Tag Archives: Breast Cancer

Immune targets for chemotherapy-resistant breast cancers identified

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Scientists have identified immune cell types that could be targeted to develop specific immunotherapies in chemotherapy-resistant breast cancers.

Researchers from King’s College London and The Institute of Cancer Research, London, with support from Breast Cancer Now, have performed a deep dive into the different immune markers within tumour tissues and blood samples of early breast cancer patients whose cancer failed to respond to chemotherapy given to them prior to surgery.

The research, published today in Clinical Cancer Research, a journal of the American Association for Cancer Research, gives insight into the function of immune cells in patients with chemotherapy-resistant breast cancers. While chemotherapy may not kill cancer cells in these high-risk patients, immunotherapy, a type of treatment that helps the immune system to attack cancer cells, may provide a benefit.

To investigate the immune environment that surrounds these chemotherapy resistant tumours, researchers employed multiple and novel complementary technologies looking at proteins and genes on both pre-treatment and post-treatment breast cancer tissue. They also measured how 1,330 cancer and immune-related genes within cancer tissues were affected by chemotherapy.

Flax seeds help women combat menstrual complications and fight post-menopausal risk of breast cancer, say studies

They found that chemotherapy resistant cancer cells had very few immune cells around them, but chemotherapy did induce changes in several immune cell types. Specifically, they found increases in the number of “innate” (first responder) cells such as neutrophils and natural killer (NK) cells. NK cells help the body to fight infection and cancer. But analysis found the increased NK cells in patients with chemotherapy resistant disease lacked cytotoxic activity – the ‘killing instinct’.

Researchers also found immune-related genes associated with NK cells were those associated with cell inhibition or exhaustion, which meant NK cells were unable to fight cancer cells. This new insight into the behaviour of NK cells could be used to develop specific immunotherapies for these high-risk patients. This would need to be investigated in future clinical trials.

These findings also show that blood monitoring during chemotherapy may help predict chemotherapy response early, potentially allow for tailoring of treatment prior to surgery.

Lead author Dr Sheeba Irshad, Cancer Research UK Clinician Scientist at King’s College London said: “Chemotherapy resistance in aggressive early breast cancers is a major reason why cancer regrows after treatment, contributing significantly to people not surviving their disease. In order to find the right targets for drug developments, it’s important to have a deep understanding of the complex mechanisms that allow some cancer cells to resist treatment, then hide from our immune system to only re-emerge later when they’re harder to eradicate.

“Our work has identified several cell types that would be worth investigating further to understand how they are interacting with the resistant cancer cell and how we can tweak that for our benefit. I am excited to continue to investigate these findings further.”

chemotherapy

Professor Andrew Tutt, Director of the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, and of the Breast Cancer Now Research Unit at King’s College London, said: “Great strides have been made in harnessing immunotherapies to treat several types of cancer, but we need to do better to realise their potential for patients with breast cancer.

“This exciting work advances our understanding of the interaction between cancer cells and the immune system during treatment, and why existing treatments work well for some patients, but not others. I hope this research will help us to enhance the anti-cancer immune response in breast cancer, particularly for patients whose cancer has not responded well to chemotherapy.”

Dr Kotryna Temcinaite, Senior Research Communications Manager at Breast Cancer Now, said: “With an estimated 35,000 people living with incurable secondary (metastatic) breast cancer in the UK, it’s vital we develop smarter, more effective treatments to ensure fewer people hear the devastating news the disease has returned and spread to other parts of the body. This exciting early-stage research, which has been part-funded by Breast Cancer Now, helps to lay the groundwork for discovering a way to target breast cancer cells that resist chemotherapy treatment. We hope by building on these findings, scientists will ultimately be able to develop immunotherapy treatments that may help more people survive breast cancer.”

Not just chemotherapy, now phototherapy is here for cancer treatment [Details]

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One approach to treating cancer is photodynamic therapy using photo-uncaging systems, in which light is used to activate a cancer-fighting agent in situ at the tumor. However, suitable agents must be stable under visible light, have an anti-tumor effect in low-oxygen environments, and have the ability to be activated by low-energy tissue-penetrative red light – a combination of properties that is difficult to achieve. Now, a team from The Institute of Industrial Science at The University of Tokyo has developed a new platform that uses, for the first time, organorhodium(III) phthalocyanine complexes to achieve this combination of traits.

Conventional photodynamic techniques depend on the formation of reactive oxygen species to destroy tumor cells, but many tumors contain environments that lack oxygen. Photo-uncaging systems, where the agent is administered in an inactive form and then activated, or “uncaged”, in the location of the tumor, address this issue. They uncage alkyl radicals, which are known to be capable of inducing cell death both with and without the presence of oxygen. Alkyl radicals are converted into terminal aldehydes in the presence of oxygen, and these terminal aldehydes can also induce cell death. The team used molecules called “organorhodium(III) phthalocyanine (Pc) complexes” to develop, for the first time, a novel platform for photo-uncaging therapy.

Researchers from The Institute of Industrial Science, The University of Tokyo have developed a streamlined photo-uncaging system for photodynamic cancer therapy, using a pulse of light for tumor-specific activation of a cancer-fighting agent/CREDIT
Institute of Industrial Science, The University of Tokyo

“The organorhodium(III) phthalocyanine (Pc) complexes we developed are highly stable under ambient light during the processes of synthesis, purification, and measurement, but can be activated by a laser that gives out nanosecond pulses of red light,” explains lead author Kei Murata. These nanosecond-pulsing lasers (pulsing for a billionth of a second) are relatively easy for medical staff to handle.

They went on to show that the compounds that were released after the organorhodium(III) phthalocyanine (Pc) complexes were activated showed toxicity to HeLa cells, a cell line developed from cancer, indicating that these compounds would have the ability to fight cancer if released inside a tumor.

“Our new technology could allow the photochemical generation of a wide variety of alkyl radicals and aldehydes, making possible the site-selective release of various bioactive molecules,” says senior author Kazuyuki Ishii. As an improvement on other photo-uncaging systems, it opens an exciting new avenue for the treatment of cancer by phototherapy.

Non-invasive ‘FAST device’ measures the changing size of tumors below the skin

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Engineers at the Georgia Institute of Technology and Stanford University have created a small, autonomous device with a stretchable/flexible sensor that can be adhered to the skin to measure the changing size of tumors below. The non-invasive, battery-operated device is sensitive to one-hundredth of a millimeter (10 micrometers) and can beam results to a smartphone app wirelessly in real-time with the press of a button.

In practical terms, the researchers say, their device—dubbed FAST for “Flexible Autonomous Sensor measuring Tumors”—represents a wholly new, fast, inexpensive, hands-free, and accurate way to test the efficacy of cancer drugs. On a grander scale, it could lead to promising new directions in cancer treatment.

Each year researchers test thousands of potential cancer drugs on mice with subcutaneous tumors. Few make it to human patients, and the process for finding new therapies is slow because technologies for measuring tumor regression from drug treatment take weeks to read out a response. The inherent biological variation of tumors, the shortcomings of existing measuring approaches, and the relatively small sample sizes make drug screenings difficult and labor-intensive.

“FAST” sensor/Photo:Stanford University

“In some cases, the tumors under observation must be measured by hand with calipers,” says Alex Abramson, first author of the study and a recent post-doc in the lab of Zhenan Bao at the Stanford School of Engineering and now an assistant professor at Georgia Tech. The use of metal pincer-like calipers to measure soft tissues is not ideal, and radiological approaches cannot deliver the sort of continuous data needed for real-time assessment. FAST can detect changes in tumor volume on the minute-timescale, while caliper and bioluminescence measurements often require weeks-long observation periods to read out changes in tumor size.

FAST’s sensor is composed of a flexible and stretchable skin-like polymer that includes an embedded layer of gold circuitry. This sensor is connected to a small electronic backpack designed by former post-docs and co-authors Yasser Khan and Naoji Matsuhisa. The device measures the strain on the membrane—how much it stretches or shrinks—and transmits that data to a smartphone. Using the FAST backpack, potential therapies that are linked to tumor size regression can quickly and confidently be excluded as ineffective or fast-tracked for further study.

The researchers say that the new device offers few significant advances.

  1. It provides continuous monitoring, as the sensor is physically connected to the mouse/human patients and remains in place over the entire experimental period.
  2. FAST can detect changes in tumor volume on the minute-timescale, while caliper and bioluminescence measurements often require weeks-long observation periods to read out changes in tumor size.
  3. FAST is both autonomous and non-invasive. It is connected to the skin, not unlike a band-aid, battery operated and connected wirelessly. The mouse/human patients are free to move unencumbered by the device or wires, and scientists do not need to actively handle the mice following sensor placement.
  4. FAST packs are also reusable, cost just $60 or so to assemble and can be attached to the mouse/human patients in minutes.
  5. FAST could significantly expedite, automate and lower the cost of the process of screening cancer therapies.

FAST’s sensor is composed of a flexible and stretchable skin-like polymer that includes an embedded layer of gold circuitry.\/Photo:Alex Abramson, Bao Group, Stanford University

The breakthrough is in FAST’s flexible electronic material. Coated on top of the skin-like polymer is a layer of gold, which, when stretched, develops small cracks that change the electrical conductivity of the material. Stretch the material and number of cracks increases, causing the electronic resistance in the sensor to increase as well. When the material contracts, the cracks come back into contact and conductivity improves.

Both Abramson and co-author Naoji Matsuhisa, an associate professor at the University of Tokyo, characterized how these crack propagation and exponential changes in conductivity can be mathematically equated with changes in dimension and volume.

One hurdle the researchers had to overcome was the concern that the sensor itself might compromise measurements by applying undue pressure to the tumor, effectively squeezing it. To circumvent that risk, they carefully matched the mechanical properties of the flexible material to skin itself to make the sensor as pliant and as supple as real skin.

“It is a deceptively simple design,” Abramson says, “But these inherent advantages should be very interesting to the pharmaceutical and oncological communities. FAST could significantly expedite, automate and lower the cost of the process of screening cancer therapies.”

Ovarian cancer detection takes a step forward with liquid biopsy

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Ovarian cancer is most often found in people of middle-age or older as the Wilmot study showed that the mean age of participants was 56.

Of the 183 participants, 42 were found to have ovarian cancer, which is 23 percent. The technology also discovered that 20 other participants had non-ovarian cancers.

Ovarian cancer symptoms can be vague, such as gas and bloating, but there are some that should not be ignored, Moore said: pelvic pain or pressure, feeling full quickly after eating, vaginal discharge or abnormal bleeding, urgency to urinate frequently, fatigue, upset stomach, pain during sex, constipation, or menstrual changes.

Because ovarian cancer is most often diagnosed in later stages.

A new type of technology can capture stray ovarian cancer cells from a simple blood test and successfully predict cancer in people who have a lesion or cyst in the pelvic region, according to a new study by a Wilmot Cancer Institute physician/scientist.

Nearly 200 local people participated in the study.

One of those local participants, Toni Masci, 51, of Fairport, took part in Moore’s study by providing blood samples for analysis. She had an ovarian cyst that burst — only to find out that a large tumor was also in her abdomen. She was treated with surgery and six rounds of chemotherapy in 2017 for stage 1 ovarian cancer, and just celebrated the milestone of five years in remission.

“I feel lucky to be part of this,” Masci said. “As most people know, ovarian cancer usually doesn’t get detected early. If Dr. Moore hadn’t been doing this research, we might not have had this advance and I might not be here.”

Currently, there is no routine ovarian cancer screening method available for people who do not have symptoms or a known lesion. And yet, the new technology, called a “liquid biopsy,” developed by United Kingdom-based ANGLE PLC, and the URMC team at Wilmot, advances the field in a couple of important ways, according to the study:

  • It confirmed for physicians quickly and accurately that cancer was present in patients who were scheduled for surgery or other procedures. The detection enabled physicians to classify which patients needed immediate care from a specially trained gynecological oncologist to improve survival.
  • The study analyzed gene expression from captured cells in blood and evaluated 72 different gene transcripts and seven blood biomarkers related to ovarian cancer (including CA125). From this collection, the study identified nine gene transcripts and four biomarkers that were useful for detecting cancers. They were used to develop an algorithm known as MAGIC (Malignancy Assessment using Gene Identification in Captured Cells). The algorithm achieved a sensitivity of 95 percent and an accuracy of 83 percent for detecting ovarian cancer.
  • In the clinical trial, MAGIC also was able to detect ovarian cancer in early and late stages. Early-stage detection is critical for survival and difficult to achieve. And, the test picked up other types of cancer that had spread to the pelvic region or originated there.

“This is an important step forward for the detection of ovarian cancer in patients with a pelvic mass,” Moore said. “The fact that we can capture circulating tumor cells and analyze them from a simple blood draw is extremely exciting.”

Being able to find circulating tumor cells is the key, Moore said. These are rare, living cells that break off from the original tumor. They have an estimated ratio in the blood of one in 100 million to one in one billion. The technology captures the rare cells and allows for genetic analysis in a single tool within a couple of hours.

 

 

Currently, if a person has a suspicious lesion, surgery is necessary to diagnose ovarian cancer, and annually, more than 200,000 people in the U.S. are in this situation. A non-invasive test that predicts malignancy beforehand would enable people with the highest risk to have surgery done by an oncology specialist with greater experience and surgical volume for these types of cases, Moore said.

Masci, a U.S. Navy veteran and esthetician at a local salon, was 46 years old in January 2017 when her cancer was diagnosed.

“I was in such shock,” she said. “Looking back, I did have some symptoms: bloating, my back hurt, weight loss, and when I would sit down to eat I would feel full right away.”

She enrolled in the study a month later, and Moore performed her ovarian cancer surgery.

“I had wonderful care from everyone at Wilmot,” Masci added, “but I can’t say enough good things about Dr. Moore. He needs to clone himself a million times.”

ANGLE Europe Limited funded the study. Moore has worked extensively with the company to test its detection system. Earlier this summer, the FDA gave approval for the same tool to be used to track breast cancer cells that have spread. Moore’s lab was the sole location nationally to test the reproducibility of the breast cancer tests, and local residents were also involved in that clinical trial.

 

Boosting physical activity/curbing sitting time likely to lower breast cancer risk:Mendelian randomisation study reveals

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Boosting physical activity levels and curbing sitting time are highly likely to lower breast cancer risk, finds research designed to strengthen proof of causation and published online in the British Journal of Sports Medicine.

The findings were generally consistent across all types and stages of the disease, reveals the Mendelian randomisation study, prompting the researchers to recommend a stronger focus on exercise as a way of warding off breast cancer.

Mendelian randomisation is a technique that uses genetic variants as proxies for a particular risk factor—in this case lifelong physical activity levels/sedentary behaviour—to obtain genetic evidence in support of a causal relationship.

Exercise/Photo:en.wikipedia.org

Observational studies show that physical inactivity and sedentary behaviour are linked to higher breast cancer risk, but proving they cause breast cancer is another matter.

The researchers therefore used Mendelian randomisation to assess whether lifelong physical activity and sitting time might be causally related to breast cancer risk in general, and specifically to different types of tumour.

They included data from 130,957 women of European ancestry: 69, 838 of them had tumours that had spread locally (invasive); 6667 had tumours that hadn’t yet done so (in situ); and a comparison group of 54,452 women who didn’t have breast cancer.

Exercise-Yoga/Photo:en.wikipedia.org

The researchers then drew on previously published studies that had used the vast repository of UK Biobank data on potential genetic explanations for overall predisposition to physical activity, vigorous physical activity, or sitting time—as measured by wrist-worn activity trackers—to genetically predict how physically active or inactive their own study participants were.

Next, the researchers estimated overall breast cancer risk, according to whether the women had or hadn’t gone through the menopause; and by cancer type,stage (size and extent of tumour spread), and grade (degree of tumour cell abnormality).

Analysis of the data showed that a higher overall level of genetically predicted physical activity was associated with a 41% lower risk of invasive breast cancer, and this was largely irrespective of menopausal status, tumour type, stage, or grade.

Similarly, genetically predicted vigorous physical activity on 3 or more days of the week was associated with a 38% lower risk of breast cancer, compared with no self-reported vigorous activity. These findings were consistent across most of the case groups.

cancer cells/photo:en.wikipedia.org

Finally, a greater level of genetically predicted sitting time was associated with a 104% higher risk of triple negative breast cancer. These findings were consistent across hormone-negative tumour types.

The findings were unchanged after factoring in the production by a single gene of two or more apparently unrelated effects (pleiotropy), such as smoking and overweight, for example.

There are plausible biological explanations for their findings, say the researchers, who point to a reasonable body of evidence indicating numerous causal pathways between physical activity and breast cancer risk, such as overweight/obesity, disordered metabolism, sex hormones, and inflammation.

“Mechanisms linking sedentary time and cancer are likely to at least partially overlap with those underpinning the physical activity relationship,” suggest the researchers.

Their findings provide “strong evidence” that more overall physical activity and less sitting time are likely to reduce breast cancer risk, they say.

And they conclude: “Increasing physical activity and reducing sedentary time are already recommended for cancer prevention. Our study adds further evidence that such behavioural changes are likely to lower the incidence of future breast cancer rates.

“A stronger cancer-control focus on physical activity and sedentary time as modifiable cancer risk factors is warranted, given the heavy burden of disease attributed to the most common cancer in women.”

JOURNAL

Some cancer immunotherapy treatments may damage fertility, women’s hormonal health

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Researchers have discovered that some immunotherapy treatments used to treat cancer can cause fertility damage.

It means these treatments could affect the future fertility and hormonal health of female cancer survivors, prompting experts to call for more research and preventative measures, such as freezing eggs.

Led by the Biomedicine Discovery Institute at Monash University and the Peter MacCallum Cancer Centre, the pre-clinical trial showed that immune checkpoint inhibitors, a common type of immunotherapy drug, resulted in permanent damage to mouse ovaries and the eggs stored inside.

cancer/photo:en.wikipedia.org

Traditional cancer therapies, such as chemotherapy and radiotherapy, are already linked to permanent, negative side effects on the ovaries. This can lead to infertility and premature menopause in young girls and women.

Researchers found that checkpoint inhibitor immunotherapy reduced the number and quality of their eggs, interfered with ovulation, and disrupted the fertility cycle.

Until now the potential fertility side effects of immunotherapy, an emerging and increasingly common cancer treatment that stimulates the immune system, have been unknown.

The study found that a type of immunotherapy called immune checkpoint inhibitors, which ‘release the brakes’ on the immune system to enhance a patient’s ability to fight cancer, could impair immediate and future fertility.

Its authors said studies in female patients were now needed to investigate the findings. In the meantime, fertility preservation through egg or embryo freezing should be considered for women using these immunotherapies.

“Initially these treatments were thought to be less damaging (than chemo and radiotherapy) in the context of off-target effects to the body in general,” Ms Alesi said. “However, it is now clear that inflammatory side effects in other organ systems are quite common with these drugs.

“Our study highlights that caution should be exercised by clinicians and their patients, for whom fertility may be a concern. Studies in women receiving these drugs must now be prioritised.”

Peter MacCallum Cancer Centre Specialist Medical Oncologist Professor in breast cancer and a senior author on the study Sherene Loi said further research into how these drugs impact the ovarian function and fertility of women receiving these drugs must be prioritised and should be included in future clinical trials involving women of reproductive age.

“Our study further highlights that fertility discussions are critical for all age appropriate women who are recommended to receive chemotherapy as well as immunotherapy,” Professor Loi said.

“Appropriate interventions that can preserve fertility and ovarian function can be implemented to facilitate pregnancies in the future, post completion of treatment. These interventions need to be implemented in a timely manner, so as not to delay anti-cancer treatment.

“Immunotherapy is now becoming a standard of care for many women with curable early stage breast cancer, due to impressive results in reducing breast cancer recurrences, but further research into the long-term effects of immunotherapy is needed.”

Apart from drugs that block ovaries from producing hormones during chemotherapy, and strategies to prevent premature menopause in younger women, Ms Alesi said egg and embryo freezing was the only fertility preservation measure available.

She said it was important to remember that embryo freezing was expensive, invasive and did not prevent ovarian damage. This meant that premature menopause could still be a risk for these women.

“Therefore, we are now prioritising investigation of targeted ovarian preservation strategies that aim to prevent the damage to the ovary from occurring in the first place, without interfering with the drugs’ ability to fight the cancer” she said.

 

Breastfeeding saved infants in Ice Age, led to bigger breast size in humans: Study

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Breast feeding might have played a criticial role in infant survival during the last ice age, and it might have led to a common genetic mutation in East Asians and Native Americans, which could have affected the shape of their teeth, says a new study.

The genetic mutation, which probably occurred 20,000 years ago, in turn led to more density of mammary ducts in the breasts, potentially providing more fat and vitamin D to infants living in the far north where the scarcity of ultraviolet radiation makes it difficult to produce vitamin D in the skin, said researchers.

If this genetic mutation is due to selection for increased mammary ductal branching, then this would be the first evidence of natural selection among the humans. "This highlights the importance of the mother-infant relationship and how essential it has been for human survival," said Leslea Hlusko, an associate professor at the University of California, Berkeley.

The gene controlling mammary duct growth also affected the shape of human incisors. The genetic mutation affected the ancestral population living in the far north during the last Ice Age, hence resulting in shovel-shaped incisors among Native Americans and northeastern Asian populations. This trait is rare in others.

The finding helps in understanding the origins of dense breasts among humans, which is a major factor behind the breast cancer.

For the study, Hlusko and her team examined the occurrence of shovel-shaped incisors in archeological populations to estimate the time and place of evolutionary selection for the trait. They found that nearly 100 percent of Native Americans prior to European colonization had shoveled incisors, and about 40 percent of East Asians today have this trait.

"When you have shared genetic effects across the body, selection for one trait will result in everything else going along for the ride," Hlusko said.

The vitamin D connection

Getting enough vitamin D is a big problem in northern latitudes because the sun is low on the horizon all year long. Sun doesn’t shine above the Arctic Circle at all for part of the year. Lack of vitamin D forced Siberians and Inuit to hunt for animal fat but babies were at a loss, thus causing the natural selection in the increased mammary duct.

Previous genetic analysis of living humans concluded that the mutation arose in northern China due to selection for more sweat glands or sebaceous glands during the last ice age but Hlusko said that it is not a satisfying explanation.

The Beringian standstill

The so-called Beringian standstill coincided with the height of the Last Glacial Maximum between 18,000 and 28,000 years ago as the climate became drier and cooler. People who had been living in Siberia moved into Beringia, where they were isolated and the species with locally adaptive traits arose.

Hlusko and her colleagues outlined many threads of evidence in their paper published in the journal Proceedings of the National Academy of Sciences.


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Photograph of human upper incisors with significant "shoveling," anatomical variation influenced by the EDAR V370A allele alongside an increase in mammary duct branching.(Christy G. Turner, II, courtesy G. Richard Scott)

Outdoor light at night linked with increased breast cancer risk in women

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  • A large long-term study found that breast cancer risk may be higher for women who live in areas with high levels of outdoor light at night.
  • The link between outdoor light at night and breast cancer was found only among women who were premenopausal and were current or past smokers, and was stronger among those who worked night shifts.

Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School of Public Health. The link was stronger among women who worked night shifts.

The study will be published online August 17, 2017 in Environmental Health Perspectives.

“In our modern industrialized society, artificial lighting is nearly ubiquitous. Our results suggest that this widespread exposure to outdoor lights during nighttime hours could represent a novel risk factor for breast cancer,” said lead author Peter James, assistant professor at Harvard Medical School’s Department of Population Medicine at Harvard Pilgrim Health Care Institute, who did the work while a research fellow in the Departments of Epidemiology and Environmental Health at Harvard Chan School.

Previous studies have suggested that exposure to light at night may lead to decreased levels of the hormone melatonin, which can disrupt circadian rhythms–our internal “clocks” that govern sleepiness and alertness–and, in turn, lead to increased breast cancer risk.

The new study, the most comprehensive to date to examine possible links between outdoor light at night and breast cancer, looked at data from nearly 110,000 women enrolled in the Nurses’ Health Study II from 1989-2013. The researchers linked data from satellite images of Earth taken at nighttime to residential addresses for each study participant, and also considered the influence of night shift work. The study also factored in detailed information on a variety of health and socioeconomic factors among participants.

Women exposed to the highest levels of outdoor light at night–those in the top fifth–had an estimated 14% increased risk of breast cancer during the study period, as compared with women in the bottom fifth of exposure, the researchers found. As levels of outdoor light at night increased, so did breast cancer rates.

The association between outdoor light at night and breast cancer was found only among women who were premenopausal and those who were current or past smokers. In addition, the link was stronger among women who worked night shifts, suggesting that exposure to light at night and night shift work contribute jointly to breast cancer risk, possibly through mechanisms involving circadian disruption. The authors acknowledged that further work is required to confirm the study findings and clarify potential mechanisms.

Periodontal disease is associated with higher risk of several cancer types

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Periodontal disease was associated with increased risk of several types of cancer in postmenopausal women, even in women who had never smoked.

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Author: Jean Wactawski-Wende, PhD, a professor in the Department of Epidemiology and Environmental Health and dean of the School of Public Health and Health Professions, State University of New York at Buffalo, was senior author. Ngozi Nwizu, BDS, MMSc, PhD, assistant professor of oral and maxillofacial pathology at The University of Texas School of Dentistry, was lead author.

Background: In recent years, research has shown that periodontal disease is a risk factor for certain cancers, including breast cancer, oral, and esophageal cancers. However, few studies have analyzed the overall risk for all types of cancers.

How the Study Was Conducted and Results: The researchers conducted a prospective cohort study of 65,869 women aged 54 to 86 who were enrolled in the Women’s Health Initiative Observational Study. The women self-reported periodontal disease on questionnaires administered between 1999 and 2003. The researchers monitored cancer outcomes through September 2013. Over an average follow-up time of 8.32 years, the researchers identified 7,149 cases of cancer.

The study showed that a history of periodontal disease was associated with a 14 percent higher risk of developing any cancer. The strongest association was for cancer of the esophagus, which was more than three times more likely in women with periodontal disease than women who did not report periodontal disease. Lung cancer, gallbladder cancer, melanoma, and breast cancer were also associated with significantly higher risk.

The researchers noted that certain cancers, such as breast cancer, lung cancer, and gallbladder cancer, were associated with higher risk in women who smoked and had periodontal disease. Others, such as melanoma, were associated with higher risk in the women who had never smoked but did report periodontal disease.

Author Comment: Wactawski-Wende said the biological mechanisms that connect periodontal disease and cancer are not yet fully understood. She said one possible explanation is that oral pathogens could potentially be carried in saliva and dental plaque, or through diseased periodontal tissues into the blood circulation to reach other body sites and contribute to carcinogenesis; this may possibly explain the strong association in esophageal cancer.

“The esophagus is in close proximity to the oral cavity, and so periodontal pathogens may more easily gain access to and infect the esophageal mucosa and promote cancer risk at that site,” Wactawski-Wende said.

“Our study findings serve to provide further evidence that periodontal disease is linked to cancer, and support the need for further investigation into how periodontal disease contributes to increased cancer risk,” said Nwizu.

The authors said the study’s large size adds to the strength of the findings.

“This study is the first national study focused on women, particularly older women,” Wactawski-Wende said. “Our study was sufficiently large and detailed enough to examine not just overall risk of cancer among older women with periodontal disease, but also to provide useful information on a number of cancer-specific sites.”

Limitations: The authors said that because the study used self-reported data, the prevalence of periodontal disease may have been under-reported. They said further research that uses more precise assessments of periodontal disease could be useful in confirming the link between periodontal disease and cancer, they added.

Birth Control Pills Increase Risk of Breast Cancer: New Study

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Contraceptive pills have become popular now but the impact will lead to higher risk of breast cancer later in life, warn scientists.

Researchers from the University of Michigan found that some commonly prescribed birth control pills can quadruple the levels of synthetic estrogen and progesterone hormones, which increase the risk of breast cancers. The treatment of breast cancer is mainly focused on hormone therapy.

The blood tests on women who use birth control pills contained much higher levels of hormones compared to those who did not and the results showed that 4 out of 7 formulations tested were found to quadruple the levels of progestin, a synthetic version of the hormone progesterone.

Another test showed 40% higher exposure to ethinyl estradiol, synthetic estrogen, another major cause for breast cancer.

Study’s lead author Beverly Strassmann said that there is an urgent need for pharma companies to redesign the birth control pills so they do not cause breast cancer among women. Their research showed that one percent of breast cancer cases are caused by the use of oral contraceptive pills.

“Not enough has changed over the generations of these drugs and given how many people take hormonal birth control worldwide – millions – the pharmaceutical industry shouldn’t rest on its laurels,” she said.

In a previous study, birth control pills were found to have caused a small but significant increase in the risk of the most common type of stroke. The study published in the journal MedLink Neurology in 2015 showed that “the risk seems higher and, in most cases, oral contraceptive use should be discouraged.”

Marisa McGinley, Sarkis Morales-Vidal, and Jose Biller of Loyola University Medical Center and Loyola University Chicago Stritch School of Medicine studied about 100 million women worldwide who used oral contraceptives. Birth control pills increase the risk 1.9 times, to 8.5 strokes per 100,000 women, which means one out of 24,000 women would experience the stroke.

Early versions of the pill contained doses of synthetic estrogen as high as 150 micrograms, though they have come down to 20 to 35 micrograms now and not more than 50 micrograms. In the United States, there are about 40 brands of oral contraceptives and 21 brands of emergency contraceptive pills.

Flax Seeds Help Women Most: Study

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Flaxseed is the new sought-after supplement in faily diet owing to its component lignans which help women to get regular menstrual cycle and also reduce the risk of breast cancer, show recent research findings.

According to the American Institute for Cancer Research, flax seed contains lignans, also called phytoestrogens, bearing a chemical structure similar to estrogen but unlike estrogen that increases the risk of breast cancer, these brown seeds do not increase cancer risk but be more protective.

In studies conducted on animals, it was shown that lignans isolated from flaxseed help women during the menstrual period and post-menopausal period by lowering the risk of breast cancer. It was also observed that flaxseed did not interfere with the effectiveness of the anti-estrogen medication tamoxifen, said the AICR study. The higher blood levels of lignans show prominent cancer-protective features, said the study.

“For people who wish to consume flaxseed as a source of omega-3 fat or dietary fiber, studies do not support fears that flaxseed could increase incidence or recurrence of breast cancer,” says Karen Collins. However, more research is to be done before recommending it as a medication for breast cancer, said Collins in the paper.

In a previous study conducted from 2002 to 2005, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) researchers used the MARIE study to take blood samples of 1,140 women who had been diagnosed with postmenopausal breast cancer. After a mean observation time of six years, they related enterolactone levels to clinical disease progression.

Compared to the study subjects with the lowest enterolactone levels, the women with the highest blood levels of this biomarker had an approximately 40 percent lower mortality risk. When the scientists additionally took account of the incidence of metastasis and secondary tumors, they obtained a similar result: Women with the highest enterolactone levels also had a lower risk for such an unfavorable disease progression.

“We now have first clear evidence showing that lignans lower not only the risk of developing postmenopausal breast cancer, but also the mortality risk,” said Jenny Chang-Claude.

There had been prior studies to determine the lignan intake by means of dietary surveys. But the results of such surveys are often unreliable and, in addition, there are big differences in the way individuals actually process the plant substances into effective metabolic products. Therefore, the Heidelberg team chose the more reliable measurement of biomarkers.

Otherwise, flax seeds have other potential medicinal properties, besides preventing growth of harmful cancer cells, even for prostate cancer. Since these seeds are found to catalyze insulin secretion in the body to regulate blood-sugar levels, diabetics are often advised to make it part of their daily diet.

In menopausal women, flaxseeds help them fight complications by maintaining balance in body hormones and reducing the risk of osteoporosis. It is also helpful in lowering bad cholesterol due to its rich nutrients.

The flipside of flaxseeds is that they are rich in calorie levels, 150 grams in four tablespoons.

Breast Cancer-Causing Gene Identified

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Breast Cancer-Causing Gene Identified

A gene called GT198, known for its ability to repair DNA, is actually causing breast cancer, found scientists hoping that it may help in diagnosing breast cancer early, said Dr. Lan Ko, cancer biologist in the Department of Pathology at the Medical College of Georgia at Augusta University and at the Georgia Cancer Center at AU.

Mutations of the gene are known to be present in both early onset breast and ovarian cancer. Now scientists have shown that the stem, or progenitor cells, which should ultimately make healthy breast tissue, can also have GT198 mutations that prompt them to instead make a perfect bed for breast cancer.

Their studies, published in the American Journal of Pathology, were done on an international sampling from 254 cases of breast cancer in pre- and postmenopausal women.

"This gene mutation can be in both the blood and the tumor tissue of patients, and in the tissue, it’s in high percentages," said Ko, the study’s corresponding author. "We believe that once this gene is mutated, it induces the tumor to grow."

GT198, which is also a coactivator of receptors for steroid hormones such as estrogen, is normally regulated by estrogen, Ko said. But once mutated, GT198 can enable tumor production without estrogen. "Regardless of how much hormone you have, it’s out-of-control growth," Ko said of the resulting classic, rapid growth of cancer.

In a cancerous breast, scientists have seen the problems with the various components of breast tissue but could not fully explain why they happened. The tissue, called the stroma, includes fat cells, or adipocytes, that provide padding; fibroblasts, which make the framework for tissue; pericytes in blood vessels, which are contractile cells that help regulate blood pressure; as well as myoepithelial cells comprising the outer layer of the ductal system through which milk flows.

The new study backs up a few steps and shows that mutated GT198 also directly affects stem cells found on blood vessels that make these various components of breast tissue. "This puts it together," Ko said.

"It’s a new target in cancer. It’s very exciting," said Dr. Nita Maihle, MCG cancer biologist, associate center director for education at the university’s Cancer Center and a study co-author. "This tells you that all the different types of stromal cells in breast tissue are affected by the GT198 mutation because they all come from a common progenitor cell."

Ko first cloned the human GT198 gene while a postdoctoral fellow at Harvard Medical School. All cells have the GT198 gene but most adult cells don’t express it. In the breast, for example, it may be transiently expressed in a pregnant woman preparing for milk production and, potentially, in the case of breast injury. Males express it in the testes.

Ductal breast cancer, which is in the ducts that carry milk, is the most common type of breast cancer and lobular carcinoma, which begins in the milk-producing glands, is the second most common. Most breast cancer comes from the cells that line those ducts, Maihle said.

BRCA1 and 2, genes whose proteins are supposed to work as tumor suppressors and also repair DNA damage, were the first known risk factor genes for familial breast cancer as well as ovarian and other cancers. About 4 percent of familial breast cancers would include inherited mutations of GT198, which is also considered a causative gene in sporadic cases, Ko said.

[tags, breast cancer, cause, gt198 gene, cause behind breast cancer, isolated]