March 5, 2024

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2021 NCCN: These genes are related to hereditary/familial tumors

2021 NCCN: These genes are related to hereditary/familial tumors



2021 NCCN: These genes are related to hereditary/familial tumors.  Tumor occurrence is caused by various mutations in genes involved in processes such as cell growth and/or DNA repair. Not all of these mutations are inherited from parents, and some sporadic mutations only occur in somatic cells and not in germ cells.

Some new mutations can also appear for the first time in egg cells, sperm cells, or in fertilized eggs in early embryogenesis. Data from long-term family studies show that some tumor types are closely related to the disease of relatives.

The presence of one or more mutations in the parental germ cells may increase the susceptibility of these individuals to tumors. The tumors that occur in these individuals can be classified as hereditary or familial tumors.

2021 NCCN: These genes are related to hereditary/familial tumors

Hereditary tumors are usually characterized by mutations that increase the risk of the tumor and inherited from parents to offspring. Familial tumors have some of the characteristics of hereditary tumors, but not all of them.

For example, although the incidence of familial breast cancer in certain families is higher than that in the general population, these patients do not show the same age of onset or genetic pattern as hereditary tumors.

Familial tumors may be related to the chance clustering of sporadic cases in the family, genetic variation of low penetrance genes, co-living environment or the combined influence of these factors.

The risk assessment of individuals suffering from familial or hereditary tumors is based on a comprehensive assessment of personal and family history. Regarding hereditary tumors, with the advancement of molecular genetics, some genes related to hereditary breast, ovarian and pancreatic cancer have been identified (such as BRCA1/2, TP53, CDH1, etc.). Tumor genetics has important significance in the prevention, screening and treatment of individual management.

2021 NCCN Genetic/Familial High Risk Assessment: Breast, Ovary, and Pancreas Second Edition, which provides a preliminary summary of many knowledge in the clinical application of the rapidly emerging field of molecular genetics, and the guide also provides a description of certain The methods of specific gene mutations in these individuals and families can be used to guide the diagnosis and treatment of individuals and families.

The guideline gives a flow chart of genetic testing (see Figure 1). According to the prompts in Table 1, it can further guide the diagnosis and treatment of individuals and families.


BRCA pathogenic/probably pathogenic mutation positive management


  • Start to “know your breasts” at the age of 18 (familiar with your breasts, you can inform their medical staff of the changes in their own breasts, regular breast self-examination, the effect of breast self-examination at the end of menstrual period is more obvious for women before menopause)
  • Receive breast clinical examination every 6-12 months from the age of 25
  • Breast screening:
  • 25-29 years old, receive MRI of the breast every year as a control. If MRI is not available, consider receiving mammography
  • If there is a diagnosis of breast cancer in the family who is younger than 30 years old, individualized examinations will be carried out based on family history 30 to 75 years old, and annual mammography and breast MRI examinations will be used as controls
  • >75 years old, need to be checked according to individual situation
  • Women with BRCA pathogenic/potentially pathogenic mutations who have not undergone bilateral mastectomy and who have undergone breast cancer treatment still need annual mammography and breast MRI


  • Explore the options of preventive mastectomy
    • The discussion should include the level of protection of the patient, the breast reconstruction plan and the risks
    • Family history, residual risk of breast cancer with age, and life expectancy should also be discussed
    • It is usually recommended to perform preventive fallopian tube-ovarian resection after childbirth between 35 and 40 years old; patients with ovarian cancer carrying BRCA2 pathogenic/potentially pathogenic mutations are better than those with BRCA1 pathogenic/potentially pathogenic mutations The average onset of patients is 8 to 10 years later. In such patients, tubal-ovarian removal can be postponed to 40-45 years old, unless family members are diagnosed at an earlier age, and preventive surgery can be performed earlier
    • Genetic counseling includes the discussion of the patient’s fertility needs, the degree of tumor risk, the degree of protection of breast and ovarian cancer, the control of menopausal syndrome, hormone replacement therapy and related drug therapy, etc. Single salpingectomy is not a standard method to reduce risk. There is a clinical research underway for the first salpingectomy and subsequent resection of the ovaries
    • Women who only receive reduced-risk single salpingectomy are still at risk of ovarian cancer; premenopausal women undergoing ovariectomy can reduce the risk of breast cancer, but its significance is not clear and may be genetically specific
    • Limited data suggest that women with BRCA1 pathogenic/potentially pathogenic mutations have a slightly increased risk of uterine serous cancer. The clinical significance of this finding is still unclear. More people with BRCA mutations should be included in the study to evaluate their risk of uterine serous cancer. The risks and benefits of preventive tubal-ovarian removal and hysterectomy should be fully discussed with patients with BRCA1 mutations. Women undergoing both hysterectomy and prophylactic tubal-ovarian removal receive single estrogen replacement therapy, which is associated with a reduced risk of breast cancer. This is in contrast to the combination of estrogen and progesterone when the patient’s uterus has not been removed.
    • Patients undergoing reduced-risk mastectomy and tubal-ovarian removal should assist them in solving psychosocial and quality of life problems
    • Although the benefit is still uncertain, patients who have not undergone prophylactic tubal-ovarian removal can begin screening for ovarian cancer with transvaginal ultrasound combined with serum antigen CA125 from the age of 30 to 35.


  • Receive training and education for breast self-examination since the age of 35
  • Receive a clinical breast examination every 12 months from the age of 35
  • Men with hyperplasia of the mammary glands from the age of 50 may consider receiving mammography examination every year, and those with confirmed male breast cancer in the family should receive mammography examination 10 years in advance
  • Starting from 40 years old: BRCA2 carriers are recommended to receive pancreatic cancer screening; BRCA1 carriers may be considered for pancreatic cancer screening

Men and women:

  • Consider applying to participate in clinical studies such as new imaging technologies or screening with shorter intervals

    Strengthen health education to identify tumor symptoms and signs, especially tumors related to BRCA gene pathogenicity/suspected pathogenicity mutations
  • There are no special screening guidelines for melanoma, but general risk management for melanoma is necessary, such as receiving annual skin examinations of the whole body and minimizing UV exposure, etc.

Relatives risk:

  • Inform relatives of possible hereditary tumor risks and provide options for risk assessment and management
  • Genetic counseling is recommended, and genetic testing may be considered for relatives at risk

Fertility options:

For individuals at childbearing age, provide options for prenatal diagnosis and assisted reproduction including preimplantation genetic diagnosis; instead, fully discuss the risks, limitations and benefits of these technologies.


(source:internet, reference only)

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