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Abstract：
Breast cancer (BC) is the most prevalent malignancy in women with Li-Fraumeni syndrome (LFS). The literature on BC in LFS is limited due to its rarity worldwide. A TP53 founder pathogenic variant (c.1010G>A; p.R337H) is responsible for the higher prevalence of this syndrome among women of Brazilian ancestry.
UNASSIGNED: The aim of the study was to describe the BC phenotype expressed by Brazilian female LFS carriers and compare the data between p.R337H and other TP53 germline pathogenic/likely pathogenic variants (non-p.R337H carriers).
UNASSIGNED: We searched for cases of TP53 germline pathogenic/likely pathogenic variant carriers affected by BC included between 2015 and 2020 in the BLiSS (Brazilian Li-Fraumeni Study) registry at the Sírio-Libanês Hospital.
UNASSIGNED: Among 163 adult female carriers from the registry, 91 (56%) had received a BC diagnosis, including 72 p.R337H carriers. BC was the first cancer diagnosed in 90% of cases. Early onset BC (age ≤45 years) was diagnosed in 78.2% of cases (11.5% <31 years; 66.7% 31-45 years; 21.8% >45 years). The median age of BC diagnosis for p.R337H carriers was 39.5 years (range 20-69 years) compared to 34 years (range 21-63 years) for non-p.R337H carriers (p = 0.009). In total, 104 breast tumors were observed in 87 women. Bilateral BC was observed in 29.3% of cases. Histology was available for 96 tumors, comprising 69 invasive breast carcinomas, which were mostly invasive ductal carcinomas (95.6%), 25 ductal in situ carcinomas and 2 soft-tissue sarcomas. Overall, 90.5% of invasive breast carcinomas were hormone receptor (HR)-positive, 39.5% were human epidermal growth factor receptor 2 (HER2)-positive, and 32.8% showed HR and HER2 co-expression. In addition, 55.4% of patients opted for contralateral prophylactic mastectomy after a first BC diagnosis. There were no significant differences in the risk of developing contralateral BC or in the immunohistochemical profile between p.R337H and non-p.R337H groups.
UNASSIGNED: The expressed phenotype of p.R337H is similar to that of other TP53 pathogenic/likely pathogenic variants, except for an average older age at the onset of disease; however, this is still younger than the general population.
UNASSIGNED: The aim of the study was to describe the BC phenotype expressed by Brazilian female LFS carriers and compare the data between p.R337H and other TP53 germline pathogenic/likely pathogenic variants (non-p.R337H carriers).
UNASSIGNED: We searched for cases of TP53 germline pathogenic/likely pathogenic variant carriers affected by BC included between 2015 and 2020 in the BLiSS (Brazilian Li-Fraumeni Study) registry at the Sírio-Libanês Hospital.
UNASSIGNED: Among 163 adult female carriers from the registry, 91 (56%) had received a BC diagnosis, including 72 p.R337H carriers. BC was the first cancer diagnosed in 90% of cases. Early onset BC (age ≤45 years) was diagnosed in 78.2% of cases (11.5% <31 years; 66.7% 31-45 years; 21.8% >45 years). The median age of BC diagnosis for p.R337H carriers was 39.5 years (range 20-69 years) compared to 34 years (range 21-63 years) for non-p.R337H carriers (p = 0.009). In total, 104 breast tumors were observed in 87 women. Bilateral BC was observed in 29.3% of cases. Histology was available for 96 tumors, comprising 69 invasive breast carcinomas, which were mostly invasive ductal carcinomas (95.6%), 25 ductal in situ carcinomas and 2 soft-tissue sarcomas. Overall, 90.5% of invasive breast carcinomas were hormone receptor (HR)-positive, 39.5% were human epidermal growth factor receptor 2 (HER2)-positive, and 32.8% showed HR and HER2 co-expression. In addition, 55.4% of patients opted for contralateral prophylactic mastectomy after a first BC diagnosis. There were no significant differences in the risk of developing contralateral BC or in the immunohistochemical profile between p.R337H and non-p.R337H groups.
UNASSIGNED: The expressed phenotype of p.R337H is similar to that of other TP53 pathogenic/likely pathogenic variants, except for an average older age at the onset of disease; however, this is still younger than the general population.
摘要：
乳腺癌（BC）是Li-Fraumeni综合征（LFS）女性中最常见的恶性肿瘤。由于世界范围内的稀有性，LFS中有关BC的文献有限。TP53创始人的致病性变异（c.1010G>A；p.R337H）是巴西血统妇女中该综合征患病率较高的原因。
UNASSIGNED：该研究的目的是描述巴西女性LFS携带者表达的BC表型，并比较p.R337H与其他TP53种系致病性/可能的致病性变异（非p。R337H载波）。
UNASSIGNED：我们在Sírio-Libans医院的BLiSS（巴西Li-Fraumeni研究）注册中搜索了2015年至2020年间受BC影响的TP53种系致病性/可能致病性变异携带者的病例。
UNASSIGNED：在注册表中的163名成年女性携带者中，91人（56%）接受了BC诊断，包括72个p.R337H运营商。在90％的病例中，BC是首次诊断出的癌症。78.2％的病例诊断为早发性BC（年龄≤45岁）（11.5％<31岁；66.7％31-45岁；21.8％>45岁）。p.R337H携带者的BC诊断中位年龄为39.5岁（范围20-69岁），而非p为34岁（范围21-63岁）。R337H载体(p=0.009)。总的来说,在87名女性中观察到104例乳腺肿瘤。29.3％的病例观察到双侧BC。有96个肿瘤的组织学检查,包括69例浸润性乳腺癌，主要是浸润性导管癌（95.6%），25例导管原位癌和2例软组织肉瘤。总的来说,90.5%的浸润性乳腺癌为激素受体(HR)阳性,39.5%的人表皮生长因子受体2（HER2）阳性，32.8%显示HR和HER2共表达。此外,55.4％的患者在首次BC诊断后选择对侧预防性乳房切除术。p.R337H与非p之间发生对侧BC的风险或免疫组织化学特征没有显着差异。R337H基团。
UNASSIGNED：p.R337H的表达表型与其他TP53致病性/可能的致病性变体相似，除了疾病发作时的平均年龄；然而，这仍然比普通人群年轻。
UNASSIGNED：该研究的目的是描述巴西女性LFS携带者表达的BC表型，并比较p.R337H与其他TP53种系致病性/可能的致病性变异（非p。R337H载波）。
UNASSIGNED：我们在Sírio-Libans医院的BLiSS（巴西Li-Fraumeni研究）注册中搜索了2015年至2020年间受BC影响的TP53种系致病性/可能致病性变异携带者的病例。
UNASSIGNED：在注册表中的163名成年女性携带者中，91人（56%）接受了BC诊断，包括72个p.R337H运营商。在90％的病例中，BC是首次诊断出的癌症。78.2％的病例诊断为早发性BC（年龄≤45岁）（11.5％<31岁；66.7％31-45岁；21.8％>45岁）。p.R337H携带者的BC诊断中位年龄为39.5岁（范围20-69岁），而非p为34岁（范围21-63岁）。R337H载体(p=0.009)。总的来说,在87名女性中观察到104例乳腺肿瘤。29.3％的病例观察到双侧BC。有96个肿瘤的组织学检查,包括69例浸润性乳腺癌，主要是浸润性导管癌（95.6%），25例导管原位癌和2例软组织肉瘤。总的来说,90.5%的浸润性乳腺癌为激素受体(HR)阳性,39.5%的人表皮生长因子受体2（HER2）阳性，32.8%显示HR和HER2共表达。此外,55.4％的患者在首次BC诊断后选择对侧预防性乳房切除术。p.R337H与非p之间发生对侧BC的风险或免疫组织化学特征没有显着差异。R337H基团。
UNASSIGNED：p.R337H的表达表型与其他TP53致病性/可能的致病性变体相似，除了疾病发作时的平均年龄；然而，这仍然比普通人群年轻。
