Multicenter Study Sheds Light on Features of Invasive Lobular Carcinoma

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A multicenter analysis of patients with invasive lobular carcinoma—the second most common histologic subtype of invasive breast cancer in the United States—showed that, despite its prevalence, invasive lobular carcinoma was detected later with worse outcomes vs invasive ductal carcinoma and had higher lymph node involvement. The study, published by Oesterreich et al in the Journal of the National Cancer Institute, showed that invasive lobular carcinoma and invasive ductal carcinoma are biologically distinct, highlighting important differences between the two diseases and the need for specific detection and treatment options for the lobular subtype.

“[Invasive lobular carcinoma] makes up about 10% to 15% of breast cancer cases, but it has historically been neglected by the research community, so we really don’t know that much about it,” said co-lead author Steffi Oesterreich, PhD, a Professor and Vice Chair in the Department of Pharmacology and Chemical Biology at the University of Pittsburgh School of Medicine, and the Co-Director of Education at the Women’s Cancer Research Center and Co-Leader of the Cancer Biology Program at the University of Pittsburgh Medical Center Hillman Cancer Center. “There has been increasing awareness that [invasive lobular carcinoma] and [invasive ductal carcinoma] are distinct, but this large multicenter study provides compelling evidence that these are two different diseases that require different management.”

Study Methods and Comparison Results

Dr. Oesterreich and colleagues analyzed the records of 33,000 patients treated at three cancer centers for invasive lobular carcinoma or invasive ductal carcinoma between 1990 and 2017.

“These findings likely indicate that detection of lobular breast cancer is delayed,” said Megan Kruse, MD, a medical oncology specialist in the Department of Hematology and Medical Oncology at the Cleveland Clinic. “When these tumors are finally detected, they’re larger and they’ve already moved to the lymph nodes, indicating [that] the cancer is spreading. We need to put more effort into improving early detection of [invasive lobular carcinoma] by developing new imaging technologies or other methodologies.”

Invasive lobular carcinoma’s key feature is the loss of the protein E-cadherin (encoded by the CDH1 gene), which helps cells stick together. As a result, lobular cancer cells grow in lines, producing tumors that look more like spider webs than the familiar round lumps of invasive ductal carcinoma, explained Dr. Oesterreich. These weblike tendrils make invasive lobular carcinoma difficult to spot on mammograms until the cancer has grown and often advanced.

The analysis found that invasive lobular carcinoma cells were lower grade than invasive ductal carcinoma cells. However, invasive lobular carcinoma tumors were diagnosed twice as often at stages III or IV. Invasive lobular carcinoma tumors were also larger in size than their ductal counterparts.

The researchers restricted the next part of their analysis to patients with tumors bearing estrogen receptors and lacking the HER2 receptor. They found that patients with invasive lobular carcinoma had worse disease-free survival and overall survival. Patients with invasive lobular carcinoma were also more likely to experience disease recurrence than those with invasive ductal carcinoma, and recurrences tended to occur later.

“In other words, more tumors are coming back, and they’re coming back later for patients with [invasive lobular carcinoma],” explained Dr. Oesterreich. “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.”

Oncotype DX Scores

A commercially available advanced genomic test (Oncotype DX) was used to predict the risk of recurrence and response to chemotherapy for patients with early-stage, estrogen receptor–positive, HER2-negative breast cancer.

The analysis found that there was a significant association between the advanced genomic test scores and cancer recurrences for patients with invasive ductal carcinoma.  Very few invasive lobular carcinoma cases were classified as high-risk, regardless of more late recurrences, highlighting the need for specific molecular tests that improve predictions for invasive lobular carcinoma.

“Despite their differences, these cancers are often treated the same.  We hope these findings will spark research aimed at developing new diagnostic tools and drugs to improve outcomes for patients with [invasive lobular carcinoma],” said Nicole Williams, MD, a medical oncologist and the Director of the BreastCARE Program in the Cancer and Aging Resiliency Clinic at the Ohio State University Comprehensive Cancer Center–James Cancer Hospital and Solove Research Institute.

Disclosure: The research in this study was supported by the Breast Cancer Research Foundation, the National Cancer Institute of the National Institutes of Health, Susan G. Komen, the Henry L. Hillman Foundation, the Hillman Fellows for Innovative Cancer Research Program, the 2019 Gianni Bonadonna Breast Cancer Research Fellowship awarded by Conquer Cancer, the Sharon MacDonald Breast Health Fund at the Cleveland Clinic, and the Anderson Breast Cancer Fund. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.