Lobular breast cancer (LBC) is a distinct type of breast cancer characterized by its unique growth pattern, where cancer cells grow in single file rather than forming a lump. This diffuse growth can make LBC more challenging to detect through standard imaging techniques like mammography. While many cases of LBC arise without a clear inherited cause, a hereditary component exists for a subset of individuals. This article explores the genetic underpinnings of LBC, its hereditary connections, the role of genetic testing, and management strategies for those at higher risk.
Understanding Cancer Heredity
Cancer development often involves changes, or mutations, in genes that control cell growth and division. Most cancers are considered “sporadic,” meaning these genetic changes occur during a person’s lifetime due to factors like aging, environmental exposures, or lifestyle choices. Sporadic cancers typically do not run in families in a predictable pattern.
In contrast, hereditary cancers arise when an individual inherits a mutated gene from a parent, predisposing them to cancer. This inherited mutation is present in nearly every cell of the body from birth. While inheriting such a mutation increases the risk, it does not guarantee that cancer will develop. Hereditary cancer syndromes account for about 5% to 10% of all cancers. These syndromes often manifest as multiple family members diagnosed with the same or related cancers, often at younger ages than typically seen in sporadic cases.
Hereditary Connections to Lobular Breast Cancer
Most cases of lobular breast cancer are sporadic, yet a significant hereditary link does exist for a smaller proportion of individuals. The primary genetic connection for hereditary LBC involves the CDH1 gene, which provides instructions for making E-cadherin, a protein crucial for cell-to-cell adhesion. Mutations in CDH1 can disrupt this protein’s function, leading to a loss of cell adhesion.
Inherited mutations in the CDH1 gene are primarily associated with Hereditary Diffuse Gastric Cancer (HDGC) syndrome, which significantly increases the risk of developing diffuse gastric cancer. However, this syndrome also carries an elevated risk for lobular breast cancer in women. For females with a CDH1 gene mutation, the lifetime risk of developing LBC by age 80 has been estimated to be between 37% and 55%.
While CDH1 is the primary gene linked to hereditary LBC, other genes like PTEN, TP53, ATM, and CHEK2 might also contribute to hereditary LBC cases. The International Gastric Cancer Linkage Consortium officially recognized hereditary lobular breast cancer as an independent syndrome in 2020. This acknowledges that some individuals can have CDH1 germline mutations and develop LBC without a family history of diffuse gastric cancer.
Genetic Testing and Counseling
Genetic testing for hereditary breast cancer is considered for individuals with specific risk factors. This includes those with a strong family history of LBC, HDGC, or multiple cases of diffuse gastric cancer. Testing may also be recommended if breast cancer was diagnosed at an unusually young age, or if there are multiple relatives with breast or related cancers.
The process typically begins with genetic counseling, where a trained professional assesses personal and family medical histories. This pre-test counseling helps determine the likelihood of an inherited mutation and discusses the benefits, risks, and limitations of genetic testing. Genetic testing usually involves a blood or saliva sample, which is analyzed for specific gene mutations.
Following testing, post-test counseling explains the results, whether positive, negative, or inconclusive. A positive result means a specific mutation, such as in the CDH1 gene, has been identified, indicating an increased cancer risk for the individual and potentially their family members. Genetic counselors help individuals understand the implications for their health and guide discussions about how to share this information with relatives.
Management for Individuals at Higher Risk
For individuals with a higher hereditary risk for LBC, such as those with a CDH1 mutation, specialized management strategies are recommended. Given the diffuse growth pattern of LBC, which can make it challenging to detect on mammograms, enhanced breast cancer screening methods are advised. This often includes yearly breast Magnetic Resonance Imaging (MRI) starting at a younger age, typically around 30 years, often alternating with mammograms.
Risk-reduction options are also discussed, tailored to the individual’s specific mutation and family history. These can include lifestyle modifications and, in some cases, chemoprevention with medications like hormone-blocking therapies. For individuals with a significantly elevated risk, prophylactic surgery, such as a risk-reducing mastectomy, may be considered. These management decisions are made in close consultation with healthcare providers to develop a personalized care plan.