Breast cancer (BC) is the most frequently diagnosed cancer among females worldwide and the leading cause of cancer-related mortality globally. According to GLOBOCAN 2024, BC accounted for an estimated 2.4 million new cases of breast cancer, and approximately 690 000 deaths occurred globally.¹ In sub-Saharan Africa (SSA), the burden of BC is escalating because of increased life expectancy and lifestyle-related risk factors, with mortality-to-incidence ratios more than double those seen in high-income countries (HICs).² Notably, an estimated 26% of new BC cases in SSA occur in females under 50 years of age.³

In South Africa, BC is the most common malignancy among females of all racial groups, with a reported lifetime risk of 1 in 28.⁴ Females in SSA, including South Africa, often present at younger ages and with more advanced disease stages compared to females in HICs.⁵ This issue is further compounded in human immunodeficiency virus (HIV)-endemic areas. Previous studies from our institution have shown that 22% of women with BC were also living with HIV, and these females were diagnosed at a median age of 45 years, approximately 10 years younger than their HIV-negative counterparts.^6,7,8 Most women living with HIV (WLWH) in the cohort self-identified as being of African ancestry. While HIV status did not significantly influence stage at diagnosis,⁶ WLWH presented with more aggressive tumour biology.⁷

Globally, approximately 8% of BC cases occur in females under 40 years, with incidence rising in low- and middle-income countries (LMICs) where populations are generally younger.⁸ Breast cancer accounts for nearly 30% of cancer diagnoses among adolescents and young adults (AYAs), defined as individuals aged 15 years – 39 years.⁹ The definition of ‘young’ in breast oncology varies, but most literature uses the cut-off of 40 years.¹⁰ Key risk factors in younger females include early menarche (before age 12 years), nulliparity and family history of BC.¹⁰ In 97% of cases, young females themselves first detect a breast abnormality.¹⁰ This group often presents with biologically aggressive tumours, advanced-stage disease and higher rates of local recurrence following breast-conserving therapy,¹⁰ contributing to a 39% higher mortality rate compared to older females.⁹

Breast cancer detection in younger females is challenging. Dense breast tissue reduces the sensitivity of mammography, making it less effective in younger age groups.¹¹ This is especially relevant for females, who tend to have denser breasts even after adjusting for age, body mass index (BMI) and other factors.¹² Physiological changes during pregnancy and lactation further complicate detection.¹¹ As a result, both ultrasound and mammography may fail to identify early-stage disease,¹³ and patients themselves often discover abnormalities.¹⁰

Histologically, the majority of BCs are ductal in origin, with invasive ductal carcinoma accounting for about 80% of cases¹⁴ and fibroadenoma as the most common benign lesion.¹⁵

Early-stage diagnosis, along with timely treatment, remains the most critical determinant of survival in young BC patients. Standard diagnostic workup includes clinical breast examination, ultrasound or mammography and image-guided core biopsy.^16,17,18 Because of higher breast density in younger females, mammography alone is often insufficient, with ultrasound generally showing higher sensitivity in females under 45 years, whereas mammography alone performs better in older populations.¹⁹

In South Africa and globally, asymptomatic screening mammography is recommended starting at age 40 years,⁴ and there is no formal screening programme for females under 40 years of age. Females generally present with self-detected breast symptoms. Magentic resonance imaging (MRI) may be used in selected cases to further characterise breast lesions and provide additional diagnostic information.²⁰ Unfortunately, MRI services are in short supply in the South African public healthcare system. Instead, young females with suspicious ultrasound findings receive a mammogram to confirm the need for subsequent image-guided core biopsies. Because mammography relies on detecting dense masses, its utility in young females with dense breast tissue is regarded as limited.

This study is therefore aimed at evaluating the diagnostic utility of mammography and breast ultrasound in symptomatic females aged 40 years and younger. We assessed the concordance between bimodal Breast Imaging Reporting and Data System (BI-RADS) and histopathology diagnostic findings in young females who were subsequently diagnosed with BC at Chris Hani Baragwanath Academic Hospital (CHBAH).^21,22

The South African Breast Cancer and HIV Outcomes (SABCHO) study is an ongoing, multicentre cohort investigating outcomes in South African females newly diagnosed with invasive BC. Initiated in 2015, the study is conducted across six tertiary public hospitals in the Gauteng and KwaZulu-Natal provinces: (1) CHBAH, (2) Charlotte Maxeke Johannesburg Academic Hospital (Johannesburg), (3) Inkosi Albert Luthuli Central Hospital (Durban), (4) Addington Hospital (Durban), (5) Ngwelezane Hospital (Empangeni) and (6) Grey’s Hospital (Pietermaritzburg).^21,22 This retrospective analysis focuses on data collected from January 2016 to December 2022, including females aged 18 years – 40 years who were enrolled at the CHBAH site and subsequently diagnosed with BC.

Chris Hani Baragwanath Academic Hospital, commonly referred to as Bara, located at 26 Chris Hani Road, Diepkloof, Soweto, Johannesburg, was established in September 1942.²³ It is the largest hospital in the southern hemisphere, spanning 173 acres with approximately 3200 beds and over 6760 staff members.²³ The hospital serves millions of residents in Soweto and is a teaching facility affiliated with the University of the Witwatersrand.²³

We included all females aged 18 years – 40 years with newly diagnosed BC who underwent diagnostic imaging (breast ultrasound and followed by mammogram for suspicious lesions with a BI-RADS of ≥ 3) and histopathological confirmation. Patients with bilateral BC were included if they fulfilled the study inclusion criteria. Imaging findings and histopathological diagnoses were assessed according to the lesion undergoing diagnostic evaluation and biopsy confirmation. We excluded females who were known to have a BC diagnosis (BI-RADS 6) where imaging was used solely for surgical planning, those unable to provide informed consent and females with missing BI-RADS classification or absence of histological diagnostic reports. The BI-RADS assessments were made based on breast imaging findings and not on lymph node involvement.

This retrospective study was conducted at CHBAH, and the study forms part of the doctoral thesis completed by the third author at the University of the Witwatersrand.

Three hundred and fifty-four females aged ≤ 40 years were diagnosed with BC at CHBAH during the study period. Of these, 28 had missing BI-RADS data and were excluded, as were a further 17 females with a known BC diagnosis (BI-RADS 6) for whom imaging was performed to assist surgical treatment. A total of 309 females were included in the final analysis (Figure 1).

The mean ± s.d. age was 35.2 ± 3.9 years, with categorical age distributions of 13.6% for ≤ 30 years of age, 32.0% for ages 31 years – 35 years and 54.4% for those aged 36 years – 40 years. The percentage of females ≤ 40 years diagnosed with BC per year from 2016 to 2022 ranged from 10.7% to 19.7%, with 2021 having the highest percentage. The percentage of females aged ≤ 40 years per year was thus not unduly affected by the coronavirus disease 2019 (COVID-19) pandemic lockdown period, which began in March 2020 (Table 1).

The prevalence of HIV in the cohort at diagnosis was 40.0%; of these, 74.0% were previously diagnosed with HIV and on antiretroviral therapy (ART), and 26.0% were newly diagnosed with HIV.

Clinical characteristics of the cohort are summarised in Table 2. Most patients presented with advanced-stage disease, comprising 48% with stage III (locally advanced) disease and 12 % with stage IV disease.

A concordance rate of 97.7% was observed between bimodal BI-RADS assessment and histopathological diagnosis. Notably, all discordant cases occurred in patients with non-metastatic stage I, stage II and stage III disease (Figure 3).

This study evaluated the concordance between bimodal BI-RADS imaging assessment and histopathological diagnosis in females aged 40 years and younger presenting with BC at a tertiary referral centre in South Africa. A high level of agreement was observed between combined mammography and breast ultrasound-based BI-RADS classification and histopathological confirmation of malignancy. These findings support the utility of multimodal breast imaging in the diagnostic evaluation of young females, a population in whom image interpretation may be complicated by dense breast tissue and overlapping benign imaging characteristics.^24,25,26 Similarly, Dehar et al. reported that ultrasound combined with diagnostic mammography represents an appropriate imaging strategy for evaluating breast symptoms in females aged 30 years – 50 years.²⁷

Although discordance between imaging assessment and histopathological diagnosis occurred in only a small proportion of cases, these findings remain clinically important. Dense fibroglandular tissue may obscure subtle lesions on mammography, thereby reducing the conspicuity of malignant masses. Furthermore, certain BCs may demonstrate atypical or less suspicious imaging features, including relatively smooth or well-circumscribed margins, potentially resulting in lower BI-RADS categorisation despite underlying malignancy. These limitations underscore the importance of correlating imaging findings with clinical assessment and maintaining a low threshold for tissue diagnosis when clinical or radiological suspicion persists.

Recent evidence suggests that contrast-enhanced mammography may improve lesion detection in females with dense breast tissue by highlighting tumour vascularity and improving lesion conspicuity.²⁸ Although this modality was not assessed in the present study, it may represent a valuable adjunct to conventional breast imaging in healthcare settings where access to MRI remains limited. Additional emerging imaging techniques, including ultrasound elastography, automated breast ultrasound (ABUS), artificial intelligence (AI)-assisted imaging, molecular breast imaging and radiomics, may further enhance breast imaging performance and diagnostic accuracy in the SSA public healthcare sector.

The demographic profile of this cohort is consistent with patterns reported in other studies of BC among young females. The age distribution observed in this study is comparable to findings by Sabiani et al., who reported a similar mean age among young BC patients.²⁹ These findings further support the recognition of BC in females younger than 40 years as a clinically distinct subgroup that may require tailored diagnostic and management approaches.

Breast cancer diagnosed at younger ages is frequently associated with more aggressive tumour biology and a more advanced stage at presentation. The predominance of locally advanced disease observed in this cohort mirrors findings from other studies conducted in low-income and middle-income countries, where delayed presentation, limited screening programmes and reduced awareness of early symptoms contribute to later-stage diagnosis.^30,31,32 These findings underscore the importance of reliable imaging pathways that support early evaluation of suspicious breast abnormalities and facilitate timely histopathological confirmation.

A substantial proportion of females in this cohort were HIV positive, reflecting the ongoing intersection between HIV and BC in South Africa. Previous South African studies have demonstrated that WLWH may present with BC at a younger age and with more advanced-stage disease than their HIV-negative counterparts.^33,34,35 Although the present study was not designed to evaluate the influence of HIV status on BI-RADS classification, imaging concordance or stage at presentation, the high HIV prevalence observed highlights the importance of integrated oncological and HIV care pathways. Further research is warranted to determine whether HIV infection influences imaging characteristics, diagnostic concordance or patterns of disease presentation in young females with BC.

Tumour laterality did not demonstrate a clear predominance in this cohort, in contrast to reports describing a higher frequency of left-sided BCs.³⁶ Abdou et al. previously reported associations between left-sided BC and more aggressive tumour biology, as well as potential long-term treatment implications related to radiation exposure.³⁶ The absence of a clear laterality pattern in the present study may reflect population-specific variation in BC presentation.

The histological profile observed in this cohort was consistent with established epidemiological patterns, with invasive ductal carcinoma representing the predominant tumour subtype (Figure 2). This finding aligns with global data identifying invasive ductal carcinoma as the most common histological form of BC worldwide.³⁷ Similar observations have been reported in African populations, suggesting that the histological spectrum of BC in younger females remains broadly comparable to that seen in the general BC population.³⁸

Several previous studies have evaluated the concordance and predictive utility of BI-RADS classification in identifying breast malignancy. Chavan et al. reported a high agreement between BI-RADS assessment and histopathological diagnosis in females presenting with breast lumps although their cohort included a broader age range extending to 75 years.³⁹ Studies focusing specifically on younger females have generally demonstrated slightly lower concordance rates, likely reflecting the challenges associated with dense breast tissue and less conspicuous imaging features in this population. Similarly, Wang et al. reported an 84.4% concordance between mammography and histopathology in females under the age of 40 years.⁴⁰

Given the limited literature from SSA, these findings contribute important context-specific data regarding the concordance between bimodal BI-RADS assessment and histopathological diagnosis in young females presenting with BC, consistent with findings from recent radiological-pathological correlation studies.^41,42

The clinical utility of BI-RADS classification in stratifying the likelihood of malignancy has been well established. The seminal work by Orel et al. demonstrated a strong association between BI-RADS categorisation and histopathological malignancy.^43,44 The predominance of BI-RADS 5 lesions in the present cohort likely reflects the symptomatic nature of disease presentation in this population, where patients commonly present with clinically apparent breast masses rather than screen-detected abnormalities.

Breast density remains an important consideration in imaging younger females, as increased fibroglandular tissue may reduce mammographic sensitivity.⁴⁵ Despite the recognised limitation, the findings of the present study support the continued utility of combined mammography and ultrasound in the evaluation of breast lesions within this population.

These findings are particularly relevant in resource-limited healthcare settings, where access to advanced imaging modalities such as breast MRI remains limited. In many South African public sector hospitals, mammography and ultrasound continue to form the foundation of breast imaging assessment. Optimising the use of these readily available modalities within a structured BI-RADS framework may assist in guiding biopsy decisions and facilitating timely histopathological diagnosis and management of BC.^46,47

In conclusion, this study demonstrated a high level of concordance between bimodal BI-RADS imaging assessment and histopathological diagnosis in females aged ≤ 40 years with biopsy-confirmed BC. These findings support the utility of combined breast ultrasound and mammography in the evaluation of supicious breast lesions in young females. In resource-constrained healthcare settings, the effective use of these widely available imaging modalities remains essential for facilitating timely diagnosis and management of BC.