients based on their molecular subtypes, biomarkers, and genetic variations. The strength of associations was estimated by calculating pooled ORs/HRs and 95% CIs, by which significance was stated using the p-value. A p-value <0.05 was considered statistically significant.

Process

Search (n=5746)

Excluded with reasons [refer to Figure 1 for detailed reasons] (n=5610)

Excluded after reviewing full-text (n=35)

Included studies (n=101)

Results

Where statistically appropriate, studies were pooled.

Molecular subtypes:

Meta-analysis demonstrated that when treated with taxane-anthracycline, Asian breast cancer patients diagnosed with HER2E or TNBC achieved better pCR compared to those who are diagnosed with Luminal breast cancer. Meanwhile, when treated with taxane-platinum, HER2E and TNBC Asian breast cancer patients achieved better pCR compared to those who are diagnosed with Luminal breast cancer. When compared with Luminal A breast cancer patients, Luminal B Asian breast cancer patients achieved better pCR when treated with taxane-platinum.

Biomarkers:

Meta-analysis demonstrated that when treated with anthracycline-based treatment, ER−, PR− and HER2− Asian breast cancer patients achieved better pCR compared to those who are diagnosed with ER+, PR+ and HER2+ breast cancer. HR− Asian breast cancer patients are also demonstrated to respond better to taxane-based treatment. For Asian breast cancer patients treated with taxane-anthracycline, it was found that those who are diagnosed with ER−, PR−, HR−, HER2+, nm23-H1−, CK5/6− and high Ki67 biomarkers responded better to the treatment. As for Asian breast cancer patients treated with taxane-platinum, it was found that those who are diagnosed with ER−, PR−, HR−, HER2+ and high Ki67 biomarkers responded better to the treatment.

Genetic variation:

Meta-analysis also demonstrated that when treated with taxane-anthracycline-based treatment, Asian breast cancer patients who had wildtype PIK3CA gene achieved better pCR compared to those who were with mutated PIK3CA gene.