Analysis of breast ultrasound imaging and pathological characteristics in patients with hereditary breast cancer-ovarian cancer syndrome / 肿瘤研究与临床

Objective:To investigate breast ultrasound imaging and pathological characteristics of patients with hereditary breast cancer-ovarian cancer syndrome (HBOC).Methods:A total of 12 patients with HBOC admitted to Shanxi Province Cancer Hospital from January 2012 to 2021 April were retrospectively analyzed. All patients were pathologically diagnosed as invasive breast cancer based on the preoperative puncture or surgical specimens, including 3 patients with double primary cancers of breast and ovary. The clinical, breast ultrasound imaging and pathological data of patients were analyzed.Results:The ultrasound imaging of HBOC usually showed regular morphology in 8 cases, clear border in 9 cases, no burr sign in 10 cases, no calcification in 10 cases, rear echo in 10 cases; the maximum blood flow velocity was (0.21±0.09) m/s, the vascular resistance index was 0.72±0.17, and aspect ratio ≤ 1 in 8 cases. Among 12 cases of HBOS, 9 cases were invasive ductal carcinoma, 3 cases were breast cancer with medullary features; histological grade: 7 cases of grade Ⅱ, 5 cases of grade Ⅲ; molecular classification: Luminal B type in 2 cases, human epithelial receptor 2 (HER2) type in 4 cases, and triple-negative type in 6 cases. The histological types of 3 patients with double primary cancers of breast and ovary were all high-grade serous carcinoma.Conclusions:HBOC is a type of neoplastic disease with a special genetic background. Ultrasound and pathological manifestations have certain characteristics. Sonographers should improve the understanding of the disease and pay attention to the medical history and family history in order to reduce the rate of misdiagnosis and increase the rate of diagnosis.

Tests genéticos brca1/2 y otros genes de predisposición al cáncer de mama: análisis retrospectivo de 106 pacientes / Genetic studies for brca1/2 and other genes related to predisposition in breast cancer: retrospective analysis of 106 patients

Introducción Si bien el cáncer de mama hereditario representa entre el 5-10% del total de los cánceres de mama, es importante la detección de pacientes portadoras de mutaciones patogénicas en genes brca1/2 y otros genes relacionados con el cáncer de mama ya que esta información permitirá tomar conductas adecuadas de prevención y/o tratamiento tanto en la paciente portadora como en sus familiares. Objetivo Llevar a cabo un análisis retrospectivo de 106 pacientes que realizaron estudios genéticos para genes brca1/2 y otros genes relacionados con el cáncer de mama. Resultados Del total de 106 pacientes, encontramos: 17 (16,03%) con mutación patogénica; 38 (35,85%) con vus (Variantes de significado incierto) informadas en el reporte original; y 51 (48,11%) con estudios negativos. De los 38 informes con vus, 7 (6,6%) fueron reclasificadas como vus verdaderas a junio de 2018. De las 17 mutaciones patogénicas encontradas, 16 correspondieron a mutaciones en los genes brca1/2 (15,09%) y 1 a mutación en el chek2 (3,77%). Conclusiones Los estudios genéticos de predisposición en cáncer de mama son, en la actualidad, una herramienta fundamental para la atención multidisciplinaria de la paciente de alto riesgo en un consultorio de patología mamaria. Es un deber del mastólogo pensar en la indicación de un estudio genético de predisposición al cáncer de mama y derivar al genetista para identificar correctamente al paciente que se va a beneficiar de esta información

Introduction Although hereditary breast cáncer represents 5-10% of all breast cancers, it is important to detect patients carrying pathogenic mutations in brca1/2 genes and other genes related to breast cáncer as this information will allow take appropriate prevention and / or treatment behaviors in both the patient carrier and their family members. Objective To make a retrospective analysis of 106 patients who carried out genetic studies for brca1/2 genes and other genes related to breast cancer. Results From 106 patients we found 17 (16.03%) with pathogenic mutations, 38 (35.85%) with vus (variant of unknown significance) in the original report, and 51 (48.11%) negatives. From 35 vus, we reclasified as true vus only 7 (6,6%) in June 2018. From 17 pathogenic mutations in 106 patients studied (16.03%), we found 16 in the brca1/2 genes (15.09%) and 1 mutation in chek2 (3.77%). Conclusions Genetic predisposition tests in breast cáncer are a fundamental tool for multidisciplinary care of the high-risk patient in a breast center query. The mastologist has to think in the first place about the indication of a genetic testing ofbreast cancer predisposition, and refer to the geneticist for a prompt consultation for patients benefit

Medium-sized deletion in the BRCA1 gene: limitations of Sanger sequencing and MLPA analyses

We describe a family with a history of breast and ovarian cancer in which MLPA analysis of the BRCA1 gene pointed to a deletion including a part of exon 11. Further characterization confirmed a loss of 374 bp in a region completely covered by conventional sequencing which had not revealed the deletion. Because this alteration was only detected serendipitously with an MLPA probe, we calculated the probabilities of detecting medium-sized deletions in large exons by methods including initial PCR amplification. This showed that a considerable fraction of medium-sized deletions are undetectable by currently used standard methods of mutation analyses. We conclude that long, widely overlapping amplicons should be used to minimize the risk of missing medium-sized deletions. Alternatively, large exons could be completely covered by narrow-spaced MLPA probes.

Hereditary Breast Cancer in Korea

About 7% of all breast cancer (BC) cases result from a genetic predisposition, and approximately 1,000 patients develop hereditary BC (HBC) every year in Korea. BRCA1 and BRCA2 are the primary genes underlying HBC. The average cumulative risks in BRCA1 mutation carriers at 70 years of age are 65% (95% confidence interval 44-78%) for BC and 39% (18-54%) for ovarian cancer (OC). The corresponding estimates for BRCA2 are 45% (31-56%) and 11% (2.4-19%), respectively. The penetrance of BRCA mutations is not the same between patients and can depend on factors such as race and birth-cohort. The Korean Hereditary Breast Cancer (KOHBRA) study is a large prospective nationwide study that includes 39 participating centers. Between May 2007 and May 2010, the first phase of the KOHBRA study was planned and fulfilled successfully. The primary aim of phase I was to estimate the prevalence of BRCA1/2 mutations and OC among a high-risk group of patients with HBC and their families. According to data collected during phase I of the study, the prevalence and penetrance of BRCA mutations were comparable to corresponding data from Western countries. For the second phase of the KOHBRA study, we are currently investigating a Korean BRCA mutation prediction model, prognostic factors in BRCA-related BC, environmental/genetic modifiers, and implementing a genetic counseling network. The final goal of the KOHBRA study is to create clinical practice guidelines for HBC in Korea. In this article, I review the genetics of HBC, summarize the characteristics of Korean HBC, and discuss current and future HBC research in Korea.

Korean Hereditary Breast Cancer

Approximately 7% of all breast cancer cases are associated with hereditary predisposition and BRCA1 and BRCA2 gene, which accounts for half of the hereditary breast cancer (HBC). Although majority of breast cancer occur sporadically, identification of HBC is important in that active adoption of preventive strategies such as surveillance, chemoprevention, and riskreducing surgery will result in the gain of life-expectancy. According to the recent studies, the prevalence and penetrance of BRCA mutation in Korean breast cancer patients are comparable to that of western countries. Genetic testing should be done in the setting of genetic counseling, which provides the patients with comprehensive information about the test procedure, the interpretation of the test result, and possible options when the test results were positive for mutation. The management of HBC is not different from that of sporadic cancer and many clinical trials investigating the chemoprevention and targeted therapy of HBC are underway. The Korean Hereditary Breast Cancer (KOHBRA) study is a nationwide multicenter study to reveal the prevalence of BRCA mutation in Korean breast cancer patients. After the completion of the KOHBRA study, we expect important basic data which will be the backbone of clinical practice guideline for Korean HBC patients.

Importancia de la historia familiar en el cáncer de mama y ovario

Objetivo: Presentar el caso de una paciente, quien acudió para evaluación ginecológica. La misma resultó clínicamente sana pero en su grupo familiar destaca la alta frecuencia de cáncer de mama y de ovario, lo cual indujo a sospechar alto riesgo para el cáncer de mama hereditario (CaMH); a propósito del mismo se revisa esta patología y se resalta la importancia de la historia familiar. Caso clínico: Mujer de 25 años de edad, que acude a la consulta para realizar control ginecológico. Diagnóstico: paciente clínicamente sana, pero con antecedentes familiares, de alta frecuencia de cáncer de mama (CaM) y cáncer de ovario, razón por la cual se procede a investigar al grupo familiar. Se revisan las historias clínicas del archivo del IAHULA y se entrevistan los familiares. Familia no consanguínea, padres sanos, mayores de 70 años sin cáncer, 3 hermanos y 7 hermanas. Cuatro hermanas fallecieron en un periodo de 9 años, en edades comprendidas entre 24 y 35 años: 3 por CaM y 1 por Ca de ovario, tía materna con CaM y abuela paterna con probable Ca de ovario (síndrome ascítico no ictérico) ambas fallecidas en el medio rural. Antecedentes personales de las 4 hermanas fallecidas: menarquia en promedio de 12.3 años, paridad y lactancia 2/4, nulípara 2/4, ninguna obesa, ni hábitos alcohólicos. Al momento del diagnóstico todas en estadios avanzados de cáncer. Tipo histopatológico del CaM: ductal infiltrante poco diferenciado (2/3), lobulillar y medular (2/3); bilateral (1/3); sin determinar receptores de estrógeno, progesterona o andrógenos. Metástasis a cerebro y pulmón (2/3) durante tratamiento. En ovario: cistoadenoma mucinoso, estadio IV, recidiva al año a pesar del tratamiento. Sobrevida de 3 meses a 3 años. A la paciente se le recomendó realizar el estudio genético para poder precisar el riesgo de padecer cáncer de Mama y ovario Hereditario (CaMH) y establecer las medidas de vigilancia. Conclusiones: Se recomienda que ante una paciente con antecedentes familiares de CaM, se investigue a fondo su historia familiar, la cual aún en ausencia de marcadores genéticos, permite sospechar la presencia de un CaMH el cual requiere de un protocolo de prevención y vigilancia diferente al CaM esporádico.

Objective: To present the case of a patient, who went for a gynecological assessment. She was healthy but in his family group stressed a high frequency of breast and ovarian cancer, which led to suspect high risk for hereditary breast cancer (HBCa). This condition is reviewed, highlighting the importance of family history. Case report: A 25 year old woman who consults for a gynecological examination. Healthy patient with a high frequency of breast cancer (BCa) in her family. Not consanguineous family. Healthy parents, 3 brothers and 6 sisters. Four sisters died within a period of 9 years, aged between 24 and 35 years old: 3 from BCa and 1 from ovarian cancer. Maternal aunt with BCa and paternal grandmother with ovarian cancer. Personal history of the 4 deceased sisters: average age of menarche 12.3 years, parity and lactation 2/4, nulliparous 2/4, no obesity, nonalcoholic habits. Initial diagnosis in advanced stages of cancer. Histopathological type of BCa: poorly differentiated (2/3), lobular and medullary (2/3); bilateral 1/3; lung and brain metastases during treatment (2/3). In ovarian: mucinous cystadenoma stage IV, recurrence in one year despite treatment. Survival between 3 months and 3 years. The patient is recommended to perform the genetic study in order to clarify the risk of suffering BCa and surveillance measures. Conclusions: It is recommended in a patient with a family history of BCa, to carry out a thorough investigation of family history, which, even in the absence of genetic markers, allows to suspect the presence of hereditary breast cancer.

Hereditary Breast Cancer in Korea: A Review of the Literature / 한국유방암학회지

Hereditary breast carcinomas associated with BRCA1/2 mutations have unique clinicopathological and epidemiological characteristics. The objective of this study is to outline the prevalence, founder effect and clinicopathological characteristics of BRCA1/2 mutations for hereditary breast cancers from an analysis of reports recently published regarding Korean subjects. The prevalence of BRCA1 and/or BRCA2 mutations is 2.5-3.1% for sporadic breast cancers, 19.4-42.9% for familiar breast cancer patients with two or more affected first- and second- degree relatives with breast or ovarian cancers and 9.6-18.3% for early breast cancers. Common mutations for the Korean subjects were 2552delC, 3476insA, 4184del4, 5589del8, and 5615del111insA for BRCA1; and 7708C>T for BRCA2. These mutations were not found in Ashkenazi Jewish or Icelandic subjects. The proportion of estrogen or progesterone receptor (ER/PR) or ER/PR/HER2 triple negative status, basal-like phenotype as detected by immunohistochemical staining, and undifferentiated histological grade in Korean BRCA mutation subjects were higher than in subjects lacking BRCA1/2 mutations. Our review found that previous studies describing BRCA mutations among Korean subjects were limited. Since the clinicopathological, phenotypic and epidemiological characteristics of the BRCA1/2 mutations among Korean subjects are different from those among subjects from the Americas and Europe, more studies of hereditary or familial breast cancer including BRCA mutations must be conducted. A largescale prospective study called Korean Hereditary Breast Cancer Study (KOHBRA) was started from May 2007, and future information provided by the KOHBRA study will make a substantial contribution to solving the basic questions in etiology, individual susceptibility and clinicopathological characteristics for hereditary breast cancer among Korean subjects.

Practice Patterns of Surgeons for the Management of Hereditary Breast Cancer in Korea / 한국유방암학회지

PURPOSE: The aim of this study is to examine practice patterns of surgeons for the management of hereditary breast cancer in Korea. METHODS: A structured questionnaire was circulated to the members of the Korean Breast Cancer Society through email distribution between 6 July and 14 August 2007. A total of 43 surgeons from 42 hospitals responded to the survey. RESULTS: Of the respondents, 81.4% (n=35) asked for information related to the family histories of cancer and 58.1% (n=25) recommended genetic testing for their patients. Indications for genetic testing recommended by the 25 surgeons were the following: breast cancer patients with family histories of breast or ovarian cancer (96%), bilateral breast cancer (80%), early-onset (64%) or male breast cancer (52%), and a double primary malignancy with breast and ovarian cancer (36%). Of the respondents, 52% (13/25) performed genetic counseling before genetic testing, and the surgeons (81.3%, 13/16) or genetic counselors (18.7%, 3/16) provided the genetic counseling. Although 154 BRCA1/2 mutation carriers of 95 families have been identified so far, only 12 family members were managed for prophylaxis by tamoxifen chemoprevention (n=2), a contralateral prophylactic mastectomy (n=2) or a prophylactic oophorectomy (n=8). There was no report of a bilateral prophylactic mastectomy being performed. CONCLUSION: Although BRCA1/2 mutation carriers for highrisk patients with hereditary breast cancer have been identified in Korea, practice and management for cancer prevention does not seem to be actively performed. The Korean Hereditary Breast Cancer (KOHBRA) Study will serve to establish the Korean guidelines of evidence-based clinical practice for hereditary breast cancer.

The Korean Hereditary Breast Cancer (KOHBRA) Study: Protocol Review / 한국유방암학회지

PURPOSE: Most epidemiological and clinical studies on BRCA1/ 2 mutations and the risk of breast cancer have been based on Western cohorts. There have been few such studies for Korean populations. The primary aim of this paper is to report the protocol of a Korean Hereditary Breast Cancer (KOHBRA) study. METHODS: The multi-centers registered in the Korean Breast Cancer Society are participating in the KOHBRA study. The objectives of the KOHBRA study till 2010 is to examine the prevalence of BRCA1/2 mutation and the prevalence of ovarian cancer among the high risk group of hereditary breast cancer patients and their families. This study is a prospective cohort study that recruited 2,250 subjects: 1) who were breast cancer patients with a family history of breast or ovarian cancers, 2) who were patients with a high risk of BRCA1/2 mutations (i.e. early onset, bilateral, male, multiple primary cancers), and 3) who had family members that were BRCA1/2 mutation carriers. The recruiting period will cover the 25th of May 2007 to the 24th of May 2010. Written informed consent is obtained at the time of enrollment. The family history and epidemiological data are obtained by a baseline questionnaire, the anthropometric data is measured and the clinical information is collected by chart-reviews by doctors. BRCA1/2 mutation testing and ovarian cancer screening are done. Blood samples are stored. Follow-up data are collected at 1, 3 and 5 yr after enrollment. RESULTS: Until now, 36 centers have joined the KOHBRA study and they are in the process of Institutional Review Board (IRB) approval. We expect to find the Korean founder mutation and to establish the Korean BRCA risk prediction model. Furthermore, the BRCA carrier cohort established from the KOHBRA study will be the groundwork to participate in an international study. CONCLUSION: The KOHBRA study will provide unique, important data to prove the etiology and natural history of Korean hereditary breast cancer. This study will be continued as genomic and proteomic epidemiological studies and future intervention studies for the prevention of hereditary breast cancer among Koreans.