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CURE

Breast Cancer Special Issue
Volume1
Issue 1

On the Fence: The Pros and Cons of Breast Screening

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Amid debate about how much screening should be used to detect breast cancer, women at average risk should know the pros and cons.

It was over the Christmas and New Year’s holidays in 2014 that Amy Bowman, a 37-year-old mom of two, first noticed a lump on her right breast.

Her OB/GYN sent her for an ultrasound because she was under 40. Those results led to a mammogram, which led to a biopsy. A day later, she found out she had cancer, invasive ductal carcinoma.

Bowman opted for a double mastectomy to avoid radiation, and she did not need chemotherapy. Today, she has no evidence of cancer. But there’s a twist: five years earlier, Bowman had seen her doctor for an unusual discharge from her right nipple. She had a mammogram and was referred for an MRI, but she discovered she was pregnant, so the techs told her to return after her pregnancy if she had more symptoms. She had a daughter but no more symptoms until the lump.

Had Bowman gotten the MRI back then, she may have been found to have ductal carcinoma in situ (DCIS). DCIS refers to “tumor cells in the breast ducts that have not invaded yet,” explains Elizabeth Morris, chief of the breast imaging service at Memorial Sloan Kettering Cancer Center in New York City. DCIS is basically stage 0 cancer, a tricky diagnosis. “We currently have no way pathologically, genetically or molecularly to look at the genomes of these cells to say this one is definitely going to spread and this one is not,” Morris says. Current protocols suggest what Bowman’s treatment might have entailed.

“They may have wanted to do a mastectomy, and I’d be on hormones and I wouldn’t have been able to have my second child,” says Bowman, who is taking tamoxifen, which can cause birth defects. “I feel very lucky I went through it at this point rather than going through it then. The course of our family and our life would have been completely changed unnecessarily. But would we have known that?”

That question sits at the center of much of the confusion and controversy over breast cancer screenings. One in eight women will get breast cancer, and approximately 40,000 women a year die from it in the U.S. — but up to tens of thousands of others will have false positives or be treated unnecessarily for lower-risk cancers. Certainly, the most common screening tool, mammogram, isn’t perfect, says Morris, also the president of the Society of Breast Imaging.

“I think mammograms have been oversold to the public,” she says. “It’s a great test, and it does save some women’s lives, but it doesn’t save every woman’s life.” For one thing, mammography can lead to over-diagnosis. “The mammogram is going to pick up some cancers that aren’t going to kill the patient because the cancer is so slow-growing, or because the woman is going to die of something else,” Morris says.

Things are different for men, for whom no regular screening is recommended due to the rarity of male breast cancer — it comprises about 1 percent of all breast cancers and occurs in about 1 in 1,000 men, says Rachel Wellner, a breast cancer surgeon at Montefiore Einstein Center for Cancer Care in New York City. Further, she says, there are no good screening tests for men, so their breast cancers are picked up strictly through physical exams, usually self-exams.

But the controversy over screening methods and their merits can leave women wondering what screening guidelines to follow to reduce the risks represented by competing statistics: dying from breast cancer versus receiving a diagnosis of a cancer that wouldn’t have been dangerous but nonetheless leads to chemotherapy, radiation or surgery, which have many side effects, some of them long-lasting.

One place to start is knowing your risk.

Knowing the Risk Factors

The two biggest risk factors are age and genetics, Wellner says. A woman’s risk of breast cancer goes up with each decade, and also if there’s a family history of breast cancer or a personal history of DCIS, lobular carcinoma in situ (LCIS) or atypical hyperplasia.

Though the best known genetic risk factor is having a BRCA mutation, that’s only implicated in about 5 percent of breast cancers, Wellner says. A woman’s risk of cancer increases to between 45 and 65 percent with BRCA, but only 1 in 500 women have that mutation (or 1 in 40 among Ashkenazi Jewish women). Other factors that move women into the highrisk category — those with a greater than 20 percent lifetime risk of invasive breast cancer — include radiation treatment to the chest area before age 30 and having other syndromes, such as Li-Fraumeni, Cowden or Bannayan-Riley-Ruvalcaba syndromes, which can increase the risk of breast cancer.

Lifestyle factors can also influence risk: obesity, hormone replacement therapy and having a first child after age 30 increase risk, but exercise, limiting alcohol intake, and breastfeeding lower it. Women with an early first period (before age 12) also have slightly increased risks, but few of these factors have as much influence as age and genetics. Women can learn whether they’re high-risk by using an online Tyrer-Cuzick risk model.

Another risk factor involves breast density, how much normal white tissue shows up on a mammogram. “The problem is that cancers are white on mammograms, so if you have a lot of normal white tissue on a mammogram, it can obscure a cancer — there’s a masking effect,” Morris says. About 40 percent of women have dense breasts, but they can only find out by getting a mammogram. And here’s the rub: Not only is it tougher to see cancer in dense breasts, but women with dense breasts have a four to six times greater risk of developing cancer, Morris says. “It’s kind of like a double whammy.”

Nevertheless, a majority of breast cancers develop in women without risk factors, creating a dilemma in deciding who and when and how often to screen.

Comparing Screening Guidelines

That double whammy is another key issue in debates about the best screening guidelines. “We’re caught between two opposing factions in this country,” Morris says. “The first is the density people, who want people to receive additional testing such as ultrasound and MRI because those can look through dense tissue and possibly pick up cancers, but there’s currently no evidence that doing these additional tests will save lives. Then on the opposing side are the people who say we’re screening too much, too often, and we’re picking up too many cancers that are not going to kill the patient.”

Women are caught in the middle.

“I think we’ve oversimplified it and dumbed it down in the past so that women go and get their mammograms, but by doing that, we have overstated claims about what mammography can do,” Morris says.

Past research suggests an overall 30 percent reduction in the risk of death from breast cancer with the use of mammography, but that’s primarily for women ages 50 to 69. The reduced risk is about 15 percent for women ages 39 to 49.

It’s screening for women at average risk where opinions diverge. Several organizations recommend clinical breast exams every three years for women under 40 and then clinical exams and mammography annually starting at 40. The American Cancer Society recommends that women at an average risk of breast cancer should wait to undergo annual screening mammography until they reach the age of 45. Additionally, after the age of 55, the guideline recommends transitioning mammography to every other year.

The U.S. Preventive Services Task Force and the American College of Physicians don’t have a clinical exam recommendation, suggesting only that women under 50 talk with their health care providers and decide individually whether to get screened. Then, USPSTF recommends that women 50 and older receive mammography every two years because that schedule captures almost as much cancer as annual mammograms while cutting the risks of false positives, over-diagnosis and over-treatment in half. For women over 70, almost no research exists for evidence-based recommendations.

One problem with these recommendations is that women under 50 are more likely to have dense breasts and to have faster-growing cancers, Morris says. African-American women also have higher rates of breast cancer in their 40s than white women do.

“I actually think it’s very paternalistic for us to say ‘You have to have a mammogram every year from the age of 40 on,’ but I also think it’s very paternalistic for us to say, ‘No, you can’t do it in your 40s and you have to have it from 50 and on,’” Morris says. She says women need to consider their breast density, their personal risk factors and their own comfort level with risk. “Women should be able to take the recommendations with full understanding and say, ‘I’m comfortable going every year’ or ‘No, I want to go every two years.’ The important thing is to go and get a mammogram,” Morris says. “That’s where the whole self-directed, patient-directed choice comes in.”

Weighing the Risks and Benefits of Screening

Choice requires understanding the risks and benefits, which gets complex and contentious. Current recommendations lead to significant over-diagnosis, according to Kenneth Mandl, a Harvard professor at the Boston Children’s Hospital Computational Health Informatics Program. He published research showing a 61 percent risk of false positives per woman over a decade if she gets annual mammography. But even these numbers depend on a woman’s baseline risk, as does every screening test. If everyone has a disease, the only possible false findings are false negatives. If no one has a disease, every positive finding is a false positive. It follows, then, that false positives occur more often among low-risk women than among high-risk women.

“What you want to do is find a tumor that you wouldn’t have otherwise found. You want to find it at an early enough stage to treat, and the treatment should save your life,” Mandl says. “But that’s only one of many possibilities.” Others include finding nothing, finding something too late to save your life, finding something that clinicians think is abnormal but would not turn out to cause harm over time — a scenario that can lead to unnecessary treatment — or getting a false-positive mammogram result that can be rapidly proven to not be cancer after all.

“I don’t think we should underestimate the impact on a whole family and their friends and support networks when they are led to believe that a person has cancer, potentially for a couple of weeks or more, before it’s all worked out,” Mandl says. “But that pales in comparison to the issue of over-diagnosis, where you’re having a mastectomy or chemotherapy or radiation or a combination of these for something that, had it not been detected, never would have harmed you.” He points out that, “once you have a positive test, it’s very hard to resist investigating what could be a tumor,” no matter who a person is or how informed he or she is.

The numbers on over-diagnosis are hard to pin down. Morris estimates them at 10 percent, but says that no clinical studies have provided a reliable number. Mandl puts them at 20 to 30 percent based on a 25-year Canadian study whose methods and findings Morris and others have criticized as poorly conducted, as well as on an integrative analysis published in the New England Journal of Medicine.

Consider these numbers from the USPSTF: For women ages 40 to 49, about 1,900 need to be screened to prevent one breast cancer death, but that will also incur nearly 200 false positives, 18 biopsies and six diagnoses of DCIS or invasive breast cancer, one of which is likely harmless but will be treated because there’s no way to know it’s harmless. These numbers change with increasing age: False positives go down, diagnoses go up and each saved life requires fewer women to be screened, with about 240 needed to be screened at age 60 to 69 to prevent one breast cancer death.

Another analysis of more than five decades of studies found that 10,000 women undergoing annual mammography starting at age 50 will lead to 6,130 having at least one false-positive test result and 940 getting unnecessary biopsies over 10 years. Of the 302 diagnosed with breast cancer in that decade of screening, it was estimated that 173 would have survived without screening, 62 will die from cancer, 57 will be treated for a cancer that wouldn’t have harmed them, and 10 lives will be saved.

Screening Modalities

The risks and benefits also shift with the screening test used: mammogram, ultrasound or MRI. Mammograms are most common, but anywhere from 6 to 46 percent of women with invasive cancer will have negative mammograms, according to the National Cancer Institute, the rates being higher for younger women or those with denser breasts. Among the 10 percent of women who will have suspicious findings according to the test, only five of 100 will have cancer, and one to two of these cancers wouldn’t require treatment if a way existed to identify which ones they were. Radiation risk from mammograms is low — a theoretical 1 in 1,000 women may develop cancer from annual mammography.

Adding ultrasound, which sends sound waves through liquid to create an image, increases the likelihood of finding a cancer but also increases false positives. Insurance usually covers mammography and ultrasound, but coverage of MRI for initial screening varies. MRI uses magnets instead of radiation and picks up the most cancers with a low false-positive rate because it maps the blood flow in the breast, Morris says. However, it requires an injection of dye, is expensive and is not available everywhere. Although the cancers MRI most often misses are DCIS, emerging evidence suggests it picks up the DCIS most likely to become invasive cancer. Two newer screening methods include a 3-D mammogram called tomosynthesis and a faster MRI that may drive down costs because it takes three minutes instead of 21, but neither of these is widely available.

Although no evidence has found that self-exams reduce risk of death from breast cancer, Mandl, Morris and Wellner all recommend them.

“Anecdotally we’ve had people find their own cancers, so we recommend it monthly,” Wellner says. “Get to know your breasts so you can recognize any changes — any masses, any changes in the skin color or nipple, any discharge.” She also recommends clinical exams by primary care doctors who have skilled hands looking for lesions or changes.

It largely comes down to knowing your body, adds Bowman.

“It’s about knowing what’s normal for you and knowing when it changes,” Bowman says. “A lot of women don’t touch their breasts and they don’t know what’s normal. I think that’s the biggest thing — knowing what’s normal and acting on it when it’s not.”

As for which screening guidelines to follow, Mandl and Morris suggest that women have frank conversations with their health care providers. “I think women should really look at this emerging literature carefully and discuss it with their physicians,” Mandl says.

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