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Editorial: US health gaps shame us all

DEEP down, Diana Garmon-Spears knew something was seriously wrong when she noticed a lump in her right breast, about the size of a peanut. “I ignored it, but then my breast started to deform. I started to form a mass of lumps all around,” she recalls.

Two years later, she doesn’t expect doctors to cure her cancer, and has been forced to give up her office work. “I don’t think there’s any employer who’s going to understand you having chemo or radiation for 2 hours a day.”

As an African American woman living in Chicago, the dice are loaded against Garmon-Spears. Across the US, death rates among black women diagnosed with breast cancer are 37 per cent higher than for whites, but in Chicago the difference is an astonishing 68 per cent (). Something about this heaving metropolis is sending black women to an early grave.

Poor access to screening and therapy is clearly an important factor. But according to a novel collaboration between sociologists and biologists, the strain of living in some of the toughest neighbourhoods in the US may cause biological changes that lead directly to earlier deaths.

Results from the collaboration indicate that social isolation and a fear of crime cause an overload of stress hormones that can change cell biology, sending tumours into overdrive. “We’re showing that your social environment can affect your health directly,” says of the University of Chicago. “It goes into gene expression. That concept is really new.”

Crucially, this insidious influence is felt most by Chicago’s African American women, who are far more likely to live in the city’s deprived areas than their white counterparts.

The provocative hypothesis highlights the need for new ways of fighting breast cancer in black women in Chicago specifically, including via social interventions. More broadly, other health researchers are hailing the union of biology and sociology as a model for future studies into a whole range of health disparities. “It’s a great example of the kind of direction in which I can see us heading,” says , an epidemiologist at the University of Pennsylvania in Philadelphia. There are already hints that stress and social deprivation could have similar effects on diabetes and cardiovascular disease.

To get a handle on how tough life in Chicago can get, a good place to start is the neighbourhood of in the city’s South Side (see diagram). Poverty in Englewood is grinding, crime is endemic and amenities that the mostly white residents of comfortable suburbs like . “Even churches have moved out,” says of Washington University in St Louis, Missouri, lead sociologist on the project.

91av got a taste of conditions on a tour of the South Side with members of Gehlert’s research team. At vacant lots strewn with beer bottles and other debris, I’m told to watch my step. A previous visitor stumbled on a bag of urine and other medical waste. Along one Englewood street, we pass three burnt-out houses. On this winter morning, the gang activity that blights the area has yet to ramp up for the day. But the grilles on the windows of the Simon Guggenheim Elementary School are a testament to the crime that stalks these streets. You wouldn’t want to be here after dark, says Charles Mininger, a graduate student on the project.

Other sociologists have documented the struggle to survive in this grim environment. But in 2003 Gehlert, then at the University of Chicago, took a novel approach when she to investigate how social circumstances might influence prospects for women with breast cancer.

From the work of Nigerian-born , the researchers knew that women of west African descent are more likely than their white counterparts to develop “triple-negative” tumours. These tumours, which usually strike before menopause, can be particularly deadly because they don’t carry large amounts of a surface protein called and also lack receptors for the sex hormones oestrogen and progesterone. As a result, they fail to respond to either of the leading breast cancer drugs: , which blocks the stimulating effect of oestrogen; or , which targets HER2/neu.

Tumour type can’t fully explain the astonishingly high death rate from breast cancer among black Chicagoan women, however. A clue that social factors might contribute to this tragic trend came from the lab of behavioural biologist , also at the University of Chicago. When she housed normally gregarious rats alone, she noticed that they tended to die early from a variety of tumours. She has since investigated the phenomenon in detail, revealing last month that isolated female rats become edgy and vigilant, have high levels of the stress hormone cortisol, and are 3.3 times more likely to develop breast cancer than animals living in groups ().

Gehlert was struck by the parallels between McClintock’s rats and the vigilant, stressed women she knew from the scariest South Side neighbourhoods. She decided to find out if the stress and isolation these women experience has direct biological effects on their health too. Over the past five years, Gehlert’s team has recruited some 230 black Chicagoan women, newly diagnosed with breast cancer, for a survey that combines interviews, analyses of crime statistics and other conditions in their neighbourhoods, plus hormonal measurements and molecular studies of biopsies from tumours. Garmon-Spears is one of the volunteers.

In a , Gehlert described her team’s findings. Most striking is the fact that the women fall into two groups based on the daily patterns of cortisol in their saliva (see graph). One-third of the women had a normal daily cycle, with a peak about 30 minutes after waking up. But the other two-thirds, dubbed “flatliners”, had no cortisol cycle at all.

It turned out that the flatliners lived in areas with more homicides and robberies, and scored higher for depression. Women who felt they had strong social networks, and scored low on a psychometric , were more likely to have a normal cycle.

“Women with ‘flatline’ cortisol cycles tended to live in areas with more homicides and robberies”

Gehlert suggests that the fear that comes with living in high-crime areas combined with scant social support causes overproduction of cortisol, similar to that seen in McClintock’s isolated rats. This eventually erodes the body’s ability to release the stress hormone, creating the flatline effect. Similar “burnout” patterns have been seen in patients with post-traumatic stress disorder.

In this respect, Garmon-Spears’s prospects may be better than many. While she grew up in a tough South Side housing project, and lost her husband to an overdose of crack cocaine over a decade ago, she feels comfortable in her present home, just north of the city centre. “I’m watchful; I’m careful, but I’m not scared,” she says. Between caring for her mother, chatting with her sisters, and attending Jehovah’s Witnesses meetings, she has a busy social life.

But among the flatliners, fear of crime and lack of amenities creates severe social isolation. “When they list their five closest ties, it’s unlikely they’ll be in the vicinity,” Gehlert says. “In the worst neighbourhoods, they have no casual ties, because businesses have moved out.”

Meanwhile, Conzen and McClintock have come up with a biological mechanism that could explain how high levels of cortisol caused by social isolation might increase women’s death rate from breast cancer. In mice that were genetically predisposed to breast cancer, the researchers found that the surge in cortisol caused by social isolation works through receptors on the surface of tumour cells to increase the activity of certain genes. This increase allows the tumour cells to use sugars and fats more efficiently. By 21 weeks of age, isolated mice had tumours that were on average more than 50 per cent larger than those in mice that were also prone to breast cancer, but housed in groups ().

Health disparities

To complete the picture, Olopade is now studying biopsies of the women’s tumours to see if the flatliners, in particular, have altered gene activity that is similar to patterns seen in the isolated mice – although she warns that a bigger sample of women may be needed to produce definitive results.

So far, the results from the collaboration have impressed other researchers interested in health disparities. “Loneliness is something that people might not think of immediately as an obvious factor on the pathway to aggressive breast cancer,” says , a diabetes specialist also at the University of Chicago. Other projects are examining whether a fusion of sociology and biology can shed light on why other disadvantaged US populations, both black and white, are disproportionately affected by cancer (see “From city streets to country roads”).

The key test of the approach, however, will be whether or not it can improve survival rates. Gehlert is already planning trial interventions for the next phase of the Chicago project. Stress-control techniques are a non-starter. “If we taught a woman relaxation, we’d be helping her biologically but she’d probably be murdered,” Gehlert says. “Where there are a lot of crimes and unsafe housing, they really do need to be vigilant.”

“Relaxation might help a woman biologically but she’d probably be murdered”

Instead, she plans to recruit “neighbourhood coordinators” within South Side communities who will help women to negotiate obstacles such as the bureaucracy that frustrates attempts to obtain housing, healthcare and other necessities. The coordinators will also work with free clinics and other community groups to find spaces where isolated women can meet one another and get the social support that is missing from their lives. “We need places where women can have some social interaction without fearing harm,” Gehlert says.

Meanwhile, biologists on the team are thinking about affordable drugs that might help. Given the apparent involvement of genes that affect the metabolism of sugars, Conzen suggests that , which decreases the amount of glucose absorbed from food and released from the liver, might starve the women’s tumours of nutrients, making them less aggressive.

Metformin is already used to treat type 2 diabetes, and there is a possibility that similar stress-induced changes in gene activity could contribute to disparities in the incidence of this disease. “There’s a lot of interest in cortisol burnout in diabetes,” says , an epidemiologist at Washington University in St Louis. Indeed, related mechanisms might help explain why disadvantaged populations suffer heavily from a whole range of major killers. “They have high cancer, high diabetes, high heart disease, and very high stroke,” Colditz says.

Could a combination of social interventions and drug treatments give Gehlert’s flatliners a fighting chance? Will it be necessary to intervene earlier to stave off cortisol burnout in younger women before the damage is done? For now, there are more questions than answers. But when answers come, they may resonate in the corridors of power. The young Barack Obama cut his teeth as a community organiser on Chicago’s South Side. His wife, Michelle, was on the planning committee for Gehlert’s project.

The women of the South Side urgently need a message of hope. But turning hope into improved health outcomes for disadvantaged populations across the US may require political action at the highest level.

Editorial: US health gaps shame us all