Invasive Lobular Carcinoma (ILC) is the second most common form of breast cancer. This article focuses on ILC classified specifically as Nottingham Grade 2, providing a clear understanding of what this classification means for the disease’s behavior and treatment planning.
Understanding Invasive Lobular Carcinoma and Tumor Grading
ILC originates in the breast’s milk-producing glands (lobules), contrasting with the more common Invasive Ductal Carcinoma (IDC) which begins in the milk ducts. ILC accounts for approximately 10 to 15 percent of all invasive breast cancer cases.
Pathologists use the Nottingham Histologic Grade (NHG) system to evaluate cancer cells. This system assesses three characteristics, each scored from one to three: the degree of tubule formation, the level of nuclear pleomorphism (variation in cell nucleus shape and size), and the mitotic rate (cell division speed).
A Grade 2 classification is an intermediate score, resulting from a total sum of six or seven points. This score indicates that the cancer cells are moderately differentiated, looking somewhat different from normal cells. Grade 2 cells have an intermediate rate of growth and potential for spread compared to Grade 1 and Grade 3 cancers. For ILC, the mitotic rate and tubule formation scores are often low, meaning the nuclear pleomorphism score heavily determines the overall Grade 2 classification.
Distinctive Growth Patterns and Diagnostic Challenges
The structural appearance of ILC is fundamentally different from IDC, creating unique challenges in diagnosis and surgical management. ILC cells classically grow in a “single-file” pattern, threading individually or in thin strands through the fatty tissue of the breast. This unique infiltration pattern occurs because the cancer cells have lost the ability to stick together.
This loss of cell cohesion is linked to the functional inactivation of the E-cadherin protein, a molecule responsible for cell-to-cell adhesion. This loss is a molecular hallmark of ILC, often resulting from a mutation in the CDH1 gene. Since the cells do not clump together to form a solid mass, ILC often presents clinically as a subtle area of diffuse thickening or fullness rather than a firm, distinct lump.
This diffuse growth pattern creates significant diagnostic challenges using standard imaging techniques. Mammography and ultrasound may struggle to clearly delineate the full extent of the tumor, often leading to an underestimation of its size before surgery. Supplemental imaging, such as a breast Magnetic Resonance Imaging (MRI), is frequently necessary to better visualize the scattered, infiltrative nature of the disease.
Treatment Approaches for Grade 2 ILC
Treatment for Grade 2 ILC leverages its unique biological profile, particularly its strong dependence on hormones for growth. Surgical removal of the tumor remains the primary local treatment, involving either a lumpectomy or a mastectomy. Due to the diffuse nature of ILC, achieving clear surgical margins (a border of healthy tissue free of cancer cells) can be more difficult than with a typical ductal carcinoma.
Systemic treatment relies heavily on endocrine therapy because most ILC tumors are Estrogen Receptor-positive (ER+) and Progesterone Receptor-positive (PR+). Endocrine agents like Tamoxifen (for premenopausal women) or Aromatase Inhibitors (for postmenopausal women) work by blocking the effects of estrogen or reducing its production. This approach is the primary therapy for minimizing recurrence risk.
Radiation therapy is typically administered after a lumpectomy to reduce the chance of the cancer returning in the remaining breast tissue. The role of chemotherapy is less pronounced in ILC, which is generally less responsive to these drugs than other breast cancer types. Chemotherapy is usually reserved for patients whose cancer exhibits higher risk features, such as extensive lymph node involvement or a high recurrence score on genetic profiling tests.
Prognosis and Long-Term Surveillance
A Grade 2 ILC classification places the tumor into an intermediate-risk category, suggesting a generally favorable outlook in the short term. While initial five-year disease-free survival rates for ILC are often comparable to IDC, ILC is known for a longer latency period before recurrence.
The risk of the cancer returning can persist well beyond the five-year mark, sometimes occurring 10 or more years after diagnosis. This requires extended systemic treatment and careful long-term monitoring. Endocrine therapy is commonly prescribed for five to ten years to manage this prolonged risk.
Long-term surveillance includes regular clinical examinations and annual imaging. A crucial aspect of ILC surveillance is monitoring for metastases in unusual locations, as ILC tends to spread to sites less common for other breast cancers. These atypical locations include:
- The gastrointestinal tract.
- The ovaries.
- The uterus.
- The serosal surfaces lining body cavities.