AI could help radiologists improve their mammography interpretation

The guidelines for screening women for breast cancer are a bit confusing. The American Cancer Society recommends annual mammograms for women older than 45 years with average risk, but other groups like the U.S. Preventative Services Task Force (USPSTF) recommend less aggressive breast screening.

This controversy centers on mammography’s frequent false-positive detections — or false alarms — which lead to unnecessary stress, additional imaging exams and biopsies. USPSTF argues that the harms of early and frequent mammography outweigh the benefits.

However, a recent Stanford study suggests a better way to reduce these false alarms without increasing the number of missed cancers. Using over 112,000 mammography cases collected from 13 radiologists across two teaching hospitals, the researchers developed and tested a machine-learning model that could help radiologists improve their mammography practice.

Each mammography case included the radiologist’s observations and diagnostic classification from the mammogram, the patient’s risk factors and the “ground-truth” of whether or not the patient had breast cancer based on follow-up procedures. The researchers used the data to train and evaluate their computer model.

They compared the radiologists’ performance against their machine-learning model, doing a separate analysis for each of the 13 radiologists. They found significant variability among radiologists.

Based on accepted clinical guidelines, radiologists should recommend follow-up imaging or a biopsy when a mammographic finding has a two percent probability of being malignant. However, the Stanford study found participating radiologists used a threshold that varied from 0.6 to 3.0%. In the future, similar quantitative observations could be used to identify sources of variability and to improve radiologist training, the paper said.

The study included 1,214 malignant cases, which represents 1.1 percent of the total number. Overall, the radiologists reported 176 false negatives indicating cancers missed at the time of the mammograms. They also reported 12,476 false positives or false alarms. In comparison, the machine-learning model missed one additional cancer but it decreased the number of false alarms by 3,612 cases relative to the radiologists’ assessment.

The study concluded: “Our results show that we can significantly reduce screening mammography false positives with a minimal increase in false negatives.”

However, their computer model was developed using data from 1999 to 2010, the era of analog film mammography. In future work, the researchers plan to update the computer algorithm to use the newer descriptors and classifications for digital mammography and three-dimensional breast tomosynthesis.

Ross Shachter, PhD, a Stanford associate professor of management science and engineering and lead author on the paper, summarized in a recent Stanford Engineering news release, “Our approach demonstrates the potential to help all radiologists, even experts, perform better.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

“Fierce, empowered… and less alone”: A 32-year-old cancer patient reflects on her new film

Photo by Kerith Lemon Productions of writer Becky Hall, left, and director Kerith Lemon.

As someone who battled against Hodgkin’s lymphoma when I was in my 20s, I can relate to Becky Hall, a young breast cancer patient at Stanford. I recently spoke with Hall about her cancer experiences and her short film, bare, which describes the night her friends shaved her head before starting chemotherapy.

When were you diagnosed with cancer?

“I was a 25-year-old graduate student in a veterinary program at UC Davis. I wanted to work with horses. I was a Stanford graduate and was all about school. Then I went for a run one Saturday and laid down on my chest to stretch — a stretch that I’ve done every day for years — and it felt like I was laying on a golf ball. The nurse at the health center said I was too young for breast cancer and didn’t have a family history so I didn’t need to worry, but she sent me to get a mammogram just to be 100 percent sure. I completely panicked, because that’s what I do. The mammogram showed lumps in my breast and lymph nodes, so they biopsied right then and everything spiraled. A week after I found the lump, I was a stage 3 breast cancer patient.

I couldn’t do such a demanding academic program during chemotherapy. So I dropped out of school and moved back in with my parents in Santa Cruz — really losing all my independence, privacy and social interactions for a year as I went through chemotherapy, surgery, radiation and biotherapies. I went into remission for about two years and then I found out my cancer had metastasized three weeks after my wedding. So I’m now a terminal, stage 4 patient. Since August 2014, I’ve been in continual treatment to keep up with and out smart my cancer.”

What was that like?

“Having cancer is always going to be traumatic and challenging, but there are additional challenges when you’re young. My 25-year-old friends were busy going out drinking, so we couldn’t relate to each other’s interests any more. And they didn’t have enough life experience and skills to cope with being a friend to someone with a major illness. So many of my friends just disappeared, because they didn’t know how to handle it. It was very isolating.

There was also the whole element of being single, because dating was terrifying after I’d been through breast cancer. I had a reconstructed breast. I had scars all over my body. I knew there was a chance that it was going to metastasize. And I had to explain all of this to someone.

And finally there was the fertility issue. I had cancer, and suddenly they ripped away this huge element of my life that I’d always envisioned for myself. When I was stage 3, I was hopeful and a little delusional, thinking that I’d still be able to have kids after chemo. When I was diagnosed stage 4, I was married to an amazing teacher who loves kids. On our honeymoon, we’d talked about how many kids we wanted and even about names. And then we got home and were told we could not have kids. And it just destroyed me. I would never be able to carry a child. Adoption is exceedingly difficult for someone with stage 4 disease, and surrogacy is pretty cost prohibitive. It’s just a whole other layer of heartbreak that cancer throws at a young woman.”

What motivated you to capture the experience of shaving your head in a short film?

“The idea of watching my hair fall out slowly was absolutely terrifying. And I was facing so many changes physically that I had no control over, but I could control when and how I lost my hair. It turned out shaving my head before chemo really helped me process some of my emotions and biggest fears — potentially dying, being unattractive, and losing a big part of my identity.

I wanted other women to feel what I felt when I looked in the mirror after shaving my head — fierce, empowered and like I could take on anything. I also wanted to help people feel less alone. In mainstream media, so many of the stories told about cancer are very rosy and falsely upbeat. I wanted to show a more honest slice of what it’s like — that you can be in the darkness, but you can emerge from it if friends are willing to just sit in the darkness with you. I also wanted to shed some light on metastatic disease and the disparities in research between early stage and late stage breast cancer.

Before the project, I felt like all I did was go to doctor appointments. The film reminded me that I’m still capable of creating and contributing. I co-wrote the script with my childhood friend Kerith Lemon and helped with the project while recovering from brain surgery and brain radiation — I’m really proud of that.”

Do you have any advice on living with cancer?

“When living with cancer, you’re constantly dealing with treatments and side effects. Everything is always up and down — one scan is good and the next is bad. It’s really, really draining. In an effort to help, people often encourage you to stay positive and upbeat. But my advice is to feel whatever you feel: sad, angry, scared or whatever.

It’s also important to find other metastatic cancer patients who understand on a deep level what you’re going through because they are going through it too. Find people to reach out to on those dark days, who can help you process and get through it when you’re ready.”

What are you doing now?

“I’m living in Santa Cruz with my husband and dog. In addition to being a full time cancer patient, I’m writing and getting involved in metastatic advocacy. My advocacy work started a couple of months ago after I participated in a panel during a screening of the film. I really enjoyed public speaking and talking about the needs of metastatic patients to a room full of people that can actually effect change. It felt like I found my purpose beyond just surviving cancer. And I give credit for this to the film.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Stanford study provides new understanding of breast growth disorders

Photo by sasint

Breast underdevelopment at puberty is associated with a shortage of several hormones produced by the pituitary gland, a condition called combined pituitary hormone deficiency (CPHD). This disorder is caused in part by loss-of-function mutations of the GLI2 gene, but the molecular pathways of how CPHD manifests are not fully understood.

Now, researchers at Stanford University School of Medicine have discovered a new way that GLI2 impacts breast development, as recently reported in Science. Led by Philip Beachy, PhD, a Stanford professor of developmental biology and of biochemistry, the research team found that GLI2 activity helps control mammary stem cells in mice.

Stem cells are responsible for the growth, homeostasis and repair of many tissues. The behavior and survival of these stem cells depends on their local microenvironment, called a stem cell niche. During breast growth, the niche must support its associated stem cells while also responding to circulating hormones that trigger the dramatic changes of puberty.

The study showed that this stem cell niche is genetically programmed to produce the signals that control breast development in response to the hormones that regulate puberty. Using mice without a functioning GLI2 gene, the researchers found that a defective stem cell niche environment may lead to the breast growth defects seen in human CPHD. In addition, the research provides insights into a new mechanism to target when developing drugs that may help prevent breast cancer.

The authors conclude:

“Whereas prior studies implicate stem cell defects in human disease, this work shows that niche dysfunction may also cause disease, with possible relevance for human disorders and in particular the breast growth pathogenesis associated with combined pituitary hormone deficiency.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

 

Genomic screening may help predict breast cancer survival

Photo by 3dman_eu

Breast cancer patients are often faced with a difficult decision at the end of their primary treatment: Should they get systemic adjuvant therapy, such as the anti-estrogen drug tamoxifen? Such therapies lower the risk that the cancer will come back, but they also carry the risk of potentially serious side effects.

What would be helpful is for physicians to have a way to predict which patients have the best prognosis and might not need adjuvant therapy. Now, researchers from the Lawrence Berkeley National Laboratory may have a solution, according to a study recently published in Oncotarget.

The research team analyzed clinical patient data and large genomic datasets of normal and tumor breast tissues — identifying 381 genes associated with the relapse-free survival of breast cancer patients. With further analysis, they were able to develop a scoring system based on a 12-gene signature that predicts breast cancer survival. Patients with a low score were more likely to live longer.

Senior author Antoine Snijders, PhD, a research scientist at Berkeley Lab, explained in a recent news release:

“Distinguishing patients with good prognosis could potentially spare them the toxic side effects associated with adjuvant therapy. Determining prognosis involves a range of other clinical factors, including tumor size and grade, the degree to which the cancer has spread, and the age and race of the patient. Our scoring system was predictive of survival independent of these other variables.”

The study showed that their 12-gene signature was effective at predicting patient survival for two specific subtypes of breast cancer — luminal-A and HER2 — but it wasn’t effective for other subtypes.

In addition, the researchers identified seven genes as potential tumor suppressors that could be targeted when developing new breast cancer therapies. They hope that their work will help doctors and patients make more informed treatment decisions, as well as help others develop better breast cancer drugs.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Education reduces anxiety about mammography

Woman received mammogram (Rhoda Baer)
Woman receives mammogram (Rhoda Baer)

My close childhood friend Kelly died from breast cancer when she was only 32 years old. This inspired me to choose a research position at Berkeley Lab to help develop new breast-imaging scanners to improve early detection. Given my expertise in this field, my friends come to me with their confusion and ask, “At what age and how frequently should I get a mammogram?”

There has been a lot of debate surrounding mammography screening since 2009 when the United States Preventive Services Task Force revised their guidelines for average-risked women, limiting routine screening to biennial mammography for women 50 to 74 years of age.

The task force recommended increasing the screening age in part due to the harmful anxiety caused by false-positive results, which are more common in younger women. The American Cancer Society recently released a new set of guidelines that recommends yearly mammograms starting at age 45, but they also considered the pain, anxiety and other potential side effects of mammography.

A recent article published in the Journal of the American College of Radiology describes a successful intervention to reduce this anxiety. The authors provided interactive one-hour educational sessions on mammography, which were led by a trained breast radiologist.

Before the lecture, a questionnaire was administered to the participants to identify their anxiety and previous mammography experience — 117 responded. Those respondents who reported having anxiety about mammography screening indicated “unknown results” and “anticipation of pain” as the primary sources of their anxiety.

A follow-up questionnaire measured the effectiveness of the informational sessions. Virtually all participants were able to correctly answer key facts that were covered in the lecture, such as recognizing that it is important to have your prior mammogram available to the radiologist for comparison.

The journal article concludes:

Attendees of these sessions reported high levels of satisfaction in their participation, with a strongly favorable impact on increased knowledge and decreased anxiety (“harm”). Education can enable women to share in informed decision making regarding if, when, and how often to attend screening mammography. Attendees also reported encouragement to attend screening mammography.

The authors hope to encourage other radiologists to provide similar proactive, public outreach education.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Why Don’t We Get Cancer More Often?

See my KQED Quest blog on Dr. Mina Bissell’s pivotal breast cancer research at Lawrence Berkeley National Lab. She will be part of a free public lecture, Science at the Theater: Health Detectives. It will be held on April 23 at 7 pm at the Berkeley Repertory Theater.

science at the theater health detectives
Image courtesy of Friends of Berkeley Lab.

Risk of Invasive Breast Cancer Predicted

Way too many of my women friends have suffered through breast cancer diagnosis, starting with a close friend who died of breast cancer in her early 30s. Her death inspired me to change careers, in hopes of developing better ways to detect and stage breast cancer. Although the focus of my work has now moved on to other medical imaging areas, I still pay particular attention to new breast cancer research.

It seems like there are reports on breast cancer research in the news daily. But my eye was particularly caught by an article published online on April 28, 2010 in the Journal of the National Cancer Institute. A group of researchers, from UCSF Helen Diller Family Comprehensive Cancer Center, are now able to predict whether women with ductal carcinoma in situ are at high or low risk of developing subsequent invasive cancer.

Ductal carcinoma in situ (DCIS) is the most common type of non-invasive breast cancer. The American Cancer Society estimates that about 60,000 women are diagnosed with DCIS in the U.S. each year. This cancer starts in the milk ducts. It is called non-invasive because it hasn’t spread beyond the milk ducts into any normal surrounding breast tissue. DCIS isn’t life-threatening and it rarely leads to death from breast cancer, but having DCIS can increase your risk of developing an invasive breast cancer in the future. Approximately 11 out of 100 women diagnosed with DCIS and treated with a lumpectomy only go on to develop invasive cancer within 8 years, and about the same number go on to develop subsequent DCIS within 8 years. That means that the majority of such women have no further tumors, but these women typically still go through some form of aggressive treatment.

So we really need a way to predict which women with DCIS have a high risk of developing subsequent tumors. The UCSF scientists report that they’ve discovered a method to do just that. They collected and analyzed data for 1162 women aged 40 years or older, who were diagnosed with DCIS and treated with a lumpectomy alone in the San Francisco Bay Area. They followed and measured clinical, histopathologic, and molecular characteristics of subsequent tumors for this large population (from 63 hospitals) for 8 years.

They found that the risk of subsequent invasive cancer was significantly increased among women whose initial DCIS was detected by palpation compared with those detected by mammography. They also found that DCIS lesions that were “triple positive” for the expression of biomarkers p16COX-2and Ki67 had an even higher risk of subsequent invasive cancer. However, these factors were not associated with increased risk of subsequent DCIS. An independent set of biomarker expression and conditions was identified for increased risk of subsequent DCIS, with the lowest risk group having disease-free surgical margins of 10 mm or larger.

Based on their findings, the UCSF scientist were able to stratify the women into 4 categories for risk of subsequent invasive cancer — Lowest (17%), Low (27%), Intermediate (28%) and High (28%). The lowest risk group had only a 4% risk of developing invasive cancer within 8 years, whereas the high risk group had a 20% risk. A similar stratification was performed for risk of subsequent DCIS with similar results.

Hopefully this new method of predicting risk for subsequent cancers will help women with DCIS chose the proper treatment. Karla Kerlikowske, the lead author, states “It will lead to a more personalized approach to treatment. As many as 44 percent of the patients (i.e., lowest and low risk groups) with DCIS may not require any further treatment, and can rely on surveillance.”

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