Latest news with #NicholasTurner
The Sun
2 days ago
- Business
- The Sun
Three-drug treatment combo ‘holds back aggressive breast cancer for a year'
A NEW triple threat drug combination could hold aggressive breast cancer at bay for an extra year, a trial found. Adding the medicine inavolisib to an already used pair of drugs delayed the need for chemotherapy by almost two years. 1 It prevented tumours from growing for an average of 17 months, compared to seven months in patients using the standard drug pairing palbociclib and fulvestrant. An estimated 1,000 British women per year could benefit. The combo works for women with a specific breast cancer type called HR+ HER2- with a PIK3CA mutation, which accounts for about three in 10 cases. Professor Kristian Helin, chief of The Institute of Cancer Research in London, said: 'We need to tackle treatment resistance head-on to continue improving survival rates. 'This triple combination approach effectively shuts down cancer's escape routes, giving people with metastatic breast cancer the opportunity to live well for longer.' The trial included 325 patients with aggressive and advanced breast cancer from 28 countries. Cancers shrank in two thirds of people receiving the triple drug combination, compared to 28 per cent of those on standard treatment. New go-to option for docs Study author Professor Nicholas Turner, of the Royal Marsden NHS hospital in London, said: 'This therapy not only helped patients live longer but it more than doubled the time before their cancer progressed or worsened. 'It also gave them more time before needing chemotherapy which is something that patients really fear and want to delay for as long as possible.' 'These results give us confidence that this treatment could become the new go-to option.' The study was presented at the conference of the American Society of Clinical Oncology. What are the signs of breast cancer? BREAST cancer is the most common type of cancer in the UK. The majority of women who get it are over 50, but younger women and, in rare cases, men can also get breast cancer. If it's treated early enough, breast cancer can be prevented from spreading to other parts of the body. Breast cancer can have a number of symptoms, but the first noticeable symptom is usually a lump or area of thickened breast tissue. Most breast lumps aren't cancerous, but it's always best to have them checked by your doctor. You should also speak to your GP if you notice any of the following: a change in the size or shape of one or both breasts discharge from either of your nipples (which may be streaked with blood) a lump or swelling in either of your armpits dimpling on the skin of your breasts a rash on or around your nipple a change in the appearance of your nipple, such as becoming sunken into your breast Source: NHS
Scottish Sun
2 days ago
- Health
- Scottish Sun
Three-drug treatment combo ‘holds back aggressive breast cancer for a year'
The treatment could benefit thousands of British women Click to share on X/Twitter (Opens in new window) Click to share on Facebook (Opens in new window) A NEW triple threat drug combination could hold aggressive breast cancer at bay for an extra year, a trial found. Adding the medicine inavolisib to an already used pair of drugs delayed the need for chemotherapy by almost two years. Sign up for Scottish Sun newsletter Sign up 1 Breast cancer gets harder to treat as cells become resistant to drugs (stock image) Credit: Getty It prevented tumours from growing for an average of 17 months, compared to seven months in patients using the standard drug pairing palbociclib and fulvestrant. An estimated 1,000 British women per year could benefit. The combo works for women with a specific breast cancer type called HR+ HER2- with a PIK3CA mutation, which accounts for about three in 10 cases. Professor Kristian Helin, chief of The Institute of Cancer Research in London, said: 'We need to tackle treatment resistance head-on to continue improving survival rates. 'This triple combination approach effectively shuts down cancer's escape routes, giving people with metastatic breast cancer the opportunity to live well for longer.' The trial included 325 patients with aggressive and advanced breast cancer from 28 countries. Cancers shrank in two thirds of people receiving the triple drug combination, compared to 28 per cent of those on standard treatment. New go-to option for docs Study author Professor Nicholas Turner, of the Royal Marsden NHS hospital in London, said: 'This therapy not only helped patients live longer but it more than doubled the time before their cancer progressed or worsened. 'It also gave them more time before needing chemotherapy which is something that patients really fear and want to delay for as long as possible.' 'These results give us confidence that this treatment could become the new go-to option.' The study was presented at the conference of the American Society of Clinical Oncology. Breast cancer symptoms you should NEVER ignore, with Dr Philippa Kaye
Yahoo
2 days ago
- Business
- Yahoo
AstraZeneca drug could help keep a common breast cancer at bay
This story was originally published on BioPharma Dive. To receive daily news and insights, subscribe to our free daily BioPharma Dive newsletter. Too often, cancer has a way of evading treatment. Tumors that were held in check begin to spread anew, forcing doctors to try different drugs in a desperate race to keep malignant cells from multiplying. For a common type of breast cancer, this usually happens because of changes in a gene called ESR1. Mutations there can drive cancer growth even as physicians' first choice of therapy chokes off the resources that tumors had relied on to survive. Afterwards, the prognosis for patients gets worse. Multiple second-line medicines exist, but 'their benefit is limited, quality of life decreases and survival rates are low,' according to Nicholas Turner, director of clinical research and development at the Royal Marsden Hospital in London. New study results from Turner and others show an experimental drug from AstraZeneca, camizestrant, can help sustain the benefit of first-line therapy. Unveiled Sunday, their research found that, once ESR1 mutations are detected, swapping out a standard component of that initial regimen for AstraZeneca's drug reduced the risk of disease progression or death by more than half. Data from the study, which AstraZeneca funded and in February said succeeded, will be presented Sunday afternoon at the American Society of Clinical Oncology's annual meeting. 'Patients have an urgent need for new treatments that can prolong time on first-line therapy and delay disease progression,' Turner said in a statement provided by ASCO. In their clinical trial, Turner and colleagues enrolled 3,256 people with advanced breast cancer positive for hormone receptors but negative for a protein called HER2. These individuals are typically treated with a kind of hormone therapy known as an aromatase inhibitor along with another type of targeted drug that interrupts cancer cell division. Participants in the study were monitored via blood tests for the emergence of ESR1 mutations, which were eventually detected in about 550 people. Three-hundred and fifteen were then randomly assigned to receive camizestrant instead of the aromatase inhibitor or to continue on with their initial regimen. These patients continued to receive those targeted drugs, 'CDK 4/6 inhibitors.' Patients who were switched to camizestrant had a 56% lower risk of their cancer progressing or killing them than those who continued on, researchers calculated. Put another way, people in the camizestrant group lived a median of 16 months without disease progression or death, compared to 9.2 months for those in the control arm. Data also showed camizestrant helped maintain quality of life for longer than did aromatase inhibitors, too. Researchers continue to follow study participants to measure differences between the groups in overall survival, but don't yet have enough follow-up data to determine whether there is a benefit on that score. Less than 2% of patients in either group discontinued treatment due to side effects, which, for camizestrant, were consistent with what AstraZeneca has observed in prior testing. Hormone receptor-positive, HER2-negative tumors are the most common type of breast cancer, accounting for an estimated 70% of cases. Hormone receptors provide a dock for estrogen, which spurs the tumor to grow. In first-line therapy, hormone therapy shuts off estrogen signaling by either gumming up hormone receptors on the surface of breast cancer cells, or by blocking the body from making estrogen. But about 40% of patients whose breast cancer is responsive to hormone therapy develop ESR1 mutations during their initial therapy, according to an estimate cited by ASCO. Research done a decade ago at Memorial Sloan Kettering Cancer Center discovered that ESR1 mutations change the shape of the estrogen receptor, essentially flipping it 'on,' whether or not cancer cells continue to receive an estrogen growth signal. Camizestrant offers a way to get ahead of that change by breaking down the estrogen receptor entirely. It's one of a new crop of so-called selective estrogen receptor degraders, or SERDs, that are taken orally rather than injected like the drug fulvestrant, which has been a staple of breast cancer treatment for decades. One member of this fresh class, Orserdu, won U.S. approval in 2023. Others from Eli Lilly and Roche, as well as a different kind of degrader from partners Pfizer and Arvinas, are in late-stage testing. Data from a Phase 3 trial involving Pfizer and Arvinas' vepdegestrant in people whose hormone receptor-positive, HER2-negative breast cancer progressed following initial treatment were presented at ASCO Saturday. The setting envisioned by camizestrant's trial is one step earlier, subbing in a SERD before initial disease progression to allow patients to remain on first-line therapy longer. 'When patients progress on scans, we're already behind. We've already lost control, in some sense,' Eleonora Teplinsky, head of breast and gynecologic medical oncology at New Jersey's Valley-Mount Sinai Comprehensive Cancer Care, said in a press conference held by ASCO. 'An early switch approach, before we see disease progression on imaging, [allows] us to stay ahead of the curve.' Switching early requires regular monitoring, which Turner and his colleagues accomplished by using 'liquid biopsies,' tests that pick up fragments of tumor DNA circulating in the blood. While these are relatively expensive, Turner said he hopes insurance would cover them should camizestrant win approval in the tested setting. Clearance would also change doctors' testing practice. Soon after Orserdu won U.S. approval, ASCO updated its treatment guidelines to recommend testing for ESR1 mutations following disease progression or recurrence. Camizestrant's benefit lies in delaying that progression, making active surveillance beforehand essential. 'The difference here is this serial monitoring for evidence of the evolving mutation,' said Julie Gralow, an oncologist and ASCO's chief medical officer, at the press conference. Establishing reimbursement and updating guidelines will be important to that goal, acknowledged Mohit Manrao, a senior vice president in AstraZeneca's U.S. oncology division. 'The good part here is that the test exists,' he added 'It is already being done at the point of progression,' he said. AstraZeneca plans to use the data presented at ASCO to request regulatory approval. It is also studying replacing aromatase inhibitors with camizestrant upfront, rather than waiting for ESR1 mutations to emerge. Two other trials are examining camizestrant's potential in early breast cancer.
Daily Mail
2 days ago
- Business
- Daily Mail
Major discovery about 'invisible' breast tumours that are too small to show up on scans
Thousands of women have been thrown a lifeline thanks to a 'next generation' drug that can destroy breast cancer tumours, months before they even grow. The daily pill, known as camizestrant, stops cancer cells from developing, slowing the spread of the disease and delaying the need for gruelling chemotherapy. Around seven in ten breast cancer patients in the UK have a type of the disease known as HR positive HER-2 negative breast cancer—the most common form. Of these, around 40 per cent can develop an aggressive genetic mutation that makes their outlook incredibly bleak. But the 'transformational' trial found patients given the drug camizestrant saw their risk of the cancer progressing slashed by more than half. It was also the first worldwide study that showed blood tests, rather than scans, can pick up early signs of cancer returning. Doctors first used the test, known as a liquid biopsy, to spot changes in the cancer's DNA—when they found signs of an ESR1 mutation, some patients were given camizestrant, while others stayed on their usual treatment. Experts presenting the findings today at the American Society for Clinical Oncology conference (ASCO) in Chicago, hailed it a 'pivotal moment in breast cancer care' and 'truly fundamental shift in how we approach cancer'. The drug is already being fast-tracked for use in the US and has been sent for approval in the UK. Professor Nicholas Turner, an expert in molecular oncology at The Institute of Cancer Research, London and the Royal Marsden NHS Foundation Trust, who co-led the major trial, said: 'This is a pivotal moment in breast cancer care. 'This proactive approach also redefines how we think about drug resistance in this type of breast cancer. 'This is a potential new treatment strategy in oncology to treat developing resistance before it causes disease progression.' Professor Kristian Helin, chief executive of The Institute of Cancer Research, London, added: 'The results represent more than a clinical milestone—they represent a transformational shift in how we approach precision medicine. 'It is very exciting to see this technology being used to delay disease progression in patients and extend the benefits of treatment in patients with this type of advanced breast cancer and delay the need for chemotherapy for as long as possible. 'These breakthroughs are helping shape personalised breast cancer treatment, allowing doctors to adjust therapies earlier and improve patient outcomes.' In the trial, 3,325 patients HR positive HER-2 negative advanced breast cancer from 23 countries were screened for ESR1 mutations using a liquid biopsy every eight to 12 weeks. Of these, 315 women who tested positive for an ESR1 mutation were given either AstraZeneca's camizestrant and a medicine known as a CDK4/6 inhibitor or another hormone therapy as well as a CDK4/6 inhibitor. Researchers found those on the camizestrant combination slashed their risk of death or the cancer progressing by 56 per cent. The drug also kept the cancer at bay for 16 months on average compared to 9.2 months on standard treatment. Just one per cent of patients stopped taking the drug over side effects. Presenting the findings at ASCO, Susan Galbraith, executive vice president of oncology at AstraZeneca said the drug had now been given 'breakthrough therapy designation' by the Food and Drugs Administration in the US, helping to speed up regulatory review. 'We are having ongoing discussions with regulatory authorities including the UK', added. Dave Fredickson, AstraZeneca's executive vice president of oncology business unit, also said the drug demonstrated a 'truly fundamental shift in how we approach cancer care. 'We're moving away from a one size fits all era and targeting cancer early.' Meanwhile, Dr Catherine Elliott, director of research at Cancer Research UK, said: 'This study is a clear example of how blood tests are starting to transform cancer treatment. 'By tracking tiny traces of tumour DNA in the blood, researchers were able to spot early signs of treatment resistance and switch therapies before cancer had a chance to grow. 'It shows how circulating tumour DNA—or ctDNA—could help doctors make smarter, more timely treatment decisions. 'This approach could become an important part of how we personalise care for people with advanced breast cancer.'
Business Wire
2 days ago
- Health
- Business Wire
Camizestrant reduced the risk of disease progression or death by 56% in patients with advanced HR-positive breast cancer with an emergent ESR1 tumor mutation in SERENA-6 Phase III trial
WILMINGTON, Del.--(BUSINESS WIRE)--Positive results from the SERENA-6 Phase III trial showed that AstraZeneca's camizestrant in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS). The trial evaluated switching to the camizestrant combination versus continuing standard-of-care treatment with an aromatase inhibitor (AI) (anastrozole or letrozole) in combination with a CDK4/6 inhibitor in the 1st-line treatment of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumors have an emergent ESR1 mutation. These results will be presented today during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL (abstract #LBA4) and simultaneously published in The New England Journal of Medicine. Results showed the camizestrant combination reduced the risk of disease progression or death by 56% compared to standard-of-care treatment (based on a hazard ratio [HR] of 0.44; 95% confidence interval [CI] 0.31–0.60; p<0.00001) as assessed by investigator. Median PFS was 16.0 months for patients who switched to the camizestrant combination versus 9.2 months for the comparator arm. Importantly, a consistent PFS benefit was observed across all CDK4/6 inhibitors and clinically relevant subgroups in the trial, including analysis by age, race, region, time of ESR1 mutation detection and type of ESR1 mutation. The camizestrant combination was also associated with a meaningful delay in time to deterioration in quality of life, where in an exploratory endpoint, the camizestrant combination reduced the risk of deterioration in global health status and quality of life by 47% compared with the AI combination (HR 0.53; 95% CI, 0.33-0.82; nominal p<0.001). The median time to deterioration of global health status was 23.0 months in patients treated with the camizestrant combination, versus 6.4 months in patients that continued treatment with the AI combination (EORTC QLQ-C30). The camizestrant combination also delayed the time to deterioration of pain compared with the AI combination. Data for the key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the time of this interim analysis. However, a trend toward extended treatment benefit was observed with the camizestrant combination based on PFS2 (HR 0.52; 95% CI 0.33-0.81; p=0.0038 [interim analysis threshold p=0.0001]). The trial will continue to assess OS, PFS2 and other key secondary endpoints. Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, London, UK, and co-principal investigator for the trial, said: 'Today's news marks a pivotal moment in breast cancer care and redefines how we think about drug resistance in this type of breast cancer. The results of the innovative SERENA-6 trial show that switching from an aromatase inhibitor to camizestrant in combination with any of the three CDK4/6 inhibitors after emergence of an ESR1 mutation more than halved the risk of disease progression or death and delayed deterioration in quality of life by nearly 18 months. This proactive approach exemplifies a new treatment strategy in oncology; by treating developing resistance before it causes disease progression and deterioration in quality of life, we can extend the benefit of 1st-line treatment to optimize patient outcomes.' Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: 'As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumor DNA to detect emerging resistance and change therapy at the earliest opportunity; SERENA-6 is redefining the clinical paradigm in breast cancer. Camizestrant is the first and only next-generation oral SERD and complete estrogen receptor antagonist to demonstrate benefit in combination with widely approved CDK4/6 inhibitors in this 1st-line setting, and these results support its potential as a new standard-of-care endocrine therapy backbone in the treatment of HR-positive breast cancer.' The safety profile of camizestrant in combination with palbociclib, ribociclib or abemaciclib in SERENA-6 was consistent with the known safety profile of each medicine. Consistent with the longer duration of exposure to the combination of camizestrant and CDK4/6 inhibitors in the trial, Grade 3 or higher adverse events from all causes occurred in 60% of patients in the camizestrant arm versus 46% in the AI arm; the majority of which were hematological events typically associated with CDK4/6 inhibitor treatment and included neutropenia (45% vs. 34%), anemia (5% vs. 5%) and leukopenia (10% vs. 3%). If experienced, photopsia - reported as brief flashes of light in the peripheral vision - did not impact daily activities of patients in the trial and was reversible. There were no structural changes in the eye or changes in visual acuity. No new safety signals were identified and discontinuation rates were very low and similar in both arms, with 1% patients discontinuing camizestrant and 2% patients discontinuing an AI. Discontinuation of the CDK4/6 inhibitor occurred in 1% of patients in both arms of the trial. SERENA-6 is the first global, double-blind, registrational Phase III trial to use a circulating tumor DNA (ctDNA)-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression. The novel trial design used ctDNA monitoring at the time of routine tumor scans to identify patients for early signs of endocrine resistance and the emergence of ESR1 mutations. Following detection of an ESR1 mutation without disease progression, the endocrine therapy of patients was switched to camizestrant from ongoing treatment with an AI, while continuing combination with the same CDK4/6 inhibitor. Based on the results of the SERENA-6 Phase III trial, camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) has been granted Breakthrough Therapy Designation (BTD) in the US by the Food and Drug Administration for the treatment of adult patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer upon emergence of ESR1 mutation during first-line endocrine-based therapy. Notes HR-positive breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 1 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally. 1 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 2 HR-positive breast cancer, characterized by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumors considered HR-positive and HER2-negative. 2 ERs often drive the growth of HR-positive breast cancer cells. 3 Globally, approximately 200,000 patients with HR-positive breast cancer are treated with a medicine in the 1st-line setting; most frequently with endocrine therapies that target estrogen receptor (ER)-driven disease, which are often paired with CDK4/6 inhibitors. 4-6 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease. 6 Once this occurs, treatment options are limited and survival rates are low with 35% of patients anticipated to live beyond five years after diagnosis. 2,6,7 Mutations in the ESR1 gene are a key driver of endocrine resistance and are widely tested for in clinical practice at time of disease progression on 1st-line therapies. 8,9 These mutations emerge during treatment of the disease, becoming more prevalent as the disease progresses and are associated with poor outcomes. 8,9 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment without disease progression. 4 The optimization of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research. SERENA-6 SERENA-6 is a Phase III, double-blind, randomized trial evaluating the efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) versus treatment with an AI (anastrozole or letrozole) in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) in patients with HR-positive, HER2-negative advanced breast cancer (patients with either locally advanced disease, or metastatic disease) whose tumors have an emergent ESR1 mutation. The global trial enrolled 315 adult patients with histologically confirmed HR-positive, HER2-negative advanced breast cancer, undergoing treatment with an AI in combination with a CDK4/6 inhibitor as 1st-line treatment. The primary endpoint of the SERENA-6 trial is PFS as assessed by investigator, with secondary endpoints including OS, and PFS2 by investigator assessment. Camizestrant Camizestrant is an investigational, potent, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist that is currently in Phase III trials for the treatment of HR-positive breast cancer. AstraZeneca's broad, robust and innovative clinical development program, including the SERENA-6, SERENA-4, CAMBRIA-1 and CAMBRIA-2 trials, is evaluating the safety and efficacy of camizestrant when used as a monotherapy or in combination with CDK4/6 inhibitors to address a number of areas of unmet need in HR-positive, HER2-negative breast cancer. Camizestrant has demonstrated anti-cancer activity across a range of preclinical models, including those with ER-activating mutations. In the SERENA-2 Phase II trial, camizestrant demonstrated PFS benefit versus fulvestrant irrespective of ESR1 mutation status or prior treatment with CDK4/6 inhibitors in patients with ER-positive locally advanced or metastatic breast cancer, previously treated with endocrine therapy. The SERENA-1 Phase I trial demonstrated that camizestrant is well tolerated and has a promising anti-tumor profile when administered alone or in combination with palbociclib, ribociclib and abemaciclib; three widely used CDK4/6 inhibitors. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment. With fam-trastuzumab deruxtecan-nxki, a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines fulvestrant and goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, the TROP-2-directed ADC, datopotamab deruxtecan-dlnk and next-generation oral SERD and potential new medicine camizestrant. PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with Merck & Co., Inc. (MSD outside the US and Canada) continue to research olaparib in these settings and to explore its potential in earlier disease. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA -mutated, HR-positive, HER2-negative advanced breast cancer. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of datopotamab deruxtecan-dlnk alone and in combination with immunotherapy durvalumab. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit and follow the Company on social media @ AstraZeneca. References Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4. doi: 10.3322/caac.21834. National Cancer Institute. Cancer Stat facts: Female breast cancer subtypes. Available at: Accessed June 2025. Scabia V, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nat Commun. 2022; 10.1038/s41467-022-30898-0. Cerner CancerMPact database. Accessed June 2025. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944. Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor–positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res. 2022; 28(5):821-30. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines). Available at: Accessed June 2025. Brett O, et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor‑positive breast cancer. Breast Cancer Res. 2021; 23:85. Zundelevich, A, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020; 22:16. US-101612 Last updated 06/25
