Loss of heterozygosity at BRCA1 locus is significantly associated with aggressiveness and poor prognosis in breast cancer

Satoko Okada, Eriko Tokunaga, Hiroyuki Kitao, Sayuri Akiyoshi, Nami Yamashita, Hiroshi Saeki, Eiji Oki, Masaru Morita, Yoshihiro Kakeji, Yoshihiko Maehara

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Abstract

Background. BRCA1 and BRCA2 are two major tumor suppressor genes for hereditary breast and ovarian cancer. In sporadic breast cancer, although somatic mutations of these genes are rare, loss of heterozygosity (LOH) at BRCA1 and BRCA2 loci is common. Methods. LOH at BRCA1 and BRCA2 loci were investigated in 202 Japanese invasive breast cancer patients. The relationships between LOH at these gene loci and clinicopathologic characteristics were analyzed. Results. Among 166 informative cases for both BRCA1 and BRCA2 loci, 69 (41.6%) and 52 (31.3%) tumors revealed LOH at BRCA1 and BRCA2 loci, respectively. LOH at BRCA1 LOH or BRCA2 locus was associated with higher nuclear grade (P < 0.0001, P = 0.0187). LOH at BRCA1 locus was associated with estrogen receptor and progesterone receptor negativity (P = 0.001 and P = 0.015) and significantly shorter disease-free survival (P < 0.0001), distant metastasis-free survival (P < 0.0001), and overall survival (P < 0.0001). In contrast, LOH at BRCA2 locus had no associations with estrogen receptor or progesterone receptor status and prognosis. LOH at BRCA1 locus was independently associated with poor prognosis in terms of disease-free survival (hazard ratio 3.08, 95% confidence interval [CI] 1.58-6.18, P = 0.0009), distant metastasis-free survival (hazard ratio 5.18, 95% CI 2.35-12.19, P < 0.0001), and overall survival (hazard ratio 4.97, 95% CI 1.84-15.1, P = 0.0013). Conclusions. LOH at BRCA1 locus could be an independent prognostic biomarker useful in identifying a subgroup of patients with poor prognosis.

Original languageEnglish
Pages (from-to)1499-1507
Number of pages9
JournalAnnals of Surgical Oncology
Volume19
Issue number5
DOIs
Publication statusPublished - May 1 2012

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Loss of Heterozygosity
Breast Neoplasms
Survival
Progesterone Receptors
Confidence Intervals
Estrogen Receptors
Disease-Free Survival
Neoplasm Metastasis
Tumor Suppressor Genes
Ovarian Neoplasms
Genes
Biomarkers
Mutation

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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Loss of heterozygosity at BRCA1 locus is significantly associated with aggressiveness and poor prognosis in breast cancer. / Okada, Satoko; Tokunaga, Eriko; Kitao, Hiroyuki; Akiyoshi, Sayuri; Yamashita, Nami; Saeki, Hiroshi; Oki, Eiji; Morita, Masaru; Kakeji, Yoshihiro; Maehara, Yoshihiko.

In: Annals of Surgical Oncology, Vol. 19, No. 5, 01.05.2012, p. 1499-1507.

Research output: Contribution to journalArticle

Okada, Satoko ; Tokunaga, Eriko ; Kitao, Hiroyuki ; Akiyoshi, Sayuri ; Yamashita, Nami ; Saeki, Hiroshi ; Oki, Eiji ; Morita, Masaru ; Kakeji, Yoshihiro ; Maehara, Yoshihiko. / Loss of heterozygosity at BRCA1 locus is significantly associated with aggressiveness and poor prognosis in breast cancer. In: Annals of Surgical Oncology. 2012 ; Vol. 19, No. 5. pp. 1499-1507.
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abstract = "Background. BRCA1 and BRCA2 are two major tumor suppressor genes for hereditary breast and ovarian cancer. In sporadic breast cancer, although somatic mutations of these genes are rare, loss of heterozygosity (LOH) at BRCA1 and BRCA2 loci is common. Methods. LOH at BRCA1 and BRCA2 loci were investigated in 202 Japanese invasive breast cancer patients. The relationships between LOH at these gene loci and clinicopathologic characteristics were analyzed. Results. Among 166 informative cases for both BRCA1 and BRCA2 loci, 69 (41.6{\%}) and 52 (31.3{\%}) tumors revealed LOH at BRCA1 and BRCA2 loci, respectively. LOH at BRCA1 LOH or BRCA2 locus was associated with higher nuclear grade (P < 0.0001, P = 0.0187). LOH at BRCA1 locus was associated with estrogen receptor and progesterone receptor negativity (P = 0.001 and P = 0.015) and significantly shorter disease-free survival (P < 0.0001), distant metastasis-free survival (P < 0.0001), and overall survival (P < 0.0001). In contrast, LOH at BRCA2 locus had no associations with estrogen receptor or progesterone receptor status and prognosis. LOH at BRCA1 locus was independently associated with poor prognosis in terms of disease-free survival (hazard ratio 3.08, 95{\%} confidence interval [CI] 1.58-6.18, P = 0.0009), distant metastasis-free survival (hazard ratio 5.18, 95{\%} CI 2.35-12.19, P < 0.0001), and overall survival (hazard ratio 4.97, 95{\%} CI 1.84-15.1, P = 0.0013). Conclusions. LOH at BRCA1 locus could be an independent prognostic biomarker useful in identifying a subgroup of patients with poor prognosis.",
author = "Satoko Okada and Eriko Tokunaga and Hiroyuki Kitao and Sayuri Akiyoshi and Nami Yamashita and Hiroshi Saeki and Eiji Oki and Masaru Morita and Yoshihiro Kakeji and Yoshihiko Maehara",
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T1 - Loss of heterozygosity at BRCA1 locus is significantly associated with aggressiveness and poor prognosis in breast cancer

AU - Okada, Satoko

AU - Tokunaga, Eriko

AU - Kitao, Hiroyuki

AU - Akiyoshi, Sayuri

AU - Yamashita, Nami

AU - Saeki, Hiroshi

AU - Oki, Eiji

AU - Morita, Masaru

AU - Kakeji, Yoshihiro

AU - Maehara, Yoshihiko

PY - 2012/5/1

Y1 - 2012/5/1

N2 - Background. BRCA1 and BRCA2 are two major tumor suppressor genes for hereditary breast and ovarian cancer. In sporadic breast cancer, although somatic mutations of these genes are rare, loss of heterozygosity (LOH) at BRCA1 and BRCA2 loci is common. Methods. LOH at BRCA1 and BRCA2 loci were investigated in 202 Japanese invasive breast cancer patients. The relationships between LOH at these gene loci and clinicopathologic characteristics were analyzed. Results. Among 166 informative cases for both BRCA1 and BRCA2 loci, 69 (41.6%) and 52 (31.3%) tumors revealed LOH at BRCA1 and BRCA2 loci, respectively. LOH at BRCA1 LOH or BRCA2 locus was associated with higher nuclear grade (P < 0.0001, P = 0.0187). LOH at BRCA1 locus was associated with estrogen receptor and progesterone receptor negativity (P = 0.001 and P = 0.015) and significantly shorter disease-free survival (P < 0.0001), distant metastasis-free survival (P < 0.0001), and overall survival (P < 0.0001). In contrast, LOH at BRCA2 locus had no associations with estrogen receptor or progesterone receptor status and prognosis. LOH at BRCA1 locus was independently associated with poor prognosis in terms of disease-free survival (hazard ratio 3.08, 95% confidence interval [CI] 1.58-6.18, P = 0.0009), distant metastasis-free survival (hazard ratio 5.18, 95% CI 2.35-12.19, P < 0.0001), and overall survival (hazard ratio 4.97, 95% CI 1.84-15.1, P = 0.0013). Conclusions. LOH at BRCA1 locus could be an independent prognostic biomarker useful in identifying a subgroup of patients with poor prognosis.

AB - Background. BRCA1 and BRCA2 are two major tumor suppressor genes for hereditary breast and ovarian cancer. In sporadic breast cancer, although somatic mutations of these genes are rare, loss of heterozygosity (LOH) at BRCA1 and BRCA2 loci is common. Methods. LOH at BRCA1 and BRCA2 loci were investigated in 202 Japanese invasive breast cancer patients. The relationships between LOH at these gene loci and clinicopathologic characteristics were analyzed. Results. Among 166 informative cases for both BRCA1 and BRCA2 loci, 69 (41.6%) and 52 (31.3%) tumors revealed LOH at BRCA1 and BRCA2 loci, respectively. LOH at BRCA1 LOH or BRCA2 locus was associated with higher nuclear grade (P < 0.0001, P = 0.0187). LOH at BRCA1 locus was associated with estrogen receptor and progesterone receptor negativity (P = 0.001 and P = 0.015) and significantly shorter disease-free survival (P < 0.0001), distant metastasis-free survival (P < 0.0001), and overall survival (P < 0.0001). In contrast, LOH at BRCA2 locus had no associations with estrogen receptor or progesterone receptor status and prognosis. LOH at BRCA1 locus was independently associated with poor prognosis in terms of disease-free survival (hazard ratio 3.08, 95% confidence interval [CI] 1.58-6.18, P = 0.0009), distant metastasis-free survival (hazard ratio 5.18, 95% CI 2.35-12.19, P < 0.0001), and overall survival (hazard ratio 4.97, 95% CI 1.84-15.1, P = 0.0013). Conclusions. LOH at BRCA1 locus could be an independent prognostic biomarker useful in identifying a subgroup of patients with poor prognosis.

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U2 - 10.1245/s10434-011-2166-5

DO - 10.1245/s10434-011-2166-5

M3 - Article

C2 - 22179631

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VL - 19

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JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

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