Multicenter Study Sheds Light on Features of Invasive Lobular Carcinoma

By the staff of ASCO Post

Posted: 2022-10-21 13:17:00

Last updated: 10/21/2022 12:52:51 PM

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A multicenter analysis of patients with invasive lobular carcinoma—the second most common histological subtype of invasive breast cancer in the United States—showed that despite its prevalence, invasive lobular carcinoma was discovered later with poorer outcomes than invasive ductal carcinoma and had higher lymph node involvement. The study published by Oesterreich et al Journal of the National Cancer Institute, demonstrated 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] accounts for about 10% to 15% of breast cancer cases, but has historically been neglected by the research community, so we really don’t know that much about it,” said the co-lead author Steffi Austria, PhD, Professor and Associate Chair in the Department of Pharmacology and Chemical Biology at the University of Pittsburgh School of Medicine, and Co-Director of Education at the Women’s Cancer Research Center and Co-Head of the Cancer Biology Program at the University of Pittsburgh Hillman Cancer Medical Center Center. “Awareness of this has increased [invasive lobular carcinoma] and [invasive ductal carcinoma] are different, but this large, multi-center study provides compelling evidence that these are two different diseases that need to be treated differently.”

Study methods and comparative results

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

“These results likely suggest that detection of lobular breast cancer is delayed,” she said Megan Kruse, MD, a medical oncology specialist in the Division of Hematology and Medical Oncology at the Cleveland Clinic. “By the time these tumors are eventually discovered, they are larger and have already moved to the lymph nodes, which suggests that [that] the cancer is spreading. We need to put more effort into improving the early detection of [invasive lobular carcinoma] through the development of new imaging technologies or other methods.”

The main feature of invasive lobular carcinoma is the loss of the protein E-cadherin (encoded by the CDH1 gene) that helps cells hold together. As a result, lobular cancer cells grow in lines and produce tumors that look more like spider webs than the familiar round lumps of invasive ductal carcinoma, explained Dr. Austria. These web-like tendrils make it difficult to detect invasive lobular carcinoma on mammograms until the cancer has grown and often progressed.

Analysis revealed that invasive lobular carcinoma cells were of lower grade than invasive ductal carcinoma cells. However, invasive lobular carcinomas were twice as likely to be diagnosed at stage III or IV. Invasive lobular carcinoma tumors were also larger than their ductal counterparts.

The researchers restricted the next part of their analysis to patients with tumors that carry estrogen receptors and lack the HER2 receptor. They found that patients with invasive lobular carcinoma had poorer 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 come back, and they come back later for patients with.” [invasive lobular carcinoma]”explained Dr. Austria. “This suggests that tumor cells hibernate somewhere in the body until they wake up again. We need to find out where these cells are and why they wake up again.”

Oncotype DX scores

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

The analysis found that there was a significant association between advanced genomic testing results and cancer recurrence in patients with invasive ductal cancer. Very few cases of invasive lobular carcinoma have been classified as high-risk cases, regardless of later recurrences, underscoring the need for specific molecular tests that improve predictions for invasive lobular carcinoma.

“Despite their differences, these types of cancer are often treated in the same way. We hope these results will stimulate research aimed at developing new diagnostic tools and drugs to improve patient outcomes [invasive lobular carcinoma],” said Nicole Williams, MDmedical oncologist and director of the BreastCARE program at the Cancer and Aging Resiliency Clinic at Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute.

Disclosure: 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 grant awarded by Conquer Cancer, the Sharon MacDonald Breast Health Fund at the Cleveland Clinic, and the Anderson Breast Cancer Fund. For full disclosures by study authors, visit

The content of 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®.

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