Multicenter study highlights deficiencies in invasive lobular carcinoma assessment

Breast Cancer Cell

A multicenter study published Friday in the Journal of the National Cancer Institute on invasive lobular carcinoma (ILC) showed that it is detected later and has worse outcomes than the most prevalent subtype, invasive ductal carcinoma (IDC). ILC is the second most prevalent subtype of invasive breast cancer in the U.S., accounting for 5% to 15% of all breast carcinomas.

The data show that ILC and IDC are biologically distinct, underscoring the need for different diagnostic and treatment options for the two subtypes.

The researchers emphasized that the study results, and the difficulties inherent in detecting ILC on mammograms, demonstrate the need for molecular tests specifically designed for ILC, as well as improvements in imaging technology and methodology that take the distinct features of ILC into account.  

The study analyzed data from more than 33,000 records of patients treated for ILC and IDC from three major cancer centers: UPMC Hillman Cancer Center, Cleveland Clinic Cancer Center, and Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). The records spanned the years between 1990 and 2017.

The study was led by Steffi Oesterreich, coleader of the Cancer Biology Program at UPMC Hillman and professor at the University of Pittsburgh School of Medicine’s Department of Pharmacology & Chemical Biology; Dr. Megan Kruse, breast medical oncology specialist at Cleveland Clinic; and Dr. Nicole Williams, breast medical oncologist at OSUCCC - James.

The analysis found that ILC cells were lower grade than IDC cells, with an appearance more like that of normal cells. ILC tumors were diagnosed twice as often at stages III and IV, in which the cancer cells have spread to the lymph nodes or have metastasized to other parts of the body. ILC tumors were also generally larger than their IDC counterparts.

One factor making ILC more difficult to detect is the manner in which it grows. ILC’s key feature is the loss of a gene called E-cadherin that enables cells to stick together. This causes lobular cancer cells to grow in lines, producing tumors with a weblike formation, with tendrils that look quite different on imaging from the discrete lumps of IDC, Oesterreich said in a statement.

While ILC tumors are larger in form than IDC tumors, they are more difficult to detect on mammograms until the cancer has grown and often advanced in stage.

The researchers focused part of their analysis on patients with early-stage tumors that had estrogen receptors but were lacking the HER2 receptor, using Exact Sciences' genomic test Oncotype DX to predict recurrence risk and chemotherapy response in these patients.

Oncotype DX scored six times more IDC cases than ILC cases as high-risk; however, that assessment of risk for ILC patients was not borne out by outcomes. The researchers found that 57% of patients with estrogen receptor (ER)-positive ILC underwent mastectomies compared with 46% of ER-positive IDC patients, a statistically significant difference. The analysis also showed that patients with ILC had lower rates of both disease-free and overall survival. Additionally, ILC patients had higher risk of disease recurrence than those with IDC, with these recurrences tending to occur later.

“In other words, more tumors are coming back, and they’re coming back later for patients with ILC,” Oesterreich said. “This suggests that tumor cells hibernate somewhere in the body until they are reawakened. We need to find where these cells hang out and why they reawaken.”

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