In countries with well-functioning health services, the benefit conferred by mammograms is relatively small. (Reuters)

Breast cancer's 'magic bullet' misfires for younger women

Martinique Stilwell
It seems counterintuitive, but mammograms may do more harm than good to women under 50.

As a fourth-year medical student at Hillbrow Hospital I was taken to see a Sotho woman in her mid-50s. She sat with her head bowed, and when the surgical registrar asked her to open her gown, she did so, exposing a breast eaten away by a malignant ulcer that left a crater as large as a fist. This, the surgical registrar informed us, was an example of advanced breast cancer. It was very painful and held a poor prognosis.

As a sixth-year student working on the medical ward of the then Johannesburg General Hospital, I saw a younger woman, her pale face puffy from steroids beneath the unnatural vitality of her wig. She had young children and breast cancer that had spread into her body. She was preparing for an onslaught of chemotherapy, followed by a bone marrow transplant, a treatment she would not survive.

I would meet more women with breast cancer over the years as I practised general medicine, first in rural KwaZulu-Natal, and then in Canada. They remain etched in my memory.

According to the Cancer Association of South Africa, breast cancer is the most common cancer in South African women and most of us know somebody who has faced the diagnosis: grandmothers, mothers or sisters, friends, perhaps even ourselves.

Historically, breast cancer has inspired heroism, not only in those afflicted, but also in those called upon to provide treatment. As writer and oncologist Siddhartha Mukherjee details in The Emperor of All Maladies: A Biography of Cancer, a Persian princess in 500BC – Atossa – had her breast tumour hacked out by a Greek slave, the first known primitive mastectomy. Over the centuries, scores of women would fall under the knife without anaesthesia, all desperate to be rid of painfully ulcerating cancers. Atossa survived, but death was the usual course as cancer spread to other parts of the body.

In the early 20th century, the surgeon William Halsted, embracing the discovery of anaesthesia, began performing increasingly radical mastectomies in an effort to save lives. Operations extended to seven or eight hours, chest ­muscles, ribs and even collarbones were removed, necks were opened up. As Mukherjee explains, for instances of the disease identified early, the drastic operations were too much – and for cancer that had already spread, they were not enough.

Radiotherapy was discovered to be a double-edged sword, x-rays could both treat cancer and cause it. By the 1950s, surgery and radiation were being combined.

In the 1970s, doctors began using chemotherapy – powerful chemicals that kill cancerous cells – to treat cancer, and in the 1980s heroic efforts were made to cure women with breast cancer that had spread to the rest of their bodies by using mega-doses of chemotherapy followed by bone marrow transplants. Only Professor Werner Bezwoda of Wits University proclaimed any success with this approach. But in a sad chapter in South African medical history, Bezwoda's results were found to be fraudulent, his patients had also died, and he was fired in disgrace.

Attention shifted to prevention and screening. If every woman had a regular mammogram, or breast x-ray, the thinking went, all cancers would be detected early and no one would die.

In 1982, American Nancy G Brinker founded the Susan G Komen for the Cure Foundation. Brinker believed her sister, who died at 36 from breast cancer, would have survived had she received early screening with a mammogram. National Breast Cancer Awareness Month in October was founded in 1985, over a quarter of a century ago, by Zeneca, (now AstraZeneca), the maker of the best-selling breast cancer drug Tamoxifen.

According to Samantha King, the author of Pink Ribbons, Inc, the aim of the awareness month from its inception was to "promote mammo-graphy as the most effective weapon in the fight against breast cancer" and to work in partnership with the American College of Radiology and other agencies such as the US government's National Cancer Institute to "raise awareness and provide access to screening services".

Breast Cancer Awareness Month has morphed into "Pinktober" a high-profile, billion-dollar campaign promoted around the world by magazines, newspapers, the cosmetic and fashion industries, pharmaceutical corporations, sports associations and nonprofit organisations, most united in the aim of raising funds and raising awareness of the need for early detection of breast cancer by screening mammography. South Africans will be spared much of the avalanche of pink consumer products, but we will still feel its influence.

So, after a quarter of a century, has "breast cancer awareness" been achieved? Not when it comes to risk, it seems.

"Most women completely overestimate or underestimate their risk of breast cancer," says Dr Irene Boeddinghaus, an oncologist who runs a private breast clinic in Cape Town. She cites a study presented to the American Society of Clinical Oncology this year that surveyed 10 000 women attending a mammogram screening programme, and found that less than 10% of them predicted their risk of developing breast cancer correctly. Roughly half tended to overestimate their chances of developing the disease, and the rest underestimated it.

This reflects what Boeddinghaus sees in her practice. She explains that women who overestimate their risk are vulnerable to feeling anxiety and fear, and may seek unnecessary ­interventions or treatment, whereas women who do not appreciate their real risk might not get the treatment they need.

What then are the risk factors for breast cancer? Research studies have shown that, aside from being a woman, the greatest risk factor for developing breast cancer is age.

"I ask people how old they think most women are when they develop breast cancer," says Boeddinghaus. "The commonest reply is, women in their 40s."

Breast cancer is in fact a disease of ageing. According to statistics from the United Kingdom, in any given year a woman in her 20s has a one in 100 000 chance of developing breast cancer. For a woman in her 30s, that figure is one in 3 000, a number that rises to one in 800 for women in their 40s. Women in their 50s have a one in 365 risk, and for women turning 60 and entering the seventh ­decade of their lives, the chances in any given year of a breast cancer ­diagnosis increases to one in 27. Women older than 85 face a ­figure of one in 23.

"Of course, Kylie Minogue and Angelina Jolie are more likely to make it on to a magazine cover than a 70-year-old," says Boeddinghaus.

Over the years, the risk adds up and, according to the organisation Cancer Research UK, one in eight British women will be diagnosed with breast cancer in her lifetime. A lifetime of 85 years, that is.

Boeddinghaus explains that breast cancer is linked to the complex interplay between the sex hormones oestrogen and progesterone during ovulatory cycles and also to factors causing increased levels of oestrogen after menopause. Therefore, an early start to periods and a late menopause – the period during which a woman's monthly menstruation stops and she becomes infertile – increase risk because more ovulatory cycles occur.

Obesity, hormone replacement therapy and more than two drinks a day raise oestrogen levels, which raises risk in menopausal women. Like ­several other clinicians, Boeddinghaus suspects that the high doses of hormones used in infertility treatments may be linked to breast cancer, but concedes that studies have yet to be done.

And although the bearing of the first of many babies before the age of 25 and breast-feeding for at least two years is known to protect greatly against breast cancer, according to Boeddinghaus this is probably not a practical option for many women. Research has shown that childlessness and late first pregnancies increase the risk of breast cancer, whereas exercise and getting enough sleep are protective.

Some women are at particularly high risk. Although 80% of women who develop breast cancer do not have a family history of the disease, women with one first-degree relative have roughly twice the average risk, according to Cancer UK. In cases where multiple close family members have had breast or ovarian cancer at an early age, and there is a known gene mutation such as BRCA1/BRCA2, that risk is far higher. Women with previous breast cancer and those who were treated as adolescents by radiation for a cancer in the chest are also at higher risk.

Boeddinghaus says it is vital to know your personal risk before beginning an individual surveillance programme of regular mammograms. Although screening programmes are appropriate for women of average risk, women at higher risk will need other, or more frequent investigations. She says it is important to distinguish between a screening mammogram and a diagnostic mammogram. Although it is the same test, the first is done to check a healthy woman whereas the second is performed when a woman has a problem that needs to be diagnosed.

Sometimes biology lags behind technology and the results of medical interventions only become apparent decades after programmes are put in place. Desperation and misplaced optimism often lead to assumptions that doing something is always better than doing nothing, and doing more is better than doing less.

In 1988, after 12 years of following 42 000 women in Malmö, Sweden, half of whom received regular mammograms whereas the other half did not, there were 63 deaths from breast cancer in the screened group and 66 in the non-screened group.

Further analysis of the evidence showed that screened women older than 55 had a 20% decrease in cancer deaths. The benefit for women younger than 55 was not discernible. Study after study continued to show similar results.

Countries such as Australia, Canada and the UK now recommend that women of average risk have a screening mammogram every two or three years from the age of 50.

Award-winning health writer Peggy Orenstein describes in her article "Our feel-good war against breast cancer", published this year in the New York Times, that despite the research and two independent task forces recommending mammograms every second year for women older than 50, the Susan G Komen for the Cure Foundation, the American Cancer Society and the Republicans have fought against these recommendations, and yearly mammograms from the age of 40 are still widely supported.

Mammograms have not proved to be the hoped-for magic bullet in the war against breast cancer, which is now understood to be a not single disease, but a collection of diseases. According to Dr Jenny Edge, a South African breast surgeon on the executive committee of the Breast Interest Group of South Africa, some cancers do not show up well on mammograms, and others are so fast-growing that they would arise even between frequent screenings. Although most cancers become more aggressive with size, others are so aggressive that they may spread before they are big enough to be seen.

Certain benign conditions appear cancerous on mammograms. These "false positives" are distressing to women, who may have to go through further tests, including biopsies, to reach the right diagnosis.

Studies have shown that mammograms often pick up small, slow-growing, unaggressive tumours that, had they not been detected by mammogram, would never have caused trouble. Women with these lesions will be treated for cancer, and possibly undergo mastectomies and radiation, for a disease that they would never have become aware of had they not gone for a mammogram. The medical term for this sequence of events is "overdiagnosis".

Breasts are composed of glandular and connective tissue and fat. According to Edge, some breasts contain a lower proportion of fat and more glandular and connective tissue. These breasts are said to be dense. Density may run in families and is not related to breast size or obesity. Mammograms are less reliable in women with dense breasts, and women with dense breasts also have a slightly higher risk of cancer. After menopause, according to Edge, breast tissue is replaced by fat and breasts become less dense, and thus easier to compress for the test and are more uniform in texture. Any malignant activity is therefore more clearly seen on a mammogram. False positives and overdiagnosis do still occur, but to a lesser extent.

Edge explains that ultrasounds are an integrated part of screening mammograms and are particularly helpful for dense breasts. But as a screening modality on its own, an ultrasound does not detect pre-cancer and the accuracy of ultrasound examinations depends very much upon who performs them.

According to the Marmot Review from the UK, for every cancer death avoided by screening women aged 50 to 70, three women will be overdiagnosed. A Canadian task force reported that if 2 100 women between the ages of 40 to 49 were screened every two years for a decade, one cancer death would be averted, 690 women would have a false positive result and 10 women would be overdiagnosed – treated for a cancer that would not have appeared in their lifetime. The Canadian task force's conclusion was that the benefit of mammograms did not justify the harm for women younger than 50, but did for those older than 50. The Canadians recommend that women of average risk be screened every two to three years from the age of 50, and that any woman being screened should understand that she is more likely to be over­diagnosed than have her life saved. The Canadians also no longer believe women should perform monthly self-examinations as they have only been shown to lead to more breast ­biopsies, and have had no effect on death rates.

In South Africa, there are no official mammogram screening guidelines or governmental screening programmes. The Cancer Association of South Africa and several private facilities, for example Netcare's Breast Care Centre in Johannesburg, recommend annual mammograms from the age of 40. These recommendations do not, however, appear to be supported by scientific evidence.

Because of its associations with advanced age, late pregnancies and post-menopausal obesity, breast cancer is considered to be a disease more likely to afflict privileged women, however but we do not have accurate South African demographics because the cancer registry last published data on cancer deaths in 2005.

In South Africa, women's lives are often cut short by interpersonal violence or infectious diseases such as TB and HIV. Following recent gains in life expectancy linked mainly to the improved management of HIV, Edge warns that government health services should be prepared for a rise in breast cancer cases. Edge, who is fighting to encourage collaborative data collection to provide accurate statistics, believes that mass mammogram screening programmes would not be appropriate in South Africa.

"In the best case scenarios in countries with well-functioning health services, the benefit conferred by screening mammograms is relatively small," says Edge, who explains that the government must ensure that diagnostic mammograms and ultrasounds are available to women who present with breast problems. Boeddinghaus agrees with Edge that mass screening is not practical in South Africa, and states that the focus should be on cervical cancer, for which there is both an effective screening tool in the form of Pap smears and a vaccine.

Edge reports that the most pressing issue among underprivileged women is lack of access to healthcare and factors such as stigma, which cause women to seek medical attention at a late stage of the disease. In the UK, where high-quality medical care is readily available, early cancer, or stage one, has a 90% five-year survival rate, which drops to 50% for stage three.

Only 13% of women with stage four can expect to survive for five years, and even fewer live for 10. Because of their late presentation and healthcare that may not be optimal, poor women in South Africa with breast cancer are therefore much more likely to die from the disease than their richer sisters.

Recently, the medical journal Lancet published a study in which volunteers were trained to do physical examination on women in a village in Sudan. Of the 17 women who were found to have cancer or pre-cancer, 12 were treated and are now disease-free. During the same time, three women with advanced disease went to hospital from the villages not visited by volunteers.

Edge concludes that, although increasing awareness of breast cancer and overcoming stigma is vitally important in order to make a difference to life expectancy in this country, women must have access to care. Clinic staff should be trained in breast examination, and efficient referral pathways to multidisciplinary breast clinics providing optimal care should be put in place.

Although mammograms prevent deaths in women older than 50, there is no evidence to suggest that the young woman I remember from my time as a medical student, who died after her bone marrow transplant, would have been saved by a timely mammogram. It is probable that the Sotho woman, who only arrived in hospital after most of her breast had been eaten away, might have been saved by something as simple as a home visit from a volunteer worker who referred her on to a well-trained clinic nurse.

Martinique Stilwell is a medical doctor and writer based in Cape Town

Have something to say? Tweet or Facebook us on @Bhekisisa_MG

breast cancermammogram machinemammograms