Breast cancer recurrent

Australian scientists have pinpointed likely 'cells of origin', the source cells that can grow into breast cancer, in women carrying a faulty BRCA2 gene who are at high risk of developing the disease. The study also showed these cells have potential to be targeted with an existing cancer drug to delay tumour growth, in findings that may lead to future preventive treatments for the disease. Australian scientists have pinpointed likely 'cells-of-origin', the source cells that can grow into breast cancer, in women carrying a faulty BRCA2 gene who are at high risk of developing the disease. The WEHI-led study also showed these cells have potential to be targeted with an existing cancer drug to delay tumour growth, in findings that may lead to future preventive treatments for the disease. Abnormal cells Women who inherit and carry a faulty BRCA2 gene have a substantially increased risk of developing breast cancer -- approximately 70% of carriers will develop the disease over their lifetime. These cancers often occur at a young age and can be clinically aggressive. Early screening is encouraged and some women undertake preventive breast surgery (mastectomy) to reduce their breast cancer risk. In a milestone finding published in Nature Cell Biology, researchers have discovered the likely 'cells-of-origin' of cancer in BRCA2 carriers. By comparing cancer-free tissue samples from both carriers and non-carriers, they identified an aberrant population of cells that divide more quickly. Study joint first author Dr Rachel Joyce said this perturbed cell population was found in the majority of tissue samples from women with a faulty BRCA2 gene. "Given they were found in most of the BRCA2 tissue samples from healthy females, we believe these may be the cells-of-origin that lead to future breast cancers in women that carry the BRCA2 mutation," Dr Joyce said. Treatment targets The aberrant cells in BRCA2 tissue, a subset of breast ductal cells called luminal progenitor cells, stood out to the scientific team because they displayed altered protein production, which is critical for the correct growth and functioning of tissues in our bodies. "These changes may also make the cells more vulnerable to certain therapies aimed at preventing or delaying breast cancer development," said study joint first author Dr Rosa Pascual. Lead author Professor Jane Visvader said the team developed a pre-clinical BRCA2 model that showed similar alterations in the ductal cells, and targeted them with the existing cancer drug everolimus, which is approved to treat patients with relapsed breast cancer. "Through pinpointing this vulnerability in protein production, we were able to show that pre-treatment with this drug delayed the formation of tumours in the pre-clinical model," said Prof Visvader, joint head of the ACRF Cancer Biology and Stem Cells Division and the Breast Cancer Laboratory at WEHI. "This raises the possibility that targeting specific aspects of protein production in this way could represent a new breast cancer prevention strategy for women with a faulty BRCA2 gene." Towards prevention The findings are an important first step towards the goal of preventative treatments for breast cancer in BRCA2-mutation carriers. Study author and cancer clinician, Professor Geoff Lindeman said that while the findings were exciting, more work was needed before they could be applied in the clinic. "While everolimus did delay tumour development in the lab, this drug can have side-effects, which might limit its capacity to be used as a preventative treatment," said Prof Lindeman, joint head of the ACRF Cancer Biology and Stem Cells Division at WEHI, and a medical oncologist at the Royal Melbourne Hospital and Peter MacCallum Cancer Centre. "Our team want to further explore which specific parts of protein processing are dysregulated, and use this information to develop more selective and tolerable preventative treatments. "There's still a way to go, but we're a big step closer. "A few years ago, we identified the likely cells-of-origin for breast cancer in females carrying a fault in the BRCA1 gene, which is also associated with a high risk of developing breast cancer. That research has since led to an international breast cancer prevention study (BRCA-P). "We hope that our new findings will now inform future treatment and prevention for women with a faulty BRCA2 gene." The study, 'Identification of aberrant luminal progenitors and mTORC1 as a potential breast cancer prevention target in BRCA2 mutation carriers', is published in Nature Cell Biology (DOI: 10.1038/s41556-023-01315-5). The research was carried out on breast tissue samples kindly donated by women undergoing breast surgery, with assistance from the Victorian Cancer Biobank (funded by the Victorian Government) and the Kathleen Cuningham Foundation Consortium for research into Familial Breast cancer. The research was supported by the National Health and Medical Research Council, Breast Cancer Research Foundation, the National Breast Cancer Foundation, The Medical Research Future Fund, the Two Sisters Foundation and the Heine Family.

40-site U.S. trial enrolling more than 300 patients could significantly change the way DCIS is treated and reduce possibly unnecessary surgery SAN FRANCISCO, Oct. 30, 2023 /PRNewswire/ -- Quantum Leap Healthcare Collaborative (QLHC) announces the enrollment launch for the Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: Ductal Carcinoma In Situ (RECAST DCIS), a Phase 2 platform study aimed at preventing the progression of DCIS to breast cancer. The study is evaluating three investigational endocrine therapy arms: (Z)-endoxifen, a selective estrogen receptor modulator (SERM) in development by Atossa Therapeutics (Nasdaq: ATOS); HAVAH T+Ai™, a proprietary combination of testosterone (T) and anastrozole (Ai) that targets the androgen and estrogen receptor pathways in development by Havah Therapeutics; and ORSERDU® (elacestrant), the only FDA approved oral selective estrogen receptor degrader (oSERD) in development by Stemline Therapeutics Inc. (Stemline), a wholly-owned subsidiary of the Menarini Group. "DCIS indicates the very earliest, noninvasive stage of the disease, that's why it is important for us to seek out alternative therapies for DCIS patients and find ways to reduce toxicity and unnecessary surgeries. We are excited to partner with three innovative companies to explore new treatments for this large and often over-treated patient population," said Laura Esserman, MD, a lead investigator for the study and founder of QLHC. Surgery is the current standard treatment for DCIS even though many patients never progress to breast cancer, which means that patients are often over-treated with invasive procedures. This new trial, sponsored and operated by QLHC, offers DCIS patients up to six months of endocrine therapy with the intent to forego surgery and instead be monitored via long-term active surveillance, if appropriate. A key element in reducing overtreatment of DCIS is identifying biomarkers that reflect the risk of progression so that those with low-risk lesions are spared surgery. RECAST DCIS features the assessment of imaging and molecular-based biomarkers in addition to evaluating new investigational agents in this setting. The study is open to enrollment with each investigational agent arm expected to enroll up to 110 patients. The three collaborators for this trial, Atossa Therapeutics, Havah Therapeutics, and Stemline, all aim to find alternative solutions for DCIS patients and are providing different agents for assessment. Atossa's (Z)-endoxifen has the potential to mitigate breast cancer risk (by reducing the density of breast tissue); to reduce cancer cell activity before surgery; and to reduce the risk of recurrent or new breast cancer after the initial treatment. According to published studies, (Z)-endoxifen is a competitive inhibitor of ERα and represses ERα transcriptional activity (Z)-endoxifen is 100-fold more potent in anti-estrogen activity compared to other SERMs. (Z)-endoxifen also binds to and disrupts protein kinase C beta one function (PKCb1, a known oncogenic protein). The National Cancer Institute (NCI) and others have studied (Z)-endoxifen and have demonstrated promising results in the treatment of breast cancer as well as for the treatment of other solid tumors. Treatment with (Z)-endoxifen may avoid off target effects of tamoxifen and remaining metabolites potentially increasing adherence by improving the safety profile. Havah Therapeutics' HAVAH T+Ai™ combines T, the natural ligand for the androgen receptior and Ai, an inhibitor of T conversion to estradiol, to modulate the growth of abnormal breast tissues. HAVAH T+Ai™ is a proprietary combination subcutaneously delivered system to overcome hormonal symptoms by balancing hormonal irregularities in the breast, developed from more than 10 years of clinical research into hormonal regulation in women. Havah has extensive clinical experience using HAVAH T+Ai™ to address pre- and postmenopausal prevention of breast disease, and the company generated data from more than 1,000 Australian women with breast disease through an ongoing open label cohort study (more than 6,200 implants), with critical safety pharmacokinetic and early efficacy data already demonstrated. Stemline's Elacestrant (ORSERDU), was approved by the U.S. Food & Drug Administration in January 2023 for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, HER2-negative, ESR-1 mutated advanced or metastatic breast cancer, following at least one line of endocrine therapy. For more information including full prescribing information and important safety information, please visit . About Quantum Leap Healthcare Collaborative Quantum Leap Healthcare Collaborative is a 501c(3) charitable organization established in 2005 as a collaboration between medical researchers at University of California, San Francisco and Silicon Valley entrepreneurs. Our mission is to integrate high-impact research with clinical processes and systems technology, resulting in improved data management and information systems, greater access to clinical trial matching and sponsorship, and greater benefit to providers, patients and researchers. Our goal is to improve and save lives. For more information, visit . About Atossa Atossa Therapeutics is a clinical stage biopharmaceutical company developing innovative medicines in areas of significant unmet medical need in oncology. Atossa's current focus is on breast cancer. More information is available at atossatherapeutics.com. About Havah Therapeutics Havah Therapeutics is a biopharmaceutical company developing innovative, proprietary hormonal therapies that aim to improve quality of life for women. Havah brings together a world-class team passionate about helping women live lives free from the suffering caused by breast pain, debilitating menopausal symptoms and breast cancer. More information is available at . About The Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4.4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit . About Stemline Therapeutics Inc. Stemline Therapeutics, Inc. ("Stemline") a wholly-owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes ORSERDU® (elacestrant) in the United States, an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs), a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States and Europe, which is the only approved treatment for BPDCN in the US and EU to date. Stemline also commercializes NEXPOVIO® in Europe, an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers. SOURCE Quantum Leap Healthcare Collaborative

SEATTLE, WA / ACCESSWIRE / September 18, 2023 / One in eight women will be diagnosed with breast cancer during their lifetime. However, breast cancer does not affect all women in the same way, and individual physiology plays a huge factor. Women with dense breast tissue face a higher risk of developing breast cancer and being diagnosed with later-stage disease. The global breast cancer treatment market was worth $31.9 billion in 2022 and is expected to reach a value of $85.5 billion by 2032, growing at a compound annual growth rate of 10.3% over the ten-year period. 50% of women have dense breast tissue, and as such there is a significant unmet need. Breast cancer remains a widely recognized type of cancer, but it is important to stress that there is still a lot of work ahead in terms of prevention and treatment. In 2022 alone, there were an estimated 287,850 new cases of invasive breast cancer and 51,400 cases of DCIS diagnosed in women across the United States. Tragically, around 43,250 women lost their lives to breast cancer. These figures highlight the urgent need for continued efforts in combating this disease and finding effective solutions. Atossa Therapeutics (NASDAQ:ATOS) is working hard to do just that. ER+ breast cancer is the most common type of breast cancer. It is characterized by the presence of estrogen receptors on cancer cells, which causes the cancer cells to grow in response to estrogen 12. According to the U.S. National Cancer Institute, around 80% of all invasive breast cancers are ER-positive. A new drug, (Z)-endoxifen, has shown promising potential in the treatment of ER+ breast cancer. It belongs to a class of targeted therapies called selective estrogen receptor modulators (SERMs) which help block estrogen and stop the cancer from spreading. What sets (Z)-endoxifen apart from other SERMs is its ability to specifically target a protein called PKCβ1, known to promote cancer growth. This drug has the ability to block all estrogen in a patient, including premenopausal women, without the need for additional medications. What also makes (Z)-endoxifen unique is its ability to potentially work in all three areas of the Breast Cancer Paradigm: the prevention window, neoadjuvant phase and adjuvant phase. The drug can reduce the density of breast tissue to mitigate the risk of developing breast cancer. In addition, it can reduce cancer cell activity before surgery and also the risk of recurrent or new breast cancer post-initial treatment. This is rare, as most existing drugs like AstraZeneca's tamoxifen only target one phase. Researchers at Atossa Therapeutics are working diligently to harness the drug's full potential across all three phases of the paradigm. The standard treatments for breast cancer include surgery, radiation and/or chemotherapy. However, long-term drug therapy is also being researched to reduce the risk of new or recurrent cancer. If successful, (Z)-endoxifen could emerge as a unique and promising treatment option in the fight against breast cancer. The company has obtained Health Canada's approval to commence the EVANGELINE study, a phase 2 clinical trial that focuses on a promising new treatment for pre-menopausal women with breast cancer. What makes this study different is its investigation of the combination therapy involving (Z)-endoxifen versus the conventional regimen of exemestane and goserelin as neoadjuvant treatment. The trial aims to include approximately 175 patients from both Canada and the U.S., all of whom have Grade 1 or 2 Estrogen Receptor positive (ER+) / Human Epidermal Growth Factor Receptor 2 negative (HER2-) breast cancer. Participants will receive the designated treatment for a period of up to six months, followed by surgical intervention. The primary objective of the study is to assess the endocrine-sensitive disease rate, specifically measured by Ki-67, after four weeks of treatment with (Z)-endoxifen in comparison to the combined regimen of exemestane and goserelin. This evaluation serves as a key indicator, showcasing the potential of (Z)-endoxifen as a novel and promising therapeutic approach. Atossa is a well-funded company that seems well-positioned to address the significant unmet need of breast cancer patients with elevated breast density and help with breast cancer treatment throughout the cancer's progression, not just at one stage. With breast cancer being the second leading cause of cancer death in American women, the company's drug pipeline could be key to the advancement of breast cancer treatment. Featured photo by Susan G. Komen 3-Day on Unsplash. Contact: Eric Van Zanten eric.vanzanten@atossainc.com SOURCE: Atossa Therapeutics View source version on accesswire.com: