Invasive Lobular Breast Carcinoma

The Institute of Cancer Research, London, strongly welcomes the decision by NICE to recommend the targeted breast cancer drug, capivasertib, in combination with fulvestrant, for treating the most common type of advanced breast cancer with specific biomarker alterations (PIK3CA, AKT1 or PTEN). The judgement makes this new drug combination available for 1,100 patients a year on the NHS in England and Wales with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer, which has advanced or spread following treatment. The new drug is suitable for patients' tumours with mutations or alterations in the PIK3CA, AKT1 or PTEN genes – found in approximately half of patients with this form of breast cancer. The treatment could eventually benefit around 3,000 patients a year. The treatment could eventually benefit around 3,000 patients a year. The recommendation follows the approval of capivasertib by the Medicines & Healthcare products Regulatory Agency (MHRA) in July 2024. Capivasertib (trade name Truqap ▼) is a first-in-class drug that works by blocking the activity of the cancer driving protein molecule AKT. Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Pharmaceuticals (and its collaboration with The Institute of Cancer Research (ICR) and Cancer Research Technology Limited). Working in the Breast Cancer Now Toby Robins Research Centre, Professor Nicholas Turner of the ICR and The Royal Marsden NHS Foundation Trust headed the international phase III CAPItello-291 trial, which led to its approval. The trial was sponsored and funded by AstraZeneca. Results from the CAPItello-291 trial showed that capivasertib doubled the time it took for cancer to progress in people with advanced HR positive, HER-2 negative breast cancer with tumours PI3K, AKT, or PTEN alterations – from 3.1 months for patients who received hormone therapy alone, to 7.3 months for those who received hormone therapy combined with capivasertib. Participants on the trial had experienced their cancer recur or progress despite standard hormone treatments, and the majority had also previously been treated with a CDK4/6 inhibitor – a class of drugs that stop cancer cells from multiplying. In the UK, patients with advanced HR-positive HER-2 negative breast cancer are otherwise offered the option to continue to receive fulvestrant hormone therapy, which is often ineffective when given on its own, or chemotherapy, a treatment which carries debilitating side effects. There is great need for new treatment options. The development of capivasertib followed years of fundamental research at the ICR, aimed at understanding how the AKT protein is regulated. The AKT protein had been identified as an attractive target for anti-cancer drugs, due to its involvement in the growth and survival of cancer cells. In 2002, ICR scientists cracked and published the 3D structure of AKT and showed how the protein is activated. Researchers in the ICR’s Centre for Cancer Drug Discovery, with funding from Cancer Research UK, then worked in collaboration with Astex Pharmaceuticals to design small-molecule inhibitors which would target AKT, based on its 3D structure. In 2005, a series of prototype drug compounds discovered by the ICR and Astex was shown to have very promising activity against a range of human tumours grown in mice and was licensed to AstraZeneca. Then, in 2010, AstraZeneca announced its discovery of capivasertib and began to develop the drug as a potential treatment for various forms of cancer. The initial clinical development of capivasertib was centred on an early-phase trial which was led by the ICR and its partner hospital The Royal Marsden. Subsequently, phase II studies were completed in the UK in collaboration with the UK Cancer Research Network. The trials used biomarkers that were developed at the ICR to show proof of concept that the AKT protein was inhibited by capivasertib. Elen, from Anglesey, worked as an NHS nurse and in social care for 30 years. She was diagnosed with primary invasive lobular breast cancer in 2008. After treatment which gave her eight years cancer-free, the disease has since returned in her bones, stomach and bowel. She has been taking capivasertib since February this year. She said: “My nurses have described it to me as ‘groundbreaking’ and a ‘gamechanger’ – and for me it has been brilliant. I have had no side effects and it is much kinder than previous drugs I have been on. It is the only drug I have ever been able to take at the recommended dose without needing any adjustments. I am doing well on it. It has not affected my energy levels and my cancer markers are down, one of them by 50%. My doctors say it is working and I feel that it is too – I feel so well. It has given me hope. I would like to get at least two good years out of it.” Professor Nicholas Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, who led the CAPItello-291 trial, said: “This positive NICE recommendation means that thousands of NHS patients with advanced breast cancer with these specific biomarkers can now receive this innovative targeted treatment to keep their cancer from progressing for longer. It’s an immensely rewarding moment to see this drug provide patients with a treatment option and precious extra time with their families. “It is now crucial that advanced breast cancer patients have their cancer tested to identify those who could benefit from this capivasertib combination.” Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said: "This announcement is a triumph that will improve treatment for these patients with the most common type of advanced breast cancer. Around half of patients with this kind of breast cancer have mutations in one or more of the genes and for these patients, capivasertib can halt disease progression. I’m delighted that access to the drug is being expanded to NHS patients in England and Wales who are in desperate need of better options. “The approval is also a significant achievement for the ICR, and a great success story for British science. Decades of discovery science work and a major drug discovery project by ICR researchers, along with a crucial partnership with Astex Pharmaceuticals, paved the way to the discovery of capivasertib by AstraZeneca.” Professor Paul Workman, former Chief Executive of The Institute of Cancer Research, London, and former Director of the Centre for Cancer Drug Discovery, and an active researcher in the AKT drug discovery project, said: “I am delighted to celebrate this landmark moment and see capivasertib become available on the NHS. The drug’s discovery and development, following early fundamental research, has been a long scientific journey for myself, and the outstanding teams of scientists at the ICR, Astex and AstraZeneca. It’s immensely gratifying that years of collaboration have contributed to this new cancer drug, which has the potential to improve the lives of so many NHS patients living with advanced breast cancer."

Scientists have developed a machine learning tool that can predict how an aggressive type of breast cancer will respond to treatment, and when it will return. Invasive lobular carcinoma (ILC) – which accounts for 15 per cent of breast cancer cases – is biologically different to other forms of breast cancer, but it lacks unique treatment options. While treatments given for ILC – which is also known as lobular breast cancer – work in the short term, the cancer often returns and spreads. Researchers at The Institute of Cancer Research, London, have developed a machine learning model – a form of artificial intelligence – to predict the clinical outcomes of ILC, based on the underlying genetics of the disease. They hope that the findings, published in British Journal of Cancer, will be used to detect cancers that are likely to return and to ultimately guide treatment options for people with ILC. Looking at genetic information from nearly 1,000 patients with ILC, the team, working in the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR) identified the differences in ILC compared to normal breast tissue. They discovered genes and biological pathways that were predictive of overall survival, cancer spreading, and ones which were associated with response to chemotherapy. The scientists, funded by Breast Cancer Now, developed a machine learning model using these biological pathways. Their model was able to accurately classify patients’ cancers into high-risk and low-risk groups. The 10-year survival for those in the high-risk group was 58.3 per cent, and for those in the low-risk group it was 80.3 per cent. The model was also able to predict the likelihood of metastasis before 10 years. The team then assessed which genes were essential to cancer cell fitness and survival. They were able to identify 16 genes that could serve as potential targets for future drug development, specifically to treat ILC. The researchers hope that their model will be used in future to predict which patients are likely to respond to chemotherapy, sparing patients from unnecessary harsh treatments. They also hope it will lead to the development of drugs that are specific to – and likely more effective for – invasive lobular carcinoma. Dr Syed Haider, study lead and Group Leader of the Breast Cancer Data Science Group at The Institute of Cancer Research, London said: “Invasive lobular carcinoma has been difficult to study as patients are often diagnosed late, and their cancer relapses many years after the initial diagnosis, meaning that long-term follow up studies are necessary to understand this disease. Therefore, discovery of treatments specific to lobular breast cancers is urgently needed. By using these approaches and integrating data from numerous independent studies, we’ve developed a machine learning tool that can predict how cancer will respond to treatment, and when it will return.” Professor Chris Lord, Professor of Cancer Genomics at The Institute of Cancer Research, London, and lead of Lobular Breast Cancer Focus Group, said: “Despite invasive lobular carcinoma being the second-most common form of breast cancer, there are no specific treatments for it and the long-term outcomes are notably worse than for other breast cancers. We desperately need to improve treatments for this disease so that patients can live longer, healthier lives without fear of their cancer returning. “Until now, we’ve known little about the underlying biology of invasive lobular carcinoma and how it relates to relapse and response to treatment. These findings pave the way for a tool to guide clinical decision making, and for specific therapies for lobular breast cancer."

Invasive lobular carcinoma (ILC), also known as lobular breast cancer, comprises 15% of all breast cancer diagnoses NEWPORT BEACH, Calif., Oct. 15, 2024 /PRNewswire/ -- As part of October Breast Cancer Awareness Month, Hoag joined the Lobular Breast Cancer Alliance (LBCA), a US nonprofit organization whose mission is to raise awareness and promote more research for an understudied type of breast cancer, to declare October 15th "Global Lobular Breast Cancer Awareness Day." Invasive lobular carcinoma (ILC), or lobular breast cancer, is the second most common type of breast cancer. But despite being so common, accounting for 15% of breast cancer diagnoses worldwide, it receives less than 1% of federal research funding and has no targeted treatments. "In collaboration with lobular scientists, researchers and patient advocates worldwide, Hoag is proud to raise awareness for lobular breast cancer and work to find better ways to detect and treat this long over-looked breast cancer type," said Gary A. Ulaner, M.D., Ph.D., F.S.N.M.M.I., F.A.C.N.M., the James & Pamela Muzzy Endowed Chair in Molecular Imaging & Therapy at the Hoag Family Cancer Institute and member of the LBCA Scientific Advisory Board. What differentiates lobular breast cancer from the more common non lobular carcinomas is the tumor cell's lack of the protein E-cadherin, which helps cancer cells form lumps. Instead of clumping together, ILC tumor cells form in thin strings like cobwebs. This makes them extremely hard to detect with mammograms, especially in women with dense breast tissue, or to image elsewhere in the body if metastasized. "More than 40,000 women are diagnosed with ILC each year," said Monica Mita, M.D., co-director of early phase development therapy and co-director of breast medical oncology. "Today it is diagnosed and treated along the same lines as usual breast cancer ductal carcinoma, although ILC has distinct biological and behavioral characteristics that make it more difficult to detect and treat, with decreased response to standard of care treatments." "As such, ILC represents an unmet need for patients and further research is crucial to help improve detection, treatment, prevention of metastasis, and ultimately, develop better treatments for people with ILC," added Chaitali Nangia, M.D., Co-Director, NK Cell Therapy Research at Hoag Family Cancer Institute. Hoag Family Cancer Institute has been at the forefront of clinical trials for patients with ILC. Dr. Ulaner has led research trials and international clinical consortiums demonstrating the value of estrogen receptor (ER)-targeted molecular imaging for patients with ILC (JAMA Network Open 2024 and Journal of Nuclear Medicine 2023). These studies demonstrate how molecular imaging may improve staging and detection of suspected recurrence for patients with ILC. "We are dedicated to continuing research on ILC to bring our patients the best methods to image and treat this type of cancer," said Dr. Ulaner. For more information, visit ABOUT HOAG Hoag is a nonprofit, regional health care delivery system in Orange County, California. Delivering world-class, comprehensive, personalized care, Hoag consists of 1,800 top physicians, 16 urgent care facilities, 11 health & wellness centers, and two award-winning hospitals. Hoag offers a comprehensive blend of health care services that includes seven institutes providing specialized services in the following areas: cancer, digestive health, heart and vascular, neurosciences, spine, women's health, and orthopedics through Hoag's affiliate, Hoag Orthopedic Institute, which consists of an orthopedic hospital and four ambulatory surgical centers. Hoag is the highest ranked hospital in Orange County by U.S. News & World Report and the only OC hospital ranked in the Top 10 in California, as well as a designated Magnet® hospital by the American Nurses Credentialing Center (ANCC). For more information, visit hoag.org. About the Lobular Breast Cancer Alliance (LBCA) Founded in 2017 by individuals with invasive lobular carcinoma (ILC), LBCA became a 501c3 nonprofit organization in 2022 dedicated to raising awareness of ILC and the need for more ILC research. As the only organization in the US dedicated to lobular breast disease, LBCA is the go-to source for information on lobular breast cancer including current studies, lobular-specific clinical trials and educational fact sheets, graphics and recorded webinars for patients. LBCA is guided by an international scientific advisory board of researchers and clinicians and a patient advocate advisory board. LBCA partners with patients, scientists, clinicians, and breast cancer organizations worldwide to increase dialogue about ILC and fund vital ILC research. Visit the LBCA website at lobularbreastcancer.org. SOURCE Hoag WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED