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Liquid biopsy predicts response to breast cancer immunotherapy

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Justin Balko, PharmD, PhD
Justin Balko, PhD, PharmD

Immunotherapy has become a standard of care in treating high-risk, early-stage breast cancers, yet it has had limited success in shrinking tumors. New biomarkers that can improve outcomes for patients are urgently needed.

Now, a study led by researchers at the Vanderbilt-Ingram Cancer Center has found that repeated blood sampling — essentially, a liquid biopsy — can assess and predict the evolving antitumor immune response to therapy.

This minimally invasive and cost-effective alternative to tissue biopsy offers “an accessible tool for tailoring treatment strategies in breast cancer,” they reported April 22 in the journal Science Translational Medicine.

The researchers performed RNA sequencing on 546 peripheral blood samples from 160 patients with high-risk, stages 2 or 3 breast cancers negative for human epidermal growth factor receptor 2 (HER2) during treatment with either chemotherapy alone or in combination with immunotherapy.

Justin Balko, PhD, PharmD, professor of Medicine and Pathology, Microbiology and Immunology at Vanderbilt Health and the paper’s corresponding author, acknowledged several co-authors — investigators from the nationwide I-SPY2 clinical trial — who, among other contributions to the study, provided the blood samples.

Co-author Laura Esserman, MD, MBA, director of the Breast Care Center at the University of California, San Francisco, is principal investigator of the I-SPY2 trial, which is assessing novel treatment strategies for subsets of breast cancer based on their molecular characteristics (biomarker signatures). Vanderbilt Health is among 42 trial locations.

Cell-free DNA testing, another form of liquid biopsy, is routinely used clinically for detection, diagnosis and therapeutic monitoring of a variety of malignancies.

Balko and his colleagues sampled the transcriptome, the transcription of genes involved in the clonal expansion and activation of antitumor immune cells called T cells. They found it predicted response to the immunotherapy drug pembrolizumab.

While validation is needed, this new liquid biopsy has the potential to “guide immunotherapy decision-making, tailor treatment regimens, and advance precision oncology, not only in (breast cancer) but potentially in other solid tumors as well,” the researchers concluded.

The paper’s first author, Xiaopeng Sun, PhD, is now at Merck. Co-authors at Vanderbilt Health are Andres Ocampo, Jacey Marshall and Julia Steele, graduate students in the Vanderbilt Program in Cancer Biology, and Susan Opalenik, PhD, senior research supervisor in the Balko lab.

The study was supported in part by National Institutes of Health grants P50CA098131, PO1CA210961, R01CA255442, U54CA274502, P30CA082103, P30CA068485 and NIH/NCI Imaging grant 28XS197 P-0518835), a Department of Defense Era of Hope Award, the Breast Cancer Research Foundation, Breast Cancer Research — Atwater Trust, Stand Up To Cancer, the California Breast Cancer Research Program and Give Breast Cancer the Boot.

The post Liquid biopsy predicts response to breast cancer immunotherapy appeared first on Vanderbilt Health News.

Genomic testing finds a higher prevalence of high-risk breast cancer in Black women

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Sonya Reid, MD, MPH

Black women in the United States are less likely than white women to be diagnosed with breast cancer, yet they are more likely to die from the disease.

In a study of more than 1,000 women, researchers at Vanderbilt Health and Agendia, which specializes in genomic testing, found that Black women were more likely to have early, high-risk breast cancer that is hormone receptor positive (HR+) and negative for the human epidermal growth factor receptor 2 (HER2-).

These findings, reported March 19 in the Nature partner journal npj Breast Cancer, highlight the critical need for tumor genomic testing for all patients to identify those with high-risk tumors, which occur more frequently in Black women, and which require more aggressive treatment to prevent recurrence.

“By moving beyond traditional clinicopathologic features and incorporating genomic classification, we can more accurately identify biologically aggressive disease and tailor more precise, personalized treatment,” said the paper’s corresponding author, Sonya Reid, MD, MPH, associate professor of Medicine at Vanderbilt Health.

“The risk of recurrence of breast cancer in Black women has often been underestimated by traditional clinical features, driven largely by their underrepresentation in clinical trials,” study co-author William Audeh, MD, Agendia’s Chief Medical Officer, said in a news release.

“By providing a genomic assessment of tumor biology, we can ensure that women with breast cancer will receive individualized care that improves their long-term outcomes,” Audeh said. The collaboration with Vanderbilt Health “underscores our shared commitment to bringing precision medicine to all women.”

The research included 1,018 women with HR+, HER2- early-stage breast cancer who were enrolled in the Breast Cancer Etiology, Survival and Treatment Outcomes (BEST) study, and the Full-genome Data Linked with Clinical Data to Evaluate New Gene Expression Profiles (FLEX) study.

The BEST study is a population-based observational cohort of women identified through state cancer registries in Florida and Tennessee who were diagnosed with breast cancer between 2005 and 2015. FLEX is a multicenter, prospective observational study of genomic profiling and its impact on prognosis, treatment decisions and clinical outcomes.

The researchers applied two RNA-based technologies developed by Agendia to evaluate tumors: “MammaPrint,” which analyzes the 70 most important genes associated with breast cancer recurrence, and “BluePrint,” which classifies tumors into subtypes based on an expression profile of 80 different genes.

They found that Black women had a higher proportion of genomically high-risk luminal B and basal-type tumors compared to white women and that survival at three years was determined by the molecular subtype of their tumors.

“Understanding the biological and tumor genomic differences by race could improve treatment decisions and promote optimal care for Black females with early-stage breast cancer,” the researchers concluded, “ultimately improving long-term outcomes.”

Co-authors from Vanderbilt Health were Lindsay Venton, Jennifer Whisenant, PhD, Anne Weidner, MPH, and Tuya Pal, MD.

The post Genomic testing finds a higher prevalence of high-risk breast cancer in Black women appeared first on Vanderbilt Health News.

Join Nicole Kidman in supporting breast cancer research and care

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Actress Nicole Kidman knows the impact when someone you love has cancer. For her, it was her mother, when Kidman was only in her teens.

Kidman’s mother lived another 40 years, for which she is grateful. The experience caring for her mother — and being able to have her mother for decades more — drives Kidman’s commitment to advancing breast cancer research.

Kidman recently donated her time, voice and influence to support breast cancer research at Vanderbilt-Ingram Cancer Center. She recorded a video alongside her friend Vandana Abramson, MD, co-leader of Vanderbilt Ingram’s Breast Cancer Research Program, sharing her story for Breast Cancer Awareness Month and beyond. The video has been posted on VICC Facebook and Instagram channels, and Kidman amplified it with her 25 million fans on Instagram and Facebook.

“We’re so grateful for the support of Nicole Kidman in raising awareness for breast cancer research at Vanderbilt-Ingram Cancer Center,” Abramson said. “Nicole witnessed her mother’s journey as a breast cancer patient, and this has inspired her to help others find healing and strength. You can stand with Nicole — and stand with us — in the fight against breast cancer. Your gift fuels research that leads to breakthroughs. It helps us personalize treatments, reduce side effects and offer hope where there was once uncertainty. It brings us closer to a world where breast cancer is no longer a life-altering diagnosis.”

We hope you’ll watch the video and share it with your family and friends on your own social media, email or other channels. To see the video, learn more and help make an impact, visit GiveToVICC.org.

In addition to this video, Kidman has also donated her time and support to be “the voice” for Vanderbilt Health’s upcoming brand advertising campaign, which will launch later this fall.

The post Join Nicole Kidman in supporting breast cancer research and care appeared first on VUMC News.

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