Invasive lobular carcinoma (ILC) is a distinct form of breast cancer that originates in the milk-producing glands, lobules, before spreading into surrounding breast tissue. While many cases arise sporadically without a clear inherited cause, some link to inherited genetic mutations. Understanding this genetic connection can help individuals assess personal risk and consider preventative measures.
The Genetic Connection to Lobular Breast Cancer
Cancer generally falls into three categories: sporadic, familial, and hereditary. Sporadic cancers occur randomly, often due to accumulated DNA damage, without a clear family pattern. Familial cancers may appear in multiple family members, suggesting shared environmental factors or common genetic variations, but lack a single strong genetic mutation. Hereditary cancers are directly linked to specific inherited gene mutations passed down through generations, accounting for about 5-10% of all breast cancer cases.
A primary genetic alteration associated with an increased risk of lobular breast cancer involves the CDH1 gene. This gene provides instructions for making E-cadherin, a protein that facilitates cell-to-cell adhesion and helps maintain normal tissue structure. When a mutation occurs in the CDH1 gene, the function of E-cadherin can be disrupted, leading to decreased cell adhesion. This loss of proper cell connection is a distinguishing feature of invasive lobular carcinoma, contributing to its unique growth pattern where cancer cells often invade in a single-file line rather than forming a distinct lump.
Women with an inherited CDH1 gene mutation face an elevated lifetime risk of developing invasive lobular breast cancer, estimated at 40% to 42% by age 80. While CDH1 is the most recognized gene for its direct association with ILC, other genes also contribute to broader hereditary breast cancer risk, including BRCA2, PALB2, and CHEK2. Mutations in these genes generally increase the risk for various breast cancer types, including lobular, but their link is not as specifically tied to the unique cellular behavior of ILC as the CDH1 mutation.
Hereditary Diffuse Gastric Cancer Syndrome
The CDH1 gene mutation also causes Hereditary Diffuse Gastric Cancer (HDGC) syndrome. This syndrome is characterized by a high lifetime risk of developing diffuse gastric cancer, an aggressive form of stomach cancer that spreads subtly through the stomach lining rather than forming a visible mass. For women with a CDH1 mutation, the lifetime risk of diffuse gastric cancer can range from 25% to 83%, and for men, it ranges from 37% to 70% by age 80.
The average age of diagnosis for gastric cancer in HDGC syndrome can vary, from 38 to 80 years, with some cases reported as early as 14 years of age. Due to the high risk and challenging nature of detecting diffuse gastric cancer early, risk management strategies are often considered. These may include intensified surveillance through annual endoscopic examinations with biopsies, or prophylactic total gastrectomy, which involves surgically removing the entire stomach before cancer develops. This preventive surgery, while effective at lowering gastric cancer risk, has lifestyle implications.
Identifying Your Hereditary Risk
Recognizing patterns in your family’s health history can help determine if you might have an increased hereditary risk for lobular breast cancer. One indicator is having multiple family members on the same side of the family diagnosed with breast cancer. The risk tends to be higher if these diagnoses occurred at a younger age, under 50 years. A family history that includes cases of male breast cancer is also a relevant factor.
A personal or family history of lobular breast cancer raises suspicion for an inherited component. The occurrence of breast cancer in both breasts in the same individual, or multiple primary cancers in one person, can also suggest a hereditary predisposition. A family history of diffuse gastric cancer alongside lobular breast cancer is a strong indicator, given the shared genetic link through the CDH1 gene.
Genetic Counseling and Testing
If your family history suggests a hereditary cancer risk, seeking genetic counseling is a recommended first step. A genetic counselor is a healthcare professional who specializes in assessing personal and family medical histories to determine the likelihood of an inherited cancer syndrome. They provide information about genetic testing, including its benefits, limitations, and potential implications for you and your relatives. This counseling helps individuals make informed decisions about whether to proceed with genetic testing.
Genetic testing involves providing a blood or saliva sample, which is then analyzed for specific gene mutations associated with cancer risk. For lobular breast cancer, this includes looking for mutations in the CDH1 gene, as well as other genes like BRCA1, BRCA2, PALB2, and CHEK2, depending on the individual’s history. Test results can indicate a positive finding (a mutation is present), a negative finding (no known mutation is found), or a variant of uncertain significance (a change is found, but its impact on cancer risk is not yet clear). Discussing these results with a genetic counselor is key to understanding their meaning for your cancer screening plan and potential preventive strategies.