A woman checking her breast for the presence of concerning lumps.
Nancy Cappello was proactive. When she turned 36, she had a baseline mammogram, a standard medical recommendation in the late 1980s and early 1990s as a comparison tool for future screenings. At 40, Cappello started getting them annually.
Her breast surgeon estimated the cancer had been festering for four to five years under the radar of her annual mammograms.
Six weeks after her 11th-consecutive normal mammogram, she was diagnosed with Stage IIIc breast cancer.
A doctor felt a lump while doing a breast exam during her annual physical and a subsequent ultrasound detected cancer that had spread to 13 lymph nodes. That's when Cappello, then 51, learned she had dense breast tissue, making mammography less likely to detect tumors in her breasts.
She also discovered through her own research that she was among the 40 to 50 percent of women with dense breast tissue — almost half the female population — but medical protocol did not require physicians to inform women of their dense tissue status. If she had known, she said, she would have gotten an ultrasound every year in addition to a mammogram that could have detected the cancer much earlier. Cappello said her breast surgeon estimated the cancer had been festering for four to five years under the radar of her annual mammograms.
Although ultrasound as a cancer screening tool has been available for decades, technological advances are helping doctors find more invasive cancers in women with dense breasts, in turn giving women who know their tissue status the opportunity for earlier detection and treatment.
"We know that the gold standard for breast cancer screening is mammography, but in women with dense breast tissue, up to one third of breast cancers can be missed with this modality alone."
Dr. Georgia Giakoumis Spear, chief of the department of breast imaging at NorthShore University HealthSystem in suburban Chicago and assistant professor of radiology at the University of Chicago, has been a leader in developing standards for the use of new ultrasound technology. She is leading a study to develop more specific national guidelines around the use of Automated Whole Breast Tissue Ultrasound (ABUS), a non-invasive procedure in which sound waves are used to scan breast tissue while a patient lies on her back with her arm over her head.
Approved by the Food and Drug Administration in 2012, ABUS provides higher quality 3D images and faster delivery to provide more accurate results than past ultrasound technology. The scan does not involve radiation, and a practitioner can complete the process in 15 to 20 minutes, from patient preparation to image creation. NorthShore has been using ABUS since 2015, Dr. Spear said, and the technology can improve breast cancer detection in women with dense breasts by up to 55 percent.
"We know that the gold standard for breast cancer screening is mammography, but in women with dense breast tissue, up to one third of breast cancers can be missed with this modality alone," Spear says. "And when we supplement screening with ultrasound in this population of women, we have found a large number of cancers by ultrasound that are not visible on the mammogram."
Mammography should still be used as the first step for breast cancer detection, but if an initial mammogram shows that a patient has dense breast tissue, studies encourage discussion of additional screening with ultrasound.
On a mammogram, dense tissue appears white. So do cancerous masses, making them easy to miss.
A radiologist determines tissue density, according to the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS). "A" and "B" breast density categories designate ratios of mostly fatty, or non-dense tissues, while the "C" and "D" categories designate heterogeneously dense and extremely dense tissue, respectively. Such patients would be classified as having dense tissue. Younger women, women with lower levels of body fat and women undergoing hormone therapy are more likely to have C and D breast density.
On a mammogram, dense tissue appears white. So do cancerous masses, making them easy to miss. Fatty tissue, in comparison, appears black, making tumors easier to spot.
The FDA stated among its policy goals for 2018 that it's placing an improved focus on recognizing technological advances to help "ensure women get the most relevant, up-to-date information about their breast density, which is now recognized as a risk factor for breast cancer." An article in the March 2018 Journal of the American College of Radiology recommended supplemental screening for women with higher-than-average breast cancer risk, placing women with dense breast tissue in that category.
To be sure, some in the medical community are reluctant to push for ultrasounds, saying that a mammogram might be enough even if the woman has dense breast tissue. A patient is advised to discuss the option of ultrasound with her physician and they can decide from there.
Access to such information became political for Cappello after her diagnosis in 2004. She said that as she underwent six surgeries, a mastectomy, chemotherapy, radiation and hormone therapy, she asked doctors why they weren't required to inform women of their dense breast tissue status. Her dissatisfaction with their responses led to the formation of Are You Dense, Inc., an advocacy group aimed to inform women of their medical options while working to pass legislation mandating that women know their tissue status. Other legislation has focused on mandating insurance coverage for breast ultrasounds.
Nancy Cappello.
(Courtesy)
Cappello's work led Connecticut to become the first state to pass an information law in 2009, and 35 states now have similar requirements. Depending on the state, the law could mandate that certain language or information about breast density be included in the patient's mammogram results, or require physicians to tell women about dense tissue if their breast density falls in the BI-RADS categories C and D. Other states might require that patients be given general information about breast density and advice to discuss their options with a physician. (Note: There is a chart on Cappello's website that shows what laws exist – or don't – in each state.)
Through her site and social media, she's connected with other women who've lobbied for laws in their states, including Dr. Spear, who recently testified before legislative committees in Illinois as they considered companion bills. The Illinois legislation is expected to be signed into law this summer.
"There should be no excuses," Cappello says. "Women should have this information. There should be no concealing or hiding of her status."
Marielle Gross, a professor at the University of Pittsburgh, shows patients a new app that tracks how their samples are used during biomedical research.
Tissue donors can track what scientists do with their samples while safeguarding privacy, through a pilot program initiated in October by researchers at the Johns Hopkins Berman Institute of Bioethics and the University of Pittsburgh’s Institute for Precision Medicine. The program uses blockchain technology to offer patients this opportunity through the University of Pittsburgh's Breast Disease Research Repository, while assuring that their identities remain anonymous to investigators.
A blockchain is a digital, tamper-proof ledger of transactions duplicated and distributed across a computer system network. Whenever a transaction occurs with a patient’s sample, multiple stakeholders can track it while the owner’s identity remains encrypted. Special certificates called “nonfungible tokens,” or NFTs, represent patients’ unique samples on a trusted and widely used blockchain that reinforces transparency.
Blockchain could be used to notify people if cancer researchers discover that they have certain risk factors.
“Healthcare is very data rich, but control of that data often does not lie with the patient,” said Julius Bogdan, vice president of analytics for North America at the Healthcare Information and Management Systems Society (HIMSS), a Chicago-based global technology nonprofit. “NFTs allow for the encapsulation of a patient’s data in a digital asset controlled by the patient.” He added that this technology enables a more secure and informed method of participating in clinical and research trials.
Without this technology, de-identification of patients’ samples during biomedical research had the unintended consequence of preventing them from discovering what researchers find -- even if that data could benefit their health. A solution was urgently needed, said Marielle Gross, assistant professor of obstetrics, gynecology and reproductive science and bioethics at the University of Pittsburgh School of Medicine.
“A researcher can learn something from your bio samples or medical records that could be life-saving information for you, and they have no way to let you or your doctor know,” said Gross, who is also an affiliate assistant professor at the Berman Institute. “There’s no good reason for that to stay the way that it is.”
For instance, blockchain could be used to notify people if cancer researchers discover that they have certain risk factors. Gross estimated that less than half of breast cancer patients are tested for mutations in BRCA1 and BRCA2 — tumor suppressor genes that are important in combating cancer. With normal function, these genes help prevent breast, ovarian and other cells from proliferating in an uncontrolled manner. If researchers find mutations, it’s relevant for a patient’s and family’s follow-up care — and that’s a prime example of how this newly designed app could play a life-saving role, she said.
Liz Burton was one of the first patients at the University of Pittsburgh to opt for the app -- called de-bi, which is short for decentralized biobank -- before undergoing a mastectomy for early-stage breast cancer in November, after it was diagnosed on a routine mammogram. She often takes part in medical research and looks forward to tracking her tissues.
“Anytime there’s a scientific experiment or study, I’m quick to participate -- to advance my own wellness as well as knowledge in general,” said Burton, 49, a life insurance service representative who lives in Carnegie, Pa. “It’s my way of contributing.”
Liz Burton was one of the first patients at the University of Pittsburgh to opt for the app before undergoing a mastectomy for early-stage breast cancer.
Liz Burton
The pilot program raises the issue of what investigators may owe study participants, especially since certain populations, such as Black and indigenous peoples, historically were not treated in an ethical manner for scientific purposes. “It’s a truly laudable effort,” Tamar Schiff, a postdoctoral fellow in medical ethics at New York University’s Grossman School of Medicine, said of the endeavor. “Research participants are beautifully altruistic.”
Lauren Sankary, a bioethicist and associate director of the neuroethics program at Cleveland Clinic, agrees that the pilot program provides increased transparency for study participants regarding how scientists use their tissues while acknowledging individuals’ contributions to research.
However, she added, “it may require researchers to develop a process for ongoing communication to be responsive to additional input from research participants.”
Peter H. Schwartz, professor of medicine and director of Indiana University’s Center for Bioethics in Indianapolis, said the program is promising, but he wonders what will happen if a patient has concerns about a particular research project involving their tissues.
“I can imagine a situation where a patient objects to their sample being used for some disease they’ve never heard about, or which carries some kind of stigma like a mental illness,” Schwartz said, noting that researchers would have to evaluate how to react. “There’s no simple answer to those questions, but the technology has to be assessed with an eye to the problems it could raise.”
To truly make a difference, blockchain must enable broad consent from patients, not just de-identification.
As a result, researchers may need to factor in how much information to share with patients and how to explain it, Schiff said. There are also concerns that in tracking their samples, patients could tell others what they learned before researchers are ready to publicly release this information. However, Bogdan, the vice president of the HIMSS nonprofit, believes only a minimal study identifier would be stored in an NFT, not patient data, research results or any type of proprietary trial information.
Some patients may be confused by blockchain and reluctant to embrace it. “The complexity of NFTs may prevent the average citizen from capitalizing on their potential or vendors willing to participate in the blockchain network,” Bogdan said. “Blockchain technology is also quite costly in terms of computational power and energy consumption, contributing to greenhouse gas emissions and climate change.”
In addition, this nascent, groundbreaking technology is immature and vulnerable to data security flaws, disputes over intellectual property rights and privacy issues, though it does offer baseline protections to maintain confidentiality. To truly make a difference, blockchain must enable broad consent from patients, not just de-identification, said Robyn Shapiro, a bioethicist and founding attorney at Health Sciences Law Group near Milwaukee.
The Henrietta Lacks story is a prime example, Shapiro noted. During her treatment for cervical cancer at Johns Hopkins, Lacks’s tissue was de-identified (albeit not entirely, because her cell line, HeLa, bore her initials). After her death, those cells were replicated and distributed for important and lucrative research and product development purposes without her knowledge or consent.
Nonetheless, Shapiro thinks that the initiative by the University of Pittsburgh and Johns Hopkins has potential to solve some ethical challenges involved in research use of biospecimens. “Compared to the system that allowed Lacks’s cells to be used without her permission, Shapiro said, “blockchain technology using nonfungible tokens that allow patients to follow their samples may enhance transparency, accountability and respect for persons who contribute their tissue and clinical data for research.”
Read more about laws that have prevented people from the rights to their own cells.