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Purpose <p>Pathogenic variants (PVs) in <i>BRCA1/2</i> increase the lifetime risk of breast cancer (BC). Predictive algorithms for <i>BRCA1/2</i> PVs, primarily developed for Caucasian BC patients, often underestimate carrier probability in Asian populations. The recently developed Asian Risk Calculator (ARiCa) aims to predict <i>BRCA1/2</i> PV likelihood in Malaysian/Singaporean BC patients. This study investigates the ARiCa’s performance in Pakistani female BC patients.</p> Methods <p>A cohort of 627 high-risk Pakistani female BC patients was evaluated. Using ARiCa, the likelihood of being a <i>BRCA1/2</i> carrier was estimated based on factors such as age at diagnosis, ethnicity, bilateral BC status, tumor histopathological features, and family history of BC or ovarian cancer. The tool’s discriminative ability was evaluated using the area under the curve (AUC).</p> Results <p>Of the participants, 133 (21.2%) were <i>BRCA1</i> carriers, 25 (4.0%) were <i>BRCA2</i> carriers, and 469 (74.8%) were non-carriers. The mean age at BC diagnosis was 34.3&#xa0;years (range 19–73). Overall, ARiCa showed well calibration for predicting <i>BRCA1/2</i> (HL 12.11, <i>P</i> = 0.147)<i>, BRCA1</i> (HL 14.17, <i>P</i> = 0.078)<i>,</i> and <i>BRCA2</i> carriers (HL 9.01, <i>P</i> = 0.342). The tool showed acceptable discrimination for <i>BRCA1/2</i> (AUC 0.77, 95% CI 0.72–0.81) and <i>BRCA1</i> carriers (AUC 0.80, 95% CI 0.75–0.84), but lower discrimination for <i>BRCA2</i> carriers (AUC 0.51, 95% CI 0.39–0.64). At a 21% threshold, ARiCa would recommend <i>BRCA1/2</i> screening for 43% of patients, with sensitivity and specificity at 73% and 68%, respectively.</p> Conclusion <p>The ARiCa tool demonstrates strong predictive performance for <i>BRCA1/2</i> carriers, specifically for <i>BRCA1</i> carriers in Pakistani BC patients, suggesting its potential clinical utility.</p>

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Predicting the likelihood of carrying BRCA1 or BRCA2 pathogenic variants in high-risk Pakistani breast cancer patients

  • 期刊论文

  • 发表日期：

    2025年5月20日

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  • Shumaila Arif,
  • Noor Muhammad,
  • Boon Hong Ang,
  • Humaira Naeemi,
  • Waqas Sami,
  • Weang Kee Ho,
  • Ute Hamann,
  • Muhammad Usman Rashid

摘要

Purpose

Pathogenic variants (PVs) in BRCA1/2 increase the lifetime risk of breast cancer (BC). Predictive algorithms for BRCA1/2 PVs, primarily developed for Caucasian BC patients, often underestimate carrier probability in Asian populations. The recently developed Asian Risk Calculator (ARiCa) aims to predict BRCA1/2 PV likelihood in Malaysian/Singaporean BC patients. This study investigates the ARiCa’s performance in Pakistani female BC patients.

Methods

A cohort of 627 high-risk Pakistani female BC patients was evaluated. Using ARiCa, the likelihood of being a BRCA1/2 carrier was estimated based on factors such as age at diagnosis, ethnicity, bilateral BC status, tumor histopathological features, and family history of BC or ovarian cancer. The tool’s discriminative ability was evaluated using the area under the curve (AUC).

Results

Of the participants, 133 (21.2%) were BRCA1 carriers, 25 (4.0%) were BRCA2 carriers, and 469 (74.8%) were non-carriers. The mean age at BC diagnosis was 34.3 years (range 19–73). Overall, ARiCa showed well calibration for predicting BRCA1/2 (HL 12.11, P = 0.147), BRCA1 (HL 14.17, P = 0.078), and BRCA2 carriers (HL 9.01, P = 0.342). The tool showed acceptable discrimination for BRCA1/2 (AUC 0.77, 95% CI 0.72–0.81) and BRCA1 carriers (AUC 0.80, 95% CI 0.75–0.84), but lower discrimination for BRCA2 carriers (AUC 0.51, 95% CI 0.39–0.64). At a 21% threshold, ARiCa would recommend BRCA1/2 screening for 43% of patients, with sensitivity and specificity at 73% and 68%, respectively.

Conclusion

The ARiCa tool demonstrates strong predictive performance for BRCA1/2 carriers, specifically for BRCA1 carriers in Pakistani BC patients, suggesting its potential clinical utility.