Increased Physical Activity Reduces Breast Cancer Risk, International Study Suggests

Increasing physical activity and reducing time spent sedentary is likely to decrease the risk of breast cancer, a study of more than 100,000 women suggests. An international team including researchers from Australia, the UK and US have used genetic analysis to establish a causal relationship between overall activity levels and cancer risk.

The study, published in the British Journal of Sports Medicine, included data from 130,957 women, 76,505 of whom had breast cancer. While previous research has shown a correlation between physical activity and lowered risk of breast cancer, proving causation has been difficult.

“There has always been a little bit of uncertainty as to whether physical activity truly causes a lower rate of breast cancer or whether that relationship is confounded by other factors,” said Associate Prof Brigid Lynch of Cancer Council Victoria, the study’s senior author.

“For example, women who tend to be more physically active might have healthier lifestyles in other ways as well.”Lynch said the new study “suggests that it is certainly a causal effect: physical activity does reduce your risk of developing breast cancer”.“We saw a risk reduction across all breast cancer types,” she said.

The researchers used a technique known as Mendelian randomisation to establish causality, which uses genetic variants as proxies for particular traits – in this case, physical activity and time spent sitting or reclining.They found that a higher level of physical activity, or general movement, was associated with a 41% reduction in invasive breast cancer risk.

In pre- and perimenopausal women, vigorous physical activity at least three days per week was linked to a 38% lower risk of breast cancer compared to no vigorous activity.“For every 100 odd minutes [of sedentary time] per day we observed a 20% risk increase in breast cancer overall, and a doubling of risk for triple-negative breast cancer [which is more aggressive and difficult to treat],” Lynch said.

Physical activity is thought to lower breast cancer risk because it decreases the amount of both oestrogen and androgen hormones circulating in the bloodstream. A reduction in inflammation may also be a factor.“There’s always been a lot of focus on other health behaviours like healthy eating, maintaining a healthy weight, reducing alcohol intake,” Lynch said. “There’s a big role for physical activity in preventing cancer.”

The research drew data from the UK Biobank as well as 76 other studies conducted as part of the Breast Cancer Association Consortium.One limitation of the study was that it only included data from women of European ancestry.“We can’t say for sure that these genetic instruments are applicable across different racial backgrounds,” Lynch said.

But she added that large observational studies in Asia and for women of different ethnicities in the US have found correlations between physical activity and reduced risk.“We do already recommend that physical activity is one of things you can do to reduce your breast cancer risk,” said Associate Prof Wendy Ingman of the University of Adelaide, who was not involved in the study.

Other factors associated with a reduced risk of breast cancer include minimising alcohol intake, and breastfeeding. “The longer a woman breastfeeds for, the less breast cancer risk she has,” Ingman said.

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Source: Increased physical activity reduces breast cancer risk, international study suggests | Australia news | The Guardian

Critics by Vanessa B. Sheppard, PhD, Kepher Makambi, PhD, Teletia Taylor, PhD, Sherrie Flynt Wallington, PhD, Jennifer Sween, MS, and Lucile Adams-Campbell, PhD

A population-based case-control study was conducted with 199 women (97 cases and 102 controls) from the Washington, DC metro area. A self-report physical activity questionnaire elicited responses on walking for exercise and vigorous physical activity (e.g., running, aerobics, etc.) in the past year. Responses were used to calculate a metabolic equivalent (MET) score [MET-hours/week = hours/week vigorous activity×7+ hours/week walking ×3]. The MET score was categorized into low, medium and high tertiles. Multivariate logistic regression examined the association between physical activity and breast cancer.

African American women who engaged in vigorous physical activity (> 2 hours/week in the past year) had a 64% reduced risk of breast cancer compared to those who did not participate in any vigorous activity (odds ratio, OR = 0.36; 95% confidence interval, CI = 0.17–0.75). We also found a 64% reduced breast cancer risk in women with a high versus low tertile of total activity (OR = 0.36; 95% CI = 0.16–0.79). For postmenopausal women, vigorous physical activity and total activity (high versus low tertile) also had an inverse relationship with breast cancer (p<.05).

Data regarding the association of physical activity and breast cancer has been equivocal and lacking for African American women. This study found that modest levels of physical activity reduced breast cancer risk in this group. Targeted efforts are needed to encourage more African American women to engage in physical activity.

Breast cancer is the leading cancer diagnosed in US women. With more than 190,000 cases diagnosed each year, there are few prevention strategies. Known risk factors, such as genetic mutations and family history of cancer, account for only 30% of a woman’s risk for being diagnosed with breast cancer. Thus, lifestyle changes may reduce a woman’s breast cancer risk.

Research suggests that an increase in physical activity, in particular, among sedentary, post-menopausal women changes their hormone levels to reflect a lower risk of breast cancer diagnosis. Therefore, physical activity may be one of the best approaches towards the primary prevention of breast cancer.

The relationship between physical activity and breast risk is complex and may be explained by certain molecular mechanisms. It is plausible that physical activity could affect breast cancer risk because it also affects other risk factors, such as menstrual cycle, body mass, immune system, and hormones such as IGF. It is well accepted that physical inactivity increases one’s risk of obesity. Obesity has separately been considered a breast cancer risk factor and there is an inverse relationship between obesity and physical activity.

How physical activity and obesity might confound each other is unknown; obesity is positively associated with breast cancer risk in postmenopausal women but inversely associated with risk in premenopausal women. Further, some data suggests that adult weight gain, rather than BMI, affects breast cancer risk, especially among non users of hormonal replacement therapy.

Studies have shown a relationship between obesity and risk of breast cancer but in samples of mostly Caucasian women.Research, although equivocal, suggest that physical activity is inversely related to breast cancer risk in both pre- and postmenopausal women. Considering African American women have higher rates of being overweight or obese, limited physical activity may be a significant breast cancer risk factor in this population. Some data in African American women suggests that breast cancer risk is reduced with increased physical activity.

In a study by Adams-Campbell et al, strenuous physical activity was associated with a reduced risk of breast cancer in African American women. This study, however, focused only on strenuous physical activity levels. Bernstein et al also found that increased physical activity reduces breast cancer risk in African-American women. However, this study also lacked data on the effect of moderate intensity exercise in this population. More research is needed to determine whether moderate levels of physical activity can also reduce breast cancer risk in this population.

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3 Things To Ask Your Doctor About Breast Cancer Treatment

As far as illnesses go, breast cancer is a relatively common one: 13 percent of women in the United States will develop breast cancer over their lifetime, according to the National Cancer Institute. That works out to one in eight women, so if you know more than eight women, odds are you probably know someone who has had or will be diagnosed with breast cancer in the future.

And if you’re trying to understand your risk of developing breast cancer or if you or a loved one are facing a diagnosis, that means one thing: You probably have questions for a doctor.

To help you assemble your list, we asked Virginia Kaklamani, MD, leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center, for her advice on what to ask. According to Dr. Kaklamani, there are a few important things to keep in mind as you’re crafting your questions, such as your family history, lifestyle risk factors, and available treatment options.

On the treatment front, Dr. Kaklamani says one of the misconceptions she hears most often is that breast cancer treatment always involves chemotherapy and is very toxic. In response, she reminds people how far treatment options—and the tools we have to determine which treatment may work best for each individual person—have come in the past 20 years.

Case in point: Just last year, a landmark study published in The New England Journal of Medicine showed that, thanks to a genomic test called the Oncotype DX Breast Recurrence Score® test, even more patients with a common type of early-stage breast cancer may be spared chemotherapy than previously thought, including those who are traditionally considered higher-risk due to their cancer spreading to at least one lymph node.

That means more treatment plans tailored to each individual patient, and less of a chance of overprescribing chemo to those who may not benefit from it.

Learning something already? With education in mind, we asked Dr. Kaklamani to share her insights on questions you should ask your doctor about breast cancer—whether you’re trying to stay on top of your health, or you’re exploring your breast cancer treatment options.

What role does race play in breast cancer?

There are many factors that contribute to breast cancer risk, including age, family history, alcohol consumption, obesity, and race. White women are most likely to develop breast cancer, Dr. Kaklamani says, though Black women are more likely to die from it (40 percent more likely, according to the Centers for Disease Control and Prevention).

Studies have shown that Black women have a higher risk of being diagnosed with later stages of disease,” Dr. Kaklamani says. “So instead of coming in with stage one or stage two, they might come in with stage two or three or even stage four breast cancer. It’s been very hard to understand why.

Most of the data suggests that it’s related both to the type of breast cancer that they get (because they get more triple negative breast cancer—that’s more aggressive, so we tend to find it later), but also to socioeconomic factors.”

By asking your doctor to discuss the connections between race and breast cancer with you, you’ll be able to more openly advocate for yourself and properly assess your personal risk factors.

What types of tests are available to provide insight about a breast cancer treatment plan?

If you have breast cancer, you should definitely ask your doctor for a thorough rundown on your treatment options, Dr. Kaklamani says, starting with the types of tests available to help craft your individual treatment plan.

Genomic tests—like the Oncotype DX® test—look at the specific genes in a tumor to see whether they are over- or under-active. For people diagnosed with early-stage invasive breast cancer (HR-positive and HER2-negative with or without involvement of the lymph nodes), the Oncotype DX Breast Recurrence Score® result tells patients and their doctors not only how aggressive their cancer is and the risk of it returning, but more importantly, whether chemotherapy might be a beneficial treatment option or if it can be safely omitted, Dr. Kaklamani says.

“The good thing about the [result that you get from the Oncotype® test] is that it’s specific to the woman that we are testing,” she says. “All of these clinical trials that we’ve done have included thousands and thousands of women, [but] none of those women are present in my office when I talk to that specific person about their breast cancer. [Each test result] represents that woman’s breast cancer.”

Personalized is obviously better when it comes to something as delicate as cancer treatment (you wouldn’t take someone else’s prescription medicine, would you?), so asking your doctor about genomic testing can help ensure you’re getting a treatment plan that’s properly tailored to your needs.

Should I be doing a self breast exam?

In 2015, the American Cancer Society stopped recommending that people perform their own breast exams, but that doesn’t mean you’re off the hook for keeping tabs on your breast health, Dr. Kaklamani says.

“The guidelines are very clear that there has to be what they call ‘breast self awareness,'” she says. “This is extremely important to be aware of what your breasts look like, and if you do notice something that has changed, that you see your physician immediately.”

Dr. Kaklmani notes that one study showed that nurses who were taught how to properly perform self breast exams were able to accurately detect their breast cancer—demonstrating that if people are properly trained, self breast exams can be effective. That training should fall on gynecologists and primary care physicians, she says, so ask yours for instructions during your next visit.

By: Dr. Kaklamani Paid consultant for Exact Sciences Corporation.

Source: 3 Things To Ask Your Doctor About Breast Cancer Treatment | Well+Good

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Beauty Products are Full of Risky Chemicals

Six years ago, I felt a lump in my breast and felt utterly betrayed by my body. Three exams, two ultrasounds, and one biopsy later, doctors discovered multiple benign breast tumors that will require a lifetime of monitoring. Lumps like mine seem to show up in people whose breast tissue is sensitive to the hormone estrogen.

I was 21 and still in college, but the seeming invincibility of youth quickly fell away; I felt anxious and vulnerable like never before. But I was inspired to learn more about my body and the chemicals I was in contact with every day, in everything from hair relaxers to styling creams.

About 10 percent of women will experience the same diagnosis, fibroadenoma, in their lifetime. While fibroadenoma hasn’t been linked to an increased risk of breast cancer, all I could think about was how I’d spend years living with the consequences of something I couldn’t see or feel: hormones.

Hormones affect all of us, as they carry messages between different parts of the body. We’re talking estrogens, androgens, progesterones, testosterone, and everything in between. Together, they make up the endocrine system, which impacts our reproductive health, metabolism, and a range of biological processes.

Over the years, I tried to limit my exposure to synthetic hormones, including hormonal birth control. But our society doesn’t make it easy, even when it comes to potentially harmful chemicals. For years, scientists have been studying potential links between human cancers and the growth hormones that farmers feed to livestock, to take just one example. An even more pervasive threat lurks in everything from cleaning products to cookware to fragrances: endocrine-disrupting chemicals (EDCs), which I’d never even heard of until I studied environmental policy in graduate school.

“It’s pretty safe to say that everyone likely has some level of EDCs in their system,” says Heather Patisaul, associate dean for research at North Carolina State University. “There are hundreds if not thousands of EDCs in the marketplace, so it’s just a question of what your personal exposure profile looks like.”

EDCs are a class of chemicals that interfere with normal hormone function. They include “forever chemicals,” also known as PFAS (per- and polyfluorinated substances), which are found in adhesives, nonstick cookware, food packaging, and even waterproof mascara. The CDC writes that PFAS are found everywhere from the soil to our bloodstream, and that in studies that fed large amounts of them to animals, they affected reproduction, immunity, and the thyroid and liver. (The CDC also notes, “Human health effects from exposure to low environmental levels of PFAS are uncertain.”)

Other EDCs like bisphenol A (BPA) and alkylphenols target estrogen receptors. And phthalates — a chemical used to make plastic soft and flexible — can be found in a slew of cosmetics, and targets both estrogen and testosterone receptors. Even low-level exposure to EDCs can result in minute changes to the body’s natural hormonal activity.

And although illnesses can come about from a combination of genetic, environmental, and behavioral factors, environmental health researchers continue to link EDC exposure as a possible risk factor in the development of immunity related diseases, neurological diseases, reproductive disorders, and breast and uterine cancer.

Our society makes potentially harmful chemicals hard to avoid

I wanted to learn how to lower my risks from personal care items with help from science, so I joined a consumer study led by the Silent Spring Institute, a research and advocacy organization that studies toxins in the environment. For three months, I meticulously tracked my personal care, right down to the brands I used and how often I used them.

It isn’t just that beauty products are full of hard-to-pronounce and potentially harmful chemicals. The study, a partnership with the Resilient Sisterhood Project and published as the POWER study, also validated previous findings that Black women like me purchase more hair products than other groups, and that these products are more likely to contain endocrine disruptors. The results rocked me to my core.

“There’s a disparity in exposure to chemicals that act like hormones,” says Robin Dodson, a chemical exposure researcher at the Silent Spring Institute. “When you look at general health trends, Black women have higher rates of hormone-mediated diseases like uterine fibroids, aggressive forms of breast cancer, fertility issues, and are more likely to have pre-term births.” As a Black woman with my own health condition related to hormones, I was starting to see connections between health issues in my community and the products we rely on.

How I purged worrisome chemicals from my beauty care

Cosmetics are a billion-dollar industry in the US, but remain woefully underregulated. Consumer protections against harmful chemicals hinge on product labels, but labels are hard to understand and aren’t always fully transparent. We’re all living with the consequences, and Black women in particular are paying a high price. Here’s how I’ve changed my beauty care with help from science and research, and how others can too.

Use a trusted source to compare products

For me, one of the most valuable parts of joining the POWER study was having a forum to navigate hair care questions with other Black women. When researchers asked participants how we discover new product recommendations, we pointed to social media, friends, and family. How many people cross-reference those word-of-mouth recommendations with a scientific database? That’s now a core step in my discovery process.

Screenshot 2022-01-04 at 21-44-09 Done For You Commission Machines

Some companies are better at avoiding chemicals of concern than others. When I’m in doubt, I look to the Environmental Working Group’s Skin Deep database, which gives a complete profile of chemical ingredients of concern in skin and hair products.

Reviewing the Toxic-Free Beauty pocket guide, tailored for products commonly used by Black women, helped me get familiar with the chemical names I might see on product labels. Keeping tabs on the FDA’s product safety alert page informs me of product recalls and FDA consumer warnings. Apps like Think Dirty will do the research for you; simply use your phone to scan a product’s barcode, and it displays a clear overview of health impacts associated with its ingredients.

Of course, these apps are only as good as the product label itself. Since new products enter the market constantly, Detox Me, developed by the Silent Spring Institute, shares practical tips for more conscious purchasing. Tools like these draw on years of scientific evidence to help you decode product labels and steer clear of potentially harmful chemicals.

Avoid unspecified fragrances

“Secret, unlabeled fragrance chemicals are hiding in personal care products, without the public’s knowledge or consent,” says Janet Nudelman, policy and program director at the advocacy group Breast Cancer Prevention Partners. “These chemicals are often linked to both environmental and public health harms, but people don’t know because companies don’t have to disclose them.”

While the FDA requires cosmetics to list other kinds of ingredients, many fragrance chemicals are protected as trade secrets and may appear as simply “perfume” or “aroma” on product labels. Fragrances are often mixed with aldehydes, which may increase cancer risks in some people, and benzophenone derivatives, which may be endocrine disruptors, according to the advocacy coalition Campaign for Safe Cosmetics.

When the campaign tested 17 of the most popular perfumes in 2010, in partnership with the Environmental Working Group, it found 14 undisclosed ingredients in the average product, among them chemicals associated with hormone disruption.

Even “unscented” products may contain fragrance ingredients to mask unpleasant smells without giving the product a notable odor.

States like California are starting to close this “fragrance loophole” with stricter product labeling laws. In the meantime, you can do your own research to avoid products with vague fragrance labeling and other undisclosed ingredients.

Understand your body and what it needs

After 10 years of relaxing my hair, I wanted to assert my newfound independence and went natural, but was soon overwhelmed by the array of creams, gels, lotions, and oils intended to smooth my curls. Trying a new hair product from the “ethnic” aisle of my local drug store became my weekend ritual. Black consumers spend nine times more on hair care than their white counterparts, and I was beginning to understand why.

Looking back, I tried too many products, including low-quality ones that actually damaged my hair, and potentially exposed myself to more harmful chemicals in the process.Instead, I wish I took the time upfront to understand what my hair needed.

Learn about your hair porosity, density, and texture (yes, even straight hair has a texture), and tailor solutions to your needs. As a type-four, low-porosity queen myself, what my hair really needed — more than it needed three different kinds of styling creams — was moisture. That’s right, plain water! Understanding your hair’s natural attributes will save you time and money on wasted products.

When researchers from the Battelle Memorial Institute tested the hair products that Black women use most frequently, a long list of chemicals turned up: cyclosiloxane, fragrances, diethyl phthalate (DEP), and parabens, all of which are known to affect the endocrine system. Chemical straighteners, also known as “relaxers,” sometimes contain carcinogens like formaldehyde and might even lead to an increased risk of breast cancer in Black women (there’s still no scientific consensus on this one). Relaxer usage among Black consumers has declined in recent years, but some women are returning to them out of convenience.

Don’t be afraid to DIY

The science of hair care may be simpler than you think. Shampoos contain surfactants that help wash away dirt, oil, and products that build up in our hair. They also balance pH and close the hair cuticle, the protective outer layer of your hair. Most hair creams and butters help to lock in moisture between washes and prevent split ends. Commercial conditioners work to seal moisture into the hair cuticle, but may rely on chemical preservatives.

If you’re only able to swap out one or two products in your rotation, consider the ones that are in contact with your body for long periods of time. “From an exposure point of view, you’ll want to reduce usage of commercial products that you leave on your hair for a longer period of time, like scalp treatments, leave-in conditioners, hair dyes, and chemical straighteners,” says Dodson.

Early on, I internalized the myth that my hair was too difficult for me to care for without the use of chemical straighteners. But I’ve realized that most of what my own hair needs — moisture retention — can be achieved with ingredients from my own kitchen.

I spent months recreating the best parts of my favorite storebought products: banana and avocado are now core ingredients in my DIY conditioner. You could consider using honey, which has emollient (hair smoothing) and humectant (water bonding) properties. Coconut oil is another great alternative, and its lauric acid delivers moisture deep into the hair shaft. Any of these natural conditioners can be used on their own or together in a hair mask, or a deep conditioning treatment for the hair.

The US needs stronger regulation of cosmetics and personal care products

In the early 1900s, cosmetics and drugs were dangerously unregulated: Lead and arsenic found their way into skin creams, and mercury brightened makeup products. As more women suffered scarring, poisonings, and in some cases death, scientists sounded the alarm about harsh chemicals in consumer goods. In 1937, elixir sulfanilamide — an untested, but heavily marketed antibiotic — killed more than 100 Americans.

But medicines are regulated more closely than cosmetics, and the FDA does not order companies to recall cosmetic products that may be unsafe. “Neither the law nor FDA regulations require specific tests to demonstrate the safety of individual [cosmetic] products or ingredients,” the FDA explains on its website. “The law also does not require cosmetic companies to share their safety information with the FDA.”Screenshot 2022-01-04 at 21-56-49 JV - PrimeStocks

While some chemicals have been outlawed (DDT, DES, lead acetate hair dyes, and BPA in baby products), the FDA has failed to prohibit many endocrine-disrupting chemicals that are still widely used in personal care products.

Politics and big business play a role in keeping regulations to a minimum, according to the experts I talked to. “The $100 billion-dollar US cosmetics industry is very invested in maintaining the status quo, and is powerfully incentivized to fight regulation,” Nudelman says. Major industry trade groups, like the Personal Care Products Council, representing 600 beauty companies, heavily promote self-regulation, through the Cosmetic Ingredient Review program (CIR).

“Industry self-regulation lacks the safeguards provided by FDA reviews. The Cosmetics Ingredient Review is financed by cosmetics manufacturers and housed inside the industry’s trade association. Many CIR findings are inconsistent with the findings by other regulatory authorities or experts,” Scott Faber, vice president of government affairs at the Environmental Working Group, testified to the House Committee on Oversight and Government Reform.

Opponents of stricter cosmetics regulation continue to muddy the link between hormone-driven disease rates and risky environmental chemicals. While some research gaps remain, an ever-growing body of evidence shows that the chemicals we absorb from our environments matter, and may be compounding existing racial disparities in health outcomes.

When Vox contacted the FDA’s Office of Cosmetics and Colors for comment, a spokesperson said that “a change in the FDA’s legal authority over cosmetics would require Congress to change the law.”

Congress has had some historical interest in better regulating cosmetics — Sens. Thomas Eagleton and Ted Kennedy tried to get traction on bills in the ’70s and ’90s, respectively, and current Rep. Ron Wyden (D-OR) has been an advocate, as well.

More recently, Rep. Jan Schakowsky (D-IL) introduced a package of four Safer Beauty bills this summer. One bill would ban 11 chemicals of concern currently outlawed for use in the EU, California, and Maryland. While Schakowsky has been trying to pass versions of the package since 2009, Nudelman of the Breast Cancer Prevention Partners believes they now have a fighting chance.

“We believe this bill package to be different from past legislative attempts,” she says. “It addresses four discrete issues that are already at the forefront of people’s minds: banning toxic chemicals, increased labeling transparency, protections for women of color, and closing the fragrance loophole.”

Occasionally, I’ll see “Just for Me” — a hair relaxer containing hormonally active ingredients and marketed specifically for children — at my local drugstore. It’s the same relaxer I used up until college and my eventual diagnosis with fibroadenoma. I’m hopeful that one day, consumers won’t have to wonder whether toxins are hiding in the products that are supposed to make us feel beautiful. But until then, research can help us look out for our own health.

Paige Curtis is a Boston-based writer covering the intersection of climate, arts, and culture in such publications as Yes! Magazine and Boston Art Review. Formally trained in environmental management from the Yale School of Environment, she’s most excited by community-based solutions to the climate crisis.

Source: Beauty products are full of risky chemicals. I tried to get rid of them. – Vox

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Cancer Without Chemotherapy A Totally Different World

Dr. Seema Doshi was shocked and terrified when she found a lump in her breast that was eventually confirmed to be cancerous. “That rocked my world,” said Dr. Doshi, a dermatologist in private practice in the Boston suburb of Franklin who was 46 at the time of her diagnosis. “I thought, ‘That’s it. I will have to do chemotherapy.’”

She was wrong.

Dr. Doshi was the beneficiary of a quiet revolution in breast cancer treatment, a slow chipping away at the number of people for whom chemotherapy is recommended. Chemotherapy for decades was considered “the rule, the dogma,” for treating breast cancer and other cancers, said Dr. Gabriel Hortobagyi, a breast cancer specialist at MD Anderson Cancer Center in Houston. But data from a variety of sources offers some confirmation of what many oncologists say anecdotally — the method is on the wane for many cancer patients.

Genetic tests can now reveal whether chemotherapy would be beneficial. For many there are better options with an ever-expanding array of drugs, including estrogen blockers and drugs that destroy cancers by attacking specific proteins on the surface of tumors. And there is a growing willingness among oncologists to scale back unhelpful treatments.

The result spares thousands each year from the dreaded chemotherapy treatment, with its accompanying hair loss, nausea, fatigue, and potential to cause permanent damage to the heart and to nerves in the hands and feet.

The diminution of chemotherapy treatment is happening for some other cancers, too, including lung cancer, the most common cause of cancer deaths among men and women in the United States, killing about 132,000 Americans each year. Breast cancer is the second leading cause of cancer deaths among women, killing 43,000.

Still, the opportunity to avoid chemotherapy is not evenly distributed, and is often dependent on where the person is treated and by whom.

But for some patients who are lucky enough to visit certain cancer treatment centers, the course of therapy has changed. Now, even when chemotherapy is indicated, doctors often give fewer drugs for less time.

“It’s a totally different world,” said Dr. Lisa Carey, a breast cancer specialist at the University of North Carolina.

Dr. Robert Vonderheide, a lung cancer specialist who heads the University of Pennsylvania’s Abramson Cancer Center, remembers his early days on the job, about 20 years ago.

“The big discussion was, Do you give patients two different types of chemotherapy or three?” he said. There was even a clinical trial to see whether four types of chemotherapy would be better.

“Now we are walking in to see even patients with advanced lung cancer and telling them, ‘No chemo,’” Dr. Vonderheide said.

The breast cancer treatment guidelines issued by the National Cancer Institute 30 years ago were harsh: chemotherapy for about 95 percent of patients with breast cancer.

The change began 15 years ago, when the first targeted drug for breast cancer, Herceptin, was approved as an initial treatment for about 30 percent of patients who have a particular protein on their tumor surface. It was given with chemotherapy and reduced the chance of a recurrence by half and the risk of dying from breast cancer by a third, “almost regardless of how much and what type of chemotherapy was used,” Dr. Hortobagyi said.

In a few studies, Herceptin and another targeted drug were even given without chemotherapy, and provided substantial benefit, he added.

That, Dr. Hortobagyi said, “started to break the dogma” that chemotherapy was essential. But changing cancer therapies was not easy. “It is very scary,” to give fewer drugs, Dr. Hortobagyi said.

“It is so much easier to pile on treatment on top of treatment,” he continued, “with the promise that ‘if we add this it might improve your outcome.’”

But as years went by, more and more oncologists came around, encouraged by new research and new drugs.

The change in chemotherapy use is reflected in a variety of data collected over the years. A study of nearly 3,000 women treated from 2013 to 2015 found that in those years, chemotherapy use in early-stage breast cancer declined to 14 percent, from 26 percent. For those with evidence of cancer in their lymph nodes, chemotherapy was used in 64 percent of patients, down from 81 percent.

More recent data, compiled by Dr. Jeanne Mandelblatt, a professor of medicine and oncology at Georgetown, and her colleagues, but not yet published, included 572 women who were 60 or older and enrolled in a federal study at 13 medical centers. Overall, 35 percent of older women received chemotherapy in 2012. That number fell to 19 percent by the end of 2019.

Cheaper and faster genetic sequencing has played an important role in this change. The technology made it easier for doctors to test tumors to see if they would respond to targeted drugs. Genetic tests that looked at arrays of proteins on cancer cells accurately predicted who would benefit from chemotherapy and who would not.

There are now at least 14 new targeted breast cancer drugs on the market — three were approved just last year — with dozens more in clinical trials and hundreds in initial development.

Some patients have reaped benefits beyond avoiding chemotherapy. The median survival for women with metastatic breast cancer who are eligible for Herceptin went from 20 months in the early 1990s, to about 57 months now, with further improvements expected as new drugs become available. For women with tumors that are fed by estrogen, the median survival increased from about 24 months in the 1970s to almost 64 months today.

Now some are in remission 10 or even 15 years after their initial treatment, Dr. Hortobagyi said.

“At breast cancer meetings, a light bulb went off. ‘Hey, maybe we are curing these patients,’” Dr. Hortobagyi said.

Dr. Doshi’s oncologist, Dr. Eric Winer of the Dana-Farber Cancer Institute, gave her good news: A genetic test of her tumor indicated she would not get any significant benefit from chemotherapy. Hormonal therapy to deprive her cancer of the estrogen that fed it would suffice.

But as much as Dr. Doshi dreaded chemotherapy, she worried about forgoing it. What if her cancer recurred? Would chemotherapy, awful as it is, improve her outcome?

She got a second opinion.

The doctor she consulted advised a “very aggressive” treatment, Dr. Doshi said — a full lymph node dissection followed by chemotherapy.

She had multiple conversations with Dr. Winer, who ended up discussing her case with four other specialists, all of whom recommended against chemotherapy.

Finally, Dr. Doshi said, “my husband said I should just pick a horse and run with it.” She trusted Dr. Winer.

Her struggles mirror what oncologists themselves go through. It can take courage to back off from chemotherapy.

One of the most difficult situations, Dr. Winer said, is when a patient has far more advanced disease than Dr. Doshi did — hers had spread to three lymph nodes but no further — and is not a candidate for one of the targeted treatments. If such a patient has already had several types of chemotherapy, more is unlikely to help. That means there is no treatment.

It falls to Dr. Winer to tell the patient the devastating news.

Dr. Susan Domchek, a breast cancer specialist at the University of Pennsylvania, can relate to those struggles.

“It is the nature of being an oncologist to be perpetually worried that you are either overtreating or undertreating a patient,” she said.

“Some cases keep me up at night,” she said, “specifically the cases where the risks and benefits of chemotherapy are close, yet the stakes still feel so high.”

When Dr. Roy Herbst of Yale started in oncology about 25 years ago, nearly every lung cancer patient with advanced disease got chemotherapy.

With chemotherapy, he said, “patients would be sure to have one thing: side effects.” Yet despite treatment, most tumors continued to grow and spread. Less than half his patients would be alive a year later. The five-year survival rate was just 5 to 10 percent.

Those dismal statistics barely budged until 2010, when targeted therapies began to emerge. There are now nine such drugs for lung cancer patients, three of which were approved since May of this year. About a quarter of lung cancer patients can be treated with these drugs alone, and more than half who began treatment with a targeted drug five years ago are still alive. The five-year survival rate for patients with advanced lung cancer is now approaching 30 percent.

But the drugs eventually stop working for most, said Dr. Bruce Johnson, a lung cancer specialist at Dana-Farber. At that point many start on chemotherapy, the only option left.

Another type of lung cancer treatment was developed about five years ago — immunotherapy, which uses drugs to help the immune system attack cancer. Two-thirds of patients from an unpublished study at Dana-Farber were not eligible for targeted therapies but half of them were eligible for immunotherapy alone, and others get it along with chemotherapy.

Immunotherapy is given for two years. With it, life expectancy has almost doubled, said Dr. Charu Aggarwal, a lung cancer specialist at the University of Pennsylvania.

Now, said Dr. David Jackman of Dana-Farber, chemotherapy as the sole initial treatment for lung cancer, is shrinking, at least at that cancer treatment center, which is at the forefront of research. When he examined data from his medical center he found that, since 2019, only about 12 percent of patients at Dana-Farber got chemotherapy alone, Dr. Jackman said. Another 21 percent had a targeted therapy as their initial treatment, and among the remaining patients, 85 percent received immunotherapy alone or with chemotherapy.

In contrast, in 2015, only 39 out of 239 patients received a targeted therapy as their initial treatment. The rest got chemotherapy.

Dr. Aggarwal said she was starting to witness something surprising — some who had received immunotherapy are still alive, doing well, and have no sign of cancer five years or more after their initial treatment.

She said: “I started out saying to patients, ‘I will treat you with palliative intent. This is not curative.’”

Now some of those same patients are sitting in her clinic wondering if their disease is gone for good.

Chong H. Hammond’s symptoms were ambiguous — a loss of appetite and her weight had dropped to 92 pounds.

“I did not want to look at myself in the mirror,” she said.

It took from October 2020 until this March before doctors figured it out. She had metastatic lung cancer.

Then Dr. Timothy Burns, a lung cancer specialist at the University of Pittsburgh, discovered that Mrs. Hammond, who is 71 and lives in Gibsonia, Pa., had a tumor with two unusual mutations.

Although a drug for patients with Mrs. Hammond’s mutations has not been tested, Dr. Burns is an investigator in a clinical trial involving patients like her.

He offered her the drug osimertinib, which is given as a pill. This allowed her to avoid chemotherapy.

Ten days later she began feeling better and started eating again. She had energy to take walks. She was no longer out of breath.

Dr. Burns said her lung tumors are mostly gone and tumors elsewhere have shrunk.

If Mrs. Hammond had gotten chemotherapy, her life expectancy would be a year or a little more, Dr. Burns said. Now, with the drug, it is 38.6 months.

Dr. Burns is amazed by how lung cancer treatment has changed.

“It’s been remarkable,” he said. “We still quote the one-year survival but now we are talking about survival for two, three, four or even five years. I even have patients on the first targeted drugs that are on them for six or even seven years.”

Mark Catlin, who is being treated at Dana-Farber, is one of those patients.

On March 8, 2014, Mr. Catlin, who has never smoked, noticed a baseball-size lump under his arm. “The doctors told me to hope for anything but lung,” he said.

But lung it was. It had already spread under his arm and elsewhere.

Oncologists in Appleton, Wis., where he lives, wanted to start chemotherapy.

“I was not a fan,” Mr. Catlin said. His son, who lives in the Boston area, suggested he go to Dana-Farber.

There, he was told he could take a targeted therapy but that it would most likely stop working after a couple of years. He is 70 now, and still taking the therapy seven years later — two pills a day, with no side effects.

He rides a bike 15 to 25 miles every day or runs four to five miles. His drug, crizotinib, made by Pfizer, has a list price of $20,000 a month. Mr. Catlin’s co-payment is $1,000 a month. But, he says, “it’s keeping me alive.” “It’s almost surreal,” Mr. Catlin said.

Gina Kolata

By:

Source: Cancer Without Chemotherapy: ‘A Totally Different World’ – The New York Times

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The Cancer Custodians Hidden Truths

woman-with-headscarf-getting-chemo-treatment-article

Part of Dennis Plenker’s daily job is growing cancer. And a variety of different ones, too. Depending on the day and the project, different tumors may burgeon in the petri dishes stocked in the Cold Spring Harbor Laboratory where Plenker works as a research investigator. They might be aggressive breast cancers.

They might be glioblastomas, one of the deadliest brain tumors that rob patients of their ability to speak or read as they crowd out normal cells. Or they might be pancreatic cancers, the fast and vicious slayers that can overtake a healthy person within weeks or even days.

These tiny tumor chunks are transparent and bland—they look like little droplets of hair gel that accidentally plopped into a plastic dish and took hold. But their unassuming appearance is deceptive. If they were still in the human bodies they came from, they would be sucking up nutrients, rapidly growing and dodging the immune system defenses.

But in Plenker’s hands—or rather in the CSHL’s unique facility—these notorious killers don’t kill anyone. Instead, scientists let them grow to devise the most potent ways to kill them. These tumor chunks are called organoids. They are three-dimensional assemblages of malignant growths used to study cancer behavior and vulnerability to chemotherapy and the so-called “targeted drugs”—the next generation therapies.

Scientists used to study tumors at a single-cell level, but because tumors grow as cell clusters in the body, it proved to be inefficient. The three-dimensional structures make a difference. For example, chemo might destroy the tumor’s outer cell layer, but the inner ones can develop resistance, so where single cells may die, a 3D mass will bounce back. Organoids can provide a window into these little-known mechanisms of drug resistance.

They can reveal how normal tissues turn malignant and where the cellular machinery goes off-track to allow that to happen. As their name suggests, organoids are scientists’ windows into organs, whether healthy or stricken with disease. You need to know your enemy to beat it, Plenker says, and cancer organoids offer that opportunity.

Taken from patients currently undergoing cancer treatments, these tumor chunks will reveal their weaknesses so scientists can find the cancers’ Achilles’ heel and devise personalized treatments. “Organoids are essentially patients in a dish,” Plenker says. Only unlike real patients, the organoids can be subjected to all sorts of harsh experiments to zero in on the precise chemo cocktails that destroy them in the best possible way.

And they will likely provide a more realistic scenario than drug tests in mice or rats, as animal models aren’t perfect proxies for humans.

These notorious killers don’t kill anyone. Instead, scientists devise the most potent ways to kill them.

The way that cancer proliferates in the body is hard to reproduce in the lab. Stem-cell research made it possible. After scientists spent a decade understanding how various cells multiply and differentiate into other cell types based on molecular cues and nourishment, they were able to make cells grow and fuse into tissues.

To stick together like bricks in a nicely laid wall, cells need a biological scaffold that scientists call an extracellular matrix or ECM, which in the body is made from collagen and other materials. Today, the same collagen scaffolds can be mimicked with a gooey substance called Matrigel—and then seeded with specific cells, which take root and begin to multiply.

Some tissue types were easy to grow—Columbia University scientists grew viable bones as early as 2010.1 Others, like kidney cells, were trickier. They would grow into immature tissues incapable of performing their job of cleaning and filtering blood. It took scientists time to realize that these cells wanted more than scaffolding and food—they needed to “feel at home,” or be in their natural habitat. Kidney cells needed the feeling of liquid being washed over them, the Harvard University group found, when they first managed to grow functioning kidney tissue in 2018.2

Cancers have their own growth requirements. In the body, they manage to co-opt the organism’s resources, but keeping them happy in a dish means catering to their dietary preferences. Different cancers need different types of molecular chow—growth factors, hormones, oxygen and pH levels, and other nutrients. Pancreatic adenocarcinoma thrives in low-oxygen conditions with poor nutrients.3 Glioblastomas feed on fatty acids.4 These nutrients are delivered to organoids via a specific solution called growth medium, which the lab personnel regularly doles out into the dishes.

Plenker is charged with keeping this murderous menagerie alive and well. He is the one who designs the cancers’ dietary menu, a specific protocol for each type. And while his official title is facility manager and research investigator who works closely with David Tuveson, director of the CSHL’s Cancer Center, he is essentially a cancer custodian, a curator of a unique collection that aims to change the paradigm of cancer treatment.

Plenker’s research area is pancreatic cancer—one of the most notorious killers known. Often diagnosed late and resistant to treatment, it is essentially a death sentence—only 8 to 10 percent of patients remain alive five years after diagnosis. The chemo drugs used to treat it haven’t changed in 40 years, Plenker says. In the past decade, physicians tried combining multiple drugs together with relative success. Identifying winning combos can save lives, or at least prolong them—and that’s what the organoids will help clinicians do better.

In a groundbreaking clinical trial called PASS-01 (for Pancreatic Adenocarcinoma Signature Stratification for Treatment), Plenker’s team collaborates with other American and Canadian colleagues to identify the most effective chemo cocktails and to understand the individual patients’ tumor behaviors, which would lead to more personalized treatments.5

Scientists know the same cancer types behave differently in different patients. Typically, all malignancies have the so-called “driver mutation”— the cancer’s main trigger caused by a mutated gene. But tumors also often have “passenger mutations” that happen in nearby genes. These additional mutated genes can generate various proteins, which may interfere with treatment.

Or not. Scientists call these mutated gene combinations tumor mutational signatures, which can vary from one patient to the next. With some cancers, doctors already know what mutations signatures they may have, but with pancreatic cancer they don’t have good tale-telling signs, or biomarkers. “There aren’t many biomarkers to help clinicians decide which chemo may be better for which patient,” explains oncologist Grainne O’Kane, who treats pancreatic cancer patients at the Princess Margaret Hospital in Toronto, Canada.

That’s the reason O’Kane participates in the PASS-01 trial—it will give doctors a better view into the exact specifics of their patients’ malignancies. As they take their patients’ biopsies, they are sending little cancer snippets to the CSHL to be grown into organoids, which will be subjected to chemo cocktails of various combinations to design more personalized regiments for them.

The hospital treats all patients with the so-called standard of care chemotherapy, which is more of a one-size-fits-all approach. Some patients will respond to it but others won’t, so the goal is to define the second line of chemo defense in a more personalized fashion. “That’s where the biopsies we send to Tuveson’s lab might be useful,” O’Kane says. “They can help us find something to benefit patients after the first line of chemo stopped working.”

Organoids are patients in a dish. Unlike real patients, organoids can be subjected to experiments.

Scientists can try all kinds of combos on the tumorous organoids, which they can’t do in living people. “You can treat 100 organoids with 100 different compounds and see which one works, or which compound does a good job and which ones don’t work at all,” Plenker says. That would also allow scientists to define the precise amount of chemo, so doctors wouldn’t have to over-treat patients with harsh drugs that create sickening side effects. Ultimately, organoids should take a lot of guesswork out of the process.

With about 150 patients’ adenocarcinomas already collected, the team hopes to come up with some answers. O’Kane says her team already has three patients for which they were able to design the more personalized second line of defense chemo, based on what their organoids revealed. They haven’t yet tried it, because the trial has only started recently, but this would be the next step.

“Being able to piece all this information together in real time as patients are moving through their therapies can really improve the outcomes,” O’Kane says. And while they may not be able to save all of those who graciously donated their biopsy snippets to science, it will help build better treatments in the future. “Even if we won’t be able to help these specific patients we’re hoping to use this info in the future clinical trials,” O’Kane says.

Organoids can also help understand how cancer develops. This is particularly true for breast cancers, says Camilla dos Santos, associate professor and a member of the CSHL Cancer Center. She studies the inner life of human mammary glands, more commonly referred to as breasts, and is also part of the cancer custodian crew. The hormonal changes that women go through during pregnancy subsequently modify breast cancer risk, sometimes lowering it and sometimes increasing—a complex interplay of the body’s chemicals.

“We know that women who get pregnant for the first time before they turn 25 years old, have a 30 percent decrease in breast cancer incidents later in life,” dos Santos says. “When they turn 60 or 70, 30 percent of them will not develop cancer.” On the contrary, those who are pregnant past 38 have a 30 to 50 percent increase in developing aggressive breast cancer types. Clearly, some molecular switches are involved, but they are very hard to study within the body. That’s where organoids can provide a window into the surreptitious process.

Using breast organoids, scientists can model the complex life of mammary glands at various stages of a woman’s life. And while most women wouldn’t want their breasts poked and pierced when they are pregnant or breastfeeding, many donate their tissues after breast reduction surgery or prophylactic mastectomy due to high-risk mutations like the BRCA gene.

That’s where organoids shine because scientists can not only grow them, but also give them the pregnancy hormonal cues, which will make cells generate milk, stop lactating, or do it again—and study the complex cellular interactions that take place in real life.

There’s a lot to study. At birth, mammary glands are similar in both genders—just little patches of the mammary epithelium tissue. But when puberty hits, the female glands fill up with the so-called mammary tree—a system of ducts for future milk production, which fully “blooms” in pregnancy.

“When a woman becomes pregnant, the duct tree expands, growing two types of cells—luminal and myoepithelial ones,” explains Zuzana Koledova, assistant professor of Masaryk University in Czech Republic who also uses organoids in her work. When the baby is born, the luminal cells, which line the inside of the ducts, produce the proteins that comprise milk.

The myoepithelial cells reside outside the ducts and work as muscles that squeeze the ducts to push milk out. Dos Santos likens this pregnancy mammary gland growth to the changes of the seasons. The images of sprouting ducts look like blossoming trees in the spring while later they shrivel like plants do in the fall.

The body governs these processes via the molecular machinery of hormones, which stimulate breast cells growth during pregnancy, and later cause them to die out. The two pregnancy-related hormones, prolactin and oxytocin, are responsible for milk production. Prolactin induces the luminal cells to make milk while oxytocin makes the myoepithelial cells contract. Once the baby is weaned, the levels of these hormones drop, causing cells to shrink back to their non-pregnant state.

With organoids scientists can observe these cellular dynamics at work. Koledova’s team had watched breast organoids secrete milk based on biological cues. They even recorded movies of cells pumping tiny milk droplets in the dish they were growing in. Using tiny snippets of donated breast tissue, the team grew the organoids inside the Matrigel matrix in the growth media and then added the two pregnancy hormones into the mix, explains Jakub Sumbal, a mammary gland researcher in Koledova’s group.

As they began to secret proteins that compose milk, the organoids, which looked like little domes inside the dish, changed from translucent to opaque. “At first, you can see through them, but then as they produce these proteins, they kind of darken,” Sumbal says. “And you can see them pushing out these little droplets.”

Cancer patients would no longer have to undergo chemotherapy by trial and error.

Dos Santos’s team, who also did similar work, outlined molecular changes that follow such dish-based hormonal cues in their recent study.6 In response to hormonal messages, cells produce proteins, which they display on their surfaces, like status symbols. During pregnancy the burgeoning cells prepping for milk production display the “proteins flags” that make them look important, attracting nourishment. When it’s time to die, they commit a cellular suicide.

They signal to the bypassing macrophages—immune system cleanup crew—to devour them. “They essentially say ‘come eat me!’ to the macrophages,” dos Santos says. “Because I’m no longer needed.”

The ability to mimic these processes in a dish, allows scientists to study the molecular switches that trigger breast cancer development—or minimize it. Scientists know that cancerous cells can hide from the immune system and even co-opt it into protecting themselves. They do it by displaying their own “do not eat me” protein flags on the surface and avoid destruction.

“Sometimes cancer cells can recruit specific types of immune cells to protect them,” dos Santos says. “They can not only say ‘do not eat me,’ but say ‘come hang out with me’ to the macrophages, and the macrophages will send suppressive signals to the B-cells or T-cells, the body defenders.” It is as if the cancer requests protection—a crew of guardians around it to defend against other cells that would otherwise wipe it out.

Scientists can’t telescope into the body to peek at these interactions, but they now can watch these stealth battles unfolding in a dish. “Right now we are looking at the proteins that are secreted by the organoids—the proteins that go on the surface of the organoids’ cells and what they would communicate to the immune system,” dos Santos says.

“Even when there’s no immune system surrounding them, they would still be doing that.” There’s a way to mimic the immune system, too. Scientists can add B-cells, T-cells, macrophages, and other players into the growth medium and watch the full-blown cellular warfare in action. “That’s the next step in our research,” dos Santos says.

Understanding what hormonal fluxes trigger breast cancer, and how it recruits other cells for safekeeping, can give scientists ideas for pharmaceutical intervention. “We can find drugs that pharmacologically turn off the switches that trigger cancer or interrupt its signaling for protection,” dos Santos says. “That opens novel ways to treat people.”

Can organoid research lead to a new standard of care for cancer patients? That’s the ultimate goal, researchers say. That’s why Plenker works at keeping his collection of cancer glops alive and well and thriving—he calls it a living biobank. And he keeps a stash in the cryogenic freezer, too.

He is also developing protocols that would allow commercial companies to grow organoids the same way chemical industries make reagents or mice suppliers grow rodents for research. A benefit of organoid experiments is they don’t involve animals at all.

Hospitals may one day start growing organoids from their patients’ biopsies to design and test personalized chemo cocktails for them. Once science crosses over to that reality, the entire treatment paradigm will change. Cancer patients won’t have to undergo chemotherapy by trial and error.

Instead their cancer organoids will be subjected to this process—knocked out by a gamut of drug combinations to find the winning one to use in the actual treatment. Plenker notes that once enough data is gathered about the tumors’ mutational signatures, scientists may create a database of tumor “mugshots” matching them to the chemo cocktails that beat them best.

And then just sequencing a biopsy sample would immediately inform oncologists what drug combo the patient needs. “We may be about 10 years away from that,” Plenker says, but for now there’s a lot more research to do. And a lot more cancers to grow.

By: Lina Zeldovich

Lina Zeldovich grew up in a family of Russian scientists, listening to bedtime stories about volcanoes, black holes, and intrepid explorers. She has written for The New York Times, Scientific American, Reader’s Digest, and Audubon Magazine, among other publications, and won four awards for covering the science of poop. Her book, The Other Dark Matter: The Science and Business of Turning Waste into Wealth, will be released in October 2021 by Chicago University Press. You can find her at LinaZeldovich.com and @LinaZeldovich.

Source: The Cancer Custodians – Issue 102: Hidden Truths – Nautilus

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Critics:

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans.

Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as Helicobacter pylori, hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV).

These factors act, at least partly, by changing the genes of a cell. Typically, many genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to inherited genetic defects. Cancer can be detected by certain signs and symptoms or screening tests. It is then typically further investigated by medical imaging and confirmed by biopsy.

Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these leads to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, (contrast) CT scans and endoscopy.

The tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate the prognosis and to choose the best treatment.

Further reading

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