From the Guidelines
Breast cancer is primarily classified into several major types with distinct genetic associations, including Ductal Carcinoma In Situ (DCIS), Invasive Ductal Carcinoma (IDC), Invasive Lobular Carcinoma (ILC), Triple-Negative Breast Cancer, and Inflammatory Breast Cancer, with BRCA1 and BRCA2 mutations being the most significant genetic factors associated with an increased risk of breast cancer, as noted in 1.
Genetic Associations
The main genetic associations include:
- BRCA1 mutations, which are strongly associated with triple-negative breast cancer, as seen in tumors that tend to be of the basal-like phenotype, have a high histologic grade, and do not commonly express the estrogen receptor (ER), progesterone receptor (PR), or Her2/neu, the so-called triple-negative tumor 1
- BRCA2 mutations, which typically lead to hormone receptor-positive cancers, as BRCA2-related tumors more closely resemble sporadic tumors 1
- Other important genetic factors, including mutations in PALB2, CHEK2, ATM, TP53 (Li-Fraumeni syndrome), PTEN (Cowden syndrome), and CDH1 genes, which also play a significant role in determining the risk of breast cancer, as outlined in 1
Hormone Receptor Status
Hormone receptor status further classifies breast cancers as:
- Estrogen Receptor (ER) positive/negative
- Progesterone Receptor (PR) positive/negative
- HER2 status (positive/negative) indicates overexpression of human epidermal growth factor receptor 2, with targeted therapies available for specific subtypes, such as hormone therapy for ER/PR positive cancers and trastuzumab (Herceptin) for HER2-positive cancers, as discussed in 1
Screening and Prevention
Understanding these genetic associations helps determine cancer risk, guides screening protocols for high-risk individuals, and enables personalized treatment strategies based on the specific molecular profile of each patient's cancer, with recommendations for genetic counseling and testing for those with a family history of breast or ovarian cancer, as outlined in 1
Key Recommendations
- Genetic counseling and testing should be recommended for breast cancer survivors with a family history of breast or ovarian cancer, or with certain characteristics, such as being younger than age 50 years at diagnosis, having a history of ovarian cancer, or having a first-degree relative who had breast cancer diagnosed before age 50 years, as noted in 1
- Screening and prevention strategies should be tailored to the individual's specific genetic syndrome and should be left to a trained professional in coordination with the oncology team and the primary care clinician, as discussed in 1
From the Research
Types of Breast Cancer
- Breast cancer is a heterogeneous disease, differing greatly among patients and within individual tumors 2, 3
- The disease can be subdivided into subtypes based on molecular features, such as activation of hormone receptors, human epidermal growth factor receptor 2 (HER2), and BRCA mutations 4
- Invasive lobular carcinoma is a type of breast cancer that differs from invasive ductal carcinoma in terms of risk factors and genetic associations 5
Genetic Associations
- Germline mutations in BRCA1 and TP53 are predominantly associated with invasive ductal carcinoma, while BRCA2 mutations are associated with both ductal and lobular cancers 5
- CDH1 mutations are associated with invasive lobular carcinoma, but not with ductal carcinoma 5
- Breast cancer subtypes have distinct biological features that lead to differences in response patterns to treatment and clinical outcomes 6
Molecular Classifications
- Molecular classifications of breast cancer are indicators of genetic tumor heterogeneity, which can lead to improved stratification into low- and high-risk groups for personalized therapy 2
- Gene signatures have been developed as predictors of response to therapy, and protein gene products have direct roles in driving the biology and clinical behavior of cancer cells 6
- Understanding the molecular and cellular mechanisms of tumor heterogeneity is a major area of research, with the goal of developing more effective diagnostic, prognostic, and predictive strategies for breast cancer 2, 3, 4