Could tumor sequencing guide therapy for early breast cancer patients?

Researchers from the Mayo Clinic (MN, USA) have highlighted the feasibility of utilizing tumor sequencing for women with newly-diagnosed breast cancer. The results of the prospective study were published recently in the Journal of the National Cancer Institute.

Previous research has demonstrated that breast cancer patients with residual disease after neoadjuvant chemotherapy have increased recurrence risk.  Tumor sequencing has become an increasingly popular method of selecting treatment for cancer patients; however, its usefulness in women with newly-diagnosed breast cancer is unknown.

Chair of the Breast Cancer Genome-Guided Therapy (BEAUTY) study Matthew Goetz from the Mayo Clinic commented: “There is great interest to use tumor sequencing data to guide therapy. However, there are limited data as to whether this approach is useful in women with newly-diagnosed breast cancer who are recommended chemotherapy prior to breast surgery.”

In this study, the researchers aimed to investigate whether tumor genomic alterations could differentiate patients with chemotherapy sensitive and chemotherapy resistant disease. To achieve this, they conducted a prospective study of 140 breast cancer patients treated with neoadjuvant chemotherapy and performed tumor and germline sequencing.

Overall, the team demonstrated that the most common and recurrent genomic alterations were equally as likely to be observed in patients that responded to chemotherapy as those that did not respond.

Although, targetable alterations were not enriched in chemotherapy-resistant tumors, the researchers hope that prioritization of drug testing based on sequence data may accelerate drug development.

The researchers also discovered many uncommon genomic alterations. Larger studies are planned to determine whether these unique alterations could identify groups of women more or less likely to respond to chemotherapy.

In order to validate their findings, the researchers generated patient-derived xenografts. By doing this, the team also demonstrated that the development of patient derived xenografts (mouse avatars) using needle biopsies from the primary breast tumor prior to surgery is feasible, and that the avatars that were developed in both patients that did and did not respond to chemotherapythey are a powerful tool for studying novel therapeutic strategies.

“The simultaneous generation of avatars and tumor sequence data from patients that did not respond to chemotherapy has allowed our research team to prioritize the selection of the new agents to study in the laboratory,” Goetz explained.

Co-chair of the BEAUTY study Judy Boughey (Mayo Clinic) commented: “The long-term goal of the BEAUTY study is to enable individualized treatment for each woman with breast cancer by using the genetic information found in blood samples and tumor biopsies to select the most effective therapies. Utilizing the data generated from this study, the Mayo BEAUTY team will launch a successor study bringing forward new drugs to women with chemotherapy resistant tumors.”


Goetz MP, Kalari KR, Suman VJ et al. Tumor sequencing and patient-derived xenografts in the neoadjuvant treatment of breast cancer  J. Nat. Cancer Inst. doi: (2017); Mayo Clinic press release