Tag: breast cancer

Categories : Cancer General InterestTags :

What I Learned on My Journey through Breast Cancer

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In Breast Cancer Awareness Month we can all do something to help

Photo by Angiola Harry on Unsplash

By Lee-Anne Bruce

I was diagnosed with breast cancer on an ordinary Thursday afternoon in February 2023. I was 34 years old. The December before, my GP had performed a breast exam as part of a general check-up and was concerned that with my dense breast tissue she might be missing something. She wanted me to have an ultrasound, but there was no rush. Her exact words to me were something like: “Don’t worry, it can wait until you have medical aid savings again in January.”

The ultrasound turned up a small shadow, just a centimetre in diameter – something that could be a cyst, but the radiologist thought we should do a mammogram “just in case”. Would I mind waiting? No, I wouldn’t mind. The mammogram was worrying enough that she got approval to do a biopsy the next day. “Just in case”. The results came in the following week.

I had none of the risk factors for breast cancer. I didn’t drink, didn’t smoke, didn’t have any family members with a history of breast cancer, was nowhere near the age of 50. A few months later, I would find out I had none of the genetic markers which can predict risk either – not only did I test negative for the genes associated with breast cancer called BRCA 1 and 2, I didn’t have any of the genes connected with any kind of cancer at all.

As I say, I was diagnosed on a Thursday afternoon. I had my first appointment with an oncologist that Friday morning. I had my first set of scans two days later on Monday and my initial surgery the following Friday. I started chemotherapy treatment within three weeks of first having the word “cancer” used in relation to my body. My doctors moved quickly because they had to. On a scale of 1 to 9 on something called the Bloom and Richardson classification, my cancer was a 9. So, even though I was only stage 1, I was also a grade 3. “Aggressive” doesn’t begin to cover it.

During this time, I held onto five facts. First, we had caught the tumour at exactly the right time. Had I gone in for screening any earlier, we might not have found the cancer yet. Had I gone any later, it likely would have grown and spread to my lymph nodes and other parts of my body and I might have needed more radical treatment and surgeries. Second, it was treatable. My particular kind of cancer ought to respond well to a combination of chemotherapy and radiation. Third, I was otherwise very healthy, aside from the cancer. Fourth, I had a medical aid which was covering almost everything I needed. And, most importantly, fifth, I had a wonderful support system of my partner and his family and our close friends to rely on.

From the beginning, I had an incredible standard of care. To the point where the doctors I saw had heated examination beds – they didn’t want their patients to experience any additional discomfort and distress during such a difficult time. And it was difficult. Chemotherapy and immunotherapy left me feeling battered and broken. Nausea, intense muscular pain, fatigue, vomiting, diarrhoea, constipation, weight gain, hair loss, brain fog, depression – some of the awful side effects it’s impossible to really prepare for. In fact, I had such a hard time mentally during treatment that at one point I had to be hospitalised.

The same day I received my diagnosis, I overheard a woman in my doctor’s office asking if it was possible to make a payment plan for her treatment. The administrators replied that treatment was likely to cost in excess of R300 000 at a minimum. I cannot even begin to imagine having to go into debt to fight off cancer. For treatment that makes you feel more than just sick, more like you’re dying. For treatment that may not necessarily work.

But this is the choice that faces most people with cancer in our country. With a relatively small number of people on comprehensive medical aids with screening benefits and prescribed minimum benefits, many face waiting for treatment in government facilities or running up huge bills at private clinics.

According to the most recent report by Statistics SA, breast cancer is the most commonly diagnosed cancer in women in South Africa, accounting for 23% of all cancers. It is also one of the most deadly, representing 17% of cancer deaths in women, just behind cervical cancer.

The Stats SA report lists “awareness of the symptoms and need for screening” as the main intervention to reduce the risk of death by breast cancer. The report also draws attention to the discrepancy in mortality rates in different population groups. For example, Coloured women have a relatively low incidence of breast cancer, but a high mortality rate – meaning that they are dying of breast cancer after being diagnosed too late. Stats SA points out that this is likely due to “poor access to cancer treatment facilities” as well as a lack of medical aid coverage. It is perhaps unsurprising that Black and Coloured women are the groups least likely to have medical aid in South Africa.

There are also some NGOs trying to step in to fill the gaps, like the aptly named I Love Boobies or the PinkDrive. These organisations make it their mission to give women a fighting chance to beat breast cancer. They provide free screenings to women around the country who would otherwise not be able to afford this necessary medical care.

I am one of the lucky ones. I officially went into remission on 30 August 2023 when I had a lumpectomy to remove the tumour in my right breast. Remission means that the cancer can no longer be detected in your body through scans and blood tests. It doesn’t mean you’re “cured”. There could still be cancerous cells in the body, which is why cancer is also often treated with radiation like mine was. Some people prefer not to use the term “survivor” until they have been in remission for over five years.

Five years is an important milestone for many people diagnosed with cancer. It’s often the period in which someone is most likely to suffer a relapse. I live with the possibility that my cancer will come back every day; I am reminded by my scars and by the fact that I am still recovering physically and mentally from a traumatic year. I still battle with periods of fatigue and depression and I will never be the same person I was before falling ill.

Still, remission is better than relapse. So far, so good. I continue to see my myriad of doctors every few months for scans and tests and examinations to check that nothing has come back yet and I feel like I’m getting stronger.

Almost a year to the day after I went into remission, my fiancé and I ran the Johannesburg Women’s Race in support of the PinkDrive. A mobile health unit was parked on the field in Mark’s Park offering free screenings all morning, which women were queuing up to access after the run. The festive atmosphere was bittersweet to me. Certainly, some of the women in that line would not know that they were starting on a long and painful journey, a journey which sometimes feels like it has no end. Hopefully, they would be starting early enough to be given a chance to become a survivor.

There’s another meaning of “remission” I wasn’t aware of until I looked it up. It can also be defined as “a cancellation of debt”. No-one with cancer should have to crowdfund in order to get treatment, but that is the reality we are faced with in our country. This October, I encourage everyone to contribute in whatever way they can to a cancer survivor’s remission. Join the Imagine Challenge, try a secret swim, pick up a pink bottle of milk or a scrunchie, support someone raising funds on GivenGain, get yourself examined. Every one of us can join the fight against breast cancer.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International Licence.

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Categories : Ageing CancerTags :

Common Treatments for Breast Cancer may Speed up Aging

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Photo by National Cancer Institute on Unsplash

A new study has revealed that common breast cancer treatments, including chemotherapy, radiation, and surgery, may accelerate the biological aging process in breast cancer survivors. The findings, published in the Journal of the National Cancer Institute, show that markers of cellular aging, such as DNA damage response, cellular senescence, and inflammatory pathways, significantly increased in all breast cancer survivors, regardless of the type of treatment received. This suggests that the impact of breast cancer treatments on the body is more extensive than previously thought.

“For the first time, we’re showing that the signals we once thought were driven by chemotherapy are also present in women undergoing radiation and surgery,” said study lead author Judith Carroll, an associate professor of psychiatry and biobehavioural sciences at UCLA. “While we expected to see increased gene expression linked to biological aging in women who received chemotherapy, we were surprised to find similar changes in those who only underwent radiation or surgery.”

Advances in cancer therapies have greatly improved survival rates, with an estimated 4 million breast cancer survivors in the US today and over 6 million expected by 2040. However, breast cancer is linked to accelerated aging, impacting physical abilities, independence, and lifespan. Biological aging processes, which drive conditions like fatigue, cognitive decline, frailty, and cardiovascular disease, appear to be a major factor. Evidence suggests that cancer treatments, like chemotherapy, can increase the risk of earlier onset of these aging-related conditions, making it crucial to understand the specific pathways involved to better target and manage them.

To examine how gene expression related to aging changes over time in women diagnosed with breast cancer, the team conducted a two-year longitudinal study that tracked women undergoing breast cancer treatment prior to receiving treatment and again following treatment to see how their biological aging markers evolved. 

The team tracked the gene expression in their blood cells using RNA sequencing, focusing on markers that signal biological aging, including a process known as cellular senescence, which is when cells stop dividing but don’t die. These so-called “zombie cells” accumulate over time and can release harmful substances that damage nearby healthy cells, contributing to aging and inflammation.

 The data was then analysed using statistical models to help identify aging-related changes.

The team found that regardless of treatment type there was an increase in expression of genes that track cellular processes involved in biological aging. Specifically, genes that capture cellular senescence and the inflammatory signal from these cells, indicating that their immune cells were aging faster than normal.

They also saw increases in DNA damage response genes, which are genes that are expressed when there is DNA damage. Although chemotherapy did have a slightly different pattern, similar to what others have shown, they also noted changes in women who did not receive chemotherapy. 

“The results suggest women who receive treatment for breast cancer have a pattern of gene expression that indicates increased DNA damage and inflammation, which could be important targets for recovering from cancer and having a better quality of life in survivorship,” said senior author of the study Julienne Bower(Link opens in new window), professor of psychology in the UCLA College and psychiatry and biobehavioural sciences and member of the UCLA Health Jonsson Comprehensive Cancer Center. 

“We’ve only just begun to understand the long-term consequences of cancer therapy and these findings are a critical step toward understanding the biological pathways that drive many post-treatment symptoms in breast cancer survivors,” added Carroll. “Our goal is to find ways to improve survivorship, not just in terms of years lived, but also in quality of life and overall health.”

The team is now exploring a new biomarker that measures a woman’s biological age and the pace at which she is aging. This could help determine whether the aging signals detected during cancer treatment have a long-term effect on biological age. The team plans to investigate factors that may influence this, with a focus on protective behaviours such as exercise, stress management and healthy sleep patterns.

Categories : CancerTags :

Oestrogens are Implicated in More than Just Breast Cancers

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Photo by National Cancer Institute on Unsplash

Oestrogens are known to drive tumour growth in breast cancer cells that carry its receptors, but a new study by Duke Cancer Institute researchers unexpectedly finds that oestrogens play a role in fuelling the growth of breast cancers without the receptors, as well as numerous other cancers.

Writing in the journal Science Advances, the researchers describe how oestrogens not only decrease the ability of the immune system to attack tumours, but also reduce the effectiveness of immunotherapies that are used to treat many cancers, notably triple-negative breast cancers. Triple-negative breast cancers are an aggressive form of disease that are negative for oestrogen, progesterone, and the HER2 receptor proteins.

Informed by retrospective analysis of patient data and experiments in mice, the researchers found that anti-oestrogen drugs reversed the effects of oestrogens, restoring potency to immunotherapies.

“The treatment for triple-negative breast cancer has been greatly improved with the advent of immunotherapy,” said senior author Donald McDonnell, PhD, professor at Duke University School of Medicine.

“Developing ways to increase the anti-cancer activity of immunotherapies is a primary goal of our research,” McDonnell said. “Here we have found a simple way bolster the effectiveness of immunotherapy for this type of breast cancer and the benefit was even seen in other cancers, including melanoma and colon cancers.”

McDonnell and colleagues, including lead author Sandeep Artham, a postdoctoral associate in the McDonnell lab, focused on a type of white blood cell called eosinophils, which are typically activated during allergic reactions and inflammatory diseases.

Eosinophils have recently been identified as important in tumours, and a phenomenon called tumour associated tissue eosinophilia, or TATE, is associated with better outcomes among patients with multiple types of cancer, including colon, oesophageal, gastric, oral, melanoma and liver cancers.

In their studies, the Duke team described how oestrogens decrease the number of eosinophils and TATE in mice. The hormone contributes to increased tumour growth in oestrogen receptor-negative breast cancer tumours and in melanoma tumours, which do not rely on oestrogen receptors for tumour growth.

Conversely, anti-oestrogen therapies inhibited oestrogen receptor signalling and enhanced the efficacy of immunotherapies, slowing tumour growth.

“These findings highlight the importance of oestrogen-receptor signalling as a regulator of eosinophil biology and TATE and highlight the potential near-term clinical application of anti-oestrogen drugs to increase the benefits of immunotherapies in multiple tumour types,” McDonnell said.

He said clinical trials are being planned using an investigational anti-oestrogen drug called lasofoxifene among patients with triple-negative breast cancers.

Source: Duke University Medical Center

Categories : CancerTags :

Breast Cancer Knows no Gender: the Rising Need for Awareness, Early Detection, and Financial Preparedness

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Breast cancer cells. Image by National Cancer Institute

Breast cancer is a significant health issue in South Africa, being the most common cancer among women, with a lifetime risk of 1 in 27. However, while breast cancer predominantly affects women, it is crucial to acknowledge that men can also develop the disease, and awareness needs to span genders. Early detection is key in improving outcomes, but the financial implications of treatment can be significant, as many medical aid schemes do not fully cover the extensive costs associated with treatment, including surgeries, chemotherapy, and follow-up care. Having gap cover in place can significantly ease the burden of out-of-pocket expenses, providing peace of mind for patients and their families.

Incidence on the rise

The latest statistics from the National Cancer Registry (NCR) indicate that breast cancer remains the most prevalent cancer among women in South Africa. According to the 2022 NCR report, breast cancer accounted for 20.4% of all cancers diagnosed in females, with a significant increase in incidence rates over the years. Although not very common, men also get breast cancer; approximately 1% of all breast cancer cases occur in men, and this number is also increasing.

Steve Kelly, a male breast cancer survivor, has been cancer-free for five years. “In December 2018, my partner spotted a lump in my right breast. It was painless, and I did not feel ill. It was diagnosed as stage 3 grade 3 breast cancer. I had surgery the following week, followed by six months of chemotherapy and six weeks of radiation therapy,” he explains.

While Kelly is one of the lucky ones, the reality is that many men who receive a diagnosis of breast cancer are not, because it is typically diagnosed late, which increases the mortality rate and also means that treatment has to be more aggressive. The increasing prevalence of breast cancer, along with the challenges of late-stage diagnoses, underscores the importance of early detection and education. Initiatives aimed at promoting regular screenings and self-examinations are vital for improving outcomes for all individuals affected by breast cancer in South Africa, including men.

Awareness is crucial

“Men do not scan and are generally poor at self-examination. More significantly, research shows that up to 33% of men would not seek medical attention if they found a painless lump in their breast. Because of embarrassment or ignorance, men would often present later with a more advanced breast cancer and a worse prognosis,” Kelly says.

Awareness campaigns need to evolve to become more inclusive. However, they also need to evolve to effectively target women, given the growing prevalence of breast cancer as well as the fact that it is increasingly affecting women at younger ages. Regular self-examination is a critical element in the early detection of breast cancers in both women and men, and having appropriate testing in place is essential.

Joanne Stroebel is another breast cancer survivor, and she credits her early diagnosis and successful treatment to her healthy lifestyle and her regular self-screenings. “Have your screenings done regularly and make sure to self-examine at least once a month. Once you have been diagnosed, involve your medical aid broker (or get one that knows the systems) and let them help you with the claims. The healthcare system can be very daunting when you have a new diagnosis, and extra stress is the last thing you need,” she recommends.

Easing the financial strain

Having medical aid is important in covering the cost of breast cancer treatment, but the reality is that many medical aid schemes do not fully fund treatments. There are many areas where you could potentially incur out-of-pocket expenses. Surgery is typically involved, which often comes with shortfalls on doctors’ accounts, such as surgeons and anaesthetists.

Prophylactic bilateral mastectomy (the preventative removal of both breasts) is generally not covered, and neither is reconstruction. Making use of a doctor who is not in a Designated Service Provider (DSP) network means additional shortfalls and co-payments. Medical aids also cover cancer in one of two ways: they either have an annual limit for cancer treatment, and once this is depleted you will only have access to Prescribed Minimum Benefits (PMBs); or they will cover you up to a certain Rand value, and once this is depleted you will incur a 20% co-payment on anything related to oncology treatment as well as the treatment itself.

Gap cover can go a long way toward alleviating the financial burden of breast cancer treatment. If your medical aid pays a lump sum, once this is depleted, then gap cover can assist with funding ongoing treatment, including in-hospital as well as outpatient treatment, pathology, and biological drugs, if these were covered by your medical aid. Gap cover can also help to pay the 20% co-payment, which can add up to significant sums, especially around biological drugs.

“Nearly a quarter (23.3%) of all Turnberry cancer claims are for breast cancer, and the highest individual claim we have seen is in excess of R80 000 resulting in a total treatment cost of more than R170 000. This is not an outlying number either – individual claims are frequently in the tens of thousands of Rands, and total treatment cost is usually over R100 000,” says Brian Harris, GM: Operations at Turnberry Management Risk Solutions.

Stroebel concludes, “Being a medical aid specialist, I was fortunate that I had the best cover available for cancer treatment. I never thought that I would need to try and raise funds for treatment, as I was confident that my medical aid and gap cover would cover any shortfalls, which was absolutely the case. I also had a dread disease policy that paid out, and being financially secure meant I never had unnecessary stress. Talk to your broker to make sure you have the best cover to suit your needs.”

Categories : Cancer GenderTags :

Yes, Men can Get Breast Cancer

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Dr Salomine Theron, a radiologist at the SCP Radiology and Dr Lizanne Langenhoven, who specialises in the treatment of breast cancer, talk about breast cancer in men, how prevalent it is as well as the radiology behind the diagnosis, treatment and surveillance for recurrence.

‘It may come as a surprise that men can develop breast cancer,’ says Dr Langenhoven. ‘In fact, about 1% of all breast cancer cases are diagnosed in men. Unfortunately, men often present with more advanced disease, because they are not aware that they can develop breast cancer in the first place.’

Dr Theron says radiology plays a pivotal role in the diagnosis and treatment of breast cancer in both men and women. However, there is a difference in terms of radiology’s initial role in screening for breast cancer. ‘In women over 40, we recommend an annual mammography,’ she says. ‘In other words, looking for cancers which are asymptomatic. So even if there are no changes to your breast visibly or a lump, we still screen for anything that may develop into breast cancer or has already.

‘In men, that is not standard practice’ Here radiology is diagnostic and the referral is as a result of a lump in the breast, under the arm, there’s puckering or nipple pain. The mammogram differs too. It is a single mammogram image of each breast so that a comparison can be made.  In men, it will also include breast ultrasound and evaluation of the lymph nodes under the armpit.

Dr Theron says, ‘the imaging of a lump may also be incidental. For example, when we do any form of CT imaging on the chest in a male, even when creating images of the lungs, we always look at the soft tissue in the breast area. If we see an asymmetric nodule with an irregular shape (almost like a star) we alert the patient’s healthcare provider, even though that wasn’t the reason for the CT scan’.

Is a breast lump always in men always cancer?

‘No,’ says Dr Langenhoven, ‘About 50% of males develop small lumps in each of their breasts during puberty, usually behind the nipples which can be tender. This is called gynaecomastia – colloquially a ‘stony’ and it’s perfectly normal. It usually goes away as they finish puberty.

‘Breast cancer, on the other hand, usually presents as a firm nodule in one breast that is not tender. There are some men who present with inflammatory breast cancer, where the breast is red, swollen and tender. This is however, a rare but aggressive type of invasive breast cancer in which cancer cells block lymph vessels in the skin.’

She says, ‘the first message is one of awareness.  Men can develop breast cancer.  And that they should see their GP if they become aware of a lump in their breasts which feels firm and asymmetrical or if the breast becomes red, swollen and tender.’

The second message is one of precaution

Women and men can inherit the harmful BRCA1 or BRCA2 gene mutation that belong to a class of genes, known as tumour suppressors and have an increased risk of breast cancer.

Dr Langenhoven says, ‘I have a patient in my practice who presented with a hard lump on his left breast. Because he was aware of his family’s history of breast cancer, he went to his GP for an examination. A mammogram and biopsy confirmed the diagnosis of breast cancer.

She says men with these genes should always be assessed by a genetic counsellor. In addition, should you have a family member diagnosed with male breast cancer, prostate cancer below the age of fifty or ovarian cancer (women), you should seek the opinion of a genetic counsellor to discuss the possible genetic risk and the option of genetic testing. Prevention is better than cure.’

The role of radiology in diagnosis

‘A suspicious lump or mass can only be definitively diagnosed by a biopsy,’ says Dr Theron. She explains that there are three biopsy options:

  • Ultrasound guided core biopsies, where a sample of tissue or blood is taken for testing by a pathologist and a marker is left in the lesion or lump where the sample was taken
  • A fine needle aspiration (FNA) is a procedure to obtain a sample of cells from your body for testing by a cytologist for cancer cells usually of a lymph node or occasionally of a breast mass
  • A vacuum-assisted biopsy can produce slightly larger samples of tissues which is sent to the pathology lab
  • If there is no lump visible on ultrasound, only suspicious calcification on the mammogram, stereotactic guided vacuum biopsy will be done. Put simply, a mammogram will help us find the abnormality to biopsy
  • If the lump is very small or has a cystic component, an ultrasound guided vacuum assisted biopsy will be performed

Radiology at every stage of cancer care

‘Radiology is integral to breast cancer management beyond diagnosis, providing critical information that guides clinical decisions at every stage of care,’ says Dr Theron. ‘This includes staging of the disease, it allows for precise treatment planning, guiding surgical procedures, effective monitoring of treatment responses, early detection of recurrence, all of which are essential for improving patient outcomes.’

Male breast cancer treatment

Men with breast cancer are treated exactly as their female counterparts. Based on the type of breast cancer and the extent (stage), treatment options include chemotherapy, hormone withdrawal therapy, targeted therapies, immunotherapy, surgery and radiotherapy.

‘Even though only one in a hundred diagnosed cases of breast cancer is men,’ says Dr Theron, ‘we still urge men and of course women to check themselves regularly and to see a doctor if they feel or see any changes in their breasts.’

Early detection can save your life.

Categories : Cancer NeurologyTags :

Breast Cancer Chemo Disrupts Gut Microbiome and Impacts Cognition

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Photo by Tima Miroshnichenko on Pexels

Chemotherapy is known to cause behavioural side effects, including cognitive decline. Notably, the gut microbiome communicates with the brain to affect behaviour, including cognition. 

“For the first time ever, our Intelligut Study found that the gut microbiome has been implicated in cognitive side effects of chemotherapy in humans,” said senior author Leah Pyter, associate professor of psychiatry and neuroscience at Ohio State University. “The potential connection between the gut and the brain would allow us to create treatments for the gut to treat the brain.”

Study findings are published in the journal Brain, Behavior, and Immunity.

This clinical longitudinal observational study explored whether chemotherapy-induced disruption of the gut microbiome relates to cognitive decline and circulating inflammatory signals. 

Faecal samples, blood and cognitive measures were collected from 77 patients with breast cancer before, during and after chemotherapy.

“We found that patients treated with chemotherapy who showed decreases in cognitive performance also had reductions in the diversity of their gut microbiome,” said Pyter, also a researcher with Ohio State’s Institute for Behavioral Medicine Research and member of the Cancer Control Research Program at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). 

This research builds on Pyter’s prior research in mouse models that found chemotherapy-induced shifts in the gut microbiome cause neurobiological changes and behavioural side effects.  The current study indicates that an association between gut microbiome and cognitive performance exists in humans as well. 

“Side effects of chemotherapy are common and may reduce quality of life, but these side effects can be dismissed as ‘part of chemotherapy’ and therefore overlooked and under-treated,” Pyter said. “We believe that gut microbiome-focused interventions, such as faecal microbial transplantation, may improve behavioural side effects of chemotherapy.” 

OSUCCC—James researchers are also conducting research studies on how the gut microbiome impacts cancer treatment effectiveness and its role in reducing or increasing cancer risk. 

“Chemotherapy is a very important tool for stopping many cancers and side effects should not deter patients who would benefit from this type of therapy from pursuing it, but we know the side effects of some treatment regimens can be quite challenging for patients to complete,” said David Cohn, MD, interim chief executive officer of the OSUCCC – James. “It’s a careful tightrope of walking between effective cancer control and side effect management – and our team is working every day, in the hospital clinics and the lab, to develop ways to manage the side effects of disease treatment with an eye toward quality of life.” 

Source: Ohio State University

Categories : CancerTags :

A Potential Pathway to Reducing Breast Cancer Brain Metastases

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Colourised scanning electron micrograph of a breast cancer cell. Credit: NIH

A study led by researchers from the University of Arizona Cancer Center at UArizona Health Sciences identified a biological mechanism that could lead to more effective treatments for breast cancer that has metastasised to the brain.

By studying the metabolic differences between primary breast cancer cells and those that metastasise to the brain, they determined that autophagy was significantly upregulated in brain metastases. Autophagy is a cellular recycling process that cancer cells can use to stay alive when faced with stressful conditions such as those triggered by anticancer drugs.

“The prognosis for individuals with brain metastases from breast cancer is extremely unfavourable, and the management of breast cancer metastases in the brain remains a formidable challenge,” said senior author Jennifer Carew, PhD. “We were able to disrupt breast cancer cells’ ability to form brain metastases by impairing the autophagy pathway.”

In the study published in Clinical and Translational Medicine, the researchers first showed that targeting the key autophagy regulating gene ATG7 significantly reduced the ability of breast cancer cells to form brain metastases in mouse models.

With the goal of developing a strategy to bring this discovery to patients, the research team investigated whether hydroxychloroquine, a Food and Drug Administration-approved drug, could potentially be used to treat breast cancer brain metastases. Hydroxychloroquine inhibits autophagy at a later point in the pathway and, importantly, readily crosses the blood-brain barrier.

“Most drugs do not efficiently cross the blood-brain barrier, and that is one of the key reasons why brain metastases are so difficult to treat,” said Carew, who is a professor of medicine at UArizona.

The research team combined hydroxychloroquine with lapatinib, which is FDA-approved to treat breast cancer. They showed that this drug combination successfully reduced the number and size of breast cancer brain metastases in mouse models.

Hydroxychloroquine has been combined with a number of other anticancer agents in early phase clinical trials, but this is the first time researchers have studied its effectiveness when combined with lapatinib for breast cancer therapy.

Carew said the team was amazed by how significantly they were able to diminish the ability of breast cancer cells to form brain metastases by targeting a single pathway.  

“Cancer cells, unfortunately, have evolved so many ways that make it difficult for us to stop their growth or kill them,” Carew said. “It is always somewhat surprising when you see how changing only one thing can have an impact.”  

“Our group and others have shown that activation of autophagy makes it harder for many different types of cancer therapies to kill cancer cells and this promotes drug resistance,” said first author Steffan Nawrocki, PhD, UArizona professor. “Because hydroxychloroquine and lapatinib are already FDA approved, we can advance this drug combination quickly into a clinical trial for patients with breast cancer brain metastases.”

Brain metastases are the most prevalent adult central nervous system tumours, with 20% to 30% of cases resulting from breast cancer patients, particularly those with triple negative and HER2 amplified disease. Managing breast cancer metastases in the brain is challenging, with only 20% of patients with breast cancer brain metastases surviving beyond five years.

Source: University of Arizona Health Sciences

Categories : Cancer Obstetrics & GynaecologyTags :

Most Young Breast Cancer Survivors can Still Have Children

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Photo by SHVETS production

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.”

Source: Dana-Farber Cancer Institute

Categories : CancerTags :

Researchers Identify New Marker for Breast Cancer Prognosis

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Photo by National Cancer Institute on Unsplash

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.

Source: Wiley

Categories : CancerTags :

In the Breast Cancer Fight, the Next Battleground is Malignancy Hibernation

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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.”

Source: University of Massachusetts Amherst