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Background <p>Estrogen receptor (ER)-low breast cancers, defined as tumors with 1–10% ER expression, exhibit clinicopathologic and molecular features, as well as chemotherapy responses, resembling triple-negative breast cancer (TNBC), leading to updated guidelines. However, current <i>BRCA1/2</i> testing guidelines classify ER-low tumors alongside ER-strong-positive cancers, potentially overlooking mutation carriers. Thus, the purpose of this study was to determine whether <i>BRCA1/2</i> genetic testing in patients with ER-low/HER2-negative breast cancer should be the same as those with TNBC.</p> Patients and Methods <p>This multicenter retrospective study included 271 unselected patients with ER-low/HER2-negative invasive breast cancer from four Korean institutions (2014–2022). <i>BRCA1/2</i> genetic testing was performed via Sanger sequencing or next-generation sequencing. A previously published unselected TNBC cohort (<i>n</i> = 920) served as a comparator. Clinical and pathological characteristics and <i>BRCA1/2</i> mutation prevalence were compared between groups.</p> Results <p>Among 271 ER-low/HER2-negative patients, 41 (15.1%) carried pathogenic <i>BRCA1/2</i> mutations (<i>BRCA1</i>: 11.8%, <i>BRCA2</i>: 3.3%), comparable to the TNBC cohort (13.2%; <i>p</i> = 0.404). <i>BRCA1</i> predominance was observed, with the highest prevalence in patients ≤ 40 years (25.4% versus 20.0% in TNBC). Mutation carriers were younger (≤40 years: 41.5% versus 21.7%; <i>p</i> = 0.006), more often premenopausal (85.4% versus 50.0%; <i>p</i> &lt; 0.001), and more frequently had a family history of breast/ovarian cancer (48.8% versus 16.1%; <i>p</i> &lt; 0.001).</p> Conclusions <p>ER-low/HER2-negative breast cancers demonstrate <i>BRCA1</i>/2 mutation prevalence and features comparable to TNBC. Applying testing criteria based solely on ER expression may underdiagnose mutation carriers. These findings support expanding <i>BRCA1/2</i> testing eligibility to include ER-low/HER2-negative tumors to ensure timely identification and access to targeted therapies.</p>

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Germline BRCA1/2 Mutation Prevalence in Unselected ER-Low/HER2-Negative Breast Cancer

  • 期刊论文

  • 发表日期：

    2025年11月14日

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  • Ji Won Yoo,
  • Jinyoung Byeon,
  • Woong Ki Park,
  • Jisun Kim,
  • Han-Byoel Lee,
  • Sung Gwe Ahn,
  • Seung Ho Baek,
  • Su Min Lee,
  • Se Kyung Lee,
  • Byung Joo Chae,
  • Jonghan Yu,
  • Jeong Eon Lee,
  • Seok Won Kim,
  • Seok Jin Nam,
  • Hyunwoo Lee,
  • Sung-Won Kim,
  • Tae-Kyung Robyn Yoo,
  • Jai Min Ryu

摘要

Background

Estrogen receptor (ER)-low breast cancers, defined as tumors with 1–10% ER expression, exhibit clinicopathologic and molecular features, as well as chemotherapy responses, resembling triple-negative breast cancer (TNBC), leading to updated guidelines. However, current BRCA1/2 testing guidelines classify ER-low tumors alongside ER-strong-positive cancers, potentially overlooking mutation carriers. Thus, the purpose of this study was to determine whether BRCA1/2 genetic testing in patients with ER-low/HER2-negative breast cancer should be the same as those with TNBC.

Patients and Methods

This multicenter retrospective study included 271 unselected patients with ER-low/HER2-negative invasive breast cancer from four Korean institutions (2014–2022). BRCA1/2 genetic testing was performed via Sanger sequencing or next-generation sequencing. A previously published unselected TNBC cohort (n = 920) served as a comparator. Clinical and pathological characteristics and BRCA1/2 mutation prevalence were compared between groups.

Results

Among 271 ER-low/HER2-negative patients, 41 (15.1%) carried pathogenic BRCA1/2 mutations (BRCA1: 11.8%, BRCA2: 3.3%), comparable to the TNBC cohort (13.2%; p = 0.404). BRCA1 predominance was observed, with the highest prevalence in patients ≤ 40 years (25.4% versus 20.0% in TNBC). Mutation carriers were younger (≤40 years: 41.5% versus 21.7%; p = 0.006), more often premenopausal (85.4% versus 50.0%; p < 0.001), and more frequently had a family history of breast/ovarian cancer (48.8% versus 16.1%; p < 0.001).

Conclusions

ER-low/HER2-negative breast cancers demonstrate BRCA1/2 mutation prevalence and features comparable to TNBC. Applying testing criteria based solely on ER expression may underdiagnose mutation carriers. These findings support expanding BRCA1/2 testing eligibility to include ER-low/HER2-negative tumors to ensure timely identification and access to targeted therapies.