Neighborhood Adversity Associated With Increased Risk of ER- Breast Cancer, TNBC for Black Women in the United States

In the United States, Black women have a 40% higher mortality rate from breast cancer than White women, explained Julie R. Palmer, ScD, MPH, Karen Grunebaum professor in cancer research at the Boston University School of Medicine, during a presentation at the 15th American Association for Cancer Research Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved. Palmer explained further that this is the worst disparity present in breast cancer data and this disparity has not improved in more than 20 years.

“We know that a big part of the reason [for this disparity] is access to care. And by that I mean true access, which takes into account everything from economics, being able to get there, to how physicians and other providers treat a person and communicate,” Palmer said. “But it’s not only that, there are other differences too.”

Palmer explained that the data show differences in the occurrence of tumor subtypes between White and Black women as well.

“We’re all aware that triple-negative breast cancer (TNBC)—which is the most aggressive, occurs at younger ages, and is more difficult to treat—occurs at least twice as often on average among Black women as in any other group in the United States,” Palmer said. “Twenty-two percent of the tumors in Black women are triple-negative versus 10% to 12% in the other [population] groups. So having more of these aggressive tumors will necessarily lead to more mortality, which then brings me to the question: Why is there more [TNBC]?”

This is a question many in the field have been working to answer for some time, Palmer explained. She noted that the answer is likely multifactorial, with some causes that are biological and perhaps even genetically derived.

There are several investigators assessing the issue from varying lenses. For example, Lisa A. Newman, MD, MPH, FACS, FASCO, FSSO, chief of the Section of Breast Surgery at the New York-Presbyterian/Weill Cornell Medical Center and leader of the Multidisciplinary Breast Oncology Programs at the New York-Presbyterian David H. Koch Center in Weill Cornell Medicine, is an investigator working to assess patterns of breast cancer subtypes in different regions of Africa.

Additionally, looking at data within the United States, Melissa Davis has been investigating evolutionarily conserved genetic variants that play a role on the immune system. Based on the data Newman and Davis have presented, Palmer explained that biology does seem to be a part of the picture in terms of risk factors.

Palmer noted there are also behavioral differences across culturally defined groups in the United States that may be contributing to the disparity in rates of breast cancer among Black women versus other population groups. In particular, a diet high in fruits and vegetables has been shown to reduce the risk of estrogen receptor-negative (ER-) breast cancer and TNBC. Because diets and access to healthy food can differ across populations, diet may be another contributing factor, Palmer said.

Additionally, breastfeeding has been found to be an important protector against TNBC, Palmer noted. For a multitude of reasons that date back through the history of Black women in the United States, Black women are often less likely to breastfeed, according to Palmer.

“So my team and others have been doing work on these factors. But then I also feel we need to go beyond just these individual factors, which leads us to some social factors, neighborhood level factors, and in particular stress,” Palmer said. “Stress is another factor that, in some ways, disproportionately affects Black individuals in this country, because of the anti-Black racism that exists, which has shown to have one of the most powerful effects on people. That was the reason for this work that we began doing.”

Although the experience of stress can be a good thing in certain situations for which it may positively impact behavior, chronic stress has significant negative impacts on the body.

“Things get overburdened in both the sympathetic nervous system and the hypothalamic pituitary adrenal system. Then different biomarkers that are involved in inflammation, depression, and the immune system come into play more,” Palmer said. “That leads to a cascade of events with possible epigenetic modifications playing a role, [as well as] telomere shortening, and all of that can lead to cancer development, including possibly breast cancer.”

Additionally, the characteristics of a neighborhood can be a contributing factor to chronic stress, including low neighborhood socioeconomic status (NSES), concentrations of disadvantaged individuals, neighborhood violence, lack of green spaces, and lack of social cohesion, as well as loud noises and associated difficulties with sleeping.

“A neighborhood that lacks safety can be a more stressful place to live. Also, randomized trials of different communities that changed the environment of similar housing so that one sees a lot of greenery and the other doesn’t have shown that [greenery] has a real impact on mental health and wellbeing. So a lack of green space can have an effect,” Palmer said. “Then simply the noise that is more likely to be a problem in disadvantaged neighborhoods can lead to sleep problems, which also leads to more stress.”

To evaluate the impact of these neighborhood factors that may contribute to chronic stress, Palmer explained it was necessary to geocode addresses, which required that the investigators place a number on every address associated with a patient included for assessment that locates the address in space. That number, which corresponds to either a house or housing unit, can then be linked to other databases that provide information about the characteristics of the people who live in a certain area in which that number exists.

“The best sources of data for these types of neighborhood variables I’m interested in are the ones that relate to social and economic conditions come from the US Census Bureau—the long form ones which most of us have probably never filled out,” Palmer said.

With these data, Palmer and her colleagues worked to develop scores representing either neighborhood disadvantage or NSES based on different variables. For example, Palmer explained that when looking at the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program data, the investigators identified where those included in the SEER data set were living, which is the score the investigators used for their assessment.

“So the analysis we did was in the Black women’s health study. This study has been going on now for over 27 years, with the same 59,000 women who enrolled back in 1995. Not everyone is still filling out the questionnaires, but a very large proportion is,” Palmer said. “So there’s a lot of data in there on individual level factors. We also have geocoded addresses for every 2 years throughout the time [period] and then linked to those 2 databases.”

When the study began, the median age of the participants was 38 years, with residence throughout the country, Palmer explained. They investigators then learned of new breast cancer cases through self-reporting in these biannual questionnaires, but also through linkage with 24 state cancer registries for states in which most participants lived. Palmer noted for patients who are lost to follow-up, they would also link to a national death index to assess rates of mortality.

When breaking up the compiled data for analysis, the investigators first looked at the variable of neighborhood concentrated disadvantage. They then used a continuous score for each person, and then divided it into quartiles.

“So we were comparing women who lived in the highest quartile disadvantaged, so those are the ones in the most disadvantaged neighborhood, versus those in the lowest quartile,” Palmer said.

Palmer explained that the data showed a statistically significant increase in incidence of ER- breast cancer in the most disadvantaged neighborhoods. Specifically, high levels of neighborhood adversity were associated with a 25% increased risk of both ER- breast cancer and TNBC.

“Given that US Black women, regardless of their own education or income, are more likely to reside in disadvantaged neighborhoods, this factor may contribute to racial disparities in incidence of ER- breast cancer and TNBC,” Palmer said.

Reference

Palmer JR. Neighborhood-level and individual-level psychosocial stressors and risk of breast cancer incidence among Black women. Philadelphia, PA: 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; September 18, 2022.