Biomarker recall and understanding among people living with metastatic breast cancer - results from an international patient survey.

1
Introduction
The global burden of breast cancer is rising, with over 2.3 million new cases in 2022, making it the second most common cancer [1]. Incidence is projected to increase by more than 45% by 2045 and approximately 30–40% of these patients will experience metastatic disease [1,2]. As part of a broader shift in cancer care, the field of oncology has been focusing on personalised medicine, where treatments are tailored to individual biomarkers of the cancer [3]. In breast cancer, this paradigm shift has transformed patient care. As understanding of breast cancer biology has evolved, the discovery of new molecular subtypes and therapeutic targets has led to treatment approaches that have significantly improved overall survival for many patients living with the disease [4,5]. Subsequently, recommendations for molecular biomarker analysis and testing have been incorporated into clinical treatment guidelines for breast cancers [6].
For those living with metastatic breast cancer (mBC), the improvement in clinical outcomes has been slow. For a long period of time, the median survival following diagnosis was between 2 and 3 years; however, new targeted therapies, especially anti-HER-2 agents and CDK4/6 inhibitors, have led to a rise in the median overall survival to about 5 years [5,7]. Continued improvement will likely be reliant on newer targeted treatment approaches, dependent on biomarker testing [8]. While these advancements benefit both patients and the healthcare community, the information that needs to be communicated by healthcare professionals (HCPs) and understood by patients is becoming more complex. Consequently, navigating an expanding range of therapeutic options has become increasingly difficult for the mBC community, with similar challenges in understanding diagnosis and treatment choices due to biomarker complexity reported in other cancers [9].
Shared decision-making (SDM) between patients and clinicians on treatment options has been associated with improved patient-reported outcomes, including reduced decisional regret and higher perceived quality of care [10,11]. In mBC, an understanding of treatment options enables patients to make decisions that balance the possibility of extending survival with maintaining or improving quality of life [12]. For patients to effectively engage in SDM and receive optimal care, they require adequate information and support to comprehend their diagnosis, prognosis, and potential treatments.
Geographically diverse data showing barriers to patients’ understanding of their mBC biomarker status are limited [13]. Therefore, to help inform improved information and support for patients, this global study seeks to assess patients' recall and understanding of mBC biomarkers, and barriers to receiving information about their mBC diagnosis.

2
Methods
A global online survey was developed by the ABC Global Alliance, designed for people with a self-reported diagnosis of mBC. In total, 15 closed-response questions were included in the survey made up of multiple-choice questions covering the following domains: (1) demographics, including age, gender, and geography, (n = 4); (2) disease history (n = 4), including time since diagnosis, and de novo vs. recurrent status; (3) biomarker terminology recall (n = 3); (4) barriers to understanding breast cancer subtype (n = 3); and (5) information sources (n = 1).
The survey was translated into 19 languages and distributed through the ABC Global Alliance network across 62 countries. Responses were collected via online submission between December 2022 and April 2024, with anonymity of participants preserved throughout. For Venezuela, patients submitted answers together with their healthcare provider with answers recorded and submitted manually, to overcome challenges in internet access. Where responses were incomplete, missing values are noted in the relevant figure legends or tables.
Descriptive statistics were used to analyse data. Results were analysed according to subgroups based on participant's reported geographic region, disease history, and information-seeking behaviours. Where applicable, statistical analysis was performed using Pearson's Chi-square test.
All participants were provided with comprehensive information regarding the study's purpose, data handling, and their voluntary participation prior to beginning the survey. No personal information was collected during this study, and the data was completely deidentified at source. The study involved no direct interventions, collected no sensitive personal identifiers, and was deemed to pose no more than minimal risk to participants. Thus, ethics approval was not deemed necessary.

3
Results
In total, 1064 responses from individuals diagnosed with mBC were received from 36 countries. Most participants were from Western Europe (n = 330), and Australasia (n = 218), with fewer responses from Africa (n = 30), Eastern Europe (n = 78), and North America (n = 84) (Fig. 1). Within certain continents, there was a high proportion of responses from specific countries; for example, the African sample was predominantly from Nigeria (87%) (Supplementary Table 1). Table 1, Table 2 summarise additional respondent characteristics, by age and time since diagnosis, respectively.
3.1
Recall of biomarker terminology
When all respondents were asked about terminology used by HCPs to discuss breast cancer with them, recall varied. Terms such as “stage” (49%; 525/1064), “TNM stages” (45%; 480/1064), and “tumour marker” (44%; 469/1064) were more commonly recalled. In contrast, “subtype” (12%; 127/1064), “biomarker” (8%; 88/1064), and “genetic marker” (12%; 127/1064) were recalled infrequently (Fig. 2A). For more specific biomarker terminology used by HCPs at initial mBC diagnosis, recall was low. Fewer than half (44%; 466/1064) reported that "hormone receptor-positive (HR+)" was used in relation to their diagnosis (Fig. 2B), although this differed markedly by region. While 73% (61/84) of North American respondents recalled the term HR+, this was considerably lower among respondents from Eastern Europe (14%; 11/78), Asia (22%; 34/156), Latin America (27%; 46/168), and Africa (33%; 10/30) (Fig. 2C).

3.2
Understanding of breast cancer subtype
When selecting statements related to learning about the subtype of breast cancer that they have, 33% (314/952) of respondents indicated that they did not understand their breast cancer subtype or its implications (Fig. 3A; Supplementary Figure 1A). Patient understanding of their specific breast cancer subtype varied by geography, with respondents from Latin America (51%; 85/168) and Africa (52%; 16/30) reporting lower levels of understanding, and those from Europe (70%; 287/408), Australasia (74%; 162/218), and North America (87%; 73/84) reporting higher levels (Fig. 3B; Supplementary Figure 1B).

3.3
Barriers to understanding breast cancer subtype
Out of 952 complete responses, less than half of respondents (44%; 415/952) reported receiving adequate information from HCPs regarding their breast cancer subtype (Fig. 4A). Additionally, specific barriers to effective communication with HCPs were identified in some regions; respondents in Africa most frequently reported encountering challenges, with 20% (6/30) indicating that HCPs used language they did not understand (Fig. 4B; Supplementary Figure 1B), and 17% (5/30) noting they were not informed about their specific breast cancer subtype (Fig. 4C). Additionally, 10% (34/330) of respondents from Western Europe also reported they had not been told by HCPs what subtype of breast cancer they have (Fig. 4C).
When all respondents were asked about information sources used to find out about the subtype of breast cancer they have, most reported using the internet (70%; 743/1064), followed closely by their doctors (64%; 676/1064) (Fig. 5). Other individuals with a prior breast cancer diagnosis were also a common source (45%; 477/1064), followed by patient advocacy groups and support groups (39%; 416/1064).
A small subset of patients (7%, 75/1064) indicated they had low motivation to learn about the subtype of breast cancer they have (Fig. 6A and B). This low-motivation subset was less likely to seek information from multiple sources (Fig. 6C). Furthermore, they demonstrated a significantly lower level of understanding regarding their breast cancer subtype and its implications (Fig. 6D). By region, Latin American patients were significantly more likely to be in the low-motivation subgroup at 17% (29/168), compared with 0–10% of respondents from other regions (p < 0.0001) (Fig. 6E).

4
Discussion
This study assessed patients' recall and understanding of mBC biomarkers and barriers to receiving information, with over 1000 respondents from 36 countries – to our knowledge, making it the most comprehensive of its kind to date. Findings reveal considerable variability in respondents' recall of key biomarker terms, with many indicating that they do not understand their diagnosis. This is consistent with findings from other studies indicating that people diagnosed with cancer often struggle to recall and understand details about their biomarker testing, including which specific alterations were assessed [14,15]. Additionally, a considerably lower percentage of patients recalled the term HR+ (44%) than would be expected based on the average prevalence of this subtype (∼78%), while HER2+ was reported by more patients than expected based on prevalence (∼14%) [16]. Notably, recall of the term “biomarker” itself was particularly low. This may reflect the fact that biomarker is a broad, umbrella term encompassing multiple molecular and receptor-level characteristics and is not routinely used in patient–clinician discussions. Similarly, the term “genetic marker” was among one of the most infrequently recalled general terms and given that testing for inherited genetic alterations is not routinely performed in mBC [17], the term “genetic” may not be clearly communicated to or understood by patients.
Responses also varied significantly by region, with North America, Western Europe, and Australasia typically displaying higher levels of recall and understanding, which likely reflects wider access to biomarker testing and targeted therapies, and access to educational support and resources, in these regions [18]. This may also reflect greater patient access to pathology reports and electronic health records in some healthcare systems, particularly in North America [19]. Nevertheless, fewer than half of all respondents across geographies reported receiving adequate information from HCPs about their breast cancer subtype, suggesting widespread gaps in patient–HCP communication.
One contributing factor could be a lack of depth or clarity of explanations HCPs provide patients with mBC. Similar international survey results have highlighted the importance of HCPs in explaining health information to patients, yet information often fails to meet patients' needs [20]. Additionally, previous research has highlighted considerable variability in the vocabulary oncologists use to explain molecular testing, which may reflect some of the variation in respondent recall of terminology observed in this study. Inconsistent biomarker terminology used by HCPs can add to patients' confusion regarding understanding their tumour's biomarker status [21].
Improved guidance on terminology for different stakeholders, including patient-friendly glossaries, will be important as additional biomarkers and classifications are introduced. Such resources could play a dual role: supporting people living with mBC through clear, translated explanations of key terms, while also promoting consistent language use among HCPs involved in diagnosis and treatment discussions. Resources such as the Cancer Support Community Precision Medicine Lexicon, which offers patient-friendly definitions for biomarker and genetic testing, provide useful examples of how to standardise communication [22]. However, tailoring to different populations based on their language, health literacy, culture, and access needs will be crucial.
Additional widely reported barriers to effective patient–HCP communication include time constraints during consultations limiting personalised explanations [23]; insufficient training in conveying complex medical information to patients with varying health literacy [24]; and a lack of confidence in interpreting and explaining biomarker results [25]. The expansion of supportive care models (such as patient navigation programmes and specialised breast cancer nurses) can help to improve two-way communication across the patient pathway in clinical practice, outside of increasingly pressured physician consultations. Additional trained personnel can also help to support nurse and physician roles with improved communication. For example, the MAGENTA study has demonstrated that genetic counsellors with specific training can provide tailored guidance and play a key role in educating patients and encouraging biomarker testing [26].
Previous studies on cancer care in low- and middle-income countries have shown that limited infrastructure and resources significantly hinder access to biomarker testing and targeted treatments [27]. This is likely to limit patients' understanding of their diagnosis and associated topics. We found that challenges in understanding breast cancer diagnoses were most pronounced in Africa. In Nigeria, where most African respondents were located, the high patient-to-oncologist ratio strains HCPs, which may lead to less effective communication and limited ability to explain diagnoses [28], aligning with findings from this study. In addition, cultural attitudes towards HCP–patient relationships and gender biases may affect women's involvement in decision-making [29]. Nevertheless, results in this survey also demonstrated that respondents from Western Europe reported not being informed by HCPs about their breast cancer subtype, suggesting communication challenges even in regions with better access to testing and resources. However, overall, the low number of patients reporting specific challenges provided in the survey, along with regional variation, suggests that the survey may not have captured all the complex barriers patients encounter.
Findings from this study highlight the internet as the primary source of information for patients following a breast cancer diagnosis, surpassing even doctors. This reliance aligns with broader trends in healthcare, where digital platforms play an increasingly central role in patient education. While patient advocacy groups and support networks offer valuable resources, their use was relatively low. Although this highlights the accessibility of online resources, it also underscores the need for more meaningful patient-HCP communication. These findings emphasise the need for healthcare leaders and advocacy organisations to improve online resources with accurate, plain-language information tailored to patient needs.
Further subgroup analysis of our respondents revealed a small percentage of patients with low motivation to seek information about their diagnosis. Patients with mBC often struggle to understand and cope with an incurable diagnosis, which can hinder communication with HCPs. Coping mechanisms like denial and a perceived lack of control have been shown to reduce patients' motivation to engage further [30]. Additionally, low health literacy, often linked to an increased reliance on HCPs’ expertise for decision-making, can reinforce a historically paternalistic model of care [31]. While a small proportion of patients displayed low motivation to seek more information about their diagnosis, this was higher among Latin American respondents. Limited access to diagnostic testing and treatments within their healthcare system may play a role in influencing this perspective [32]. Religious factors may further complicate this issue, as patients may place their faith in God as the sole determinant of the outcomes of the disease course [33]. By contrast, North America demonstrated higher patient awareness and understanding, which could be attributed to several factors. Improved access to diagnostic information, and more established healthcare models may play a role, as these systems often prioritise patient education and encourage engagement with medical information and decisions. Additionally, robust advocacy efforts in the region may have further strengthened awareness and engagement among patients. For instance, campaigns such as No One Missed which are driven by the US organisations LUNGevity and Living Beyond Breast Cancer and show the value of educating patients about biomarker testing and encouraging conversations with HCPs [34]. Tailoring these initiatives to specific populations and sharing learnings from the region could provide a useful method to improve patient engagement and understanding globally.
4.1
Study limitations
This study has several limitations that must be acknowledged. First, regional responses were disproportionately weighted toward specific countries, which may have influenced the representativeness of the findings. Additionally, for specific questions missing data is associated with certain countries which may introduce geographical bias. Second, the availability of the survey only in English in certain countries may have limited participation and affected comprehension, particularly in settings where local language translations were not provided. Additionally, the translatability of certain survey items may have impacted the consistency of responses across linguistic and cultural contexts. Finally, the online delivery method inherently restricted participation to individuals with internet access and adequate digital literacy, potentially excluding populations with limited resources or technological proficiency. These factors highlight the need for cautious interpretation of the results and suggest avenues for refining future research methodologies to ensure broader inclusivity and generalisability.

5
Conclusion
This study was able to assess patients' recall and understanding of mBC biomarkers and identify barriers to receiving biomarker information, highlighting gaps in patient–HCP communication about diagnosis across regions. Importantly, findings indicate that recall of key biomarker terminology is highly variable, and many patients lack a clear understanding of their diagnosis, which may hinder effective shared decision-making. Findings underscore the challenges posed by a combination of complex medical terminology, limited access to biomarker testing, and systemic communication barriers between patients and HCPs. These challenges may be exacerbated for patients with lower health literacy or socioeconomic status, particularly in low-and-middle-income countries. Addressing these issues through regionally tailored educational resources, guidance for patient–HCP communication, and empowerment of patients through advocacy, will be crucial to improving patient understanding and engagement in clinical decision-making, ultimately improving the quality-of-care patients receive. This study provides directional findings that could inform strategies to close education and communication gaps for patients receiving a diagnosis of mBC.

CRediT authorship contribution statement
Eva Schumacher-Wulf: Writing – review & editing, Writing – original draft, Validation, Methodology, Formal analysis, Conceptualization. Lesley Fallowfield: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Formal analysis, Conceptualization. Runcie C.W. Chidebe: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Formal analysis, Conceptualization. Vicki Durston: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Formal analysis, Conceptualization. Alexandru Eniu: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Formal analysis, Conceptualization. Ranjit Kaur: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Formal analysis, Conceptualization. Renate Haidinger: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Formal analysis, Conceptualization. Nisha Pillay: Writing – review & editing, Writing – original draft, Visualization, Validation, Project administration, Methodology, Formal analysis, Data curation, Conceptualization. Daniel Egbase: Writing – review & editing, Writing – original draft, Visualization, Validation, Project administration. Yi Han: Writing – review & editing, Visualization, Validation, Methodology, Formal analysis, Data curation. Fatima Cardoso: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Resources, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.

Declaration of competing interest
Lesley Fallowfield has received honoraria from Voluntis, Genomic Health, NanoString Technologies, Novartis, Pfizer, MSD, AbbVie, and Clovis Oncology; served in a consulting or advisory role for Puma Biotechnology, Voluntis, AstraZeneca, Takeda, Genomic Health/Exact Sciences, Lilly, Seagen, and Roche; received research funding from Bristol Myers Squibb, Novartis, and Lilly; and received travel, accommodations, or other expenses from Genomic Health.
Fatima Cardoso has served in a paid consultancy or advisory role for Amgen, Astellas/Medivation, AstraZeneca, Bayer, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, IQVIA, Macrogenics, Medscape, Merck Sharp & Dohme, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva, and TouchIME. Given her role as Editor, Dr. Fatima Cardoso had no involvement in the peer-review of this article and has no involvement in the peer review of this article and has no access to information regarding its peer review.
Ranjit Kaur has received honoraria from Novartis, Roche, Pfizer, and AstraZeneca; served in a consulting or advisory role for Novartis, Roche, Pfizer, and AstraZeneca; received research funding from Novartis, Roche, Pfizer, and AstraZeneca; and participated in speakers’ bureau activities for Novartis, Roche, Pfizer, and AstraZeneca.
Vicki Durston has served in a consulting or advisory role for General Assembly ABC Global Alliance, WHO GBCI-TWG, and Breast Cancer Network Australia.
Alexandru Eniu has the following financial interests: served in an institutional advisory board role for AstraZeneca and Gilead; received personal fees as an invited speaker from Novartis; served in a personal advisory board role for Daiichi Sankyo and Pfizer; received personal fees for writing engagements from Lilly; is employed full-time by the European School of Oncology (ESO); and has acted as a local principal investigator with institutional financial interest for Roche and AstraZeneca.
Daniel Egbase, Nisha Pillay, and Yi Han are employees of VML Health. Medical writing support provided by these individuals was funded by AstraZeneca. AstraZeneca's role was limited to a courtesy review of the final version of the manuscript.
All remaining authors have declared no conflicts of interest.