Willingness of Chinese Breast Cancer Patients for Their Children to Undergo BRCA1/2 Genetic Testing and Associated Factors

Introduction

In modern oncology, cancer management has evolved beyond the treatment of established disease to include prevention, risk stratification, and individualized care. With the development of precision medicine, genetic information has become increasingly important in identifying individuals at high risk of cancer, guiding preventive strategies, and informing clinical decision-making.¹ In breast cancer, hereditary susceptibility genes are central to this paradigm, particularly the breast cancer susceptibility genes BRCA1 and BRCA2, which play a critical role in hereditary breast cancer. Pathogenic variants in BRCA1/2 substantially increase the risk of breast cancer; by the age of 70, the cumulative risk of breast cancer is estimated at 37.9% (95% CI: 24.1%–54.4%) for BRCA1 mutation carriers and 36.5% (95% CI: 26.7%–51.8%) for BRCA2 mutation carriers—more than tenfold higher than that of the general population.² International consensus guidelines recommend that when pathogenic BRCA1/2 variants are identified in a breast cancer patient, genetic testing should be extended to relatives, given the autosomal dominant inheritance pattern of these mutations.³ Identifying healthy carriers enables timely risk management strategies, including intensified surveillance, chemoprevention, and bilateral risk-reducing mastectomy (BRRM), which has been shown to markedly reduce breast cancer risk in unaffected BRCA1/2 carriers.⁴

In hereditary cancer care, this process is closely related to cascade genetic testing, in which biological relatives of a proband are informed of familial risk and offered genetic counseling and testing. Decisions regarding genetic testing are influenced by multiple factors, such as psychological burden, testing costs, fear of disease, and insurance coverage. When considering risk-reducing interventions, patients must balance the potential reduction in cancer risk against personal and family-related concerns, including fertility, breastfeeding, and family dynamics. Previous studies have demonstrated considerable variability in genetic testing uptake among first-degree relatives of probands with BRCA1/2 mutations, with participation rates falling below 30% in some cohorts.^5–7 These findings suggest that hereditary cancer testing is not only an individual medical issue, but also a family-based decision-making process. In addition, attitudes toward hereditary risk and genetic testing may vary across sociocultural settings. In China, health-related decisions are often made within a family-centered framework, and perceptions of hereditary disease may also be shaped by intergenerational responsibility, concerns about psychological burden on children, and broader cultural attitudes toward genetic disorders. Therefore, understanding patients’ willingness for their children to undergo BRCA1/2 testing may provide useful insight into family-based hereditary cancer decision-making in the Chinese context.

Our research group has previously reported on factors influencing the uptake of BRCA1/2 genetic testing and contralateral prophylactic mastectomy among Chinese breast cancer patients, with a primary focus on patients’ own willingness to undergo genetic testing and risk-reducing strategies.⁸ In contrast, the present study extends this line of research by shifting the focus from patients’ personal risk management to their willingness for their children to undergo BRCA1/2 genetic testing, thereby addressing an intergenerational dimension of hereditary cancer risk perception and family-based decision-making that remains insufficiently explored in Chinese breast cancer patients.

In this study, we enrolled 608 newly diagnosed breast cancer patients and systematically evaluated their knowledge of genetic testing and hereditary risk, as well as the factors associated with their willingness for their children to undergo BRCA1/2 testing. These findings may provide useful evidence for family-centered genetic counseling and clinical decision-making in China.

Methods

Patients

This study employed a structured paper-based questionnaire that included the following domains: demographic characteristics and personal/family history of cancer; knowledge and attitudes toward genetic testing; reasons for supporting or declining genetic testing; and willingness for children to undergo BRCA1/2 genetic testing in adulthood, under the hypothetical scenario that the patient herself was found to carry a pathogenic BRCA1/2 variant.

The questionnaire was developed by our research team after reviewing a large body of relevant literature and identifying potential influencing factors reported in previous studies. The draft questionnaire was reviewed by a genetics specialist and a statistical expert, and revised for content appropriateness and clarity before formal administration. However, no formal psychometric validation, reliability testing, or cognitive pretesting was performed.

From May 2020 to May 2025, a total of 608 newly diagnosed breast cancer inpatients at the Department of Breast Surgery, Peking University International Hospital, completed the questionnaire in full. This was a single-center study conducted at a tertiary hospital. Participants were eligible if they were aged ≥18 years, had intact cognitive function and sufficient communication capacity to complete the survey, and completed the questionnaire preoperatively at the time of initial breast cancer diagnosis.The study was approved by the Ethics Committee of Peking University International Hospital (No. 2020011) and conducted in accordance with the Declaration of Helsinki (2013 revision). Informed consent was obtained from all participants.

Statistical Analysis

Descriptive statistics were used to summarize demographic variables, disease-related factors, predictor variables, and outcome variables. The primary outcome was patients’ reported willingness for their children to undergo pathogenic BRCA1/2 genetic testing in the above hypothetical scenario. Statistical analyses were performed using SPSS version 25.0 (IBM Corp. Armonk, NY, USA). Categorical variables were expressed as frequencies and percentages. Continuous variables were assessed for normality using the Shapiro–Wilk test; normally distributed data were presented as mean ± standard deviation (SD). Variables with P < 0.05 in univariate analyses were entered into a binary logistic regression model. Because the questionnaire-based outcome reflected stated willingness rather than actual testing behavior, the regression model was used to identify factors associated with reported willingness. A two-sided P < 0.05 was considered statistically significant.

Results

Table 1 summarizes the demographic characteristics of the study population. The participants ranged in age from 22 to 87 years, with a mean age of 51.8 ± 12.3 years. A total of 589 patients (96.9%) were married, and nearly 90% had children. Low-income individuals (monthly income ≤ 5,000 RMB) accounted for 62.7% of the cohort. Only 14.3% reported a family history of breast cancer. A total of 63 patients (10.4%) had a history of other malignancies, including thyroid cancer (n=27), colorectal cancer (n=11), lymphoma (n=2), lung cancer (n=8), uterine malignancies (n=10), and ovarian cancer (n=5).

Table 1 Characteristics of 608 Breast Cancer Patients

Table 2 presents participants’ knowledge of hereditary breast cancer risk. Overall, 57.6% correctly recognized that breast cancer could be hereditary, 37.2% were uncertain, and 5.3% believed breast cancer was not hereditary. Regarding awareness that men can develop breast cancer, 61.7% acknowledged this possibility, 36.0% were uncertain, and 2.3% believed men could not develop breast cancer. Approximately half of the participants (52.8%) correctly identified that carrying a pathogenic BRCA1/2 variant was associated with an increased risk of breast cancer, whereas 42.2% did not recognize this relationship.

Table 2 Knowledge and Attitudes Regarding Hereditary Breast Cancer Risk

With respect to attitudes toward genetic testing, 67.4% (n=410) reported willingness for their children to undergo BRCA1/2 testing in adulthood. The most commonly cited perceived benefit of testing was understanding the risk of transmitting pathogenic variants to offspring (48.5%), followed by the possibility of more individualized treatment (29.8%). The most frequently reported concern was the potential psychological burden on children (44.7%), followed by worry about personal psychological stress (28.9%).

In terms of sources of knowledge about hereditary breast cancer, 44.6% reported actively seeking breast cancer-related information, whereas only 23.2% had received genetic risk counseling from healthcare professionals. In addition, 51.8% were aware of Angelina Jolie’s decision to undergo bilateral preventive mastectomy as a healthy carrier of a pathogenic BRCA mutation, and 71.7% indicated that the medical decisions of public figures were relevant to their own healthcare choices (Table 2).

Univariate analysis showed that age (P=0.000), educational level (P=0.001), reproductive status (P=0.000), monthly income (P=0.003), prior genetic risk counseling from healthcare professionals (P=0.002), actively seeking breast cancer-related information (P=0.000), and awareness of the “Angelina Jolie effect” (P=0.000) were significantly associated with willingness for children to undergo BRCA1/2 testing (Table 3). In the multivariable logistic regression model, older age (OR=0.976, 95% CI: 0.960–0.992; P=0.003) and having only sons (OR=0.310, 95% CI: 0.142–0.677; P=0.003) remained significantly associated with lower reported willingness for children to undergo testing, whereas awareness of the “Angelina Jolie effect” was significantly associated with higher reported willingness (OR=2.036, 95% CI: 1.360–3.048; P=0.001) (Table 4). These variables were retained in the present regression model based on the factors assessed in the questionnaire and should be interpreted as variables associated with reported willingness within this study population.

Table 3 Univariate Analysis of Breast Cancer Patients’ Willingness for Children to Undergo BRCA1/2 Genetic Testing

Table 4 Multivariate Analysis of Breast Cancer Patients’ Willingness for Children to Undergo BRCA1/2 Genetic Testing

Discussion

In the clinical management of hereditary cancer, risk assessment should not be limited to the patient but must also extend to their biological relatives. Once a pathogenic variant is identified in a proband, the systematic process of offering genetic counseling and testing to biological relatives—known as cascade genetic testing⁹—becomes crucial. This process is particularly important for unaffected carriers who harbor familial pathogenic variants, as it enables early surveillance and implementation of risk-reducing interventions. Although BRCA1/2 genetic testing has been available for more than two decades and has been promoted through extensive professional education and public awareness campaigns, only a fraction of carriers have been identified to date. Considering the critical role of genetic testing in early detection, preventive interventions, and reproductive decision-making, it is essential to evaluate whether high-risk patients are willing for their children to undergo testing, as well as to identify barriers that may hinder guideline adherence. In this large-scale cohort of Chinese breast cancer patients, younger age and awareness of Angelina Jolie’s public disclosure were independently associated with higher reported willingness for children to undergo BRCA1/2 testing, whereas having only sons was independently associated with lower reported willingness. These findings provide useful insights for improving public awareness, supporting family-centered risk communication, and informing clinical practice. They also suggest that willingness toward hereditary cancer testing should be interpreted within a broader family and sociocultural context, rather than as an entirely individual medical decision.

Previous studies have shown that the uptake of cascade testing remains limited. Among first-degree relatives of probands carrying BRCA1/2 mutations, the proportion of those undergoing BRCA1/2 genetic testing varies considerably across countries. For example, Lee DSC⁶ in Malaysia reported an uptake rate of 21.6% (102/473), Jeong GW¹⁰ in Korea reported 30.5% (129/423), Trevisan L¹¹ in Italy reported 55.8% (169/303), and Finlay E¹² in the United States reported 55.9% (260/465). Predictors of cascade testing uptake included higher educational attainment, female sex, having children (particularly daughters), and a personal history of cancer. In Western populations, the cumulative risk of breast cancer by age 70 in male carriers of BRCA1 and BRCA2 mutations is estimated at 1.2% and 6.8%–7.1%, respectively, which is substantially higher than the baseline risk of 0.1% in the general male population.¹³ In our study, patients who had only sons were significantly less willing for their children to undergo BRCA1/2 testing (OR = 0.310, 95% CI: 0.142–0.677, P =0.003). This association may reflect a persistent misconception that hereditary breast cancer risk is primarily relevant to women. Clinicians should therefore emphasize that genetic testing also has important implications for men, including cancer surveillance, family counseling, and broader hereditary risk assessment. In the Chinese context, this issue may be further shaped by family-based decision-making norms, in which perceptions of risk, responsibility, and future planning for children are often discussed within the family rather than determined by the patient alone.

Since 2013 and 2015, when Angelina Jolie publicly disclosed her maternal BRCA1 mutation and family history of cancer and subsequently underwent risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), the events have drawn widespread public attention to hereditary cancers. In Western countries, these disclosures markedly increased the uptake of breast cancer screening, genetic testing, and preventive surgeries, a phenomenon commonly referred to as the “Angelina Jolie effect”.¹⁴ In the year following her announcement, genetic counseling and preventive surgery rates increased by approximately 2.5-fold.¹⁵ In our study, awareness of Angelina Jolie’s medical decisions was independently associated with greater willingness for children to undergo BRCA1/2 testing. Patients who were aware of her case appeared more likely to support genetic testing for their children as part of family risk assessment. In clinical practice, we frequently observed patients actively referring to Angelina Jolie’s case, and 71.7% of participants reported that the medical choices of celebrities were relevant to their own healthcare decisions. Nevertheless, this finding should be interpreted as a sociocultural association rather than direct evidence that celebrity exposure changes behavior. Public health education and outreach initiatives may still benefit from appropriately designed health communication strategies that improve public engagement with hereditary cancer prevention. At the same time, attitudes toward hereditary testing may also be influenced by concerns about stigma associated with genetic disorders, including worry about psychological burden, family labeling, or potential effects on children’s future marriage and life planning. These considerations may be particularly important when patients are asked to consider testing for their children rather than for themselves alone.

Most newly diagnosed breast cancer patients lack adequate awareness of the cancer risks associated with BRCA1/2 mutations. In our study, nearly half of the participants failed to correctly recognize the hereditary risk of breast cancer, and more than one-third (38.3%) were unaware that men can also develop breast cancer. Given patients’limited understanding of genetic risk, doctors play a critical role in risk communication. They not only help patients comprehend the significance and implications of genetic testing but also provide emotional support and coping strategies. A study¹⁶ conducted in Japan involving 125 probands carrying BRCA1 or BRCA2 mutations reported that 21.6% (92/425) of their first-degree relatives underwent cascade testing. The strongest predictor of cascade testing uptake was whether relatives attended professional genetic counseling together with the proband. The highest testing rates were observed among daughters (49.3%), followed by sisters (17.4%), sons (16.2%), mothers (15.6%), fathers (15.2%), and brothers (13.7%). Unlike in many western countries where patients are referred to specialized genetic counselors, frontline clinicians in China frequently assume the dual role of both treating doctors and genetic counselors. In our study, receiving professional explanations of hereditary risk from healthcare providers showed a significant difference in univariate analysis (OR = 1.975, P = 0.002), suggesting that professional counseling by medical personnel may be associated with more accurate risk perception and greater openness toward family-based testing.

Several limitations of this study should be acknowledged. First, the study was conducted in a hypothetical context, and the primary outcome reflected reported willingness rather than actual cascade genetic testing behavior. Second, as a cross-sectional questionnaire-based study, the findings indicate associations rather than causal relationships. Third, the logistic regression model should be interpreted as an exploratory association model, as several potentially relevant psychosocial and informational factors were not comprehensively assessed. Fourth, the knowledge-related items were relatively simple, and the questionnaire did not undergo formal psychometric validation. Finally, this was a single-center study conducted at a tertiary hospital; therefore, the findings may not be fully generalizable to the broader population of Chinese breast cancer patients. Nevertheless, the large sample provides useful insight into attitudes toward BRCA1/2 testing for children among newly diagnosed breast cancer patients in China.

Conclusions

Chinese breast cancer patients showed limited awareness of hereditary breast cancer risk. This study provides descriptive evidence regarding patients’ attitudes toward BRCA1/2 testing for their children and suggests that several demographic and sociocultural factors were associated with reported willingness for children to undergo BRCA1/2 testing, including age, having only sons, and awareness of the Angelina Jolie effect. These findings may help inform family-centered genetic counseling and risk communication in China, although the observed associations should be interpreted cautiously given the hypothetical and cross-sectional nature of the study and should not be considered evidence of actual cascade genetic testing decisions.