October is Breast Cancer Awareness Month, so it’s a good time to take stock of the many developments in breast cancer research during the past year. An emphasis on breast cancer may be especially important right now, as one in three women have delayed their mammograms due to COVID-19, and nearly half are reluctant to visit their doctor, according to a new survey. To that end, here are seven important new developments in breast cancer research. Predicting breast cancer in an embryo In a new study in Nature Scientific Reports, researchers describe how an inexpensive genomic analysis can predict a person’s health risk for a range of diseases, including breast cancer, heart disease, diabetes, and more. “New methods from machine learning and AI, combined with large genomic datasets, allow us to predict disease risk from DNA alone. In some cases, such as breast cancer, the new polygenic predictors can identify ten times as many high-risk individuals as the older single-gene tests,” said senior author Stephen Hsu, PhD, vice president for Research & Innovation at Michigan State University and co-founder of the company Genomic Prediction. “Our findings indicate unprecedented insight into an individual’s disease risk during their lifetime, bringing us a meaningful step closer to personalized and ultimately, predictive, medicine,” Dr. Hsu said. Computing the polygenic risk can correctly predict—with 70% to 90% reliability—which one of two siblings will develop a condition such as breast cancer, diabetes, or coronary artery disease. The technique is even better at comparing relative risk in random pairs of individuals, the researchers noted. Parents pursuing in vitro fertilization will have the ability to screen for potential disease risk factors before an embryo is even selected for transfer, according to a news release from Genomic Prediction. Cancer found between mammograms is more deadly Breast cancer that’s discovered in between mammography screenings is 3.5-times more deadly than breast cancer found during screenings, according to a recent retrospective cohort study published in JAMA Network Open. “[A]lthough indolent cancers with likelihood of better outcomes are detected easily by screening mammography…, many of the aggressive and lethal forms of breast cancers either go unnoticed on mammogram or develop in the interval between mammograms,” the authors wrote. The researchers speculated that these more aggressive and deadly cancers may be less sensitive to mammography screening or overlooked as false negatives. “Strategies beyond current mammographic screening practices are needed to reduce incidence, improve detection, and reduce deaths from these potentially lethal breast cancers,” they concluded. heart attack hastens breast cancer growth Following breast cancer treatment, many patients are vulnerable to other diseases, not the least of which is cardiovascular disease. But in a recent article in Nature Medicine, researchers found that the reverse is also true: Having a heart attack can accelerate breast cancer. Worse, they found that a cardiovascular event also increased the risk of cancer recurrence by 59% and death from cancer by 60%. Experiments in a mouse model indicated that heart attack causes epigenetic changes that reprogram immune-fighting monocytes in bone marrow to become immune-suppressing monocytes that can spur tumor growth. FDA approves therapy for metastatic triple-negative breast cancer In April 2020, the FDA approved Trodelvy (sacituzumab govitecan-hziy) to treat metastatic triple-negative breast cancer in patients who’ve received at least two previous treatments for metastatic disease. Trodelvy is an antibody‒drug conjugate and the first Trop-2–related therapy to be approved by FDA. An antibody‒drug conjugate delivers a cytotoxic payload directly to cancer cells. For sacituzumab govitecan, the antibody component binds specifically to the Trop-2 protein on the surface of cancer cells. The entire antibody‒drug conjugate is drawn into the cancer cell and the cytotoxin is released, killing the cancer cell. “It’s what we call a ‘smart bomb’ idea, where you target the toxin directly to the cancer cell,” said principal investigator Hope S. Rugo, MD, director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco. In a clinical trial, the drug had an overall response rate of 33.3% with a median duration of 7.7 months. Median progression-free survival was 5.5 months and overall survival was 13.0 months. AI increases accuracy in reading mammograms In a recent JAMA Oncology study, an artificial intelligence (AI) algorithm was as accurate as, or better than, an average radiologist at identifying breast cancer on screening mammograms. The AI had a sensitivity of 81.9% compared with a sensitivity of 77.4% for a first-reader radiologist. When a first-reader radiologist was paired with the AI, their ability to detect breast cancer was even greater, with 88.6% sensitivity at 93.0% specificity. Earlier this year, researchers from Google Health and other centers published results in Nature that showed their AI algorithm bested the performance of six radiologists at identifying breast cancer on mammograms, with 5.7% fewer false positives and 9.4% fewer false negatives. “These analyses highlight the potential of this technology to deliver screening results in a sustainable manner despite workforce shortages,” the researchers wrote. New drug approvals for HER2-positive breast cancer Approximately one in five cases of breast cancer is HER2-positive. Fortunately, the FDA approved a spate of drugs in the past year designed to treat HER2-positive breast cancer: Enhertu (fam-trastuzumab deruxtecan-nxki) received accelerated approval in December 2019. It’s for patients with unresectable or metastatic HER2-positive breast cancer who have already received two or more prior HER2 regimens for metastatic disease. Approved in February 2020, Nerlynx (neratinib) is indicated for use in combination with capecitabine for treating advanced or metastatic HER2-positive breast cancer in patients who’ve received two or more previous HER-2 treatments for metastatic disease. Tukysa (tucatinib), approved in April 2020, is used in combination with trastuzumab and capecitabine for patients with advanced unresectable or metastatic HER2-positive breast cancer who’ve received at least one prior HER2 therapy for metastatic disease. This includes patients whose cancer has metastasized to the brain, a complication that occurs in more than 25% of patients with metastatic HER2-positive breast cancer and is known to be very difficult to treat. Approved in June 2020, Phesgo is a combination injection of pertuzumab, trastuzumab, and hyaluronidase-zzxf. It’s intended for use along with chemotherapy for patients with early HER2-positive breast cancer, and for use with docetaxel for patients with HER2-positive breast cancer that has metastasized. Liquid biopsy for breast cancer A simple blood test to detect the presence of cancer—a liquid biopsy—has been the long-sought Holy Grail in cancer research. The past year marked the beginning of the transition when liquid biopsies for breast cancer make the leap from bench to bedside. A liquid biopsy for breast cancer has several advantages over current methods, such as tissue biopsy. Liquid biopsy holds the possibility of detecting a tumor anywhere in the body, while a tissue biopsy only samples from one location. Plus, a blood draw can be done in almost any clinic and without the need for an invasive procedure. A liquid biopsy can also be done repeatedly, not only for early cancer detection but for continuous monitoring of cancer status following treatment. But until now, the stumbling block has been that it’s extremely difficult to detect the presence of a few scant cancer cell biomarkers or particles of circulating tumor DNA (ctDNA) in the blood—it’s like searching for a needle in a haystack the size of Texas. To that end, different researchers have reported promising results with technology that ramps up the detection of tumor DNA. For instance, researchers from the Translational Genomics Research Institute and the Mayo Clinic in Arizona reported that their test called TARDIS (TARgeted DIgital Sequencing) detected ctDNA in as few as two parts per 100,000 in blood. Moreover, researchers at Memorial Sloan Kettering recently used a liquid biopsy in women with estrogen receptor-positive metastatic breast cancer to identify mutations in two genes that promote resistance to estrogen-blocking medications. This finding shows that liquid biopsies can be used to alter treatment right as the cancer evolves. Source
