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1 in 8: what you may not know about breast cancer.

A friend, a colleague, a cousin, a mother, sister, or daughter. We all know someone who has been diagnosed with breast cancer. A woman's lifetime risk is one in eight. And unlike heart attacks or stroked or diabetes, breast cancer seems to strike women who have no obvious risk factors. "That's one reason it's so frustrating, especially to younger premenopausal women who have breast cancer," says Walter Willett, of the Harvard School of Public Health. "They say, 'I'm doing everything right,' and they are. Being health conscious does not seem to prevent breast cancer." Nevertheless, the disease isn't a total mystery. There are ways to lower your risk. But misunderstandings abound. Here's what you may be missing.

An estimated 232,670 U.S. women will be diagnosed with breast cancer in 2014, and roughly 40,000 will die of the disease. Only one other cancer--lung--kills more women. But unlike lung cancer, breast cancer has no obvious cause. Here's what you may not know.

1. Breast cancer is not a total mystery.

"We know how to prevent almost all breast cancer," says Walter Willett, chair of the nutrition department at the Harvard School of Public Health. It's just not a very good solution.

"First, you keep girls in a semi-starved state as they're growing to prevent them from menstruating until they are about 17 or 18," he says. "Then you make sure they get pregnant and have child after child and keep breastfeeding so that they don't menstruate in between."

Why would that work?

"Breast cancer risk is related in part to the number of menstrual cycles a woman has," explains Willett. "The cycles make the breast tissue multiply, and the more that cells multiply over a lifetime, the higher the risk."

That may be why both early menarche and late menopause raise the risk (see "Are You at Risk?" p. 6).

"In China until quite recently, the onset of menstrual cycles was around 17 or 18 years of age," notes Willett. "Girls were working the fields for long hours."

Until the twentieth century, a life with fewer menstrual cycles was the norm.

"Unfortunately, our lifestyle--which has many benefits that we certainly don't want to give up--has set us up for breast cancer," adds Willett.

Even if you look beyond menstrual and reproductive cycles, we know how to prevent many breast cancers.

"It's clear that weight gain during adult life is related to the risk of postmenopausal breast cancer," says Willett.

Taking hormones after menopause also puts women at risk. (1,2) "Hormone replacement therapy, especially estrogen plus progestin, increases risk," he explains.

"On average, Japanese women do not gain weight during adult life, and until very recently have not used hormone replacement therapy. Those two factors account for half of the difference between the United States' higher breast cancer rates and Japan's lower rates. So those are very important pieces of the picture." (3)

2. Extra weight matters.

If you're postmenopausal, extra pounds boosts your risk of breast cancer. And it doesn't have to be many pounds. (4)

"It's not just obesity," notes Regina Ziegler, senior investigator at the National Cancer Institute. "Postmenopausal women who are overweight have a higher risk than those who are normal weight."

(Premenopausal women who are heavy have a lower risk of breast cancer. But excess weight raises their risk of type 2 diabetes and other health problems.)

How does extra pounds promote post menopausal breast cancer? After menopause, a woman's ovaries stop producing estrogen. At that point, most of her estrogen is made by fat cells. So the more fat cells she has, the higher her blood levels of estrogen--which travels through the blood as estradiol.

"Women who are obese have about three times the circulating levels of estradiol compared to lean women," says Willett. "That's a huge difference. And we see some increase in risk even in women who gain 5 to 10 pounds. It's not just women who gain 50 or 60 pounds."

Roughly 80 percent of breast tumors are hormone-receptor positive--that is, they are fueled by estrogen and/or progesterone. (5) (Those tumors are usually easier to treat--with drugs that block estrogen production--than tumors that are not fueled by those hormones.)

But estrogen alone may not explain why heavier women have a higher breast cancer risk. They're also more likely to have higher insulin levels, which may also fuel tumors.

When researchers looked at women who were not taking estrogen after menopause, those with the highest insulin levels had 2 1/2 times the risk of breast cancer of those with the lowest insulin levels, after taking estradiol levels and weight into account. (6)

"Extra weight works only partially by raising estradiol," explains Ziegler.

What's more, extra pounds may increase the risk of a recurrence in women who have had breast cancer, according to the American Cancer Society and a workshop at the Institute of Medicine (IOM), which is part of the National Academy of Sciences. (7,8)

But regardless of how extra padding works, the message is the same.

"The main point for postmenopausal breast cancer is to weigh as close as you can to what you weighed at age 18," says Willett.

"To anybody who's afraid of estrogen-like chemicals in the environment, I would say, we have seen the enemy and it is us," he adds. "We are the big source."

3. Environmental estrogens may not matter.

Could estrogen-like chemicals like BPA and other plasticizers explain why breast cancer strikes so many women?

So far, there isn't much evidence from human studies that those chemicals matter. That's what the Institute of Medicine found in its 2011 report, Breast Cancer and the Environment: A Life Course Approach, which was commissioned by Susan G. Komen for the Cure. (9)

"I am not a fan of pesticides in food or chemicals in the environment that we now find ubiquitously in human tissues," says David Hunter, the Vincent L. Gregory professor in cancer prevention at the Harvard School of Public Health.

"We definitely can't give them a pass. But the evidence of an association with breast cancer in humans is very limited, so a lot depends on how confident you are extrapolating from test-tube and animal data to give advice to people."

And it has gotten tougher to gather data in humans.

"Increasingly, there is evidence that childhood and adolescent and young adulthood exposure is important," says Hunter, who served on the panel of experts who wrote the IOM report.

"We've made it even more difficult to gather human evidence by pointing the exposure window back to many decades prior to the cancer diagnosis. Nobody's got a 50-year prospective study."

Of course, it's sensible to avoid potentially harmful chemicals anyway.

"If women are worried about their children, and it's possible to avoid exposure to pesticides and plasticizers without greatly altering one's lifestyle, I would say, why not?" says Hunter.

"That may have other health benefits that have nothing to do with breast cancer," he adds. "But we can't pretend that we know for certain that that's going to reduce a child's breast cancer risk later in life. It's just very, very hard to establish cause and effect, particularly with cancer, when you may be looking at a 40- or 50-year exposure."

4. Genes play a small role in most women.

Some call it the "Angelina effect."

Since May 2013, when actress Angelina Jolie announced that she had had a double mastectomy to lower her risk of breast cancer, doctors have seen a jump in the number of women getting tested for genes that cause the disease.

Jolie had good reason to get tested: her mother had breast cancer and died of ovarian cancer at age 56, her grandmother died of ovarian cancer at age 45, and her aunt died of breast cancer at age 61, shortly after Jolie announced her mastectomy.

The U.S. Preventive Services Task Force doesn't recommend that all women get tested, because most don't have the genes that make a big difference in risk. (10)

"Two types of genetic susceptibility variants affect risk," says Hunter. "First, there are the BRCA1 and BRCA2 mutations, which increase the risk of breast cancer 20-fold or more."

The BRCA mutations--Jolie has BRCA1 --account for about 5 to 10 percent of breast cancers (and 10 to 15 percent of ovarian cancers). They're broken versions of the genes for building proteins that prevent tumors by repairing damaged DNA.

The second type of genetic susceptibility variants increase the risk of breast cancer by only 10 to 20 percent. "We now have a catalogue of over 100 so-called low-risk variants," says Hunter.

Are some women at greater risk because those variants make them metabolize pesticides (or other chemicals in the environment) differently?

"We thought if we found a lot of the low-risk variants in these carcinogen-metabolizing genes, that would point the finger at environmental factors," explains Hunter. "The fact is, almost none of them have been found in those genes."

Instead, those variants seem to regulate how cells change as we grow and develop.

"They seem to be controlling when genes get switched on and off in which organs and at what time of life," says Hunter. "So again, this points back to earlier life events, not to the environment."

5. Alcohol boosts risk.

"Alcohol is related to both premenopausal and postmenopausal breast cancer," says Willett. "And the more you drink, the higher your risk."

Drinking over more of your life also matters. "Women who started drinking earlier in life and then stopped, their risk goes down," Willett explains. "The highest risk is in women who started consuming alcohol early and continued."

And it's not just women who overdo it. (11)

"We now see a 17 percent increased risk with only one drink every other day," notes Willett. "What's remarkable is how modest that amount is. With colorectal cancer, you don't see much increase in risk until you get to over two drinks a day."

Alcohol's ability to raise blood estrogen levels appears to explain at least part of the increased risk. (12) "But we're still not entirely sure whether it's limited to the increase in estrogen or whether there's more to it than that," adds Willett.

Could teenage drinking pose a particularly potent threat?

"That's been a worry from the beginning, because the breast is more sensitive then," says Willett.

When he and others tracked nearly 6,900 teens aged 13 to 20 for five years, each daily serving of alcohol they consumed was linked to a 50 percent higher risk of benign breast disease. (13) (Some types of benign breast disease are risk factors for cancer.)

"So far we haven't seen a massive time bomb due to teenage drinking," says Willett. "But it deserves some more looking."

6. Keep moving.

"More than 100 epidemiological studies have looked at the risk of breast cancer and physical activity," says Heather Neilson, a Canadian exercise researcher at Alberta Health Services in Calgary.

"The majority have found that women who are the most physically active have a 10 to 25 percent lower risk than women who are the least physically active."

Most studies have tracked postmenopausal women, but some have looked at younger women. (14-15) And others have looked at those who already have breast cancer. (16)

"The evidence is growing that women have a lower risk of dying of breast cancer if they are more active after diagnosis," notes Neilson.

Of course, something else about women who exercise might explain their lower risk of getting or dying of the disease. Only trials that randomly assign women to exercise or not can find out.

A recent year-long trial--the Nutrition and Exercise for Women (NEW) study-- was a surprise.

The trial assigned 439 overweight or obese postmenopausal women to:

* a weight-loss diet, or

* aerobic exercise (45 minutes a day for five days a week), or

* diet plus exercise, or

* a control group (which was told not to make diet or exercise changes).

The results: estradiol, insulin, inflammation, and other markers of risk improved (just about equally) in both the diet and diet-plus-exercise groups (which lost an average of 20 pounds). However, the exercise-only group's markers were not significantly different from the control group's. (17)

"The NEW trial strongly implies that for overweight or obese postmenopausal women, most of the benefit of exercise comes from weight loss," says Neilson.

Still, exercise could lower breast cancer risk by some mechanism that wasn't examined in the NEW study.

"The epidemiological evidence that exercise lowers the risk of breast cancer is quite strong, so there's probably something about physical activity that we don't understand, or different pathways that we're not measuring," says Kristin Campbell, an associate professor of physical therapy at the University of British Columbia who co-authored the NEW trial.

For example, says the National Cancer Institute's Regina Ziegler, "we're looking at whether physical activity changes how the body metabolizes estrogen."

In the meantime, they all recommend exercise, whether you lose weight or not.

"Physical activity helps prevent weight gain in the future and helps maintain weight loss," says Campbell. "And it improves cardiovascular health, type 2 diabetes, mental health, and quality of life, so it's obviously a great benefit."

7. Beware of radiation from CT scans.

Studies in humans find little evidence that non-ionizing radiation--like microwaves or radio waves-- is a cause of breast cancer, said the Institute of Medicine report. (8) But it did point a finger at another kind of radiation: CT (also called CAT) scans.

"There's been a large increase in medical imaging that involves ionizing radiation, particularly with CT scans," says Harvard's David Hunter. That's partly because the imaging is so much better than it was 20 or 30 years ago. (18)

"Nobody thinks that CT scans are a major driver of breast cancer rates in the United States," adds Hunter. "It's just that here is a known carcinogen where the exposures have actually increased over time, even as the machines have in theory been made safer and become better regulated."

Most people--including some doctors-- g don't realize that in order to produce a 3-D image, a CT scan of the abdomen exposes the body to 400 times more radiation than an ordinary chest X-ray. (19)

"The doses from mammograms are much lower," says Hunter. (A virtual colonoscopy is a CT scan. An MRI causes no radiation exposure.)

And then there's the possibility of errors. "There have been documented incidences of overdoses," notes Hunter.

"Regulations probably need to be tighter, given the proliferation of these machines."

Hunter's bottom line: "Nobody should be subjected to medical imaging using ionizing radiation without a good rationale for it. If the situation is not urgent, women should ask about the risks and benefits of having the procedure."

(1) JAMA 288: 321, 2002.

(2) N. Engl. J. Med. 356: 1670, 2007.

(3) JAMA 278: 1407, 1997.

(4) BMJ 335:1134, 2007.

(5) J. Natl. Cancer Inst. 106: dju0557, 2014.

(6) J. Natl. Cancer Inst. 101: 483, 2009.

(7) CA Cancer J. Clin. 2014. doi:10.3322/caac.21142.



(10) uspsbrgen.htm.

(11) JAMA 306:1884, 2011.

(12) J. Natl. Cancer Inst. 93: 710, 2001.

(13) Pediatrics 125: e1081, 2010.

(14) Curr. Nutr. Rep. 3: 22, 2014.

(15) Breast Cancer Res. Treat. 137: 869, 2013.

(16) J. Natl. Cancer Inst. 704: 1,2012.

(17) J. Clin. Oncol. 30: 2314, 2012.

(18) N. Engl. J. Med. 357: 2277, 2007.

(19) Radiation Emitting Products and Procedures/ Medicallmaging/MedicalX-Rays/ucm115329.htm.

Are You at Risk?

These factors raise the risk of a first (or subsequent) breast cancer. To better judge your risk, talk to your doctor or go to: or

Your risk is more than 4 times higher than someone without these factors if:

* you are 65 or older (though the risk keeps increasing until age 80)

* you have been diagnosed with atypical hyperplasia after a biopsy

* you have a genetic mutation for breast cancer (BRCA1 and/or BRCA2)

* you have been diagnosed with lobular carcinoma in situ (abnormal cells in breast lobules)

* your mammogram shows dense breasts

* you had breast cancer before age 40

* two or more of your first-degree relatives (mother, sister, or daughter) had breast cancer before age 50

Your risk is about 2 to 4 times higher than someone without these factors if:

* you had breast cancer at age 40 or later

* your estrogen or testosterone levels are high (and you're postmenopausal)

* you have had high-dose radiation to the chest (often as treatment for Hodgkin lymphoma)

* one of your first-degree relatives (mother, sister, or daughter) has had breast cancer

Your risk is 10% to 2 times higher than someone without these factors if:

* you drink alcohol regularly

* you are of Ashkenazi (Eastern European) Jewish heritage

* you or your mother took diethylstilbestrol (DES) while pregnant (before 1971)

* your menstrual periods started before age 12

* you are tall

* you were older than 30 during your first full-term pregnancy

* you went through menopause after age 55

* you never breastfed a child

* you had no full-term pregnancies

* you are overweight or obese (and postmenopausal)

* you have had ovarian, uterine, or colon cancer

* you took estrogen plus progestin after menopause for more than five years (though the risk diminishes five years after you stop)

These factors do not increase your risk:

* abortions, antiperspirants, breast implants, hair dyes, underwire bras

Adapted from Breast Cancer Facts & Figures 20132014, American Cancer Society ( cancerfactsstatistics/breast-cancer-facts-figures).

Still Hazy After All These Years

Here's the latest on some still-uncertain links between diet and breast cancer.

* Fruits & vegetables. "Several studies have reported that women who consume more fruits and vegetables, especially ones that are rich in carotenoids like beta-carotene, have a reduced risk of postmenopausal breast cancer, especially for estrogen-receptor negative disease," says the National Cancer Institute's Regina Ziegler. (1)

"And any lifestyle change that reduces the risk of estrogen-negative breast cancer would be really, really good." That's because researchers know less about tumors that aren't fueled by estrogen.

"Estrogen-negative breast cancer is more lethal than estrogen-positive cancer, and less is known about preventing it, so that makes this finding especially interesting," says Harvard's Walter Willett. "Fruits and vegetables have a pretty small impact overall on cancer, but this is one case where there may be some benefit."

* Vitamin D. Earlier evidence had suggested that women with higher blood levels of vitamin D have a lower risk of breast cancer, but the picture is muddy.

"We're now analyzing vitamin D levels for 24,000 women from 17 cohorts around the world," says Ziegler. "That should tell us whether the blood levels that people currently attain from sunlight, food, and supplements protect against breast cancer."

Meanwhile, the VITAL trial is testing whether women who take 2,000 IU a day of vitamin D for several years are less likely to get breast cancer than placebo takers. "That should tell us whether high doses reduce risk," notes Ziegler.

* Soy. Over the years, the pendulum has swung from seeing soy as a food that prevents breast cancer to seeing it as one that promotes breast cancer (see "Soy Oh Soy," p. 9).

"We can't look at soy very well in our studies of U.S. women, because they don't consume enough," says Willett. "Data from a study in Shanghai suggest that soy consumption during adolescence and early life may reduce breast cancer risk, but there's not much benefit later in life." (2)

* Meat or saturated fat. Some studies have reported a higher risk of breast cancer in women who consume more saturated fat. (3) "But the effect of saturated fat during midlife or later is weak, if it's there at all," says Willett.

However, a meat-heavy diet may boost risk, he argues, especially if it's eaten in early adulthood. (4)

"Looking at diet earlier in life, when we know that the breast is more susceptible, we've seen some increase in the risk of premenopausal breast cancer with red meat," says Willett.

It's not clear why. "It's probably something in red meat other than the fat," he says. But so far, heme iron or carcinogens that are created when meat is cooked doesn't seem to explain the risk.

(1) J. Natl. Cancer Inst. 105: 219, 2013.

(2) Am. J. Clin. Nutr. 89:1920, 2009.

(3) J. Natl. Cancer Inst. 106: dju068, 2014.

(4) BMJ 2014. doi: 10.1136/bmj.g3437.

Bottom Line

* Lose (or don't gain) excess weight.

* Don't take hormones (estrogen plus progestin) after menopause.

* Shoot for 30 to 60 minutes a day of moderate-to-vigorous aerobic exercise.

* Drink alcoholic beverages only occasionally.

* Don't get a CT scan unless you're sure that it's necessary (see

* For more information:






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Title Annotation:COVER STORY
Author:Liebman, Bonnie
Publication:Nutrition Action Healthletter
Date:Sep 1, 2014
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