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Purpose <p>The risk of second non-breast primary cancer in Chinese women with breast cancer who carry germline <i>BRCA1/2</i> pathogenic variants (PVs) is largely unknown.</p> Methods <p>From October 2003 to February 2023, 11,212 women with breast cancer were recruited. <i>BRCA1/2</i> mutation status of these patients was determined; the age-specific cumulative risk of second non-breast primary cancer was estimated.</p> Results <p>Of the 11,212 breast cancer patients, 284 carried <i>BRCA1</i> PVs, 433 carried <i>BRCA2</i> PVs, and 10,495 were non-carriers. After a median follow-up of 8.4&#xa0;years, 10.9% of <i>BRCA1</i> carriers, 7.2% of <i>BRCA2</i> carriers, and 3.6% of non-carriers developed second non-breast primary cancers; and 6.7% of <i>BRCA1</i> carriers, 1.4% of <i>BRCA2</i> carriers, and 0.1% of non-carriers developed ovarian cancer. Cumulative risks of second primary cancer to age 70&#xa0;years were 28.4% for <i>BRCA1</i> carriers, 17.3% for <i>BRCA2</i> carriers, and 6.2% for non-carriers. Cumulative risks of ovarian cancer to age 70&#xa0;years were 19.8% for <i>BRCA1</i> carriers, 3.9% for <i>BRCA2</i> carriers, and 0.4% for non-carriers. No <i>BRCA1</i> and <i>BRCA2</i> carriers developed ovarian cancer before the ages of 40 and 45&#xa0;years, respectively. <i>BRCA2</i> carriers had higher risks of thyroid cancer (relative risk [RR] 2.16; 95% CI, 1.04–4.51; <i>P</i> = 0.039) and endometrial adenocarcinoma (RR 3.90; 95% CI, 1.47–10.32; <i>P</i> = 0<i>.</i>006) than non-carriers.</p> Conclusions <p><i>BRCA1/2</i> carriers exhibit a 2- to 3-fold higher risk of second primary cancer than non-carriers. Ovarian cancer represents the majority of second primary cancers in <i>BRCA1</i> carriers, while <i>BRCA2</i> carriers have a wider spectrum of second primary cancers.</p>

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Risk of second non-breast primary cancer in Chinese breast cancer patients with germline BRCA1/2 pathogenic variants

  • 期刊论文

  • 发表日期：

    2026年1月6日

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  • Jiaming Liu,
  • Futao Chu,
  • Lu Yao,
  • Jie Sun,
  • Jiuan Chen,
  • Juan Zhang,
  • Ye Xu,
  • Yuntao Xie

摘要

Purpose

The risk of second non-breast primary cancer in Chinese women with breast cancer who carry germline BRCA1/2 pathogenic variants (PVs) is largely unknown.

Methods

From October 2003 to February 2023, 11,212 women with breast cancer were recruited. BRCA1/2 mutation status of these patients was determined; the age-specific cumulative risk of second non-breast primary cancer was estimated.

Results

Of the 11,212 breast cancer patients, 284 carried BRCA1 PVs, 433 carried BRCA2 PVs, and 10,495 were non-carriers. After a median follow-up of 8.4 years, 10.9% of BRCA1 carriers, 7.2% of BRCA2 carriers, and 3.6% of non-carriers developed second non-breast primary cancers; and 6.7% of BRCA1 carriers, 1.4% of BRCA2 carriers, and 0.1% of non-carriers developed ovarian cancer. Cumulative risks of second primary cancer to age 70 years were 28.4% for BRCA1 carriers, 17.3% for BRCA2 carriers, and 6.2% for non-carriers. Cumulative risks of ovarian cancer to age 70 years were 19.8% for BRCA1 carriers, 3.9% for BRCA2 carriers, and 0.4% for non-carriers. No BRCA1 and BRCA2 carriers developed ovarian cancer before the ages of 40 and 45 years, respectively. BRCA2 carriers had higher risks of thyroid cancer (relative risk [RR] 2.16; 95% CI, 1.04–4.51; P = 0.039) and endometrial adenocarcinoma (RR 3.90; 95% CI, 1.47–10.32; P = 0.006) than non-carriers.

Conclusions

BRCA1/2 carriers exhibit a 2- to 3-fold higher risk of second primary cancer than non-carriers. Ovarian cancer represents the majority of second primary cancers in BRCA1 carriers, while BRCA2 carriers have a wider spectrum of second primary cancers.