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Yale Cancer Center Study Offers Clue to Why Some Young Women Develop Breast Cancer

December 09, 2021

New research led by Yale Cancer Center reveals young women with breast cancer and a family history of the disease, but no high penetrance germline mutations, have an increased number of rare germline variants in cancer-relevant genes. The discovery may help explain why some young women develop breast cancer earlier than others. The findings were reported today at the 2021 San Antonio Breast Cancer Symposium in San Antonio, Texas.

Most cases of breast cancer occur in women aged 50 or older, yet a significant number of younger women are diagnosed with the disease. According to the Centers for Disease Control and Prevention, 11% of new breast cancer cases in the U.S. occur in women aged 44 or younger and an estimated 30% of young patients with breast cancer are found to have a germline gene mutation that could cause cancer.

In this study, researchers included 94 women diagnosed with breast cancer aged 65 and under with no cancer family history identified from the Yale Generations project. Whole-exome sequencing (WES) was performed on peripheral blood from the 94 cases, 149 controls, and 42 matched tumors. WES data was also analyzed from 1,112 female breast cancer cases with a family history of breast cancer and 50,887 healthy women without breast cancer family history from the database UKBiobank. The patients identified from the Yale Generations project had a higher average burden of rare gHFI or cancer-biology-related gene variants in cancer hallmark genes, but did not show a higher germline burden. Similarly, patients identified from the UKBiobank with breast cancer and a family history of the disease had a higher germline variant burden in hallmark genes.

“Our study revealed that these young women have a higher somatic mutation rate of cancer-relevant genes,” said Mariya Rozenblit, MD, Instructor of Medicine (Medical Oncology) at Yale Cancer Center and Smilow Cancer Hospital and lead investigator of the study. “For women who test negative for the BRCA gene and other high penetrance mutations, we believe that a combination of germline mutations in single nucleotide polymorphisms and somatic mutations play a role in breast cancer risk.”

Yale’s Tao Qing is a co-first author of the research. Lajos Pusztai, MD, DPhil, is senior author of the study.

Funding for the study was provided by the Conquer Cancer American Society of Clinical Oncology (ASCO) Young Investigator Award and the Breast Cancer Research Foundation.

Submitted by Anne Doerr on December 08, 2021