Breast cancer in South Asian Association for Regional Cooperation countries: A scoping review of clinicopathological and molecular patterns

INTRODUCTION

Breast cancer is the most common malignancy among women worldwide^[1,2], and its burden is rising rapidly in South Asia.^[3] Yet data on epidemiology, clinicopathological, and molecular profiles across SAARC nations (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka) remain scattered and heterogeneous. With the region home to nearly one-quarter of the global population, even modest improvements in early detection, molecular profiling, and treatment access could substantially reduce global breast cancer mortality. This scoping review synthesis available evidence on epidemiology, clinicopathological features, and molecular subtypes across SAARC countries.

MATERIAL AND METHODS

This scoping review systematically mapped existing evidence on the epidemiology, clinicopathological features, and molecular subtype distribution of breast cancer across countries in the SAARC nations.

The objectives were to identify prevailing patterns and to highlight gaps in the literature to inform future research and policy. The review followed the methodological framework of Arksey and O’Malley^[4], with subsequent refinements recommended by the Joanna Briggs Institute (JBI).^[5] Reporting adhered to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist [Supplementary File 1].^[6]

The research question was: “What are the clinicopathological characteristics and molecular profiles of breast cancer in SAARC countries?” Eligible studies included those reporting on women (and where available, men) diagnosed with breast cancer in SAARC countries, providing data on tumour histology, grade, stage, nodal status, hormone receptor status, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or molecular subtypes. We included peer-reviewed original articles, national cancer registry reports, dissertations, and relevant grey literature. Exclusions were: studies focused solely on treatment outcomes; case reports or series with <10 patients; and studies lacking country-specific data. Studies restricted to highly selective cohorts (e.g., HER2-positive trials) were also excluded, as they risked introducing bias and limiting representativeness. Only studies with consecutive, unselected, or broadly representative patient cohorts reporting comprehensive baseline data were included to ensure comparability.

A comprehensive search was conducted in PubMed, Embase, and Google Scholar, supplemented by grey literature searches in ClinicalTrials.gov and the Clinical Trials Registry of India (CTRI) for studies published between 1st January 2000 and 30th April 2025. Search strategies combined Medical Subject Headings (MeSH) and keywords for breast cancer, molecular subtypes, hormone receptors (ER, PR, HER2), and SAARC country names [Supplementary File 2].

Two reviewers independently screened titles and abstracts, followed by full-text assessment of potentially eligible articles. Discrepancies were resolved by consensus. Study selection was documented using a PRISMA-ScR flow diagram [Figure 1]. A standardised data-charting form was used to extract author, year, country, study design, sample size, demographics, clinicopathological features, molecular subtypes, key findings, and limitations.

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Figure 1:

PRISMA flow diagram PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses, TNBC: Triple-negative breast cancer, Her2neu: Human epidermal growth factor receptor 2. *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.

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Data were synthesised descriptively, with results summarised in tables. Thematic analysis was used to identify emerging patterns, and subgroup analyses were performed by country and population characteristics. In line with scoping review methodology, no formal critical appraisal of study quality was undertaken. As this review involved no primary data collection, ethical approval was not required.

RESULTS

This scoping review included 18 studies from six SAARC countries - India, Nepal, Bangladesh, Pakistan, Afghanistan, and Sri Lanka, with sample sizes ranging from 44 to 2,062 patients.^[7–25]

Most studies originated from India (n=8), followed by Nepal (n=3), two each from Afghanistan, Bangladesh, and Pakistan, and one from Sri Lanka. Reporting on menopausal status was limited; among six studies, the proportion of post-menopausal women ranged from 15%^[8] to 54.5%^[13], underscoring demographic variability across regions [Table 1].

A country-level subgroup analysis highlights variability in LABC proportion, menopausal status, and molecular subtype distribution across SAARC nations [Table 2]. Locally advanced breast cancer (LABC) constituted a large share of cases. Particularly high rates were reported from Jabalpur, India (62%), Pakistan (60%), Western Nepal (56.6%), and Guwahati, India (55%).^[12,15,20]

Even in smaller cohorts from Bangladesh and Afghanistan, LABC remained common.^[15–18]

Immunohistochemistry (IHC)-based molecular subtyping was inconsistently reported. Where available, the luminal subtype was most frequent, ranging from 25% in Bangladesh^[17] to 61% in Sri Lanka and 64% in Mumbai, India.^[9,24]

HER2-enriched tumoursshowed marked variability, peaking in Afghanistan (44.6%)^[15] but lower in India and Sri Lanka (10.5–30.4%). Triple-negative breast cancer (TNBC) was consistently high: 43% in Lucknow, India, 32% in Guwahati, India, and ~27–32% in Nepal and P.^[7,10,22,23]

Thematic analysis

1. Delayed diagnosis and high LABC burden: Across countries, a high proportion of patients presented with locally advanced disease. Studies from India (Jabalpur: 62%, Guwahati: 55%, Bihar: 44.5%) ^[8,12,13] and elsewhere (Pakistan: 60%, Western Nepal: 56.6%) consistently reported LABC in >40% of cases.^[20,22]

2. Heterogeneous molecular subtype distribution: Subtype distribution varied considerably. Luminal tumourspredominated overall but ranged widely (25% in Bangladesh to 64% in Mumbai).^[9,17] TNBC showed disproportionately high prevalence in many settings (Lucknow, India: 43%, Nepal: 27–33%, Pakistan:,^[7,20,22] suggesting possible ethnic/genetic factors or delayed diagnosis. HER2-enriched cancers were particularly common in Afghanistan.^[15])

3. Underreporting of key parameters: Several studies lacked data on menopausal status, nodal involvement, or full IHC profiles.

4. Non-uniform application of IHC and molecular testing: In some reports, only subsets were tested (e.g., 124 of 183 patients from Nepal)^[19], while others omitted markers such as Ki-67.

DISCUSSION

This scoping review provides an updated synthesis of breast cancer clinicopathological and molecular patterns across SAARC countries, highlighting persistently high rates of locally advanced breast cancer (LABC) and triple-negative breast cancer (TNBC), alongside marked heterogeneity in molecular subtype distribution.

LABC continues to account for over 40% of cases in many regions, particularly in India, Nepal, and Pakistan. This aligns with Agarwal et al.^[25], who nearly two decades ago reported that more than half of breast cancer patients in developing Asian countries presented at advanced stages due to lack of awareness, absence of screening programs, and sociocultural barriers. Our findings confirm that these systemic challenges remain largely unresolved across SAARC nations.

In contrast, high-income Asian countries demonstrate a very different trajectory. Saxena et al.^[26] reported that in Singapore, earlier-stage presentation and better survival are the norm. Their comparison between Malaysia and Singapore revealed that even modest disparities in diagnostic access can translate into a 67% higher risk of death for patients. The same is reflected in our findings in SAARC countries; limited and inconsistent use of immunohistochemistry (IHC) impedes accurate diagnosis and optimal treatment planning, underscoring deep-rooted gaps in healthcare infrastructure.

A striking finding is the disproportionately high prevalence of TNBC up to 43% in Indian cohorts and consistently above 25% in Nepal, Pakistan, and Bangladesh. This contrasts with earlier data from Agrawal et al.^[25], who reported lower receptor negativity in early 2000s cohorts from India and Malaysia. Rising TNBC rates could reflect evolving tumourbiology or greater IHC availability in recent years, yet incomplete and selective testing in many centreslikely obscures the true picture. Standardising and expanding IHC access is therefore critical to defining molecular profiles and guiding treatment strategies.

Our review also revealed significant underreporting of fundamental clinical variables such as menopausal status, tumourgrade, and nodal burden. Unlike registry-based datasets used by Saxena et al.^[26], which enabled stage-specific survival analysis, the fragmented, hospital-based data from SAARC countries limitgeneralizability and hinderpolicy-level planning. Building robust, population-based cancer registries and culturally sensitive awareness programs is essential to closing these gaps.

This review has limitations. Study heterogeneity, incomplete reporting, and reliance on hospital-based cohorts precluded meta-analysis and may have introduced selection bias. IHC testing was often partial, and high-quality recent data were lacking from several studies. Nonetheless, this is the first review to comprehensively compare breast cancer patterns across all SAARC nations, including underrepresented regions such as Afghanistan, Nepal, and Bangladesh. Its strengths lie in geographic breadth, systematic methodology, and comparative subgroup analysis, which together provide unique insights into intra-regional variability—particularly the high TNBC burden and late-stage presentation that define breast cancer in the region.

TAKE HOME MESSAGE

This scoping review reveals stark gaps and regional disparities in breast cancer clinicopathological features and molecular profiles across SAARC countries. The disproportionately greater burden of advanced-stage disease and triple-negative subtypes across SAARC nations demands urgent regional action—earlier detection, equitable access to diagnostics, and standardised reporting must be prioritised without delay.