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Lynn Sage Breast Cancer Symposium

Ruth O’Regan, MD, division head of Hematology and Oncology in the Department of Medicine at the University of Wisconsin School of Medicine and Public Health, discusses treatment for premenopausal patients with breast cancer.

Overall, only 20% of breast cancer occur in women who are still having regular periods, states O’Regan. Less than 10% occur in women of the age of 40 and less than 2% in women under the age of 35.

If one looks biologically what you find is that they are more likely to get triple-negative breast cancer (TNBC), explains O’Regan. They are less likely to get luminal A cancers. However, there are data demonstrating that as the age increases, the rate of TNBC goes down and the rate luminal A goes up.

Dr. O'Regan on Treatment of Breast Cancer in Premenopausal Women

José Baselga, MD, PhD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses biomarker research for patients with breast cancer.

According to Baselga, the community is still in the process of validating some of the targets. There is a need to incorporate next-generation sequencing platforms into clinical practice.

It no longer makes sense to only check for estrogen receptor mutations or HER2 proliferation, but rather to look at comprehensive panels of genes. This will open opportunities for new ways to detect these abnormalities. For example, researchers are very excited by the prospect of developing liquid biopsies, which have the capacity to look for these DNA alterations in the blood. That would be a non-invasive approach, states Baselga.

More from the Lynn Sage Breast Cancer Symposium

Dr. Baselga on Biomarker Research for Breast Cancer

Benjamin O. Anderson, MD, a surgical oncologist at the Seattle Cancer Care Alliance, discusses the biggest unmet need for patients with breast cancer in low- and middle-income countries.

The biggest need is to address the system’s obstacles, states Anderson. In countries with fewer resources, financial constraints are a big issue that needs to be managed. However, an even more significant problem is the systematic disorganization that is common in limited resource environments.

This is a problem because prior to 2011, infectious diseases were thought to be the primary health issue in low- and middle-income countries, explains Anderson. What is happening globally is that this is being overtaken by non-communicable diseases (NCDs), meaning heart disease, lung disease, diabetes, and cancer. The World Health Organization has been tasked by the United Nations to address the NCDs.

Dr. Anderson on the Unmet Need in Low- and Middle-Income Breast Cancer Care

Multigene panel testing offers a new but often puzzling tool for breast cancer treatment, since the results are often difficult to interpret, both for relative risk and risk management, according to a talk by Mark Robson, MD, at the 19

 annual Lynn Sage Breast Cancer Symposium.

 1 and 2, but these new ones are challenging," said Robson, clinic director of the clinical genetics service at Memorial Sloan Kettering Cancer Center (MSK), at the symposium, which was sponsored by Northwestern University's Robert H. Lurie Comprehensive Cancer Center.

Figuring out how a certain genetic result might change not only the type of intervention but its timing is the chief challenge. Robson recommended using available data to put each patient on an "age-specific spectrum of risk," adjusting the timing of interventions to match the patient's risk of disease relative to the general population. For example, if a woman in the general population should start screening mammograms at age 40, a woman carrying the 

 gene variant has the same level of disease risk at age 30, and should start having screenings earlier.

Robson's presentation covered nine genes associated with moderate cancer risk (with relative risk levels between 2 and 5): 

CHEK2, ATM, PALB2, BRIP1, RAD51C, RAD51D, BARD1, NBN

, and the Lynch genes. A review of available studies has revealed a mixed picture. For example, 

 overall is associated with about the same level of risk, 2.3 to 2.4, as having one first-degree relative with breast cancer. However, some 

These are far from the only possibilities, of course. Tests are available for dozens of gene variants that may make some contribution to breast cancer risk, either alone or in combination with other genes or risk factors. Some represent a low risk of breast cancer but elevated risk for ovarian cancer—or vice versa. Some don't represent any increased risk until the patient hits a certain age, and then the risk may spike to moderate or high.

Robson said clinicians must answer 2 questions as they expand the use of multigene panels in their practices. First, are the results "actionable": is the association large enough and robust enough to change a treatment recommendation? And second, do they have "clinical utility": that is, if the test is used to direct care, do patients have better outcomes? It's too early to answer the second question with large-scale studies, but Robson said some consensus is beginning to build around the first for some gene variants.

It is likely that a number of patients have these moderate risk gene variants, if testing is completed. Reviews of commercial lab data on almost 80,000 breast cancer patients showed that several genes associated with breast cancer risk have a prevalence that's comparable to 

, showed a prevalence of 1.28%, and the prevalence of 

Robson noted that genome sequencing is still too expensive to justify a large-scale controlled study that would reliably measure prevalence in populations that don't have breast cancer, but some studies are using data from public databases like the Exome Aggregation Consortium, a broad sample of genomic data acquired for other studies, as a reasonable proxy.

"The more we do, the more complicated it gets, unfortunately," Robson said, because gene variations can have several different versions, and some mutations have a much larger effect than others.

Patients given multigene panel tests at MSK are usually referred by their physicians because of a disease diagnosis or a strong family history, though there is no standardized path and some patients self-refer, Robson said. With the increasing availability of genome sequencing and other gene assays, more patients are likely to acquire information about cancer risk genes as a result of seeking testing on their own, or being tested for something else.

Regardless of how they learn about it, what should clinicians tell a 25-year-old patient who's facing elevated risk a decade or two from now? He suggesting the following example: "We understand more about your lifetime risk, and we know that when you're 40, we need to start doing something different."

Robson added that it's important to keep in mind that the patient hasn't received a diagnosis (even though it may feel that way to her), but merely a clearer understanding of her risks.

Multigene panel testing offers a new but often puzzling tool for breast cancer treatment, since the results are often difficult to interpret, both for relative risk and risk management.

Multigene Testing Adds Complexity to Decision Making Process

Even with advancements in technology, the prospect of artificial intelligence that can treat patients with cancer still remains out of reach.

That may soon change, according to Andrew Seidman, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center (MSK), who is helping IBM develop an application called Watson for Oncology. Watson has potential to be a valuable partner in helping him process the deluge of new information in his field, he said.

"We are faced with exponentially growing data from all over the world," Seidman said during a presentation at the 19th Annual Lynn Sage Breast Cancer Symposium. "At best, I might scan some article titles at the end of a long day, but it's hard for me to stay at the cutting edge and feel I'm making optimal decisions."

Seidman said oncologists are particularly challenged to keep up with the data regarding cancer-associated genes. While genomic analysis may yield a long list of actionable cancer biomarkers for a given patient, Seidman says the list is about as useful to most oncologists as a clay tablet full of hieroglyphics when it comes to making treatment decisions. Crunching large amounts of data is where computers shine, and computer decision support will become increasingly important as genomic discoveries and new treatments proliferate.

But Watson needs to be taught how to crunch, and Seidman and his MSKCC colleagues spend a lot of time figuring out how to instill their expertise into Watson's computations. He estimates that Watson for Oncology and its team are "beyond 8th grade, but not yet in high school." For each individual case used to train Watson, Seidman estimates that a human physician needs to spend 5 to 7 minutes telling the computer everything it needs to know. While Watson may do well at aggregating research findings, it needs help understanding an individual patient's ability to tolerate a treatment.

The Watson for Oncology development team's "to-do" list is long:

Add surgery and radiation to the medical oncology care plans it has been learning so far

Incorporate new treatments and care advances

Teach Watson how to match patients to appropriate clinical trials

Create an interface for patients to interact with Watson

Improve Watson's ability to link data in the literature to treatment of individual patients

Connect Watson's treatment choices with outcomes. Though several hospitals have already availed themselves of Watson for Oncology for treatment recommendations, Seidman acknowledges that the work needs to be validated. Two basic studies need to be done. "The first level is, does Watson lead to physicians changing their preconceived treatment recommendations?" he said. "That kind of study is just beginning." The second is more difficult, though more important: measuring whether Watson's recommended treatment plans lead to better patient outcomes than treatment plans left entirely to physician discretion. "We are thinking about how you would design that kind of clinical trial," Seidman said.

While Seidman does not expect to be replaced, Watson may help him and other subspecialists share their expertise more widely than they can now. "There are only so many consultations you can give, and [having access to Watson] could democratize cancer consultations." A Watson-based consultation would lack the give-and-take that two physicians can have over the phone or in email, but the computer can link the physician to relevant literature and do comparative tabulations of outcomes for different regimens. Developments in natural language processing may enable actual dialogue someday, Seidman says.

Even now, Watson occasionally outsmarts its teachers, coming up with treatment recommendations that they recognize as superior to their own. During training, which is an iterative process, Watson and MSK oncologists assess possible treatments for each case, scoring each one green (recommended), yellow (for consideration), or red (not recommended). The team hopes for overall agreement, and dreads "red-green" disagreement. Most common is a "yellow-green" disagreement. While human judgment still makes the better choice most of the time, Seidman says, “Sometimes we realize, 'Watson got that one right and we got it wrong.'"

Even with advancements in technology, the prospect of artificial intelligence treating patients with cancer still remains out of reach. At least, for now.

IBM's Watson has Potential Partnership With Oncologists

Extra vigilance, careful management, and an emphasis on empathy makes treating cancer pain more effective during an opioid addiction epidemic, Judith A. Paice, PhD, RN, discussed during a presentation at the 2017 Lynn Sage Breast Cancer Symposium. 

Both patients and physicians now approach opioid use with extra caution that is understandable in the current climate, but their caution may be excessive in some cases, said Paice, director of the Cancer Pain Program and a research professor of medicine at Northwestern University's Feinberg School of Medicine, as well as a past president of the American Pain Society.

More patients than ever are living with pain. As of 2012, there were 32.6 million people worldwide living with cancer and that number is expected to jump to 52.2 million by 2030, according to the International Agency for Research on Cancer.

Improvements in cancer treatment have led to millions of patients surviving for a decade or more, with a corresponding increase in the number who live with pain. Paice cited a review in the journal Pain estimating that 40% of cancer survivors live with some degree of pain, and 5% to 10% have severe chronic pain that limits their ability to function.

 One in 5 childhood cancer survivors report pain.

Amid the hype concerning overuse of opioids, Paice is concerned that some patients still remain undertreated due to addiction fears that do not match the evidence. "After Prince died, people asked me to take them off their fentanyl patches, and I had to reassure them that Prince hadn't died from a fentanyl patch," she said. Though long-term opioid addiction often begins with the use of prescription painkillers like oxycodone, Paice cited research showing that 3 out of 4 such addicts acquired those pills illicitly rather than through a legitimate prescription.

Paice said both primary care physicians and insurance companies sometimes treat last year's CDC guidelines for opioid treatment as a mandate,

 even though they may be too conservative to be applied to cancer-related pain. "Many of us protested the recommendation that patients be given no more than 50 mg of morphine and only a 3-day supply at discharge," she said. "Imagine that 80-year-old woman who lives far from the hospital, relies on family members, is discharged on a Thursday, and now on a Saturday or Sunday has to get a new prescription."

Paice also cited statistics showing that while there is a rough correlation between sales of prescription opioids and deaths from opioid overdose, the number of deaths specifically from prescription opioids has plateaued (though deaths from illicit opioids are still climbing).

Nonetheless, the addiction danger is real and there are possible long-term health complications from sustained opioid use, even when the patient is not an addict, Paice said. "We didn't see these effects when I was starting out in practice because we only prescribed opioids at the end of life." They include constipation, mental clouding, upper gastrointestinal symptoms, various endocrinopathies, sleep apnea, and a poorly understood risk of opioid-induced hyperalgesia. There is even some evidence suggesting that prolonged opioid use hinders healing and may increase risk of cancer recurrence.

Paice recommended the following measures when giving cancer patients the full benefit of opioid pain relief in order to minimize risks:

Assess the patient's potential for addiction. Do they smoke, drink, use other drugs, or gamble? Have they done so in the past? Do any of their biologically close relatives demonstrate addictive behavior? Have they been sexually abused (a strong risk factor for addiction)? Do they worry about becoming addicted?

Do a urine tox screen at least annually for each patient on opioids, and more frequently for those at a higher risk of addiction, to assess whether they are overusing their pain medication or abusing other substances. Use your state's prescription drug management program, available in all states, except Missouri, to check whether your patients are getting multiple opioid prescriptions filled at the same time. (Paice discovered 1 patient was getting hydrocodone from both her and an orthopedic surgeon, from 2 different pharmacies.)

It's important to make sure patients are using their opioids for pain, rather than to relieve anxiety or help them sleep. "It's acceptable to take your medication before bed if you have vertebral fractures," and know that you'll have pain when you lie down, Paice said. "But if you're taking it every night at 9 to make you sleepy, we have a problem."

 Illicit users of prescription opioids get their drugs from legitimate users, so patients need to be on guard. If patients come up short on their pills, they may be taking too many—or maybe someone is stealing them, Paice said. "I tell patients, 'Maybe it's not your grandkids, but it's their friends.'" Patients who have pills they no longer need should dispose of them through a formal drug take-back program.

All cancers (excluding non-melanoma skin cancer) estimated incidence, mortality and prevalence worldwide in 2012. International Agency for Research on Cancer website. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed September 14, 2017.

Heathcote LC, Eccleston C. Pain and cancer survival: a cognitive-affective model of symptom appraisal and the uncertain threat of disease recurrence. Pain. 2017;158(7):1187-1191. doi: 10.1097/j.pain. 0000000000000872.

Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain — United States, 2016. JAMA. 2016;315(15):1624-1645. doi: 10.1001/jama.2016.1464.

Extra vigilance, careful management, and an emphasis on empathy makes treating cancer pain more effective during an opioid addiction epidemic.

"Opioid Epidemic" Increases Challenge of Treating Cancer Pain

William F. Symmans, MD, professor of Pathology, The University of Texas MD Anderson Cancer Center, discusses the staging system for patients with breast cancer. 

With the anticipated 8th addition of the staging system, a current question is what is to be expected in the staging setting? A lot of attention has been placed in the post-neoadjuvant staging, discusses Symmans.  

We can anticipate greater clarity for the practicing pathologists and more solid guidelines for defining how to measure tumor burden in the challenging area of breast pathology going forward, explains Symmans. 

William F. Symmans, MD, professor of Pathology, The University of Texas MD Anderson Cancer Center, discusses the staging system for patients with breast cancer.

Dr. Symmans on the Staging System for Breast Cancer

Judith Paice, PhD, RN, director of the Cancer Pain Program, Division of Hematology-Oncology, and research professor of Medicine, Northwestern University, discusses the pain management for patients with breast cancer.

Cancer pain management has become complicated by the opioid misuse epidemic, explains Paice. As a result, patients can be fearful of taking pain medications and clinicians, similarly, can be fearful of prescribing these medicines.

There is misinformation that needs to be clarified, discusses Paice. Clinicians need to assess a patient

Lynn Sage Breast Cancer Symposium | Conference