Germline BRCA Mutation and Clinical Outcomes in Breast Cancer Patients Focusing on Survival and Failure Patterns: A Long-Term Follow-Up Study of Koreans

Kim, Hakyoung; Choi, Doo Ho; Park, Won

doi:10.3390/medicina56100514

“…Other studies conducted in France and Switzerland found significantly superior 5‐year DFS of BRCA1 carriers than non‐carriers, but not significant for BRCA2 carriers 43 . In contrast, a study conducted in Korea found significantly inferior 10‐year DFS and more contralateral breast cancer in BRCA1/2 carriers than non‐carriers, but no significant difference in 10‐year OS 44 . Furthermore, a study of Korean patients found that clinical nodal status is the only significant factor associated with DFS, even after adjusting for clinical nodal stage, BRCA status, hormonal receptor status, and Ki‐67.…”

Section: Discussionmentioning

confidence: 86%

“… 43 In contrast, a study conducted in Korea found significantly inferior 10‐year DFS and more contralateral breast cancer in BRCA1/2 carriers than non‐carriers, but no significant difference in 10‐year OS. 44 Furthermore, a study of Korean patients found that clinical nodal status is the only significant factor associated with DFS, even after adjusting for clinical nodal stage, BRCA status, hormonal receptor status, and Ki‐67. Consistent with these findings, adjusted multivariable analysis in the present study revealed that the only significant factor associated with DFS was the stage at diagnosis, whereas BRCA1/2 carriers had inferior DFS compared with BRCA non‐carriers; however, the difference was not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of breast cancer patients tested for germline BRCA1/2 mutations by next‐generation sequencing in Ramathibodi Hospital, Mahidol University

Oranratnachai

¹

,

Yamkaew

²

,

Tunteeratum

³

et al. 2022

Cancer Reports

4

0

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Germline mutations in BRCA1/2 are the most common cause of hereditary breast and ovarian cancer (HBOC) syndrome. A few studies have reported the prevalence of germline BRCA mutations in Asian patients with breast cancer. Here, we aimed to explore the prevalence and characteristics of breast cancers in Thai patients with germline BRCA1/2 mutations. We retrospectively reviewed breast cancer patients tested for germline BRCA1/2 mutations in our institute during 2014-2018. BRCA mutations were detected using next-generation sequencing and con rmed using Sanger sequencing. We analyzed the characteristics of patients with or without BRCA mutations, disease-free survival (DFS), and associated factors. Among the 67 included patients, 12 (18%) were BRCA1/2 carriers (6 each), 4 (6%) harbored variants of uncertain signi cance, and 51 (76%) were non-carriers. We discovered two novel frameshift mutations in BRCA2 (c.2380delA and c.8855dupT). Mean ages at breast cancer diagnosis in BRCA1 carriers, BRCA2 carriers, and non-carriers were 39.8, 46.2, and 42.0 years, respectively. The 12 tumors of BRCA carriers were mostly the luminal-B subtypes. Two of these tumors were HER2-positive luminal-B; however, the triple-negative subtype was not observed. After adjusting for stages and luminal subtypes, BRCA carriers experienced worse 3-year DFS than non-carriers (81.5% vs. 90.3%, HR 2.04 (0.64-6.49), P = 0.229). The stage at diagnosis was the sole factor signi cantly associated with 3-year DFS (100%, 84.8%, and 72.7%; stages I, II, and III, respectively). In summary, breast cancers in Thai patients with germline BRCA1/2 mutations were mostly the luminal-B subtypes and experienced a worse prognosis than those without mutations. data in the electronic medical records (EMRs) of Ramathibodi Hospital were unavailable. The EMRs were retrospectively reviewed. We collected demographic data at diagnosis, including sex, age, and Eastern Cooperative Oncology Group (ECOG) performance status as well as TNM staging according to AJCC 8th edition [21]. Besides, we also collected tumor characteristics, including pathological subtype, histological grading, ER, progesterone receptor (PR), human epidermal growth factor receptor (HER2), and Ki-67 status as described in the pathological reports. There are some variations from time to time in the reporting systems for ER and PR immunohistochemistry (IHC) staining. In the present study, ER and PR were considered negative if the nuclei of tumor cells were stained < 1%. HER2 expression, which was routinely assessed through IHC staining intensity, was classi ed as negative, 1+, 2+, or 3+. Furthermore, uorescence in situ hybridization (FISH) was performed to con rm and document registration for trastuzumab reimbursement. Luminal subtypes were classi ed according to the Saint Gallen Guidelines 2015 [22]. Treatments and outcomes such as surgical management, adjuvant therapies, recurrent/metastasis of disease, secondary primary cancer, and death were also collected.The Ethics Committee on Human Rights related to resea...

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“…Moderate-penetrance variants that confer two- to five-fold increased risks [ 8 ] also contribute to a minority of BC cases. According to epidemiological studies, 15–20% of familial BC cases and less than 5% of all BCs are caused by germline variants in the BRCA1 and BRCA2 genes [ 9 ]. Carriers of pathogenic or likely pathogenic variants (PVs) in these genes have a 60–85% risk of developing BC by the age of 70 [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Determination of genetic predisposition to early breast cancer in women of Kazakh ethnicity

Zhunussova,

Omarbayeva,

Kaidarova

et al. 2023

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Breast cancer (BC) is the most common type of cancer among women in Kazakhstan. To date, little data are available on the spectrum of genetic variation in Kazakh women with BC. We aimed to identify population-specific genetic markers associated with the risk of developing early-onset BC and test their association with clinical and prognostic factors. The study included 224 Kazakh women diagnosed with BC (≤40 age). Entire coding regions (>1700 exons) and the flanking noncoding regions of 94 cancer-associated genes were sequenced from blood DNA using MiSeq platform. We identified 38 unique pathogenic variants (PVs) in 13 different cancer-predisposing genes among 57 patients (25.4%), of which 6 variants were novel. In total, 12 of the 38 distinct PVs were detected recurrently, including BRCA1 c.5266dup, c.5278-2del, and c.2T>C, and BRCA2 c.9409dup and c.9253del that may be founder in this population. BRCA1 carriers were significantly more likely to develop triple-negative BC (OR = 6.61, 95% CI 2.44–17.91, p = 0.0002) and have family history of BC (OR = 3.17, 95% CI 1.14–8.76, p = 0.03) compared to non-carriers. This study allowed the identification of PVs specific to early-onset BC, which may be used as a foundation to develop regional expertise and diagnostic tools for early detection of BC in young Kazakh women.

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Characteristics of breast cancer patients tested for germline BRCA1/2 mutations by next-generation sequencing in Ramathibodi Hospital, Mahidol University

Oranratnachai¹,

Yamkaew²,

Tunteeratum³

et al. 2021

Preprint

View full text Add to dashboard Cite

Germline mutations in BRCA1/2 are the most common cause of hereditary breast and ovarian cancer (HBOC) syndrome. A few studies have reported the prevalence of germline BRCA mutations in Asian patients with breast cancer. Here, we aimed to explore the prevalence and characteristics of breast cancers in Thai patients with germline BRCA1/2 mutations. We retrospectively reviewed breast cancer patients tested for germline BRCA1/2 mutations in our institute during 2014–2018. BRCA mutations were detected using next-generation sequencing and confirmed using Sanger sequencing. We analyzed the characteristics of patients with or without BRCA mutations, disease-free survival (DFS), and associated factors. Among the 67 included patients, 12 (18%) were BRCA1/2 carriers (6 each), 4 (6%) harbored variants of uncertain significance, and 51 (76%) were non-carriers. We discovered two novel frameshift mutations in BRCA2 (c.2380delA and c.8855dupT). Mean ages at breast cancer diagnosis in BRCA1 carriers, BRCA2 carriers, and non-carriers were 39.8, 46.2, and 42.0 years, respectively. The 12 tumors of BRCA carriers were mostly the luminal-B subtypes. Two of these tumors were HER2-positive luminal-B; however, the triple-negative subtype was not observed. After adjusting for stages and luminal subtypes, BRCA carriers experienced worse 3-year DFS than non-carriers (81.5% vs. 90.3%, HR 2.04 (0.64–6.49), P = 0.229). The stage at diagnosis was the sole factor significantly associated with 3-year DFS (100%, 84.8%, and 72.7%; stages I, II, and III, respectively). In summary, breast cancers in Thai patients with germline BRCA1/2 mutations were mostly the luminal-B subtypes and experienced a worse prognosis than those without mutations.

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Germline BRCA Mutation and Clinical Outcomes in Breast Cancer Patients Focusing on Survival and Failure Patterns: A Long-Term Follow-Up Study of Koreans

Cited by 3 publications

References 22 publications

Characteristics of breast cancer patients tested for germline BRCA1/2 mutations by next‐generation sequencing in Ramathibodi Hospital, Mahidol University

Characteristics of breast cancer patients tested for germline BRCA1/2 mutations by next‐generation sequencing in Ramathibodi Hospital, Mahidol University

Determination of genetic predisposition to early breast cancer in women of Kazakh ethnicity

Characteristics of breast cancer patients tested for germline BRCA1/2 mutations by next-generation sequencing in Ramathibodi Hospital, Mahidol University

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