Cancer is a disease that occurs when cells begin to multiply uncontrollably, forming tumours that can invade nearby tissues and, in some cases, spread to other parts of the body (metastasis). Their appearance can be linked to external factors such as chemical (tobacco), physical (ionising radiation) and/or biological (viruses) agents, but they can also be the consequence of failures in cellular processes, such as mutations that alter the cell cycle. Of the more than 200 known types of cancer, breast cancer is one of the most common.
In Spain, breast cancer is the main cancer diagnosed in women, with 35,000 new cases per year, according to data from the Spanish Society of Medical Oncology (SEOM). Advances in detection programmes and treatments have been fundamental in improving both the prognosis and survival of patients, with 90% of cases detected in early stages. Despite this, it is estimated that one in three patients will develop metastases during the course of their disease, highlighting the importance of early diagnosis and appropriate follow-up, especially in cases of hereditary breast cancer.
Hereditary breast cancer
Although most cases of breast cancer are sporadic (70-80%), 15-20% have a family history, known as familial aggregation. This may be due to common environmental factors or similar lifestyles within the family. However, in 5-10% of cases, an inherited genetic cause of cancer predisposition is detected.
The BRCA1 and BRCA2 genes are mainly associated with hereditary breast cancer, and also increase the risk of ovarian cancer, especially of the high-grade serous type. In addition to these genes, variants in the genes TP53 (related to Li-Fraumeni syndrome), PTEN (Cowden syndrome), STK11 (Peutz-Jeghers syndrome) and PALB2, among others, may also increase the risk of breast cancer. In ovarian cancer, pathogenic variants in the RAD51C, RAD51D, BRIP1 and DNA repair genes, such as the MMR genes, are also implicated.
Clinical diagnosis
Diagnosis of breast cancer requires a multidisciplinary approach including:
- Anamnesis (including personal and/or family history associated with cancer).Hereditary breast cancer: Diagnosis and prevention Marina Sánchez Soler 1
- Complete physical examination (palpation of the breasts, regional lymph nodes and evaluation of signs of possible metastasis).
- Radiological tests (mammography, ultrasound and magnetic resonance to assess the size and extent of the tumour).
- Pathological analysis (by biopsy of the affected tissue to determine the nature of the tumour and its aggressiveness).
If a possible genetic cause is suspected due to the type of cancer or personal and/or family history, a genetic study using panels of genes associated with cancer predisposition should be considered. To ensure proper interpretation of the results and informed decision making, it is essential that this process is accompanied by a genetic counselling consultation.
Criteria for genetic testing
According to the recommendations of the NCCN (National Comprehensive Cancer Network, v1.2025) and SEOM (2019) guidelines, genetic screening should be considered in the following scenarios:
- Patients under 50 years of age with a personal history of breast cancer.
- Patients with pathological findings indicating triple negative breast cancer, multiple primary breast cancer (synchronous or metachronous), and lobular breast cancer with a personal or family history of diffuse gastric cancer.
- Male patient with breast cancer. – Family history with:
- ≥1 family member with breast cancer under the age of 50.
- ≥1 family member with ovarian, pancreatic, metastatic prostate or male breast cancer.
- ≥3 first-degree relatives from the same family branch diagnosed with breast and/or prostate cancer at any age.
- Prevention and reproductive options
Knowing the genetic cause makes it possible to individualise treatment in affected patients, as well as offering the possibility of screening at-risk relatives, which improves both prevention and follow-up in those who have not yet developed the disease. This makes it possible to implement stricter surveillance measures and, in some cases, to consider prophylactic preventive options, thus reducing the risk of cancer development.
In addition to optimising treatment, the identification of the genetic cause also helps in reproductive decision-making. Assisted reproductive techniques, such as preimplantation genetic diagnosis of monogenic diseases (PGT-M), make it possible to select embryos without the pathogenic variant identified in the patient or her partner, thus reducing the risk of genetic transmission to future generations.
Conclusions
Hereditary breast cancer, although less common than sporadic cases, represents a significant percentage of cancer cases in women and some men. Thanks to advances in technology and scientific knowledge, especially with the use of multigene panels, it is possible to identify those at risk. This allows them to be offered personalised care, from surveillance to treatment and prevention, thus improving clinical outcomes and quality of life.
Bibliography:
González-Santiago, S., Ramón y Cajal, T., Aguirre, E. et al. SEOM clinical guidelines in hereditary breast and ovarian cancer (2019). Clin Transl Oncol 22, 193-200 (2020).
https://doi.org/10.1007/s12094-019-02262-0
NCCN Guidelines Version 1.2025 Breast, ovarian, and Pancreatic Cancer Genetic Assessment.
