1. Gallagher, Amy

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The Lobular Breast Cancer Alliance (LBCA) states invasive lobular carcinoma (ILC) is the sixth most diagnosed cancer of women in the U.S. It is the second most common histological subtype of breast cancer, comprising 10-15 percent of all breast cancers, and impacts more women than cancers of the kidney, brain, pancreas, liver, ovaries, or non-Hodgkin lymphoma, according to the American Cancer Society.

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While ILC is not a rare cancer, the LBCA estimates new cases of ILC diagnosed each year at 39,000. In addition, approximately 450,000 patients in the U.S. who are alive today are either currently receiving treatment or completed treatment.


"Despite unique clinical features, most systemic therapy guidelines for ILC are derived from clinical trials that do not focus on invasive lobular breast cancer (ILBC) as the primary objective," said Zeina Nahleh, MD, FACP, Director of the Maroone Cancer Center at Cleveland Clinic Florida, Weston Hospital. "ILBC is a distinct subtype of breast cancer."


Historically, however, all patients with this diagnosis were included among other subtypes in (previous) clinical trials without much differentiation, she noted. Knowing specifically how to treat those patients diagnosed with ILBC with the goal of reaching the optimal overall survival (OS) and limit treatment toxicity prompted this research project.


During the recent 2021 San Antonio Breast Cancer Symposium (SABCS), the LBCA featured multiple posters on ILBC research. One of the poster presentations highlighting Clinical Translational Updates in Invasive Lobular Carcinoma was presented with the question: "Does chemotherapy benefit patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative ILBC?" The presentation was conducted by researchers with Cleveland Clinic Florida and the Cleveland Clinic Foundation, led by Nahleh as the principal investigator with co-investigators at the Cleveland Clinic Weston in Florida and Cleveland Clinic in Ohio.


Four Treatment Cohorts

The primary objective of the research study assessed whether patients with ILC that is HR-positive and HER2-negative derive a significant benefit from chemotherapy above what the anti-hormonal therapy can provide, Nahleh explained. "We included data from 15,271 patients diagnosed with HR+ and HER2- ILBC at Stages I, II, or III."


A patient portal from the National Cancer Database registry was accessed to compare early-stage ILBC treated with various systemic therapy regimens, including those who underwent surgery, using an elaborate statistical method including stratified simple random sampling to select 10 percent of the patients.


Analyzed between 2010 and 2016, the patients were grouped into four treatment cohorts representing surgery only (S), endocrine/hormonal therapy (ET), chemotherapy (CT), and combined chemotherapy followed by endocrine therapy (CET), with 60 percent of patients receiving ET, 26 percent CET, 2 percent CT, and 12 percent surgery only.


"We compared the OS among the groups of patients who received chemotherapy followed by anti-estrogen hormonal therapy and those who received hormonal therapy alone with no chemotherapy or those who received no treatment (chemotherapy nor hormonal therapy) following surgery," Nahleh explained.


She noted that both the 60 percent treated with ET and 25 percent treated with CET showed a 90 percent 5-year OS.


"Very few were treated with surgery or chemotherapy alone, reflecting real-word practices of using hormonal therapy as the mainstay of treatment in ILBC," she added. "In the two groups, we did not observe any difference in the OS between ET and CET cohorts, which together totaled more than 15,000 patients after adjusting for clinico-pathological characteristics."


Avoiding Chemotherapy

Using an elaborate statistical analysis to assess chemotherapy benefits, Nahleh said the researchers analyzed the outcome based on biomarkers and other important clinical criteria.


"The 5-year OS was significantly better for patients who received ET (91%) or CET (90%) as compared to CT (79%) or S only (80%)," she said. "Our research demonstrated that chemotherapy appears to have no significant added benefit to hormonal therapy in patients with ILBC, even in those tumors with a high 21 gene recurrence score."


She explained the high gene recurrence score as a genomic molecular assay used in clinical practice to predict benefit from chemotherapy based on the recurrence score generated from assessing the tumor biology profile in the lab.


"This suggests that the treatment for ILC should be based primarily on hormonal ET and chemotherapy may not add more benefit in terms of improving survival," she said. "The implication of avoiding chemotherapy means less cost, less toxicity, and fewer disruptions at work while at the same time, enjoying a better quality of life.


"In view of its biological differences and being known as less-sensitive to chemotherapy treatment overall, our research further increases the understanding about this unique breast cancer subtype and calls for a more personalized approach to avoid the unnecessary toxicities from chemotherapy," said Nahleh.


"These results call for more research to confirm these findings in large prospective clinical trials with a better selection of patient population to determine whether chemotherapy can be avoided in patients with ILC and which subgroups of patients benefit from the addition of chemotherapy," she concluded.


Amy Gallagher is a contributing writer.