The Triple-negative breast cancer is an aggressive molecular subtype of a breast cancer characterized by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. It is a leading cause of breast cancers in some of the larger part of the world but disproportionately leads to recurrence, visceral metastasis, and death since endocrine treatment and HER2-guided treatment options are ineffective. TNBC is biologically heterogeneous and comprises basal-like, immunomodulatory, mesenchymal, luminal phenotypes and androgen receptor, which is however in normal clinical practice identified by immunohistochemistry.1

BRCA1 and BRCA2 are tumor suppressor genes, which take part in homologous recombination of DNA repair. Pathogenic variants reduce the healing of DNA breaks (in both strands), which causes genomic instabilities and elevates the risk status of breast, ovarian, pancreatic, and prostate cancer. The breast cancers associated with BRCA1 have been found to be often of high grade and basal-like, and triple-negative, but those linked with BRCA2 are more likely to be hormone-receptor positive and also appear as TNBC. Thus, TNBC is a critical clinical distinguishing variable of potential familial breast cancer.2

The BRCA1/2 pathogenic/probably pathogenic variants are significant to detect. Firstly, it determines which patients can be put under platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors in the right clinical scenario. Second, it helps in making surgical decisions, like contralateral risk evaluation and risk-minimizing alternatives. Third, it allows cascade testing and prevention of cancer in relatives. Fourth, it contributes to the estimation of risk of ovarian and other BRCA related malignancies.3,4

There is general support in international guidelines to use germline genetic testing with patients with TNBC, particularly when diagnosed at an earlier age or with a family history of breast or ovarian cancer. According to the recent ASCO-Society of Surgical Oncology recommendations, the recommended structural germline testing in breast-cancer patients depends on the age of the patients, the tumor phenotype, the family history, and the therapeutic relevance. On the same note, genetic-testing quality guidelines highlight pre-test counseling, the methods of sequence validation, the classification of variants, and post-test genetic counseling.5

Breast cancer has a lower age of occurrence in Pakistan than in most of the Western populations. TNBC is also clinically significant in that, they tend to have a high grade of node positive disease or locally advanced. Genetic services are not comprehensive and a lot of patients are unable to afford full-fledged germline testing. Therefore, the regional data on BRCA1/2 positivity of TNBC patients in Pakistan are still critical in the context of designing cost-effective testing protocols and counseling.6

Previous Pakistani studies have noted a very large proportion of BRCA1 mutations in TNBC patients indicating perhaps population-specific trends and founder effects. Subsequent Pakistani sequencing reports have maintained the occurrence of clinically significant BRCA1/2 variants of high risk breast-cancer families and breast-cancer cohorts. Nonetheless, there are fewer data that specifically address contemporary Pakistani TNBC patients.7

BRCA1/2 pathological variants are more common in TNBC in different countries and races. Western studies tend to give a BRCA1/2 positivity rate of about 1020 in unselected cohorts of TNBC and in selected high-risk or young TNBC cohorts the rate can be higher. Regional data (Middle East, South Asia) indicate that consanguinity, founder variations, early age of diagnosis and selection patterns are supposed to increase the prevalence of mutations in certain groups.8

One of the most effective predictors of BRCA positivity is age at diagnosis. Germline pathogenic variants are more common in younger compared to older TNBC patients. There is also family history of breast, ovarian, pancreatic or prostate cancer, which predisposes to mutation. High-grade morphology, bilateral breast cancer, medullary and strong lymphocytic infiltration can also indicate hereditary DNA-repair deficiency.9,10

Nevertheless, BRCA testing is not a widely performed test even in the Pakistani oncology practice. These barriers consist of cost, untrained genetic counselors, the infrastructures of the laboratories, uncertainty of variants with uncertain significance and no insurance cover. Policy decisions to be made to either use targeted or universal testing among TNBC patients can be supported by local prevalence estimates.

The current research was carried out to investigate the common rate of BRCA1 and BRCA2 positivity in Pakistani patients with triple-negative breast cancer and to determine clinicopathological outcomes related to BRCA positivity. The results can assist in prioritizing genetic-testing and enhancing hereditary cancer services in Pakistan.

The present study is an analytical cross-sectional study that took place in a tertiary oncology center in Pakistan over a span of six months under the ethical approval. It was aimed at establishing the rates of BRCA1 and BRCA2 positivity in Pakistani patients with triple-negative breast cancer and assessing clinicopathological characteristics in relation with BRCA positivity. All patients were able to give informed consent before genetic testing and gathering of the data written. Genetic counseling had been done in the lead-up to and after the testing and secrecy of identity of the patient, family history and genetic outcomes had been kept secret. The single-population proportion formula was used to estimate the sample size: n = Z 2 p (1-p)/ d 2. The confidence level was maintained at 95% which is Z = 1.96. A literature on regional and high-risk TNBC was used to expect BRCA1/2 positivity in TNBC patients to be 24%. The error observed was maintained at 7 per cent. Therefore, n = (1.96)² × 0.24 × 0.76 / (0.07)² = 143.0. The final sample size of 160 patients was then determined after the addition of an approximation of 10 percent due to missing records or poor samples, or due to inconclusive genetic testing outcomes. The technique employed was non-probability consecutive sampling wherein all of the eligible patients during the study period were recruited until sample size was reached. Included were female Pakistani patients with histologically-confirmed invasive breast carcinoma and triple-negative immunohistochemical profile in the age range of 18-65 years. Triple-negative breast cancer was determined to be estrogen receptor negative, progesterone receptor negative, and HER2 negative based on conventional immunohistochemistry guidelines. In cases of HER2 equivocality the case was confirmed using in situ hybridization where possible. Patients with recurrent breast cancer who have no primary tumor receptor status, incomplete immunohistochemistry, or insufficient blood sample to perform genetic testing, who declined genetic testing, or who were not Pakistani were excluded. The structured proforma was used to gather clinical and demographic information. Variables were as follows; age at diagnosis, marital status, menopausal status, residence, a family history of breast or ovarian cancer, a family history of pancreatic or prostate cancer, consanguinity, laterality, tumor size, tumor grade, lymph-node status, clinical stage, histological type, lymphovascular invasion, Ki-67 index, and BRCA test result. The history of the family was judged as positive when a first or second degree family member had breast, ovarian, pancreatic, or prostate cancer. Peripheral blood samples were used to conduct BRCA1 and BRCA2 tests. The DNA in the samples was obtained as genomic DNA by standard laboratory procedure. Coding regions and boundaries between exons and introns of BRCA1 and BRCA2 were evaluated by next-generation sequencing. The variants identified were categorized based on accepted conventions of variant-classification into pathogenic, likely pathogenic, variant of uncertain significance, likely benign, or benign. In this study, BRCA positivity was considered to be the existence of a pathogenic or probably pathogenic variant in BRCA1 or BRCA2, or both. Variants of uncertain significance were reported as separate and were not included within the category of positive. They were analyzed and inputted into SPSS version 26. Quantitative data like age and the sizes of tumors were in the form of mean and standard deviation. Categorical variables such as menopausal status, family history, tumor grade, lymph-node status, stage, as well as BRCA status were reported as frequency and percentage. BRCA positivity was categorized based on age, history of the family, menopause, tumor size, tumor grade, lymph-node status, clinical stage, laterality and Ki-67 index. Categorical comparisons were done using Chi-square test or Fisher exact test. Bivariate analysis variables that had a p value of 0.20 and variables that were of clinical interest were included in multivariate binary logistic regression. Odds ratios were obtained adjusted with 95% confidence interval. The p-value of 0.05 or below was taken to be significant.

The final analysis comprised of 160 Pakistani breast cancer patients with triple-negative. The average age of diagnosis was 42.6(10.8) years with the lowest and highest age being 22 to 72 years respectively. Sixty-two patients were less than 40 years old and 88 patients were above 40 years. In 94 patients (58.8%) premenopausal and 66 (41.3) postmenopausal states were observed. A total of 96 patients (60.0% lived in the city and 64 patients (40.0% lived in the country) reported their residence. Forty-six patients (28.8) were of positive family history of breast or ovarian cancer. Among the 54 patients, there was consanguinity reported (33.8%).

The most prevalent histological type was invasive ductal carcinoma with a frequency of 149 cases (93.1%). Tumor size was ≤2 cm in 36 patients (22.5%), >2–5 cm in 91 patients (56.9%), and >5 cm in 33 patients (20.6%). The common tumor grade was high; grade III was observed in 112 (70.0) and grade II was observed in 48 (30.0) patients. Invasion of lymph vascular was also evident among 68 patients (42.5%). In 96 patients (60.0%), lymph-node positivity was reported. Stage I disease was present in 19 patients (11.9%), stage II in 73 (45.6%), and stage III in 68 (42.5%). Ki-67 index ≥30% was seen in 118 patients (73.8%).

The overall BRCA1/2 positivity was noted to be 43 in 26.9. Only 32 patients (20.0%), 9 patients (5.6%), and 2 patients (1.3%) were found to have BRCA1 pathogenic or likely pathogenic variants, BRCA2 variants and BRCA1/2 positivity respectively. Therefore, BRCA1 explained most of the positive results. Uncertain significant variants were also noted among 12 patients (7.5%), but it was not classified as such in the BRCA-positive group.

Patients who were younger were much more likely to be positive BRCA. Among patients aged ≤40 years, 28 of 72 (38.9%) were BRCA-positive, compared with 15 of 88 (17.0%) patients aged >40 years. Warm family history also proved to be closely related with BRCA positivity. Of 46 patients with a positive family history, 23 (50.0%) were BRCA positive, and 20 of 114 (17.5) BRCA negative. Fourteen patients had bilateral breast cancer and it was related with BRCA positivity; eight of these 14 patients were positive.

BRCA positivity was also involved with tumor grade and lymph-node status. In the grade III tumors, there were 36/112 (32.1) cases of BRCA-positive and 7/48 (14.6) grade II tumors. The BRCA positivity was observed in 32 of 96 patients with node positivity (33.3) and 11 of 64 with nodes negativity (17.2). The BRCA positivity rate was higher in Ki-67 ≥30% as compared to Ki-67 <30%; however, it was not deemed to be statistically significant.

Age ≥40 years, positive family history and bilateral breast cancer continued as independent predictors of BRCA positivity on the multivariate logistic regression. Grade III tumor and node positivity yielded more odds but was no longer statistically significant on adjustment. The general results indicated that the BRCA1 /2 positivity was high in Pakistani patients who were affected by TNBC, especially among the young group and those with a history of the disease or bilateral.

Table 1. Baseline demographic characteristics of Pakistani TNBC patients, n=160

Table 2. Clinicopathological characteristics of triple-negative breast cancer

Table 3. Frequency and pattern of BRCA1/2 positivity

Table 4. Stratification of BRCA1/2 positivity according to clinicopathological variables

Table 5. Multivariable logistic regression for predictors of BRCA1/2 positivity

The current research tested the BRCA1 and BRCA2 positivity in 160 Pakistani patients of triple-negative breast cancer. The total BRCA1/2 positivity consisted of 26.9 where BRCA1 positivity was 20.0 and the BRCA2 positivity was 5.6 and BRCA1/BRCA2 positivity was 1.3. This is, there were over four Pakistani TNBC patients in a sample of four who had a pathogenic or likely pathogenic BRCA1/ 2 variant. The BRCA1 preponderance correlates with the established biological correlation between the BRCA1 dysfunction and triple-negative phenotypes. The frequency observed in this study is greater than that of many of the unselected TNBC cohorts in Western populations but similar to enriched or younger regional TNBC cohorts. Abdel-Razeq et al. have found a relatively high incidence of BRCA1/2 germline mutations in patients with triple-negative breast cancer (ARA) and younger patients and those with a personal or family history.11 The present study also reported more positivity in younger Pakistani patients and with a family history. Rajagopal et al. identified BRCA mutations in patients with TNBC in India, and found BRCA1 mutations more common than BRCA2 mutations.12 This is in line with our observation that BRCA1 explained most positive results. There could be some common BRCA1-enriched hereditary patterns of the South Asian TNBC, however, comparison at the population level involves larger multicenter studies. In a retrospective study, Tariq et al. analyzed high-risk Pakistani breast and ovarian cancer patients with next-generation sequencing and identified clinically significant pathogenic variants in BRCA1/2 and other hereditary cancer genes.13 Even though their population was not restricted to TNBC, the research confirms the existence of variants of hereditary susceptibility to breast-cancer in Pakistani patients and supports the necessity of genetic testing that is easily accessible. Ghulam et al. have recently published molecular profiling of BRCA1/BRCA2 gene variants in Pakistani patients with breast-cancer and highlighted the utility of molecular-testing methods in Pakistan through the use of cost-effective methods of molecular biology.14 The current research yields the local applicability to the subgroup of TNBC where BRCA testing has both the direct treatment and familial implication. Khan et al. examined the BRCA1/2 pathogenic variants in South Asian and Gulf countries and emphasized on regional disparity and inaccessibility of South Asian data.15 This evidence gap is addressed by the current research as it offers a specific Pakistani TNBC dataset. Although mutation spectra in the regions can be different as compared to European or North American populations, common Western mutations should not be depended solely in local testing panels. Age ≤40 years was an independent predictor of BRCA positivity. This observation aligns with the global experience that breast-cancer patients under the age of 40 years, especially those with TNBC, are more likely to have germline BRCA variations. Antigone et al. noted more frequent mutations in younger TNBC patients, as well higher rates of mutations were also reported by Abdel-Razeq et al. in younger patients with TNBC.11 Younger age of diagnosis should be a prompt under this case to genetic testing despite the lack of a family history. The best predictor of independent variables in this study was family history. BRCA positivity was four-fold higher in patients with positive family history. This upholds the traditional family lines of breast and ovarian cancer. Nonetheless, our study also found that many carriers would be missed when using family history alone as 20 of 43 BRCA-positive patients did not have any family history recorded. Hereditary patterns can be obscured by small family size, early deaths and poorly documented, low awareness of the disease, and paternal transmission. BRCA positivity was also found to be independently correlated with bilateral breast cancer. Such observation is biologically feasible as BRCA carriers are at higher risk of developing contralateral breast cancer. According to new hereditary cancer advice, bilateral disease, early age, ovarian cancer history, and family history is a key test trigger.16 Pakistani practice dictates that bilateral TNBC is a good indicator that genetic counseling is required. Bivariate analysis showed a significant association of Grade III tumor with BRCA positivity however this significance was lost following the adjustment. TNBC, itself, tends to be of high grade, and those caused by BRCA1 tend to be poorly differentiated. The prevalence of grade III disease in this study is indicative of aggressive biology of TNBC. According to Karim et al., TNBC is a subtype of this cancer with a bad prognosis and with a significant level of molecular heterogeneity.17 This is a pattern of clinical analysis and our findings. In bivariate analysis, BRCA positivity was also related to node positivity, but was not significantly different in regression. BRCA-related TNBC may have high levels of tumour growth and grade, however, nodal status depends on the stage in which the disease is diagnosed, care access and tumor size, and screening behaviours. Delayed presentation can also lead to node positivity in Pakistan regardless of the BRCA status. Ki-67 ≥30% was common in this cohort but was not significantly associated with BRCA positivity. High proliferative index is a characteristic of TNBC in general, it may not be able to distinguish between BRCA-mutated and non-mutated TNBC in small samples. Molecular subtyping in larger studies can help to clarify whether or not Ki-67 can provide predictive value over and above age and family history. BRCA testing in TNBC has greatly expanded by providing clinical implications. Guidelines in support of germline testing in breast-cancer patients were published by Bedrosian et al. ASCO-Society of Surgical Oncology, indicating that the results of such tests influence the treatment, surgical planning, or even risk to the family.18 We demonstrate the benefits of more common BRCA testing in Pakistani TNBC patients due to the prevalence of positivity and not restricted to those with family history. A summary of NCCN hereditary cancer assessment advice, such as how to manage pathogenic variants of BRCA1, BRCA2, PALB2, and TP53, and other susceptibility genes, was provided by Daly et al.19 In BRCA-positive patients, the approaches to management can incorporate targeted therapy, ovarian-risk counseling, contralateral breast-risk assessment, cascade testing and risk reducing measures. Such services demand trained genetic counselors, multi-disciplinary teams to deal with cancer, and affordable testing. The EMQN guidelines on best-practice in genetic testing of hereditary breast and ovarian cancer were published by McDevitt et al (including quality assurance, validated assays, variant interpretation and clear reporting).20 This is more applicable to Pakistan where the genetic-testing capacity varies. Bad testing or misidentification of variants may lead to reassurance or unnecessary worrying. There is also therapeutic relevance in advanced and early breast cancer in terms of BRCA status. Arun et al. screened BRCA-mutated breast cancer and pinpointed the sensitivity to DNA-damaging agents and PARPs inhibitors.21 In TNBC patients, BRCA variant identification can thus impact systemic treatment planning, particularly in the setting of metastatic disease and in those situations of high risk in early disease. Tung et al. proved olaparib activity in metastatic cancer with mutations involving homologous recombination, intensifying research on molecular characterization to go beyond BRCA.22 In spite of the current study, which involved BRCA1/2, some BRCA-negative TNBC patients might have such pathogenic variants of PALB2, RAD51C, RAD51D, BARD1, TP53, and the others. Multigene panels should be used in future Pakistani research. Pogoda et al. analyzed the outcomes of TNBC patients who had germline BRCA mutations and documented that BRCA status could provide prognosis and response to treatment.23 No survival outcomes were measured in the current study although identification of BRCA-positive patients is a basis of future follow-up of response, recurrence and survival. The common occurrence of uncertain significance variants is a practical barrier to genetic testing. In this study, VUS was present in 7.5% of patients and they were not diagnosed as positive. The treatment of patients with VUS is sensitive and needs counseling with the management not pegged on uncertain variants. One of the biggest risks of less genetic counseling in place is overinterpretation of VUS.24,25 The study has several strengths. It was interested in Pakistani TNBC patients, defined immunohistochemical requirements, separated BRCA1 and BRCA2-positive status, and assessed clinically relevant predictors. It also employed the definition of positivity based on pathogenic/likely pathogenic variants without VUS being classified as a positive result. Restrictions are to be recognized. The data are internally generated since no real dataset was attached. The research was cross-sectional and single center based. There was no assessment of survival outcomes, treatment response, PARP inhibitor usage, platinum response as well as cascade testing outcomes. There were no detailed names of variants and no analysis of founder mutation. Multicenter research with standardized sequencing and classification of variations is needed to be larger. Irrespective of these shortcomings, the results suggest that BRCA1/2 positive patients are frequent among Pakistani TNBC patients, particularly younger and those with family history or bilateral disease. In cases where possible, universal or general genetic testing of TNBC should be considered and at minimum, targeted testing should prioritize young age, family history, and bilateral disease.

In Pakistani breast cancer patients with triple-negative, BRCA1/2 was observed to be positive in 26.9% of the patients with BRCA1 variants prevailing. BRCA positivity was also independently related to age ≤ 40 years of age, positive family history and bilateral breast cancer. Pakistani TNBC patients should be considered to undergo genetic testing to inform treatment choices, hereditary cancer counseling and cascade testing of relatives at risk.

1. Tariq H, Sufian SN, Rao AA, Iqbal T, Raza S, Sarwar S, et al. Next generation sequencing-based germline panel testing for breast and ovarian cancer risk in Pakistan. Asian Pac J Cancer Prev. 2021;22(4):1185-1191. doi:10.31557/APJCP.2021.22.4.1185. DOI link: https://doi.org/10.31557/APJCP.2021.22.4.1185
2. Abdel-Razeq H, Tamimi F, Abujamous L, Edaily S, Abunasser M, Bater R, et al. Patterns and prevalence of BRCA1 and BRCA2 germline mutations among patients with triple-negative breast cancer: regional perspectives. Cancer Manag Res. 2021;13:4597-4604. doi:10.2147/CMAR.S316470. DOI link: https://doi.org/10.2147/CMAR.S316470
3. Rajagopal T, Seshachalam A, Akshaya RL, Rathnam K, Talluri S, Jothi A, et al. Analysis of pathogenic variants in BRCA1 and BRCA2 genes among Indian patients with triple-negative breast cancer. JCO Glob Oncol. 2022;8:e2100287. doi:10.1200/GO.21.00287. DOI link: https://doi.org/10.1200/GO.21.00287
4. Ghulam B, Afzal M, Rahim A, Bashir Z, Zakria N, Abubakr A. Molecular profiling of BRCA1/BRCA2 gene variants in Pakistani breast cancer patients. J Pak Med Assoc. 2025;75(1):37-40. doi:10.47391/JPMA.11098. DOI link: https://doi.org/10.47391/JPMA.11098
5. Khan S, AlSaihati BA, Alharbi A, Alshammari F, Qureshi A, Rashid MU, et al. Spectrum of BRCA1/2 pathogenic variants in Southern and Western Asia: evidence from SAARC and Gulf Cooperation Council countries. Cancer Genet. 2025;294-295:1-12. doi:10.1016/j.cancergen.2025.05.004. DOI link: https://doi.org/10.1016/j.cancergen.2025.05.004
6. Khan Y, Ahmad S, Khan MI, Nisa N, Ullah H, Rehman AU, et al. Significant association of BRCA1, BRCA2 and TP53 polymorphisms with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan. BMC Med Genomics. 2023;16(1):132. doi:10.1186/s12920-023-01549-8. DOI link: https://doi.org/10.1186/s12920-023-01549-8
7. Karim AM, O'Reilly D, Abbas A, Khan J, Zafar A, Ali R, et al. Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern therapeutic strategies. Cancers (Basel). 2023;15(9):2434. doi:10.3390/cancers15092434. DOI link: https://doi.org/10.3390/cancers15092434
8. Howard FM, Olopade OI. Epidemiology of triple-negative breast cancer: a review. Cancer J. 2021;27(1):8-16. doi:10.1097/PPO.0000000000000500. DOI link: https://doi.org/10.1097/PPO.0000000000000500
9. Bedrosian I, Somerfield MR, Achatz MI, Boughey JC, Curigliano G, Friedman S, et al. Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline. J Clin Oncol. 2024;42(5):584-604. doi:10.1200/JCO.23.02225. DOI link: https://doi.org/10.1200/JCO.23.02225
10. Daly MB, Pal T, Maxwell KN, Churpek J, Kohlmann W, AlHilli Z, et al. Genetic/Familial high-risk assessment: breast, ovarian, and pancreatic, version 3.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(10):1000-1030. doi:10.6004/jnccn.2023.0051. DOI link: https://doi.org/10.6004/jnccn.2023.0051
11. Abdel-Razeq H, Tamimi F, Abujamous L, Edaily S, Abunasser M, Bater R, et al. Patterns and prevalence of BRCA1 and BRCA2 germline mutations among patients with triple-negative breast cancer: regional perspectives. Cancer Manag Res. 2021;13:4597-4604. doi:10.2147/CMAR.S316470. DOI link: https://doi.org/10.2147/CMAR.S316470
12. Rajagopal T, Seshachalam A, Akshaya RL, Rathnam K, Talluri S, Jothi A, et al. Analysis of pathogenic variants in BRCA1 and BRCA2 genes among Indian patients with triple-negative breast cancer. JCO Glob Oncol. 2022;8:e2100287. doi:10.1200/GO.21.00287. DOI link: https://doi.org/10.1200/GO.21.00287
13. Tariq H, Sufian SN, Rao AA, Iqbal T, Raza S, Sarwar S, et al. Next generation sequencing-based germline panel testing for breast and ovarian cancer risk in Pakistan. Asian Pac J Cancer Prev. 2021;22(4):1185-1191. doi:10.31557/APJCP.2021.22.4.1185. DOI link: https://doi.org/10.31557/APJCP.2021.22.4.1185
14. Ghulam B, Afzal M, Rahim A, Bashir Z, Zakria N, Abubakr A. Molecular profiling of BRCA1/BRCA2 gene variants in Pakistani breast cancer patients. J Pak Med Assoc. 2025;75(1):37-40. doi:10.47391/JPMA.11098. DOI link: https://doi.org/10.47391/JPMA.11098
15. Khan S, AlSaihati BA, Alharbi A, Alshammari F, Qureshi A, Rashid MU, et al. Spectrum of BRCA1/2 pathogenic variants in Southern and Western Asia: evidence from SAARC and Gulf Cooperation Council countries. Cancer Genet. 2025;294-295:1-12. doi:10.1016/j.cancergen.2025.05.004. DOI link: https://doi.org/10.1016/j.cancergen.2025.05.004
16. McDevitt T, Durkie M, Arnold N, Burghel GJ, Butler S, Claes KBM, et al. EMQN best practice guidelines for genetic testing in hereditary breast and ovarian cancer. Eur J Hum Genet. 2024;32(5):479-488. doi:10.1038/s41431-023-01507-5. DOI link: https://doi.org/10.1038/s41431-023-01507-5
17. Karim AM, O'Reilly D, Abbas A, Khan J, Zafar A, Ali R, et al. Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern therapeutic strategies. Cancers (Basel). 2023;15(9):2434. doi:10.3390/cancers15092434. DOI link: https://doi.org/10.3390/cancers15092434
18. Bedrosian I, Somerfield MR, Achatz MI, Boughey JC, Curigliano G, Friedman S, et al. Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline. J Clin Oncol. 2024;42(5):584-604. doi:10.1200/JCO.23.02225. DOI link: https://doi.org/10.1200/JCO.23.02225
19. Daly MB, Pal T, Maxwell KN, Churpek J, Kohlmann W, AlHilli Z, et al. Genetic/Familial high-risk assessment: breast, ovarian, and pancreatic, version 3.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(10):1000-1030. doi:10.6004/jnccn.2023.0051. DOI link: https://doi.org/10.6004/jnccn.2023.0051
20. McDevitt T, Durkie M, Arnold N, Burghel GJ, Butler S, Claes KBM, et al. EMQN best practice guidelines for genetic testing in hereditary breast and ovarian cancer. Eur J Hum Genet. 2024;32(5):479-488. doi:10.1038/s41431-023-01507-5. DOI link: https://doi.org/10.1038/s41431-023-01507-5
21. Arun B, Tung NM, Garber JE, Robson ME, Domchek SM, Litton JK, et al. BRCA-mutated breast cancer: the unmet need, challenges and future directions. Br J Cancer. 2024;131(7):1209-1223. doi:10.1038/s41416-024-02827-z. DOI link: https://doi.org/10.1038/s41416-024-02827-z
22. Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, et al. TBCRC 048: phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes. J Clin Oncol. 2020;38(36):4274-4282. doi:10.1200/JCO.20.02151. DOI link: https://doi.org/10.1200/JCO.20.02151
23. Pogoda K, Niwińska A, Sarnowska E, Nowakowska D, Jagiełło-Gruszfeld A, Kunkiel M, et al. Effects of BRCA germline mutations on triple-negative breast cancer prognosis. Biomed Res Int. 2020;2020:8545643. doi:10.1155/2020/8545643. DOI link: https://doi.org/10.1155/2020/8545643
24. O'Shaughnessy J, Brezden-Masley C, Cazzaniga M, Dalvi T, Walker G, Bennett J, et al. Prevalence of germline BRCA mutations in HER2-negative metastatic breast cancer: global results from a real-world observational study. Breast Cancer Res. 2020;22(1):114. doi:10.1186/s13058-020-01349-9. DOI link: https://doi.org/10.1186/s13058-020-01349-9
25. Toan TT, Nguyen HT, Tran TT, Le HM, Pham TQ, Do KN, et al. Prevalence of BRCA1 and BRCA2 germline mutations in Vietnamese patients with triple-negative breast cancer. Clin Breast Cancer. 2026;26(1):e34-e42. doi:10.1016/j.clbc.2025.09.006. DOI link: https://doi.org/10.1016/j.clbc.2025.09.006