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TOPLINE:

Universal testing identified germline pathogenic variants in 7.3% of women with breast cancer, suggesting that traditional risk-based criteria may miss more than a third of BRCA1, BRCA2, or PALB2 carriers.

METHODOLOGY:

  • Traditional risk-based criteria, including family history and ancestry, are used to guide genetic testing decisions in women with breast cancer. However, these criteria may overlook patients with actionable genetic variants, particularly those outside the typical risk profile.
  • To assess the efficacy of universal genetic testing, researchers conducted a cross-sectional study that included 729 women (median age at diagnosis, 53 years; 65.4% White women) newly diagnosed with invasive breast cancer between September 2019 and April 2022 at three Canadian institutions.
  • All patients received genetic counseling followed by testing for the presence of germline pathogenic variants in 17 breast cancer susceptibility genes. The primary gene panel included screening for BRCA1, BRCA2, and PALB2, and the optional secondary panel included 14 additional breast cancer susceptibility genes.
  • Of the participants, 659 (90.4%) were tested for both primary and secondary gene panels, whereas 70 (9.6%) underwent testing for only the primary panel. The majority of the cohort (66.8) were diagnosed with estrogen receptor–positive breast cancer, while 15.4% had triple-negative breast cancer.

TAKEAWAY:

  • The prevalence of germline pathogenic variants was 7.3% (53 patients) — 5.3% for the primary gene panel and 2.1% for the secondary panel.
  • Younger age (< 40 years; odds ratio [OR], 6.83), family history of ovarian cancer (OR, 9.75), high-grade disease (OR, 1.68), and triple-negative breast cancer (OR, 3.19) were independently associated with the presence of pathogenic genetic variants in BRCA1, BRCA2, or PALB2.
  • Overall, 34.3% of patients with germline pathogenic variants in BRCA1, BRCA2, or PALB2, and 85.7% of carriers of secondary panel variants would not have qualified for traditional genetic testing according to the current risk factors.
  • A total of 13 patients with BRCA1, BRCA2, or PALB2 variants had confirmed pathogenic mutations and were eligible for poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors.

IN PRACTICE:

These findings have “informed our clinical practice, and we now offer mainstream, oncology-led genetic testing to all women diagnosed with incident invasive breast cancer younger than 50 years of age, those with triple-negative breast cancer and/or bilateral breast cancer, those potentially eligible for PARP inhibitors,” as well as to men with breast cancer, the authors wrote.

SOURCE:

The study was led by Zoulikha Rezoug, MSc, Lady Davis Institute of the Jewish General Hospital, McGill University in Montreal, Québec, Canada. It was published online on September 3, 2024, in JAMA Network Open.

LIMITATIONS:

The COVID-19 pandemic resulted in a 6-month recruitment pause. Adjustments in recruitment criteria, focus on younger patients and those with triple-negative breast cancer could have overestimated prevalence of genetic pathogenic variants among women aged ≥ 70 years.

DISCLOSURES:

The study was supported by grants from the Jewish General Hospital Foundation and the Québec Breast Cancer Foundation, as well as an award from the Fonds de Recherche du Québec - Santé. Two authors reported receiving grants or personal fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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TOPLINE:

Universal testing identified germline pathogenic variants in 7.3% of women with breast cancer, suggesting that traditional risk-based criteria may miss more than a third of BRCA1, BRCA2, or PALB2 carriers.

METHODOLOGY:

  • Traditional risk-based criteria, including family history and ancestry, are used to guide genetic testing decisions in women with breast cancer. However, these criteria may overlook patients with actionable genetic variants, particularly those outside the typical risk profile.
  • To assess the efficacy of universal genetic testing, researchers conducted a cross-sectional study that included 729 women (median age at diagnosis, 53 years; 65.4% White women) newly diagnosed with invasive breast cancer between September 2019 and April 2022 at three Canadian institutions.
  • All patients received genetic counseling followed by testing for the presence of germline pathogenic variants in 17 breast cancer susceptibility genes. The primary gene panel included screening for BRCA1, BRCA2, and PALB2, and the optional secondary panel included 14 additional breast cancer susceptibility genes.
  • Of the participants, 659 (90.4%) were tested for both primary and secondary gene panels, whereas 70 (9.6%) underwent testing for only the primary panel. The majority of the cohort (66.8) were diagnosed with estrogen receptor–positive breast cancer, while 15.4% had triple-negative breast cancer.

TAKEAWAY:

  • The prevalence of germline pathogenic variants was 7.3% (53 patients) — 5.3% for the primary gene panel and 2.1% for the secondary panel.
  • Younger age (< 40 years; odds ratio [OR], 6.83), family history of ovarian cancer (OR, 9.75), high-grade disease (OR, 1.68), and triple-negative breast cancer (OR, 3.19) were independently associated with the presence of pathogenic genetic variants in BRCA1, BRCA2, or PALB2.
  • Overall, 34.3% of patients with germline pathogenic variants in BRCA1, BRCA2, or PALB2, and 85.7% of carriers of secondary panel variants would not have qualified for traditional genetic testing according to the current risk factors.
  • A total of 13 patients with BRCA1, BRCA2, or PALB2 variants had confirmed pathogenic mutations and were eligible for poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors.

IN PRACTICE:

These findings have “informed our clinical practice, and we now offer mainstream, oncology-led genetic testing to all women diagnosed with incident invasive breast cancer younger than 50 years of age, those with triple-negative breast cancer and/or bilateral breast cancer, those potentially eligible for PARP inhibitors,” as well as to men with breast cancer, the authors wrote.

SOURCE:

The study was led by Zoulikha Rezoug, MSc, Lady Davis Institute of the Jewish General Hospital, McGill University in Montreal, Québec, Canada. It was published online on September 3, 2024, in JAMA Network Open.

LIMITATIONS:

The COVID-19 pandemic resulted in a 6-month recruitment pause. Adjustments in recruitment criteria, focus on younger patients and those with triple-negative breast cancer could have overestimated prevalence of genetic pathogenic variants among women aged ≥ 70 years.

DISCLOSURES:

The study was supported by grants from the Jewish General Hospital Foundation and the Québec Breast Cancer Foundation, as well as an award from the Fonds de Recherche du Québec - Santé. Two authors reported receiving grants or personal fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

 

TOPLINE:

Universal testing identified germline pathogenic variants in 7.3% of women with breast cancer, suggesting that traditional risk-based criteria may miss more than a third of BRCA1, BRCA2, or PALB2 carriers.

METHODOLOGY:

  • Traditional risk-based criteria, including family history and ancestry, are used to guide genetic testing decisions in women with breast cancer. However, these criteria may overlook patients with actionable genetic variants, particularly those outside the typical risk profile.
  • To assess the efficacy of universal genetic testing, researchers conducted a cross-sectional study that included 729 women (median age at diagnosis, 53 years; 65.4% White women) newly diagnosed with invasive breast cancer between September 2019 and April 2022 at three Canadian institutions.
  • All patients received genetic counseling followed by testing for the presence of germline pathogenic variants in 17 breast cancer susceptibility genes. The primary gene panel included screening for BRCA1, BRCA2, and PALB2, and the optional secondary panel included 14 additional breast cancer susceptibility genes.
  • Of the participants, 659 (90.4%) were tested for both primary and secondary gene panels, whereas 70 (9.6%) underwent testing for only the primary panel. The majority of the cohort (66.8) were diagnosed with estrogen receptor–positive breast cancer, while 15.4% had triple-negative breast cancer.

TAKEAWAY:

  • The prevalence of germline pathogenic variants was 7.3% (53 patients) — 5.3% for the primary gene panel and 2.1% for the secondary panel.
  • Younger age (< 40 years; odds ratio [OR], 6.83), family history of ovarian cancer (OR, 9.75), high-grade disease (OR, 1.68), and triple-negative breast cancer (OR, 3.19) were independently associated with the presence of pathogenic genetic variants in BRCA1, BRCA2, or PALB2.
  • Overall, 34.3% of patients with germline pathogenic variants in BRCA1, BRCA2, or PALB2, and 85.7% of carriers of secondary panel variants would not have qualified for traditional genetic testing according to the current risk factors.
  • A total of 13 patients with BRCA1, BRCA2, or PALB2 variants had confirmed pathogenic mutations and were eligible for poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors.

IN PRACTICE:

These findings have “informed our clinical practice, and we now offer mainstream, oncology-led genetic testing to all women diagnosed with incident invasive breast cancer younger than 50 years of age, those with triple-negative breast cancer and/or bilateral breast cancer, those potentially eligible for PARP inhibitors,” as well as to men with breast cancer, the authors wrote.

SOURCE:

The study was led by Zoulikha Rezoug, MSc, Lady Davis Institute of the Jewish General Hospital, McGill University in Montreal, Québec, Canada. It was published online on September 3, 2024, in JAMA Network Open.

LIMITATIONS:

The COVID-19 pandemic resulted in a 6-month recruitment pause. Adjustments in recruitment criteria, focus on younger patients and those with triple-negative breast cancer could have overestimated prevalence of genetic pathogenic variants among women aged ≥ 70 years.

DISCLOSURES:

The study was supported by grants from the Jewish General Hospital Foundation and the Québec Breast Cancer Foundation, as well as an award from the Fonds de Recherche du Québec - Santé. Two authors reported receiving grants or personal fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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