WEBPATHOLOGY / Science Source
The findings in this case are suggestive of invasive lobular carcinoma (ILC).
Globally, breast cancer remains the most common life-threatening cancer diagnosed and the second leading cause of cancer-related deaths in women. In the United States, approximately 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 deaths were attributed to breast cancer in the same year. Worldwide, approximately 2.3 million new diagnoses and 685,000 breast cancer-related deaths were reported in 2020.
ILC is one of the leading histologic types of invasive carcinoma, second in incidence only to invasive carcinoma of no special type. ILC accounts for 5%-15% of all invasive breast cancers, and its incidence has been steadily increasing — particularly among postmenopausal women — over the past two decades. ILC has distinct molecular and histopathologic features, including the loss of cell-cell adhesion molecule E-cadherin, resulting in small, discohesive cells proliferating in single-file strands; positivity for both the estrogen and progesterone receptor; and human epidermal growth factor receptor 2 negativity.
The diagnosis of ILC can be challenging, as it is difficult to detect both on physical examination and with standard imaging techniques. Patients are often diagnosed with late-stage disease, characterized by large tumors and lymph node involvement. The signs of ILC are often vague, such as skin thickening or dimpling. In addition, measuring the extent of ILC can be challenging, as traditional screening methods (eg, mammography and ultrasonography) have a low sensitivity for detecting ILC compared with other invasive breast tumors. This difficulty is usually ascribed to the diffuse infiltrative growth pattern of ILC. MRI has a greater sensitivity for detecting ILC.
Risk factors for the development of ILC have been identified and include:
• Alcohol consumption
• Use of combined hormone replacement therapy
• Early menarche (menarche before the age of 12 years)
• Late-onset menopause (menopause after the age of 55 years)
• Nulliparity/low parity (defined by World Health Organization as fewer than five pregnancies with gestation periods of ≥ 20 weeks)
• Late age at birth (> 30 years)
• Family history (eg, hereditary diffuse gastric cancer syndrome)
• Genetics (eg, CDH1 mutations)
Treatment protocols for ILC align with those used in other breast cancer subtypes and typically involve a multidisciplinary approach comprising surgery, radiotherapy, and systemic therapies. Cancers that are deemed resectable will typically be managed surgically upfront, although some patients may require neoadjuvant therapy to reduce tumor burden and facilitate surgical intervention. Breast-conserving surgery using a wide local excision can frequently be performed; however, in up to 65% of cases, a second surgery will be required (re-excision or mastectomy). Axillary lymph node status is a crucial factor in the prognosis of all breast cancers and affects surgical planning. Sentinel node biopsy is the standard method of assessing the axilla.
Systemic therapy is an integral part of the multidisciplinary approach to treating breast cancer and usually involves the use of chemotherapy. However, because of the unique molecular biology of ILC, treatment response to chemotherapy is often poor, resulting in lower rates of complete pathologic response and higher rates of mastectomy. Conversely, ILC has been shown to respond well to endocrine therapy, making it the optimal treatment choice. Novel therapeutic approaches are under investigation.
Detailed guidance on the treatment of ILC is available from the National Comprehensive Cancer Network.
Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.
Avan J. Armaghani, MD, has disclosed no relevant financial relationships.
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