A new study by Dana-Farber Cancer Institute investigators, which tracked nearly 200 young women treated for breast cancer, found that the majority of those who tried to conceive during a median of 11 years after treatment were able to become pregnant and give birth to a child.
The findings, to be presented at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO), are particularly noteworthy because they answer several questions left open by previous studies of pregnancy and live-birth rates among breast cancer survivors, the study authors say.
“Earlier studies were limited because they included select subgroups of patients, followed patients for a relatively short period of time, and didn’t ask participants, during the study period, if they had attempted pregnancy,” says the study’s senior author, Ann Partridge, MD, MPH, the founder and director of the Program for Young Adults with Breast Cancer at Dana-Farber. “This study was designed to address those gaps by tracking pregnancy and live birth rates among a group of breast cancer survivors and patients who indicated they’d attempted to conceive following their cancer diagnosis.”
The patients in the study were participants in the Young Women’s Breast Cancer Study, which is tracking the health of a group of women diagnosed with breast cancer at or under age 40. Of 1213 eligible participants, 197 reported an attempt of pregnancy over a median follow-up period of 11 years. Within this latter group, the median age at the time of diagnosis was 32 years, and most were diagnosed with hormone receptor-positive breast cancer. Participants were periodically surveyed about whether they had tried to become pregnant and whether they had conceived and given birth.
Over the course of the study, 73% of women attempting to conceive achieved a pregnancy and 65% had a live birth, researchers found. Those who opted for fertility preservation by egg/embryo freezing before cancer treatment tended to have a higher live birth rate, while older participants tended to have lower pregnancy and live birth rates
Participants in the study had breast cancers ranging from stage 0, which are non-invasive and confined to the inside of the milk duct, to stage III, in which the cancer has spread to the lymph nodes. There was no statistically significant association with stage of the disease at diagnosis and achieving a pregnancy or live birth.
“For many young women with breast cancer, the ability to have children following treatment is a major concern,” says the study’s first author, Kimia Sorouri, MD, MPH, of Dana-Farber. “The findings of our study can be helpful when counselling patients about fertility issues. The finding that egg/embryo freezing before treatment was associated with a higher live birth rate underscores the need for accessibility to fertility preservation services for this population.”
A protein called retinitis pigmentosa GTPase regulator interacting protein 1-like (RPGRIP1L) performs various functions that are important for development and for health throughout life, and mutations in the RPGRIP1L gene have been linked to different diseases. New research published in The FASEB Journal indicates that expression levels of the RPGRIP1L gene might serve as a new prognostic marker for individuals with invasive breast cancer.
When investigators examined breast tissue specimens from different women, they found that the expression of RPGRIP1L was elevated in invasive breast cancer specimens compared with normal breast tissue specimens. Also, among patients with invasive breast cancer, those with higher RPGRIP1L gene expression had shorter survival times than those with low expression. Furthermore, elevated expression of RPGRIP1L corresponded with a spectrum of unfavourable clinicopathological features such as the presence of more aggressive forms of cancer and larger tumours.
The researchers also identified 50 genes and 15 proteins whose expression was positively related to RPGRIP1L expression, with most of these proteins and genes being involved in different aspects of the immune response and metabolism.
Finally, the team found that 4 compounds used against cancer – abrine, epigallocatechin gallate, gentamicin, and tretinoin – showed potential for reducing the expression of RPGRIP1L in lab experiments.
“The findings of our research underscore the potential of RPGRIP1L as a significant prognostic biomarker for breast cancer and suggest the viability of novel therapeutic strategies that may modify disease progression, thus potentially enhancing survival rates among affected individuals,” said co–corresponding author Jie Zeng, PhD, of the First Affiliated Hospital of Hunan Normal University, in China.
There is a surprising dearth of research about how breast cancer cells can go dormant, spread and then resurface years or even decades later, according to a new review of in vitro breast cancer studies conducted by researchers at the University of Massachusetts Amherst.
“[Our review found that] less than 1% of all these studies that combine cells with designer environments look at dormancy,” says Shelly Peyton, Provost Professor of Chemical Engineering. “It’s not enough. We just don’t understand what’s happening – and it’s killing patients.”
Breast cancer dormancy is a phenomenon in which breast cancer cells metastasise (typically to the liver, lungs, brain or bones) but don’t grow. “They’re not detectable or symptomatic tumours,” Peyton explains. “A patient will have their primary tumour removed and appear to be disease-free for months, years, even decades. And for reasons we don’t understand, something changes about the environment that causes those cells to start regrowing, and then you have a deadly metastasis.”
Patients with metastatic breast cancer have a 30% five-year survival rate, compared to a 99% survival rate for localised breast cancer. “Early detection is key, particularly in the Western world,” says Peyton. “You can have lumpectomies, radiation, small surgeries. And women can survive. It’s when that cancer has spread that it becomes much harder to treat.”
This relapse in distant organs impacts 40% of early-stage breast cancer patients, and breast cancer dormancy is a contributing factor. But while metastasis has known biomarkers, dormant cancer cells are very hard to identify.
“When you have a single dormant breast cancer cell that’s hiding in a distant tissue, it’s really hard to detect that,” says Nate Richbourg, lead author on the paper and postdoctoral researcher in the Peyton Lab. “And you don’t want to do an invasive biopsy or prescribe toxic chemotherapy for something that might not be a problem.”
With these challenges in mind, the review, published in Science Advances, aimed to identify gaps in the research, particularly focusing on in vitro studies, or research using benchtop-model environments instead of animal models or humans. In vitro studies allow for the precise control of the environment, which Peyton’s research group says may play a deciding role in whether a cell remains dormant or reactivates into a deadly metastatic tumor.
“What can we control in these artificial environments that will give us insight into how breast cancer dormancy happens, and what we can do to treat it as well?” Richbourg asks, describing the importance of in vitro modelling. “When we create this artificial dormancy, we can see how many of those cells could turn back into proliferating and potentially deadly cells.”
Their review highlights just how complex the role of the environment is. “If you have a [breast cancer] cell somewhere in the bone marrow, you’re going to have other cells there, the physical factors in your environment, and the biochemical factors,” Richbourg gives as an example. “We try to use reductive models to separate the thing that is influencing this behaviour. But what we’re seeing is that everything works together to create this breast cancer dormancy effect. The better we can create models that capture all that nuance, the better we’re going to be able to understand it.”
For Peyton, their work is also a call to action. “The paper is calling out to the field that we need to do more,” she says. This includes being more creative with the materials that already exist and developing new materials; identifying ways to model the decades-long progression of dormancy that is impossible to recreate in a single study; and expanding the diversity of cell lines used for research (Richbourg points out that many of the studies they reviewed used the same cell line, MDA-MB-231, derived from one 40-to-50-year-old white woman).
Finally, the researchers have an eye to the ultimate goal: better treatments to save patients. “We see that that there are some clinical trials that are happening that are derived from some of those in vitro models,” says Ninette Irakoze, graduate student in the Peyton Lab. “The paper gives hope that, with more development of these in vitro models, eventually we could find treatments to eradicate dormant cancer.”
For decades, hormonal treatment of breast cancer has been going in one direction: blocking oestrogen. Now, a global study has discovered there may be another, less toxic way to defeat the most common form of breast cancer. The results, published inThe Lancet Oncology, showed that the androgen receptor (AR) agonist enobosarm, is effective against oestrogen receptor-positive (ER+) breast cancer, which constitutes up to 80% of all breast cancer cases.
“The effectiveness of enobosarm lies in its ability to activate the AR and trigger a natural defence mechanism in breast tissue, thereby slowing the growth of ER+ breast cancer, which relies on the hormone oestrogen to grow and spread,” said senior co-author Professor Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories at the University of Adelaide.
“This clinical study is supported by our pre-clinical research, previously published in Nature Medicine, which established that the AR is a tumour suppressor in both normal breast tissue and ER+ breast cancer.”
Along with investigators from the University of Adelaide and Dana-Farber Cancer Institute (DFCI) in Boston, USA, the international study also included researchers from the University of Liverpool in the UK and other experts around the world.
The team assessed enobosarm’s efficacy and safety in 136 postmenopausal women with advanced or metastatic ER-positive, HER2-negative breast cancer.
Enobosarm showed significant anti-tumour activity and was well-tolerated by patients, without adversely affecting their quality of life or causing masculinising symptoms.
This discovery represents the first advancement in hormonal treatment of ER+ breast cancer in decades and offers a promising new oral treatment strategy for the most prevalent form of breast cancer.
The new hormonal strategy differs from the existing standard-of-care hormonal treatments, which have been around for decades and involve suppressing oestrogen activity in the body or inhibiting the ER.
Although successful initially, treatments targeting ER can cause severe side effects and treatment-resistant progression of the disease is common.
“Our findings are very promising. They demonstrate that stimulating the androgen receptor pathway with enobosarm can be beneficial,” said senior co-author and study Principal Investigator Dr Beth Overmoyer from DFCI.
“This is the first time a non-oestrogen receptor hormonal treatment approach has been shown to be clinically advantageous in ER+ breast cancer. The study supports further investigation of enobosarm in earlier stages of breast cancer as well as in combination with targeted therapies, such as ribociclib, a CDK 4/6 inhibitor.”
estrogen to grow and spread,” said senior co-author Professor Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories at the University of Adelaide.
“The data strongly encourages more clinical trials for AR-stimulating drugs in treating AR-positive and ER-positive breast cancer. The fact that this drug is well-tolerated also opens possibilities for its use in breast cancer prevention,” said co-author Dr Stephen Birrell, a clinical affiliate of the University of Adelaide.
Diagnoses of breast cancer have increased steadily in women under age 50 over the past two decades, with steeper increases in more recent years, according to a study published in JAMA Network Open. The surge is driven largely by increases in the number of women diagnosed with oestrogen-receptor positive (ER+) tumours.
While overall trends show increases, however, some decreases have occurred in specific tumour types and among specific groups of women. Such changes in disease rates in young women observed over time – analysed by age, race, tumour type, tumour stage and other factors – may offer clues to possible prevention strategies.
“For most women, regular breast cancer screening does not begin until at least age 40, so younger women diagnosed with breast cancer tend to have later-stage tumours, when the disease is more advanced and more difficult to treat,” said senior author Adetunji T. Toriola, MD, PhD, a professor of surgery and co-leader of the Cancer Prevention and Control Program at Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University School of Medicine. “This research offers a way to begin identifying the factors driving these increasing rates, with the goal of finding ways to slow or reverse them. It also could help identify young women who are at high risk of developing early-onset breast cancer, so that we can design interventions to evaluate in clinical trials to see if we can lower that risk.”
The research team analysed data from over 217 000 U.S. women diagnosed with any type of breast cancer from 2000 through 2019. In 2000, the incidence of breast cancer among women ages 20 to 49 was about 64 cases per 100 000 people. Over the next 16 years, that rate slowly went up, increasing at about 0.24% per year. By 2016, the rate had reached about 66 cases per 100 000. But after 2016, for reasons researchers do not yet understand, the trend line made a steep uphill turn, suddenly increasing at 3.76% per year. By 2019 the rate had reached 74 cases per 100 000.
An additional intriguing aspect of the data is that the increase in breast cancer incidence is due almost entirely to an increase in tumours that are ER+ according to Toriola, who is also a William H. Danforth Washington University Physician-Scientist Scholar. These tumours have proteins on their surfaces that bind to oestrogen, which fuels tumour growth. In fact, the incidence of tumours without the oestrogen receptor decreased over the 20 years of data analysed in the study.
“We need to understand what is driving the specific increase in oestrogen-receptor positive tumours,” Toriola said. “We also hope to learn from the decrease in oestrogen-receptor negative tumours. If we can understand what is driving that rate down, perhaps we can apply it in efforts to reduce or prevent other breast tumour types.”
The researchers also found higher rates of breast cancer among Black women, especially among those ages 20 to 29. Black women in this age group have a 53% increased risk of breast cancer compared with white women of the same age group. A higher risk for Black women also continues from ages 30 to 39, but the increased risk is smaller, at about 15% greater risk compared with white women of the same age range. Then, from ages 40 to 49, the rate for Black women drops below that of white women.
Toriola said his group is evaluating breast tumour tissue from cancer patients of different ages and races to see if there are molecular differences that could shed light on what is driving cancer to develop more in young Black women. Of note, Hispanic women in the study had the lowest incidence of breast cancer of any group.
The researchers also showed an increase in diagnoses of stage 1 and stage 4 tumours, and a decrease in diagnoses of stage 2 and stage 3 tumours. Toriola said such data suggest that improvements in screening over the past two decades, and perhaps greater awareness of family history and genetic risk factors for breast cancer, have led to many tumours being caught earlier. But it also suggests that when stage 1 tumours are missed in younger women, the tumours tend not to be found until they reach stage 4.
The researchers also found differences in breast cancer risk by year of birth. Toriola said the most dramatic difference was a greater than 20% increased risk of breast cancer among women born in 1990 compared with women born in 1955.
“We are hopeful this study will offer clues to prevention strategies that will be effective in younger women, especially younger Black women, who are at particularly high risk of developing breast cancer before age 40,” Toriola said.
Including patients as partners for making decisions about their medical treatments is an important aspect of patient-centred care. A new study from England examined choices that patients with breast cancer make when considering where to have surgery for their condition and assessed how policies that offer such choices might affect inequalities in the health care system. The findings are published in CANCER.
For the study, investigators analysed data from the National Health Service (NHS), the publicly funded health care system in the United Kingdom that offers patients with cancer the opportunity to select any hospital providing cancer treatment, and identified all women diagnosed with breast cancer from 2016 to 2018 who had breast-conserving surgery or a mastectomy.
Records showed that 22 622 of 69,153 patients undergoing breast-conserving surgery (32.7%) and 7179 of 23 536 patients undergoing mastectomy (30.5%) bypassed their nearest hospital to receive surgery farther away from home. Women who were younger, without additional medical conditions, of white ethnic background, or lived in rural areas were more likely to travel to more distant hospitals.
Patients were more likely to be treated at hospitals classified as specialist breast reconstruction centres even if they personally were not undergoing breast reconstruction after surgery. Patients who had a mastectomy and immediate breast reconstruction were more likely to travel to hospitals that had surgeons with a strong media reputation for breast cancer surgery, and patients were less likely to travel to hospitals with shorter surgical waiting times. Patients did not seem to make choices based on hospitals’ research activity, quality rating, breast re-operation rates (to remove additional cancer cells that were missed), or status as a multidisciplinary cancer centre (where patients can receive all their care at one location).
The investigators noted that this separation – elderly patients, those with comorbidities, and those from ethnic minority backgrounds receiving care at their local hospital, while others travel to other hospitals and specialist centres – could further drive inequalities in access to quality care.
“As marginalized groups already face barriers to high-quality care, it is important for policy makers to consider measures that mitigate against the risks of increasing inequalities in access and outcomes, by for example providing free transport, accommodation, or even protection against loss of income,” said co-author Lu Han, PhD, of the London School of Hygiene & Tropical Medicine. “Moreover, patients prefer to access information on the quality of breast cancer care of the hospitals in their region at the start of the management pathway when a diagnosis is sought. Such information should be easy to understand and presented in a format that can support the trade-offs that patients have to make.”
Immunotherapy in combination with chemotherapy has become an important therapeutic treatment option in some patients with metastatic breast cancer. Which patients will benefit the most, however, remains unclear; current biomarkers such as PD-L1 that are used to predict response are mediocre at best. Vanderbilt researchers led a clinical trial combining atezolizumab, an immunotherapy, in combination with chemotherapy in patients with metastatic triple-negative breast cancer to both evaluate the efficacy of the treatment combination and to understand biomarkers of response to immunotherapy.
Atezolizumab became the first approved immunotherapy for breast cancer when the Food and Drug Administration granted it accelerated approval in 2019, but two years later, its maker voluntarily withdrew the indication after additional data from a follow-up clinical trial failed to corroborate its efficacy. Atezolizumab had been approved for metastatic PD-L1-positive triple-negative breast cancer in combination with the chemotherapy nab-paclitaxel. Results from Vanderbilt’s clinical trial, published in JAMA Oncology, indicate that this immunotherapy does have a clinically meaningful benefit with a different chemotherapy partner and the correlative analyses provide insight to which patients will respond.
The clinical trial combined atezolizumab with carboplatin – a chemotherapy that works differently than nab-paclitaxel. The new combination significantly improved progression-free and overall survival of patients with metastatic triple-negative breast cancer. Atezolizumab with carboplatin lengthened progression-free survival from a median of 2.2 months to 4.1 months. Overall survival increased from a median of 8.6 months for the control group, who received carboplatin alone, to 12.6 months for those who received the combination therapy.
The phase 2 randomized clinical trial was conducted at six cancer centers through the Translational Breast Cancer Research Consortium and involved 106 patients of diverse ethnicities.
“Triple-negative breast cancer is difficult to treat because we don’t have a clear target, and understanding the underlying factors that affect response to a treatment is key. This study is so important because we were able to collect biopsies in all of the participants and really understand factors that affect response,” said Vandana Abramson, MD, the Donna S. Hall Professor in Cancer Research and co-leader of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center.
The researchers hypothesised that atezolizumab would have superior efficacy to carboplatin because the chemotherapy is a platinum agent, which causes structural DNA changes and generates neoantigens that may stimulate an immune response. Nab-paclitaxel chemotherapy works differently: it is a microtubule-stabilising agent that stops cancer cell division.
“The tremendous knowledge gained from our multidisciplinary analyses of the patients and their tumours will continue to be important for clinical decision-making. After our first description of the triple-negative breast cancer subtypes over 10 years ago, more recently, we refined the subtypes further into four, which were analysed in this study: two basal-like subtypes, a mesenchymal subtype and a lumen androgen receptor-expressing subtype. When we refined the triple-negative breast cancer subtypes, we revealed an immune-modulatory descriptor or correlation.
“This JAMA Oncology study and others continue to confirm that lymphocytes, as measured by the immune-modulatory correlation, have predictive value for better relapse-free survival for triple-negative patients. Further, this study provides evidence that the luminal androgen receptor subtype is more like oestrogen receptor-positive (or ER+) disease. Prior studies investigating immunotherapy in breast cancers have shown that patients with ER+ disease have less benefit from immunotherapy, and we found that to be the case with patients with luminal androgen-positive tumours in this trial,” said Jennifer Pietenpol, PhD, the study’s corresponding author.
Interestingly, patients with higher body mass indexes and uncontrolled blood glucose levels had greater benefit from atezolizumab with carboplatin. The researchers noted that these patients may have more immune cells upon which anti-PD1/PD-L1 therapies can act. A lower risk of disease progression was also associated with high mutation burden and increased tumour-infiltrating lymphocytes.
“In this study, we observed that patients received benefit with atezolizumab even if the tumours were PD-L1 negative. We also show that, like prior clinical trials in melanoma and renal and lung cancers, tumours with high mutation burdens and the presence of immune cells within or around the tumour receive greater benefit from immunotherapy. This makes sense because each mutation has the potential to be recognised as non-self by the immune system, increasing the probability of immune cells already positioned around the tumour to recognise and target the cancer,” said Brian Lehmann, PhD, Research Associate Professor of Medicine and lead correlative scientist on the study.
“One surprising finding was the trend toward greater benefit for patients with higher body mass indexes and patients with uncontrolled blood glucose at prediabetic and diabetic levels while on the study. Both obesity and diabetes are linked to systemic inflammation, and the increased benefit may be attributed to higher adipose tissue composition in the breast and augmented by metabolic syndrome conditions such as Type 2 diabetes. Further studies are necessary to validate these findings and delineate the effects of blood glucose and obesity on immunotherapy,”
The combination therapy was generally well-tolerated, and toxic effects were consistent with previous reports for atezolizumab. The most common drug complications on the combination arm of the clinical trial were low blood platelet counts, anaemia, lymphocytopenia, nausea, fatigue and increased liver enzymes. The participants identified as 69% white, 19% African American, 10% unknown and 1% Asian.
University of Bristol researchers have created a robotic hand that could carry out Clinical Breast Examinations (CBE). The device is able to apply very specific forces over a range similar to forces used by human examiners and can detect lumps using sensor technology at larger depths than before.
This could revolutionise how women monitor their breast health by giving them access to safe electronic CBEs, located in easily accessible places, such as pharmacies and health centres, which provide accurate results. The technology is described in the journal Sensors.
Precision, repeatability and accuracy are of paramount importance in these tactile medical examinations to ensure favourable patient outcomes. A range of automatic and semi-automatic devices have been proposed to aid with optimising this task, particularly for difficult to detect and hard to reach situations such as during minimally invasive surgery.
The research team included a mix of postgraduate and undergraduate researchers, supervised by Dr Antonia Tzemanaki from Bristol Robotics Laboratory. Lead author George Jenkinson explained: “There are conflicting ideas about how useful carrying out Clinical Breast Examinations (CBE) are for the health outcomes of the population.
“It’s generally agreed upon that if it is well performed, then it can be a very useful and low risk diagnostic technique.
“There have been a few attempts in the past to use technology to improve the standard to which healthcare professionals can perform a CBE by having a robot or electronic device physically palpate breast tissue. But the last decade or so of technological advances in manipulation and sensor technology mean that we are now in a better position to do this.
“The first question that we want to answer as part of this is whether a specialised manipulator can be demonstrated to have the dexterity necessary to palpate a realistic breast size and shape.”
The team created their manipulator using 3D printing and other Computerised Numerical Control techniques and employed a combination of laboratory experiments and simulated experiments on a fake (silicone) breast and its digital twin, both modelled on a volunteer at the Simulation and Modelling in Medicine and Surgery research group at Imperial College London.
The simulations allowed the team to perform thousands of palpations and test lots of hypothetical scenarios such as calculating the difference in efficiency when using two, three, or four sensors at the same time. In the lab, they were able to carry out the experiments on the silicone breast to demonstrate the simulations were accurate and to experimentally discover the forces for the real equipment.
George added: “We hope that the research can contribute to and complement the arsenal of techniques used to diagnose breast cancer, and to generate a large amount of data associated with it that may be useful in trying to identify large scale trends that could help diagnose breast cancer early.
“One advantage that some doctors have mentioned anecdotally is that this could provide a low-risk way to objectively record health data. This could be used, for example, to compare successive examinations more easily, or as part of the information packet sent to a specialist if a patient is referred for further examination.”
As a next step, the team will combine CBE techniques learned from professionals with AI, and fully equip the manipulator with sensors to determine the effectiveness of the whole system at identifying potential cancer risks.
The ultimate goal is that the device and sensors will have the capability to detect lumps more accurately and deeper than it is possible only from applying human touch. It could also be combined with other existing techniques, such as ultrasound examination.
“So far we have laid all of the groundwork,” said George. “We have shown that our robotic system has the dexterity necessary to carry out a clinical breast examination – we hope that in the future this could be a real help in diagnosing cancers early.”
Colourised scanning electron micrograph of a breast cancer cell. Credit: NIH
A novel therapeutic approach that combines human epidermal growth receptor factor 2 (HER2)-targeted therapies with the cholesterol-lowering drug lovastatin can reduce the number of cancer treatments required to prevent tumour growth. Monitored by immuno-PET scans, this combination therapy has the potential to personalise treatment for cancer patients and spare them from harmful side effects. This research was published in The Journal of Nuclear Medicine.
Antibody-drug conjugates (ADCs) have become an eminent cancer treatment because of their ability to precisely target tumours with potent efficacy. HER2-ADC therapies have been effective in treating breast, lung, bladder, and stomach cancers. Although usually well-tolerated, multiple doses of the drugs can result in severe side effects, including low blood counts, liver damage, and lung damage. Strategies that reduce toxic side effects caused by ADCs and predictive biomarkers of ADC toxicity are currently an unmet clinical need.
“In this study, we sought to determine whether a single dose of HER2-ADCs could be administered in combination with lovastatin (which temporarily elevates cell-surface HER2) to achieve therapeutic efficacy similar to that of a multiple dose regime,” said Patricia Pereira, PhD, assistant professor at the Washington University School of Medicine. “We also used HER2-targeted immuno-PET to monitor changes in HER2 expression after ADC therapy.”
Researchers injected mice with cultured gastric cancer cells and patient-derived gastric cancer cells. When tumours grew sufficiently, the mice were divided into groups and received various treatment schedules (no treatment, multiple doses of ADC, multiple doses of ADC with lovastatin, single dose of ADC, or single dose of ADC with lovastatin). Immuno-PET was used to investigate the dosing regimen and the efficacy of the treatment schedules.
A single dose of ADC therapy combined with lovastatin was found to reduce tumour volume at rates similar to those resulting from multiple doses of ADC in a preclinical setting. The study results showed that immuno-PET can noninvasively monitor HER2 tumour levels after treatment with HER2-targeted ADC therapies.
“This preclinical work is significant because it has the potential to improve therapy for patients with HER2-positive cancers,” noted Pereira. “It not only simplifies treatment by exploring single-dose schedules of antibody-drug conjugates but can also reduce side effects by minimizing the number of doses required. Additionally, it personalises therapy using molecular imaging, enhancing treatment efficacy.”
She continued, “The findings suggest a future where molecular imaging techniques play a critical role in guiding drug development and cancer treatment decisions, particularly as various ADCs are being tested and approved for cancer treatment. Currently, there is no perfect way to select tumours or monitor their response to ADCs. This research indicates that molecular imaging can bridge this gap by providing real-time insights into therapy response.”
New research has uncovered high rates of hyperglycaemia among breast cancer patients being treated with the oral medication alpelisib. The researchers say that patients receiving this medication should have their blood sugar levels monitored and managed well before treatment with alpelisib. The results are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.
Alpelisib targets the phosphoinositide 3-kinase (PI3K) protein that is involved in cell growth and when mutated can fuel cancer. In 2019, the US Food and Drug Administration approved the use of this drug in combination with fulvestrant, an oestrogen receptor blocker, for certain cases of metastatic breast cancer that have mutations in the gene that codes for a PI3K subunit.
Unfortunately, targeting PI3K can lead to hyperglycaemia as a side effect which, if severe, can result in dehydration or kidney damage and can require hospitalisation. Sherry Shen, MD, of Memorial Sloan Kettering Cancer Center, and her colleagues set out to describe the incidence, risk factors, and treatment patterns of alpelisib-associated hyperglycaemia in patients with metastatic breast cancer treated in a clinical trial or as standard care at their institution.
Among 147 patients treated with alpelisib as standard care, the rate of hyperglycaemia was 80.3%, and the rate of serious hyperglycaemia was 40.2%. Among 100 patients who were treated during a clinical trial, rates were lower (34.0% any grade and 13.0% serious hyperglycaemia). The median time to onset of hyperglycaemia after initiating alpelisib was 16 days. An initially elevated haemoglobin A1c, an indicator of high blood sugar such as in prediabetes or diabetes, was a risk factor for later developing hyperglycaemia.
Among patients who developed hyperglycemia, 66.4% received treatment, most commonly with the diabetes drug metformin.
“If a patient is identified to have a PI3KCA mutation and thus eligible for treatment with alpelisib, we should be checking haemoglobin A1c level and partnering with the patient’s primary care physician and/or endocrinologist to optimise their blood sugar levels,” said Dr Shen. “This needs to be done months before initiating alpelisib, because once alpelisib is started, hyperglycaemia usually develops within the first two weeks of treatment. Being pre-emptive about improving glycaemic status and treating prediabetes/diabetes will hopefully lower the patient’s risk of developing hyperglycaemia and thus, lower their risk of needing to discontinue a drug that could be effective for their cancer.”
Senior author Neil M. Iyengar, MD noted that optimising a patient’s blood sugar levels often involves changes to dietary and exercise patterns, and potentially introducing certain medications. “Improving metabolic risk factors through lifestyle interventions may also improve dose delivery of alpelisib, and ongoing clinical trials by our group and other groups are testing whether metabolic interventions such as the ketogenic diet or newer medications used to treat diabetes could also improve the treatment efficacy of cancer therapies that target the PI3K pathway,” he said.
