‘How I knew I had endometrial cancer’: Six survivors share their stories
When Should Preventive Mastectomy Be Offered For Women At Higher Risk Of Breast Cancer
A new analysis, published in JAMA Oncology, has found that the surgical technique was a cost-effective way of reducing the likelihood of developing breast cancer compared to breast screening and medication. Current guidelines on who is offered mastectomy may need to be revised to reflect these new findings.
Clinicians currently use personalised risk prediction models which combine genetic and other data to identify those women who are at a higher risk of developing breast cancer (BC). Subsequent treatment options – including mammograms, MRI screening, surgery, and medication – are then offered dependent on each woman's level of risk.
Risk reducing mastectomy (RRM) is recommended for women at high risk, but in practice this surgery is only clinically offered to those carrying faults (called pathogenic variants) in genes that are known to increase the likelihood they will develop the disease (BRCA1/ BRCA2/ PALB2 PV).
Professor Ranjit Manchanda from Queen Mary University of London, Dr Rosa Legood from London School of Hygiene and Tropical Medicine, along with colleagues from Manchester University and Peking University created a new economic evaluation model to accurately predict the level of risk that would make RRM a more cost-effective treatment.
For their model, researchers used guidelines from the National Institute for Health and Care Excellence (NICE) to determine whether a treatment is considered cost-effective. Their model showed that mastectomy was a cost-effective treatment for women aged 30 or above who have a lifetime breast cancer risk greater than or equal to 35%. Offering RRM to women in this cohort could potentially prevent 6,500 of the 58,500 cases of breast cancer that are diagnosed every year in the UK.
Professor Manchanda, Professor of Gynaecological Oncology at Queen Mary and Consultant Gynaecological Oncologist, said: "We for the first time define the risk at which we should offer RRM. Our results could have significant clinical implications to expand access to mastectomy beyond those patients with known genetic susceptibility in high penetrance genes- BRCA1/ BRCA2/ PALB2 - who are traditionally offered this. This could potentially prevent can potentially prevent ~6500 breast cancer cases annually in UK women. We recommend that more research is carried out to evaluate the acceptability, uptake, and long-term outcomes of RRM among this group"..
Dr Legood, Associate Professor in health economics at the London School of Hygiene & Tropical Medicine, said: "Undergoing RRM is cost-effective for women 30-55years with a lifetime breast cancer risk of 35% or more. These results can support additional management options for personalized breast cancer risk prediction enabling more women at increased risk to access prevention."
Dr Vineeth Rajkumar, Head of Research at Rosetrees, said: "Rosetrees is delighted to fund this truly groundbreaking research that could have a positive impact on women worldwide."
The researchers used data from women aged between 30 and 60 with varying lifetime breast cancer risks between 17% and 50%, and who were either undergoing RRM or receiving screening with medical prevention according to currently used predictive models.
NICE deems a treatment cost effective if it typically brings one additional year of health for no more than £20,000-£30,000 per patient (known as the 'willingness to pay' threshold, or WTP). The researchers' model used a threshold of £30,000/Quality Adjusted Life Year.
'Risk-reducing' Surgery Could Prevent Thousands Of Breast Cancer Cases
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Your support makes all the difference.Read moreThousands of breast cancer cases could be averted each year if more women were offered "risk-reducing" breast removal surgery, a new study suggests.
This intervention, known as a mastectomy, is currently used to treat existing cancer or offered to those with a high genetic predisposition, specifically women carrying the BRCA1, BRCA2, or PALB2 genes.
The analysis indicates that approximately 6,500 cases of breast cancer could be prevented annually if preventative mastectomies were more widely adopted.
Crucially, the research proposes expanding eligibility beyond the currently recognised genetic markers.
Women with other genes linked to increased risk, such as ATM, CHEK2, RAD51C, and RAD51D, may also benefit.
Furthermore, the study highlights that a combination of other factors, including a family history of breast cancer, parity (number of children), breastfeeding history, and mammogram density, should be considered in assessing a woman's overall high risk for the disease, potentially making them candidates for risk-reducing mastectomies.
Women in the UK have an 11 per cent chance of developing breast cancer across their lifetime.
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Risk-reducing mastectomies (RRM) are currently only offered to women with the BRCA1, BRCA2, PALB2 genes, experts said (Alamy/PA)Medics can calculate a woman's risk of breast cancer using tools which combine the effect of various risk factors.
Researchers from Queen Mary University of London and the London School of Hygiene and Tropical Medicine (LSHTM) found that if health officials could identify all women aged 30 to 55 who have a 35 per cent or higher risk of breast cancer, and they all went on to have RRM, then an estimated 6,538 breast cancer cases could be prevented in the UK each year.
This is the equivalent of around 11 per cent of the 59,000 women in the UK who are diagnosed with breast cancer each year.
The academics point out that women who have one of the other genes linked to breast cancer, who may be at high risk of disease, could potentially be found by a mechanism called "cascade testing" – where genetic tests are offered to family members of women who have been found to have these different genes linked to breast cancer.
The economic evaluation study, published in the journal JAMA Oncology, concludes: "Undergoing RRM appears cost-effective for women at 30-55 years with a lifetime BC-risk 35 per cent (or more).
"The results could have significant clinical implications to expand access to RRM beyond BRCA1/BRCA2/PALB2 pathogenic variant carriers."
Corresponding author on the paper, Professor Ranjit Manchanda, professor of gynaecological oncology at Queen Mary and consultant gynaecological oncologist, said: "We for the first time define the risk at which we should offer RRM.
"Our results could have significant clinical implications to expand access to mastectomy beyond those patients with known genetic susceptibility in high penetrance genes- BRCA1/ BRCA2/ PALB2 – who are traditionally offered this.
"This could potentially prevent can potentially prevent (around) 6500 breast cancer cases annually in UK women.
"We recommend that more research is carried out to evaluate the acceptability, uptake, and long-term outcomes of RRM among this group".
open image in gallery
Medics can calculate a woman's risk of breast cancer using tools which combine the effects of various risk factors (PA)Dr Rosa Legood, associate professor in health economics at LSHTM, added: "Undergoing RRM is cost-effective for women (aged) 30 to 55-years with a lifetime breast cancer risk of 35 per cent or more.
"These results can support additional management options for personalised breast cancer risk prediction enabling more women at increased risk to access prevention."
Women deemed to be at high risk of breast cancer can also be offered regular screening and medication.
Louise Grimsdell, Breast Cancer Now senior clinical nurse specialist, said: "While this modelling provides valuable insights into the cost-effectiveness of risk-reducing mastectomy for women with a high risk of developing breast cancer, each individual must be offered all risk-management options that are suitable for them.
"Choosing to have risk-reducing surgery is a complex and deeply personal decision that comes with emotional and physical implications.
"So, it's vital women can consider all their options, including screening and risk-reducing medications, and are supported by their clinician to make an informed decision that's right for them.
"It's also crucial that the unacceptably long waits that far too many women who chose risk-reducing surgery are facing are urgently tackled."
Monitoring And Follow-upClinical Guidance - Healio
Ongoing AssessmentBreast cancer is a systemic disease and can affect other organs as well. Regular monitoring of primary breast cancer and other metastatic sites, such as the bones, liver or lungs, ensures that the disease remains controlled. Treatment strategies may need to be adapted based on systemic disease status to prevent metastases and manage the primary tumor.
Monitoring includes periodic assessment of symptoms, physical examination, routine laboratory tests, imaging studies and blood biomarkers where appropriate. Results of monitoring are classified as response/continued response to treatment, stable disease, uncertainty regarding disease status or progression of disease. The clinician must assess and balance results to decide whether disease is being controlled and the toxicity of treatment is acceptable. Clinicians should take into account patient preferences through a shared decision-making process.
Analysis of circulating tumor DNA (ctDNA)is a non-invasive monitoring tool…
Ongoing AssessmentBreast cancer is a systemic disease and can affect other organs as well. Regular monitoring of primary breast cancer and other metastatic sites, such as the bones, liver or lungs, ensures that the disease remains controlled. Treatment strategies may need to be adapted based on systemic disease status to prevent metastases and manage the primary tumor.
Monitoring includes periodic assessment of symptoms, physical examination, routine laboratory tests, imaging studies and blood biomarkers where appropriate. Results of monitoring are classified as response/continued response to treatment, stable disease, uncertainty regarding disease status or progression of disease. The clinician must assess and balance results to decide whether disease is being controlled and the toxicity of treatment is acceptable. Clinicians should take into account patient preferences through a shared decision-making process.
Analysis of circulating tumor DNA (ctDNA) is a non-invasive monitoring tool that complements tissue biopsies and correlates with tumor burden, prognosis, stage and treatment response in breast cancer. CtDNA can identify lingering molecular traces of cancer after treatment, referred to as minimal residual disease, and detect signs of molecular relapse.
The optimal frequency of repeat testing has not been established and is largely based on the monitoring strategies utilized in breast cancer clinical trials. The frequency of monitoring must balance the need to detect progressive disease, avoid unnecessary toxicity of any ineffective therapy, resource utilization and optimize cost. Reassessment of disease activity should be performed in patients with new or worsening signs or symptoms of disease, regardless of the time interval from previous studies.
The management of patients with metastatic disease involves treatment and a comprehensive survivorship plan. Patients should be encouraged to report any new or worsening symptoms, which could indicate disease progression, treatment effects or other unrelated medical issues. Health monitoring, management and immunizations should be performed under the care of a primary care provider.
Regular brain imaging through techniques, like MRI or CT scans, is crucial for monitoring the status of brain metastases and assessment of brain lesion size, number and location. Imaging can reveal changes in the metastatic lesions, which may indicate disease progression or response to treatment. Imaging information is essential for making informed decisions about treatment adjustments or interventions.
Regular neurological assessments help evaluate the patient's cognitive and functional status, which are critical for detecting neurological deficits or changes associated with brain metastases. Changes in cognitive function, motor skills, coordination or other neurological symptoms can indicate disease progression or treatment-related adverse events, which may necessitate timely identification.
Cardiac evaluation before, during and after trastuzumab treatment can be performed with conventional echocardiography. Echocardiography does not require radiation exposure and can be used to assess the complete cardiac structure. However, there is high interobserver variability, dependency on image quality, insensitivity to detect small LVEF changes and false-positive rate of cardiotoxicity.
Cardiac MonitoringAssessment of the global longitudinal strain (GLS) using speckle tracking echocardiography is a method to detect and quantify subtle disturbances in global left ventricular systolic function. GLS is important in diagnosing the cardiotoxicity of cancer treatment, with a relative decrease of more than 15% suggesting subclinical cardiac dysfunction. GLS assessment is complemented by the measurement of biomarkers indicating myocardial damage or overload. Low GLS combined with elevated brain natriuretic peptide and N-terminal pro B-type natriuretic peptide serum concentrations after chemotherapy increases the accuracy for detecting early onset cardiotoxicity. Combined assessment of GLS with serum troponin levels is another effective way of detecting cardiotoxicity.
The optimal frequency of cardiac monitoring during trastuzumab therapy has not yet been formally established. The product label of trastuzumab recommends left ventricular ejection fraction (LVEF) monitoring prior to initiation of trastuzumab and every 3 months during and upon completion of adjuvant trastuzumab treatment. After completion of 1 year of adjuvant treatment, LVEF monitoring can be done every 6 months for at least 2 years. If trastuzumab is withheld for significant LV cardiac dysfunction, cardiac monitoring should be performed monthly. The American Society of Clinical Oncology recommends cardiac monitoring 6 to 12 months after completion of therapy in high-risk patients.
Regular follow-up discussions about the goals of care, therapy cessation and care coordination may be necessary to improve both survival and quality of life for patients with metastatic breast cancer. Surveillance and follow-up plans should be individualized, particularly for older patients and those with multiple comorbidities.
Posttreatment SurveillanceThe aim of surveillance in patients after primary breast cancer treatment is to detect second breast cancers before symptoms develop, which allows interventions that permit improved survival and quality of life. Mammography is a key aspect of breast cancer screening and surveillance, and digital breast tomosynthesis, whole-breast ultrasound and breast MRI may also be available. Surveillance also helps monitor long-term effects of therapy, including informing the need to address physical adverse events like lymphedema and fatigue, as well as psychological challenges like fear of recurrence and anxiety.
Routine screening, evaluation and assessment for supportive care interventions and referrals are needed. At each step of disease progression, health care professionals must address all treatment options, including the possibility of supportive care or hospice care for patients with advanced disease. When appropriate, involvement of a palliative care team should be considered to provide advance care planning, goals of care discussions, care transitions, psychosocial support and management of cancer and therapy-related symptoms.
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