Sgroi Lab

About the Lab

The overarching goals of research in the Sgroi laboratory are to detect molecular alterations in breast cancer that identify breast cancer patients who are at risk of developing a recurrence and those who will benefit from specific therapies to prevent disease recurrence. We have developed a clinical test in which the measurement of two genes, HOXB13 and IL17RB predicts whether a patient with estrogen receptor (ER) positive breast cancer will benefit from extending hormonal targeted therapy. Using mouse models of ER-positive and ER-negative breast cancer, we are currently studying the biological role of HOXB13 in human breast cancer, and we are using this knowledge to develop novel therapeutic strategies for not only ER-positive but also ER-negative breast cancer.

My laboratory focuses on integrating multiomic approaches to identify biomarkers that will predict clinical outcome and treatment response. Our lab has developed and the Breast Cancer Index (BCI) gene expression biomarker, and we have validated it prognostic and treatment-predictive performance in multiple randomized clinical trial of extended adjuvant hormonal therapy in post-menopausal women with ER+ breast cancer. Our successful validation of the BCI biomarker has led to clinical adoption in the NCCN and ASCO treatment guidelines. Presently, BCI is being assessed in premenopausal women with ER+ breast cancer who are treated with ovarian suppression. A significant research aim of my lab is now to understand the mechanistic contribution of the gene HOXB13, the primary determinant of the prognostic and predictive performance of the BCI assay. Using HOXB13-expressing mouse models of ER-positive, we have shown that HOXB13 creates a tumor growth advantage by modulating the tumor microenvironment.

Furthermore, we have shown that HOXB13 creates an identical alteration of the tumor microenvironment in a mouse model of triple negative breast cancer. Several tumor microenvironment alterations are amendable to therapeutic targeting, and we are developing combinatorial strategies to counter the tumor promoting effect of HOXB13. To validate our mouse model f indings in human breast cancer, we use multiplex immunofluorescence imaging to correlate HOXB13 expression with various protein targets across a large, wellannotated cohort of triple negative breast cancer patients. Lastly, we have recently shown that HOXB13 is frequently co-gained or co-amplified with ERBB2, and that a subset of patients with HOXB13/ERBB2 coamplification are associated with interstitial deletion of BRCA1. Tumors with HOXB13/ ERBB2 co-amplification are unique to breast cancer patients, and such patients display worse clinical outcomes than those with ERBB2-only amplification. We are currently validating this finding in additional patient cohorts, and exploring therapeutic strategies to treat such tumors.

Group Members

Meet our research team:

• Dennis Sgroi, MD
• Marinko Sremac, PhD

Selected Publications

PubMed Biblioography

Mamounas E, Bandos H, Rastogi P, Zhang Y, Treuner K, Lucas P, Geyer C, Fehrenbacher L, Chia S, Brufsky A, Walshe J, Soori G, Dakhil S, Paik S, Swain S, Sgroi D, Schnabel C, Wolmark N. Breast Cancer Index and Prediction of Benefit from Extended Aromatase Inhibitor Therapy in Hormone Receptor-positive Breast Cancer: NRG Oncology/NSABP B-42. Clin Cancer Res. 2024 Feb 20.

Sgroi DC, Treuner K, Zhang, Y, Piper T, Salunga R, Ahmed I, Doos L, Thornber S, Taylor KJ, Brachtel E, Pirrie S, Schnabel CA, Rea D, Bartlett JMS. Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study. Breast Cancer Res. 2022 Dec 16;24(1):90.

Bartlett JMS, Sgroi DC*, Treuner K, Zhang Y, Piper T, Salunga RC, Ahmed I, Doos L, Thornber S, Taylor KJ, Brachtel EF, Pirrie SJ, Schnabel CA, Rea D. Breast Cancer Index is a predictive biomarker of treatment benefit and outcome from extended tamoxifen therapy: final analysis of the TransaTTom study. Clin Cancer Res. 2022; 28:1871-80.

Nunes R, Sella T, Treuner K, Atkinson J, Wong J, Zhang Y, Exman P, Dabbs D, Richardson A, Schnabel C, Sgroi D, Oesterreich S, Cimino-Mathews A, Metzger Filho O. Prognostic utility of Breast Cancer Index to stratify distant recurrence risk in invasive lobular carcinoma. Clin Cancer Res. 2021 Oct 15;27(20):5688-5696.

Li K, Li T, Feng Z, Huang M, Wei L, Yan Z, Long M, Hu Q, Wang J, Liu S, Sgroi DC, Demehri S. CD8+ T cell immunity blocks the metastasis of carcinogen-exposed breast cancer. Sci Adv. 2021 Jun 18;7(25): eabd 8936.

Bartlett JMS, Sgroi DC*, Treuner K, Zhang Y, Ahmed I, Piper T, Salunga R, Brachtel EF, Pirrie SJ, Schnabel CA, Rea DW. Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial. Ann Oncol. 2019 Nov 1;30(11):1776-1783.

*Denotes co-first author