MD Anderson Research Highlights: SABCS 2022 Special Edition

ABSTRACTS GS1-07, GS5-08, PD6-11, HER2-01

The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into basic, translational and clinical cancer research from MD Anderson experts. This special edition features breast cancer presentations at the 2022 San Antonio Breast Cancer Symposium (SABCS) focused on the combination of everolimus and hormone therapy, a new driver for brain metastases in inflammatory breast cancer, improving treatment for men with breast cancer, and a new understanding of the importance of HER2 expression for patients with early-stage triple-negative breast cancers. More information on SABCS content from MD Anderson can be found at MDAnderson.org/SABCS.

Adding everolimus to hormone therapy does not improve breast cancer outcomes (Abstract GS1-07)
Breast cancers commonly have abnormalities in the PI3K/AKT/mTOR signaling pathway that are associated with resistance to hormone, or endocrine, therapy. Everolimus, an mTOR-inhibitor, increased progression-free survival when combined with endocrine therapy in the metastatic setting and is thought to oppose endocrine therapy resistance.

The Phase III SWOG S1207 trial, led by Mariana Chavez Mac Gregor, M.D., evaluated the role of everolimus in combination with endocrine therapy in the adjuvant setting among patients with high-risk hormone receptor-positive, HER2-negative breast cancer. The combination did not improve invasive disease-free survival (DFS) or overall survival (OS). Patients in the everolimus arm were less likely to complete their assigned experimental treatment and had more adverse events. A total of 1,939 patients were randomized on the trial, and the median follow-up was 50.5 months. The five-year invasive DFS rate was 74.8% with everolimus and 73.9% with placebo, and the OS rate was 87.6% in the everolimus arm and 85.5% in the placebo arm. Premenopausal patients saw a benefit in invasive DFS and OS, but additional translational studies are needed to evaluate predictors of everolimus benefits and toxicity. Chavez MacGregor will present the results Dec. 6.

Study identifies biomarker and driver for brain metastases in inflammatory breast cancer (Abstract GS5-08)
Patients with inflammatory breast cancer (IBC) are more likely to develop brain metastases, which leads to poor survival rates. There is a critical unmet need to understand this increased risk in order to improve patient outcomes. Researchers led by Xiaoding Hu, M.D., Ph.D., and  Bisrat Debeb, D.V.M, Ph.D., sought to uncover the possible role of soluble E-cadherin (sEcad) in the development and progression of brain metastases.

By analyzing serum levels of sEcad in 348 IBC patients, researchers found higher levels correlated with lower overall survival (OS) as well as earlier and increased development of brain metastases. Additionally, overexpressing sEcad in laboratory models promoted primary tumor growth and shortened OS, with a significant increase in the incidence of brain metastases, metastatic burden and number of metastases. Further analysis showed that sEcad increases cancer cell adhesion to brain cells, promotes the induction of harmful reactive astrocytes, binds with and activates a known inhibitor of cell death, and activates the NF-kB inflammatory signaling pathway. These results highlight the role of sEcad in promoting brain metastasis in IBC, providing a possible prognostic indicator and potential therapeutic targets. Hu will present the results Dec. 9.

SET2,3 gene expression index shows prognostic value in early male breast cancer (Abstract PD6-11)
Few studies have compared characteristics between breast cancers in men and women. To evaluate whether hormone receptor-related gene expression differs between genders, researchers led by Danielle Zakon, M.D., and Fraser Symmans, M.D., evaluated 321 tumor RNA samples from men with early-stage HR-positive, HER2-negative breast cancer included in the retrospective cohort study of the EORTC 10085/BCG/TBCRC/BIG/NCTN International Male Breast Cancer Program.

Using the sensitivity to endocrine therapy (SET2,3) index, developed by Symmans, they found gene expression measurements in male patients with breast cancer did not differ from those of female patients. SET2,3 was prognostic for overall survival in male breast cancer and suggested that chemotherapy may improve the poor prognosis for men with breast cancer and a low SET2,3 index score. The poster will be presented Dec. 7.

HER2-low and HER2-zero triple-negative breast cancer show distinct biological differences (Abstract HER2-01)
Low HER2 expression is associated with clinical benefit for metastatic breast cancer patients that receive trastuzumab deruxtecan, a HER2-targeting antibody drug conjugate, but its prognostic value for earlier-stage cancers is unknown. Researchers led by Clinton Yam, M.D., and Debu Tripathy, M.D., evaluated the significance of low HER2 expression in 367 patients with early-stage triple-negative breast cancer receiving neoadjuvant therapy.

They found that low HER2 expression was associated with increased expression of the androgen receptor and genes associated with both fatty acid and steroid hormone metabolism. Further analysis showed different potential causes of resistance to neoadjuvant chemotherapy between HER2-low and HER2-zero tumors, which may influence personalized treatment for patients with early-stage triple-negative breast cancer. The poster will be presented Dec. 7.