Breast screening exams from the Breast Cancer Surveillance Consortium reveal disparities in access to improved detection technologies

UC Davis School of Medicine Professor and Division Chief of Biostatistics Diana Miglioretti was among a team of researchers that conducted a cross-sectional study recently published in JAMA Network Open. Researchers evaluated accessibility to, and usage of, digital breast tomosynthesis (DBT) based on a variety of factors including race, ethnicity, education and income. 

“We were concerned that new technologies could widen persistent disparities in breast cancer mortality if there isn’t equitable uptake by facilities accessed by underserved communities,” Miglioretti said via email. 

According to the author contributions of the study, Miglioretti was involved in developing the concept and design of the study, acquiring data, conducting statistical analysis, interpreting the results, obtaining funding and supervising.

Miglioretti has a personal connection to her research that makes early detection of cancer especially important to her. 

“My great-grandmother died of breast cancer in her early 30s and my grandmother and aunt were both diagnosed with breast cancer in their 40s,” Miglioretti said. “All eligible individuals in the US should have access to high-quality screening and follow-up care.”

According to the study, prospective trials and observational studies reveal that DBT, also known as 3-dimensional mammography, can be used to improve breast cancer screening outcomes when compared to digital mammography, more commonly known as DM, or 2-dimensional mammography. 

DBT is a “relatively new technology,” according to a FAQ published by the FDA. 

“3D mammography improves screening performance through lower false positive rates and small increases in cancer detection for some subgroups of individuals,” Miglioretti said. “If underserved communities do not have access to this new technology, they do not get to benefit from these improvements.” 

Professor of Radiology at the University of Washington School of Medicine Christoph Lee said that underserved populations are usually the last to have access to new medical technologies. 

“If 3D mammography does not diffuse into clinical settings in an equitable fashion, then differential technology adoption could exacerbate existing screening outcome disparities,” Lee said via email. 

The results of the study lead to the general conclusion that women of minority races and ethnicities along with those of lower socioeconomic statuses have less access to DBT screening. 

“Access to the best diagnostic tools for detecting breast cancer shouldn’t depend on your zip code or your income level,” said Associate Professor of Radiology at the UC Davis School of Medicine and Chief of the Breast Imaging Section Shadi Aminololama-Shakeri, via email. “That’s why this type of research is critical to enveil existing healthcare disparities. Only then can we start to address these inequalities and help patients access the latest lifesaving screening technology that gives us the best chance at detecting cancer.” 

In particular, only 37.7% of Black women, 44% of Hispanic women, and 42.8% of Asian Americans were able to acquire DBT when both screening technologies were available.

Additionally, while 50.6% of women with a college degree obtained DBT, only 40.8% of women with less than a highschool diploma were able to access this technology. 

“It is important to identify inequalities in the diffusion of new technologies so that healthcare providers, policy makers and advocacy groups can focus on ways to ensure more equitable access to these technologies,” Miglioretti said.

Similarly, only 43.9% of women living in zip codes associated with the lowest income quartiles obtained DBT in comparison to the 51.4% of women in the highest income quartile. 

“We need more clear guidance on what subpopulations of women are most likely to benefit from 3D mammography, and to lower barriers to access for these women,” Lee said. “These include providing evidence to third-party payers for clinical effectiveness of 3D mammography in specific populations.” 

These results were determined from approximately 2.3 million “routine screening mammography examinations among women aged 40 to 89 years,” collected from 92 imaging facilities in five different states between Jan. 1, 2011 and Dec. 31, 2017, according to the study. This data was provided by the Breast Cancer Surveillance Consortium.

“The Breast Cancer Surveillance Consortium is unique in that all of their facilities prospectively collect very detailed woman-level information at each imaging exam,” Lee said. “This allowed us to associate individual social determinants of health with their exam-level outcomes.”

Miglioretti said classifying individuals as coming from an underserved community proved to be a challenging task.

“We used crude measures based on self-reported race/ethnicity and education and geocoded measures of income and rural/urban residence,” Miglioretti said. “In future research, we would like to evaluate other measures of social determinants of health including measures of structural racism.” 

Miglioretti said that one of her top priorities is providing high-quality health care for all by ensuring each individual has access to high-quality screening, follow-up and treatment.

“At UC Davis, 3D mammography is available to every woman who walks through our doors,” Shakeri said. 
Written by: Aarya Gupta — science@theaggie.org

A recent study on eradicating green crabs from an estuary along the California coast showed an increase in the population instead of the desired reduction

In a study led by Ted Grosholz, a professor in the Department of Environmental Science and Policy at UC Davis, it was demonstrated that removing an invasive species would not lower its abundance, but increase the population size of the species instead. A possible explanation for this phenomenon is compensation: when large quantities of larvae survive in response to low quantities of adults present.

The study was originally funded to prove that eradicating green crabs in the event of a new and isolated invasion was possible in a place more remote than the locations included in the study. The initial experiment was to figure out if researchers could eradicate a small, isolated population given a certain budget and field effort, according to Grosholz.

“We selected Seadrift Lagoon because it is relatively small and largely cut off from other bays except for limited times through the year,” Grosholz said via email.

For five years, Grosholz and his team used baited traps to remove crabs. This lowered the green crab population from about 100,000 crabs in 2009 to less than 10,000 crabs five years later in 2013, according to Grosholz.

In a turn of events, the population exploded in 2014 with 300,000 green crabs present in Seadrift Lagoon. The majority of the crabs were juveniles. An explanation for the decrease of adult control of recruitment, the process through which new individuals are added to a population, was a lack of cannibalism of the juveniles. The study confirmed that adult cannibalism of recruits was size-dependent and could control recruitment.

“This was an important lesson about not trying to eradicate a population like this and that the best strategy was to keep the population at low abundance, which we have for the past five years, relying on community scientists and volunteers,” Grosholz said via email.

Future plans for eradication processes of invertebrates and fishes like the green crab can look at this case study and decide to take a different approach to controlling invasive species to avoid another population explosion.

“The focus should be functional eradication and not total eradication for several reasons,” Grosholz said via email. “This is achievable, should provide most of the same benefits and there is usually data available to determine the target.”

Marcella Heineke, a junior specialist at the Grosholz Lab, has experience working with invasive species as well. Heineke started working at the lab in June 2019 and was a part of a grant exploring native oyster restoration in the San Francisco Bay. Heineke researched an invasive oyster drill, a generalist invasive predator in the east coast that was destroying native oyster restoration efforts. 

“Our thought was if we could bring in the predator of the oyster drill and reduce oyster drill populations levels, the oyster restoration success would increase,” Heineke said. 

The native predator of oyster drills are rock crabs. In the San Francisco Bay and at Bodega Marine Laboratory where Heineke was based, there were trials to put oyster drills and crabs in the same tank and see how the drill’s behavior changed in the presence of the crabs, according to Heineke.

The invasive oyster species are generalists, meaning they can eat almost anything and do not have a restricted diet. This characteristic allows them to survive in a variety of different habitats, according to Heineke. 

“The drill oysters will eat mussels, clams, oysters and pretty much anything they can get their hands on,” Heineke said.

Jessica Weidenfeld, who is now at UC San Diego, was also a part of the Grosholz Lab during her time at UC Davis and was exposed to the trials of controlling invasive species. Her advice to help with the research for invasive species is to go out and vote to elect leaders who rely on data and listen to scientists. 

“It can feel overwhelming to think of what you can do as an individual, but those are some things we can do to help with invasive species,” Weidenfeld said. 
Written by: Francheska Torres — science@theaggie.org

A deep dive into PCR testing

Though polymerase chain reactions (PCR) tests have been one of the most common laboratory tests in biochemical research for decades, they have only recently become a topic of discussion for the public as they have been at the center of the COVID-19 testing efforts. PCR tests have been seen as the gold standard for proving that a person does not have COVID-19, being required for everything from surgical procedures to international air travel in order to prevent the spread of disease. But what is a PCR test and why are they so effective at proving that someone doesn’t have a disease like COVID-19? 

To answer these questions, it is important to understand exactly what a PCR test is. The PCR test is a method of searching for the presence of small amounts of DNA based on the principle of amplification through something called a polymerase chain reaction, according to Dr. Ken Hilt, a lecturer in the UC Davis Department of Molecular and Cellular Biology.

“The polymerase chain reaction makes copies of the piece of DNA that you wish,” Hilt said via email. “It requires primers, short strands of single-stranded DNA that recognize your gene of interest, deoxynucleotides, a heat resistant polymerase (enzyme) and a machine (thermocycler) to raise and lower the reaction temperature several times during one cycle. The machine is programmed to go through many cycles in the course of three hours. During that time, you have made many copies of the gene of interest.” 

This polymerase chain reaction allows for the amplification of a single piece of DNA over and over again. This amplification process means that even if only a small amount of the DNA is present in the initial sample, it can be replicated enough times until the DNA is abundant and easily detectable. 

When the COVID-19 pandemic began in March 2020, PCR tests were quickly considered the best way to detect the presence of the virus. However, the process of using PCR tests to detect viruses was slightly different than the traditional approach. Viruses use ribonucleic acid (RNA) as their molecular code while PCR tests are designed to look at DNA, so in order to detect the presence of the virus by PCR test, its RNA was first converted to DNA.

Dr. Nam Tran, an associate clinical professor in the Department of Pathology and Laboratory Medicine at UC Davis, explained how PCR tests were adapted to detect SARS-CoV-2. 

“PCR works by targeting specific genes within DNA which are then copied over and over,” Tran said. “This allows one to amplify a single piece of DNA many times over so we can detect it. For SARS-CoV-2 testing, the virus is an RNA virus, thus we use reverse transcription PCR, or RT-PCR to first convert the RNA to DNA. Thereafter, we amplify the complementary DNA which is detected.” 

While this amplification/replication process of the DNA can theoretically happen nearly infinitely, according to Tran, there is also a tradeoff between how sensitive the test is and how specific the results of the test can be. 

“[A]s you increase sensitivity, it comes at a tradeoff of specificity. How sensitive something is helps you determine the number of false negatives,” Train said. “While the specificity helps you determine the number of false positives, there is always a tradeoff between sensitivity and specificity. This is not unique to COVID-19. This is taught to medical students, and health care is well versed with this concept.”

As Tran mentioned, sensitivity refers to the minimum amount of DNA required to get a positive result. In this case, higher sensitivity means more cycles of amplification have occurred, and specificity refers to the ability to correctly identify who is not infected with disease. This is an important concept in clinical medicine because sensitivity and specificity are inversely related—as sensitivity increases, specificity decreases. 

Put another way, the more sensitive the test is, the more likely it is to get a false positive (less specificity). This happens because increasing the sensitivity (achieved by increasing the number of times you amplify the DNA) means an individual might take something that is too small to cause infection and amplify it to the point where it would appear to be clinically significant. As a result, the balance of sensitivity and specificity must be carefully determined when using PCR tests as a clinical diagnostic tool. 

While PCR tests are seen as the gold standard in detection of DNA, they are not a perfect tool. False positives and false negatives do happen, but false positives are more common in a PCR test because of the idea of sensitivity versus specificity; if the test is too sensitive, then it is possible for a small contaminant to enter at some point in the process which can be amplified to the point of detection. 

Dr. Marcelo Prado, the supervisor of the Molecular Pathology Laboratory at UC Davis, and its scientists Carl Sax, Rick Westerman and Mary Grace Laya, explained the complications of a PCR test in a joint statement.

 “PCR testing is highly sensitive and target-specific, and false-positive results rarely occur,” Prado said via email. “However, they can occur due to specimen mix-up, processing issues or lab contamination (as opposed to test limitations). All it takes is an improperly sealed PCR plate to aerosolize those amplicons and then all your subsequent runs might be contaminated. That is why molecular testing is performed according to strict standard operating procedures.” 

Prado continued, “False negative results can occur from improper specimen collection and can vary depending on the stage of infection.”

False test results are possible, but they are extremely unlikely. The work done in clinical laboratories is precise and careful to prevent these false results from occurring. While false positive results are more common than false negatives, they are still extremely rare and generally only occur when the sensitivity is far too high. For this reason, it is common to report the number of cycles of amplification that the sample went through when reporting a positive PCR test. The clinician is then responsible for interpreting this information and deciding whether the specificity and sensitivity is enough to issue a diagnosis or if further tests are required. If a clinician believes that the sensitivity was too high and that there is a possibility the result is a false positive, they can often order other types of tests that have lower sensitivity, such as an antigen test for COVID-19 which has a higher chance of a false negatives but a lower chance of a false positive. The clinician can then integrate the data from multiple tests to ultimately determine the patient’s diagnosis.

PCR testing is an accurate way to detect the presence of DNA or RNA in a sample—and provided that the sample is collected and stored properly, it can be an extremely effective diagnostic tool for detecting diseases such as COVID-19. As for the pandemic, PCR tests remain an important tool for ensuring that people are not infected by COVID-19. 

Written by: Justin Weiner – science@theaggie.org