
Fast Five Quiz: Metastatic Breast Cancer Treatment Issues
How well do you understand the treatment complications of metastatic and advanced breast cancer? Take this quick quiz and test your knowledge.
Human epidermal growth factor receptor-2 (HER2) targeted therapies are associated with a higher risk for treatment-related cardiovascular toxicity, particularly in causing cancer therapy–related cardiac dysfunction during and after treatment. Anthracycline-based and HER2-targeted therapies pose significant risks of cardiovascular toxicity, including heart failure, making them a major concern for long-term breast cancer survivors.
Although antibody-drug conjugates and immune checkpoint inhibitors are being rapidly developed and used alongside traditional chemotherapy, their cardiovascular toxicity risks remain less well understood and appear to be lower compared with HER2-targeted treatments. Additionally, sodium glucose cotransporter-2 inhibitors have shown promise in cardioprotection rather than contributing to cardiovascular toxicity.
Learn more about HER2-targeted therapies.
A key complication associated with whole-brain radiotherapy is neurocognitive decline. Whole-brain radiotherapy can cause long-term impairments in verbal learning, memory, executive function, and verbal fluency, primarily due to hippocampal dysfunction. Stereotactic radiosurgery can affect verbal learning, memory, fine motor coordination, and executive function.
Meningitis, seizures, and hemorrhage are complications more commonly associated with surgical treatment of brain metastases, not whole-brain radiotherapy.
Learn more about brain metastasis in metastatic breast cancer.
According to a comprehensive analysis, non-Hispanic Black patients with late-stage breast cancer had higher rates of chemotherapy-related complications compared with non-Hispanic White patients. This includes higher rates of cardiomyopathy, diarrhea/enteritis, fatigue, nausea/vomiting, neuropathy, lung disease, pain, dehydration/hypovolemia, rash, and infusion reactions. Non-Hispanic Black patients also had higher rates of cardiovascular toxicities such as acute myocardial infarction and pneumonitis. Non-Hispanic White patients had higher rates of being diagnosed with psychological issues, although non-Hispanic Black patients had higher rates of cognitive decline and dementia.
There were no significant differences in overall immune-related toxicities between non-Hispanic Black and non-Hispanic White patients. These racial disparities in breast cancer treatment-related adverse events might be due to non-Hispanic Black and non-Hispanic White patients receiving different treatments. Non-Hispanic Black patients have a higher probability of receiving adjuvant therapy, whereas non-Hispanic White patients have a higher probability of undergoing curative-intent breast cancer surgery and being prescribed endocrine therapy.
Learn more about breast cancer treatment protocols.
A systematic review and meta-analysis indicated that although various postoperative complications can occur, seroma is the most frequently reported. It involves the accumulation of fluid at the surgical site, which can lead to discomfort, delayed wound healing, and, in some cases, infection. Other complications, such as hematoma, surgical-site infection, and chronic neuropathic postoperative pain, are also recognized but occur less frequently.
Learn more about surgical treatment of breast cancer.
Calcium channel blockers are preferred for managing cancer therapy-related cardiac dysfunction in patients with advanced breast cancer and hypertension, due to their cardiovascular benefits. Calcium channel blockers, particularly in combination with renin-angiotensin system inhibitors, provide superior cardiovascular outcomes compared with beta-blockers and diuretics in hypertensive patients undergoing cardiotoxic chemotherapy. They effectively reduce blood pressure variability and arterial stiffness, contributing to improved cardiovascular health.
Although diuretics are commonly used to manage hypertension and heart failure, they do not provide the same protective cardiovascular benefits as calcium channels blockers or renin-angiotensin system inhibitors in this specific patient population. Although statins might reduce oxidative stress and inflammation, their efficacy in preventing cancer therapy-related cardiac dysfunction remains controversial due to conflicting results from major clinical trials. Beta-blockers are used for heart failure management but are not the preferred antihypertensive agents in patients undergoing cardiotoxic chemotherapy.
Learn more about signs and symptoms of hypertension.

Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles


Medscape
an hour ago
- Medscape
Targeted but Toxic? Addressing the Safety Challenges of ADCs
Antibody-drug conjugates (ADCs) are an evolving class of targeted cancer therapy that combines a monoclonal antibody with a cytotoxic payload or agent via chemical linkers. Attaching the monoclonal antibody with the cytotoxic agent enables an ADC to target cancer cells, maximizing efficacy and minimizing off-target toxicity. Several ADCs, including HER2+, HR+, and triple-negative breast cancer (TNBC) subtypes have shown significant efficacy in treating breast cancer. The ADCs currently approved by the FDA for the treatment of metastatic breast cancer and as an adjuvant treatment for HER2+ breast cancer include trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), patritumab-DXd, and sacituzumab govitecan (SG). Although ADCs have demonstrated significant efficacy, treatment-related toxicity, mainly from off-target effects of cytotoxic payloads and unintended bystander damage, remains a concern. A recent systemic review and meta-analysis by Zhu et al on ADCs found treatment-related adverse events of 91.2% for all-grade adverse events and 46.1% for grade ≥ 3 adverse events. Lymphopenia (53%) was the most common all ‐ grade adverse event, and neutropenia (31.2%) was the most common grade ≥ 3 adverse event. Approximately 13.2% of patients discontinued ADC treatment due to serious toxic events. This article discusses some of the common hematologic, cardiac, and gastrointestinal (GI) toxicities/adverse events associated with ADCs and their management. Managing Hematologic Adverse Events Neutropenia, anemia, and thrombocytopenia are common hematologic toxicities associated with ADCs. The most common cytopenia associated with T-DXd is neutropenia. In the DESTINY-Breast03 trial, any-grade neutropenia was observed in 42.8% of patients taking T-DXd. Although grade 3 or higher neutropenia was reported in 19.1% of patients, the DESTINY-Breast01 trial reported only 1.6% of patients experienced febrile neutropenia associated with T-DXd. The incidence of all-grade neutropenia associated with T-DM1 across trials ranges from 5% to 11% with grade ≥ 3 neutropenia, including febrile neutropenia, occurring in up to 6% of patients. Neutropenia-associated with ADC toxicity can be managed through dose modifications and temporary treatment holds. Prophylactic granulocyte colony-stimulating factor can decrease the incidence, duration, and severity of neutropenia and is indicated for patients with a history of neutropenic complications. Since the risk of developing febrile neutropenia with T-DXd is low (≤ 10%), prophylactic granulocyte colony-stimulating factor is typically not indicated. Regarding anemia, the EMILIA and TH3RESA trials reported the incidence of anemia associated with T-DM1 to be only 2.7%. However, findings from a randomized open-label phase 3 trial found grade 3 or higher anemia in 8.1% of patients receiving T-DXd. A phase 1/2 multicenter open-label study reported anemia in 18.7% of patients receiving patritumab-DXd, a HER3-directed ADC. A common approach to managing grades 3 and 4 anemia associated with ADCs involves withholding the treatment until anemia is lower than grade 2. The WSG-ADAPT, TH3RESA, and EMILIA trials found all-grade thrombocytopenia occurs in up to 28% of patients receiving T-DM1. The EMILIA trial reported severe thrombocytopenia in up to 12% of patients treated with T-DM1; the DESTINY-Breast03 trial reported grades 3 and 4 thrombocytopenia in 7% of patients receiving T-DXd; and a phase 2 study reported grades 3 or higher thrombocytopenia in 1.7% of patients receiving HER3-DXd. Managing thrombocytopenia involves reducing the dose of the ADC until patients recovery to grade 1 is achieved and continuing with the reduced dosage for the duration of treatment. Managing Cardiotoxicity Cardiotoxicity is a known adverse event of HER2-targeted therapies such as T-DM1 and T-DXd. HER2 receptors are usually expressed on cardiomyocytes and play a key role in normal fetal heart development and the growth and survival of adult cardiomyocytes. Preclinical studies suggest T-DM1 can exert more cardiotoxic effects than trastuzumab, though clinical evidence remains low. A pooled meta-analysis by Pondé et al of data from 1961 patients exposed to T-DM1 in seven trials found 3.37% experienced at least one cardiac event. Most of the events (2.04%) were grade 1 or 2 left ventricular ejection fraction (LVEF); grade 4 LVEF events were rare. Although no specific guidelines exist for the management of T-DM1-associated cardiotoxicity, general recommendations for ADC treatment from the 2022 European Society of Cardiology Cardio-Oncology guidelines suggest a baseline ECG prior to treatment initiation and then echocardiography every 3 months thereafter, along with natriuretic peptide monitoring throughout treatment. Treatment interruption and reassessment are indicated for patients whose LVEF drops to ≥ 10% from pretreatment value or to < 40%. For T-DXd, cardiac events were minimal in DESTINY-Breast01 and Breast03 trials, with few patients experiencing reversible LVEF reductions; no events of heart failure were reported. However, the DESTINY-Breast04 trial showed that 11.9% of patients receiving T-DXd who had not been previously treated with an anti-HER2 agent had LVEF reductions of 10%-19%, and 1.5% had > 20%. Management of ADC-related cardiac events includes reducing or permanently withdrawing treatment. Following treatment interruption, ADCs may be resumed with increased monitoring if cardiac function recovers. Permanent discontinuation may be required for patients whose LVEF remains significantly low or who develop heart failure. Managing Gastrointestinal Toxicity Nausea and vomiting are two of the most common GI toxicities associated with T-DXd treatment. In the DESTINY-Breast03 trial, 72.8% (187 of 257) and 6.6% (17 of 257) of patients had any grade and grade ≥ 3 nausea, respectively, post-T-DXd treatment. Vomiting was also commonly reported, with 44.0% (113 of 257) and 1.6% (4 of 257) of patients experiencing any grade and grade ≥ 3 vomiting, respectively. Based on these findings and other clinical trial data, the National Comprehensive Cancer Network Clinical Practice in Oncology guidelines reclassified T-DXd as highly emetogenic. The emetogenic classification of SG varies by guideline but is generally categorized as high-moderate or high. According to pooled analysis data by Pedersini et al, 65.6% and 43.7% of patients experienced nausea and vomiting, respectively, with SG therapy. Most cases of nausea and vomiting were grade 1 or 2, and approximately 10% were grade 3 or 4. T-DM1 is categorized as a low emetogenic since its associated toxicities are easier to manage. Prophylactic antiemetic therapy for nausea and vomiting associated with ADCs varies based on guidelines and emetogenic categorization. Due to their higher emetogenic risk, a 3- or 4-drug antiemetic regimen (eg, 5-hydroxytryptamine 3 receptor antagonist, dexamethasone, neurokinin-1 receptor antagonist, olanzapine) is recommended for T-DXd and SG. Due to its low emetic risk, prophylactic antiemetics are not usually recommended for T-DM1 but may be considered based on a patient's individual risk factors. In general, dose interruption or modification is recommended for patients on T-DXd or SG who experience grades 3 or 4 nausea and vomiting until they recover to grade 1 toxicity. Treatment with SG may be permanently stopped if grade 3 or 4 toxicity lasts for more than 3 weeks. Diarrhea is another common GI adverse event associated with ADC use and is reported to occur in 59.7% of patients treated with SG, 30.2% with T-DXd, and 17.5% with T-DM1. Management for ADC-associated diarrhea includes loperamide, intravenous fluids, metoclopramide with or without dexamethasone, and olanzapine for refractory cases. Preventive strategies include dietary modifications (eg, high fiber diet), oral supplements and probiotics, and nutritional counseling. Managing Interstitial Lung Disease Interstitial lung disease (ILD) is a group of lung disorders characterized by fibrosis or scarring of the lungs. Risk factors for the development of drug-induced ILD include increased age (≥ 60 years), smoking, pre-existing lung conditions, higher alcohol consumption, and renal failure. A pooled analysis of eight T-DXd monotherapy studies suggested 15.8% of the population developed ILD/pneumonitis with 77.7% experiencing grade 1 or 2 events. The DESTINY-Breast03 trial showed the incidence of drug-related ILD/pneumonitis with T-DXd to be lower at 10.5%. In phase 3 of the ASCENT trial, ILD associated with SG or T-DM1 was rare in patients with metastatic TNBC. In addition, the phase 1/2 study, U31402-A-J101, investigating HER3-DXd reported ILD in 6.6% of patients; most cases were grade 1 or 2, three were grade 3, and one was grade 5. Regular monitoring and assessment of patients are important to prevent ILD/pneumonitis. Per the current T-DXd ILD/pneumonitis guidelines, a computed tomography scan should be obtained prior to initiating ADC treatment and every 9-12 weeks thereafter during treatment. Patients who develop ILD/pneumonitis should undergo CT scans every 1-2 weeks (or as clinically indicated). In cases of suspected ILD/pneumonitis, consultation with a pulmonary specialist is recommended. Treatment for ILD/pneumonitis includes initiation of corticosteroid therapy immediately upon detection of grade ≥ 2 ILD/pneumonitis; corticosteroid treatment may be considered in patients with grade 1 ILD/pneumonitis. Guidelines for treating ILD/pneumonitis include starting corticosteroids immediately after detecting grade ≥ 2 ILD/pneumonitis and considering corticosteroid treatment in case of grade 1 cases. Future Directions Regular monitoring and prophylactic management are essential to reduce and mitigate ADC-related toxicities and maximize treatment benefits. Other toxicities associated with ADCs include neurological, embryo-fetal, ocular, and dermatological events. Continued research is needed to understand the mechanisms that contribute to ADC-related toxicities and provide additional management approaches to reduce risk. In addition, future research efforts should focus on the development of highly targeted therapeutics aimed at specific antigens, the creation of safer drug payloads, and the innovation of new linker technologies to reduce off-target effects. Novel ADCs are in development to enhance cancer immunotherapy by targeting immune cells or components of tumor microenvironment rather than tumor-associated antigens directly. These include immunostimulatory antibody conjugates that use immune-activating payloads (eg, Toll-like receptors 7 and 8, stimulators of interferon genes agonists) instead of traditional cytotoxins. Early clinical trials have evaluated immunostimulatory antibody conjugates against targets like HER2 and carcinoembryonic antigen. In addition, other ADCs are being developed to target elements of the tumor microenvironment such as T cells and fibroblasts. These novel approaches are likely to produce unique toxicity profiles, highlighting the need for a deeper understanding of their safety as development progresses.
Yahoo
19 hours ago
- Yahoo
Conspiracy theorist reprimanded by coroner at inquest into daughter's death
A University of Cambridge graduate who refused chemotherapy wrote in statements before her death that she was 'anti-vax' and always turned to her mother first for health advice, an inquest has heard. Paloma Shemirani, 23, died at Royal Sussex County Hospital in Brighton on July 24, 2024 after declining the treatment for non-Hodgkin lymphoma. She grew up in Uckfield and attended Roedean School for sixth form. Her mother, Kay 'Kate' Shemirani, rose to prominence on social media while sharing Covid-19 conspiracy theories, the inquest at Oakwood House in Maidstone, Kent, heard previously. In written statements submitted to the family division of the High Court in Spring 2024, Paloma said she declined chemotherapy partly because of her 'background in natural healing', the inquest heard on Monday. The proceedings, which involved the Maidstone and Tunbridge Wells NHS Trust, were on the appropriateness of her care and Paloma said she was 'delighted' with her alternative treatment and 'sure' she would 'make a full recovery' if left to continue it, the inquest was told. She also claimed her human rights had been violated by NHS practitioners in the statements, which were read by lawyer Alison Hewitt. Ms Shemirani, who attended the inquest via video link, wept and held pictures of Paloma to the camera as they were read. It said: 'I am far from being a vulnerable young adult. Apart from becoming independent after I moved to Cambridge for university, I have practised the same principles that I grew up with. 'I have always been extremely health conscious: sticking to all-organic produce, I prepare all my own meals and I absolutely do not drink or cook with tap water. 'I have never taken drugs, despite pressure to, and I rarely drink alcohol. 'If I became ill, I've always turned to my mum first for advice as she is a trained nurse and qualified nutritionist. 'Practically fanatical about my health, my close friends know me as a staunch advocate for all proven natural healing'. Gabriel Shemirani, outside Oakwood House in Maidstone, Kent, for the inquest into the death of his sister (Image: PA) She also described her mother as 'an extremely forceful advocate for natural health' who is 'misquoted' by people claiming 'those natural solutions are conspiratorial'. Ms Shemirani was struck off as a nurse in 2021, with a Nursing and Midwifery Council (NMC) committee finding that she had spread Covid-19 misinformation that 'put the public at a significant risk of harm', the inquest heard previously. Another statement in Paloma's name added 'my friends know me as a staunch advocate of the Gerson therapy' and she stated that she is 'anti-vax'. She said she had been using Gerson therapy as one mode of treatment on the advice of her mother's ex-fiancé, Doctor Patrick Villers, and that at 15 years old she spent three weeks in his camp in Mexico where it was practised. Gerson therapy involves a strict organic vegetarian diet and enemas and has been used in cancer treatment, though Cancer Research UK says that there is no scientific evidence it can be used as a treatment for cancer. Her GP was also monitoring her blood and progress, she said. The former Cambridge student went on to deny having the disease and said 'I was not diagnosed with non-Hodgkin's lymphoma… I have never had a shadow on my lung, this is absurd fantasy, no proof'. She described the diagnosis as 'suspected and unconfirmed', and said a 'differential diagnosis' only meant cancer could not be ruled out. Paloma understood that she had a one in five chance of surviving the commonplace R-CHOP treatment that was offered, and feared it would likely make her infertile, the inquest heard. 'I do not want to undergo such a harsh treatment that could even kill me when there is a possibility this is not cancer', she said. The High Court statement alleged multiple violations of human rights in her care, the inquest heard, including Articles 3, 6 and 8 and possibly Articles 1, 5 and 12. 'I am so shocked, as are others assisting me, especially my mother, that this could take place today', the statement said. 'These were put in place forever to prevent what Dr Mengele did in the Second World War. How could this happen today?', it continued. Notorious Nazi doctor Josef Mengele performed experiments on his victims in Auschwitz. The patient said symptoms she presented in hospital with – including a swollen face, excruciating chest pain and being unable to move her arm – had subsided. Coroner Catherine Wood reprimanded Ms Shemirani multiple times during proceedings. Ms Shemirani cross-examined Dr Amit Goel, a consultant histopathologist at Maidstone Hospital who carried out a biopsy. She repeatedly put to him that insufficient tissue was taken to carry out a FISH test that could rule out other diseases and alter Paloma's treatment plan. The doctor denied that this would have influenced Paloma's care multiple times, and the coroner told Ms Shemirani the inquest is trying to look at 'how Paloma came about her death' but 'you are apparently trying to get information which is incorrect, factually incorrect, in the statements you are making'. 'I think your questions are just designed to take up time and delay matters by the way you're asking them repeatedly,' she added. The mother accused participants of mis-pronouncing her name, which eventually led Ms Wood to say: 'I am going to rise, for Ms Shemirani to reflect on her behaviour in court, this is unacceptable. 'Let's have a pause for tempers to die down because you are clearly becoming over-fixated on a detail.' At the opening of the hearing Ms Shemirani made an application for a lawyer to recuse herself. The coroner rejected the application and said had seen the 'hundreds of emails that have been sent in' and that 'you have requested that everybody recuse themselves at various times', including the coroner herself. The inquest continues.
Yahoo
19 hours ago
- Yahoo
'Anti-vax' woman died after refusing chemotherapy
A woman who died after refusing treatment for cancer told a court she was "anti-vax", an inquest has heard. Paloma Shemirani, who had declined chemotherapy for non-Hodgkin lymphoma, suffered a fatal heart attack caused by her tumour at the Royal Sussex County Hospital (RSCH) on 24 July last year. The 23-year-old's mother Kay (Kate) Shemirani, who shared Covid conspiracy theories on social media, has blamed doctors' interventions for her daughter's death. Paloma had also claimed her human rights had been violated by NHS practitioners, likening it to what the Nazis did during WWII, the inquest was told at Oakwood House in Maidstone, Kent. In previous written statements - submitted to the family division of the High Court in spring 2024 and read out at the hearing on Monday - she described the alleged violations as akin to experiments carried out at Auschwitz. Paloma, who grew up in Uckfield, East Sussex, denied even having non-Hodgkin lymphoma, calling it an "absurd fantasy, with no proof". The Cambridge graduate described the diagnosis as "suspected and unconfirmed", adding that she had a "background in natural healing". In addition, she feared that if she were to survive chemotherapy it might make her infertile. "I do not want to undergo such a harsh treatment that could even kill me when there is a possibility this is not cancer", she said. She described her mother, who was struck off as a nurse in 2021, as "an extremely forceful advocate for natural health" who was often "misquoted". Paloma had turned to Gerson therapy - a strict organic vegetarian diet involving enemas - on the advice of her mother's ex-fiancee, Dr Patrick Villers, though Cancer Research UK said there was no scientific evidence of it being an effective treatment. The proceedings, which involve Maidstone and Tunbridge Wells NHS Trust, were on the appropriateness of her care and heard how Paloma had said she was "delighted" with her alternative treatment and "sure" she would "make a full recovery" if left to continue it. The inquest, led by coroner Catherine Wood, continues. Additional reporting from PA Media. Follow BBC Sussex on Facebook, on X, and on Instagram. Send your story ideas to southeasttoday@ or WhatsApp us on 08081 002250. More on this story 'Our sister died of cancer because of our mum's conspiracy theories' Concern mum 'influenced daughter's chemo refusal' Related internet links Kent and Medway Coroner's Service