3 Questions on…

Answers straight from the experts on the latest news and topics in oncology

Monday, March 5, 2018

With Reshma Jagsi, MD, DPhil, at the University of Michigan

By Sarah DiGiulio

Some people work to put food on the table. Some people work because they love their jobs. Some people work because it gives them a sense of purpose. And a lot of people work for some combination of all of those reasons and more. Getting diagnosed with breast cancer, among other conditions, can cause huge disruptions to this otherwise routine and important part of many people's lives.

That's what led a group of researchers at University of Michigan to investigate how different breast cancer treatments and making different breast cancer treatment decisions affected women's employment. The study was recently published in the journal Cancer (2017;123(24):4791-4799).

"Many more women are undergoing aggressive surgical procedures to treat early-stage unilateral breast cancer these days," the study's lead author Reshma Jagsi, MD, DPhil, Professor and Deputy Chair in the Department of Radiation Oncology and Director of the Center for Bioethics and Social Sciences in Medicine at University of Michigan, Ann Arbor, shared with Oncology Times. Yet, the procedure has not necessarily been shown to improve survival for these women, she added. "Professional societies and physicians are worried about overtreatment because more aggressive procedures do have additional risks."

And the new data she and her colleagues collected show those more intensive treatments can also bear an effect upon employment opportunities and trajectories for women.

"That's why we think the findings of this study are important," Jagsi stated. "When patients are being counseled about surgical treatment options, the potential impact on employment outcomes should be discussed in order to ensure that patients are making choices fully informed about potential consequences."

For the study, the researchers analyzed survey responses from 1,006 women between 20 and 79 who had had a prior stage 0 to stage II breast cancer who had been working before their diagnosis. The survey inquired about treatment decisions, how the women's treatment affected how much work was missed, and whether or not treatment affected the women's decision to stop work during or after treatment.

Here's what Jagsi said are the most important findings—and some key implications of the work.

1. What are the key findings from this study that were not previously known about how breast cancer treatment affects women's work?

"In the relatively recent sample of working-aged women in our study, more than one in five had undergone bilateral mastectomy.

"And we observed a strong association between more aggressive treatments, especially more aggressive surgery, and missed work. Women who had bilateral mastectomy with reconstruction to treat their early-stage breast cancer had nearly eight times the odds of missing over a month of work, and three times the odds of stopping work altogether, as compared to women who received lumpectomy.

"I found the financial impact of missed work to be striking. Nearly one in five (19%) of the patients in our study reported losing 10 percent or more of their annual household income because of missed work since diagnosis of breast cancer."

2. What do these data say about what breast cancer treatments women should choose and how they should make those decisions?

"Women diagnosed with early-stage breast cancer have a dizzying array of options from which to choose. What is important is for them to be fully informed of what to expect, both in terms of benefits and in terms of risks, from each approach. And impact on employment is a potentially important consideration that women should be given information about so they can take that into account when making their decisions.

"Further research needs to evaluate interventions that help physicians communicate clearly about the information needed by patients making complex treatment decisions like these. Follow-up research to examine the longer-term outcomes of the patients in the current study will also be important to provide a more complete picture of their experiences, which can be valuable in guiding patients making similar decisions in the future."

3. What would you say is most important for all practicing oncologists and cancer care providers to know about this research?

"Practical actions by clinicians are essential in order to reduce the overuse of aggressive treatments.

"It may be very helpful for practitioners to have access to data on the real-life employment experiences of other women for use when counseling patients about what they might expect with different treatment decisions. After all, understanding the employment effects of different surgical decisions is critically important to the many patients who consider surgical treatments more aggressive than medically necessary to treat their cancer.

"Surgeons who treat patients with breast cancer can now provide compelling evidence that women who undergo mastectomy experience considerably higher risks of missed work than those who receive breast-conserving therapy. Moreover, the current data allow quantification of the financial impact of this missed work, and these data may be very useful in helping patients understand the full impact of treatment decisions."

Tuesday, February 20, 2018

With Abiola Ibraheem, MD, of University of Chicago Medicine

By Sarah DiGiulio

"After 3 decades of interventions in racial/ethnic health care disparity outcomes, statistics continue to show overall death rate disparities between black and white patients for virtually all cancer types," coauthors Abiola Ibraheem, MD, a third-year oncology fellow, and Blase Polite, MD, Associate Professor of Medicine, both at the University of Chicago Medicine, write in a recent editorial (Cancer 2017;123(24):4752-4756).

The disparity does not end there. Black patients are also more likely to be diagnosed with cancers at later stages than white patients. Black patients are more likely to die of their cancers than white patients. And though patients with cancer who are Hispanic, Asian, and Pacific Islander have lower rates of incidence of cancer and suffer fewer deaths compared with patients who are white, they are more likely to be diagnosed at a later stage.

That's all according to the latest cancer incidence data available, including from the Cancer Statistics 2017 report from the American Cancer Society (CA Cancer J Clin 2017;67:7-30).

One major problem, which Ibraheem and Polite focus on in their editorial, is that black patients and other minorities are underrepresented in cancer clinical trials. One study from the FDA that the coauthors cite in their editorial found that, for new anticancer drugs approved between 2011 and 2016, blacks represented only 5 percent of participants in clinical trials supporting those approvals.

The solution to this problem needs to focus on multiple strategies aimed at multiple levels of the issue: solutions that focus on the patient, provider, and trial design, according to Ibraheem and Polite. They say such solutions might include the following:

  • better health education tools about cancer clinical trials for patients;
  • using patient navigation to improve delivery of clinical trial education;
  • improving quality of communication between patients and providers to reduce and prevent potential mistrust (which means better and more education for providers about diversity);
  • billing codes (from the federal government through the Medicare program) that clinicians can use to get reimbursed for the additional time required for discussion, consent, and getting patients enrolled in clinical trials;
  • better evaluating patients for eligibility in clinical trials (and not excluding minority patients who may have comorbidities that don't threaten the scientific integrity of that protocol); and
  • recruitment targets for racial and ethnic minority patients for new drugs seeking FDA approval (which would create incentives for pharmaceutical companies to also get involved and help pay for other individual action items that would push the needle on this issue and improve minority clinical trial participation).

In an interview with Oncology Times, Ibraheem elaborated on this issue and why addressing it now is critical.

1. Why is this issue such an important one to talk about and better to address now?

"The death rate disparity between African-American and white patients continues to persist despite interventions. [And] cancer therapies are more personalized on a molecular and genetic level, and as such it is now paramount to have minority patients well-represented in clinical trials.

"In recent times, especially in pharma-directed clinical trials, patients with African ancestry have been woefully represented. We may not be clear about the response or toxicity of our new therapies to these patients since they have been sparsely involved in trials. This, in addition to other factors, may begin to widen the disparity gap we have worked so hard to improve on. As such, it is important to address this problem sooner than later."

2. What will help solve this problem and what are the most interesting ongoing efforts now in the works?

"Before the FDA approves therapies, there should be a certain percentage of represented minorities relative to the incidence for that cancer subtype.

"Multiple policies were put into place—such as the NIH Revitalization Act 1993 and the FDA Modernization Act of 1997—that encouraged the representation of minority groups in clinical trials, thereby enhancing heterogeneity of trial populations. An important initiative, The Minority-Based Community Clinical Oncology Program, was created by the NIH in September 1990 to expand the NCI's clinical trials network to minority populations with a major goal of reducing racial disparities in cancer incidence, treatment, survival, and mortality rates.

"These aforementioned initiatives were better functioning when clinical trials were conducted by cooperative groups. Now we have seen a shift to trials being conducted by pharmaceutical industries in multiple sites and emphasis is not laid on enrolling minority patients."

3. What is the bottom line that practicing oncologists and cancer care providers should know about this problem and what they can do to help address it?

"We need to pay attention to the clinical trials [for the drugs and therapies they're using] and interpreting them in the context of our minority patients.

"For providers who write clinical trial protocols or place patients on clinical trials, we need to make an effort in actively recruiting minority patients on study."

Monday, February 5, 2018

With Noelle Loconte, MD, Associate Professor of Medicine, Division of Hematology/Oncology, University of Wisconsin

By Sarah DiGiulio

ASCO recently issued the organization's first statement on alcohol and cancer, which was published in the Journal of Clinical Oncology (2017;36:83-93).

"Alcohol can increase your cancer risk," the statement's lead author Noelle LoConte, MD, Associate Professor of Medicine in the Division of Hematology/Oncology at University of Wisconsin, told Oncology Times. "We aren't saying 'don't drink,' but we are saying know your risks and talk to your health team about what amount of alcohol makes sense for you given your medical history and family history.

"And even cutting back without quitting will decrease your risk," she added.

According to the statement, between 5 and 6 percent of new cancers and cancer deaths globally can directly be attributed to alcohol.

The new statement includes a review of the most recent evidence on the link between drinking alcohol and cancer incidence. It also includes relevant findings from ASCO's recent National Cancer Opinion Survey about public perception on the link between drinking and cancer. And the statement includes several evidence-based policy recommendations to reduce excessive alcohol consumption.

Here's what else LoConte said was important to know about the new statement.

1. This is ASCO's first statement on the link between alcohol use and cancer. Why now?

"Yes, this is the first statement from ASCO on alcohol and cancer. This came to my attention while talking to my peers about what cancers were caused by alcohol (most did not know for sure). And then in reviewing our policy statements, the ASCO Prevention Committee realized we did not have a statement on alcohol, so I offered to help to write it.

"Around the same time, ASCO did a large survey which showed only 30 percent of people surveyed were aware of the link. So we also viewed this as an opportunity to raise awareness for both providers and the lay public."

2. Alcohol is widely consumed and many (even health-focused) organizations support drinking alcohol in moderation. Is ASCO calling for a sea change?

"We (myself and the statement coauthors) could not find substantial scientific evidence that there are 'heart health' benefits to alcohol. We also consulted with preventive cardiologists, who agreed. In fact, the American Heart Association (AHA) no longer recommends red wine for heart health. We are supporting the recommendations of the American Cancer Society and the AHA for women to drink no more than one drink per day, and for men no more than two per day. Also, if you don't drink, don't start.

"Do I think people ought to abstain completely? No, absolutely not. I liken it to skin cancer. We know sun exposure increases risk of skin cancer, but I don't tell people to not go outside in the sun. Rather, think about whether you can use sunscreen and shade and long sleeves when you can.

"It has been interesting to see people fight back against the science supporting alcohol as a carcinogen. I thought I might get push back, but I was not anticipating that people would question that alcohol is a carcinogen. (The Lancet wrote a really nice editorial supporting our statement that says this much [2017;390:2215-2218].)"

3. What would you say is the bottom line message that practicing oncologists and cancer care providers should know about this statement—and about the link between drinking alcohol and cancer?

"One of the areas of needed research that we feel is urgent is what ongoing alcohol use does for current oncology patients. Should they stop drinking? Cut down? Continue? Increase? There is a bit of data (cited in the statement) that alcohol use increases the rate of head and neck cancer recurrence, as well as overall mortality—but there is also data saying it may reduce or increase breast cancer recurrence. We really need better studies to answer this question for oncologists to know how to counsel their patients.

"The role of the oncologist now is to be vocal in their community about the risk of alcohol and cancer and support local policy strategies aimed at reducing high-risk alcohol consumption to decrease the number of patients diagnosed with cancer.

"For those that do prevention work, addressing alcohol use may be a strategy that can be applied in your clinic to reduce someone's risk of developing cancer."

Friday, January 19, 2018

With Kenneth Offit, MD, Chief of the Clinical Genetics Service at Memorial Sloan Kettering Cancer Center

By Sarah DiGiulio

Identifying inherited genetic mutations known to predispose an individual to a higher risk of certain cancers has opened up vast new opportunities for screening patients for cancer risk earlier and advising them on steps and actions that can be taken to lower cancer risk. The implications for preventive cancer care are immense.

And now, as genetic testing for such mutations becomes part of standard practice, a recent study investigated how well current guidelines in this area are working. The data suggests that in some patients with advanced cancer broader sequencing of germline and tumor DNA for cancer-related genes may detect more potentially clinically significant heritable mutations than the approach recommended in current guidelines: a more targeted sequencing that only looks at the tumor DNA (and not the germline DNA).

In a sample of 1,040 patients with advanced cancer, 182 (17.5%) had clinically actionable inherited mutations (as identified via tumor DNA and germline DNA testing). Yet, 55.5 percent of the patients in that subset (101) would not have found out about those mutations if they had undergone DNA sequencing recommended in current guidelines. The study was published in the Journal of the American Medical Association (2017;318:806-815).

"The high proportion of findings that were unanticipated by the guidelines-based testing was certainly striking," Kenneth Offit, MD, Chief of the Clinical Genetics Service and Robert and Kate Niehaus Chair in Inherited Cancer Genomics at Memorial Sloan Kettering Cancer Center, New York City, told Oncology Times.

Offit noted that the research presented a logistical challenge, as patients had to be provided with increased genetic counseling services to understand the options they had to learn about potential genetic mutations in their tumors and in their normal non-cancerous DNA. Nevertheless, these findings are significant—and have implications for practice, including how to potentially update future guidelines.

Here's what else he shared about this research and why it's important.

1. What was the goal of your research when you set out to do this study?

"Oncologists are increasingly performing sequencing of tumors to identify targeted therapies [that might help a certain patient]. To be most accurate, this also involves sequencing 'normal' DNA at the same time. The goal of this project was to determine the prevalence of inherited cancer predisposing mutations in patients with advanced cancer tested 'agnostically,' regardless of family history. The pressing question we sought to answer was to determine what proportion of inherited genetic mutations we would have 'missed' if we had used standard family history and 'phenotypic' criteria for testing instead of the 'agnostic' approach.

"This study was important to do now because some academic and commercial companies either do not test normal DNA at the time of tumor testing, or do not return these results. We were seeking an evidence base to learn the advantages of returning this information."

2. You found that, indeed, you would have "missed" a significant number of those inherited mutations. What are the implications of that?

"We found a relatively high burden of clinically actionable inherited mutations—17.5 percent—in patients with advanced disease. We broke the data down by ancestry—as individuals descended from those of Ashkenazi Jewish (non-Jewish European) ancestries have certain 'founder' mutations at higher frequency.

"We then found that between a third and half of mutations detected would not have been predicted by our guidelines-based rules. We also found that a subset of patients had clinically actionable inherited mutations that impacted discussion of targeted treatment. For example, PARP inhibitors or checkpoint blockade drugs were discussed in 38 of the 182 patients with inherited mutations.

"These findings will need to be confirmed by other groups doing this same type of tumor-normal sequencing. We need to prove, using laboratory-based or epidemiology approaches, that some of the unusual mutations detected using this 'agnostic' approach are indeed linked to the cancers in these families. Until this is done, we should not change guidelines.

"But it is fair to say that guidelines are already allowing broader 'panel'-based approaches for those with certain types of cancer. How broad, or how focused, these panels should be remains to be determined."

3. What is the most important takeaway for practicing oncologists and cancer care providers to know about this research?

"To guide practice, all of these new genetic data need to be used in a decision-analysis type model that weighs cost as well as benefit. I think it is fair to say that this type of broad genetic screening is the most sensitive. But for the clinician in practice now, using family history information has been the accepted and cost-efficient way to go.

"For large cancer centers committed to precision medicine and tumor-sequencing approaches, and for patients seeking this type of 'cutting-edge' approach, I think this study makes a strong argument to return genetic results to patients to target their cancer treatment and to guide their families to take preventive action."

Friday, January 5, 2018

With Kevin S. Hughes, MD, FACS, at Massachusetts General Hospital

By Sarah DiGiulio

The time is now for population-level screening for hereditary cancer susceptibility mutations. That's the argument from Kevin S. Hughes, MD, FACS, Co-Director of the Avon Foundation Comprehensive Breast Evaluation Center at Massachusetts General Hospital, Boston, who penned a recent editorial in the Journal of Clinical Oncology (2017;35:3789-3791).

"Our problem, which desperately cries out for a solution, is that huge numbers of high-risk patients who could be identified by genetic testing are instead developing cancer and often dying of that disease," writes Hughes, who is also Associate Professor of Surgery at Harvard Medical School and Medical Director of the Bermuda Cancer Genetics and Risk Assessment Clinic.

Hughes' article is published in the same issue of JCO as a recent study that estimated the rate of patients in the U.S. who are at high risk of having heritable mutations that have been linked to breast or ovarian cancer and who have not been tested for those mutations (2017;35:3800-3806). That research, led by Christopher Childers, MD, a resident physician in the Department of Surgery at the David Geffen School of Medicine at UCLA, found that fewer than one in five individuals with a history of breast cancer or ovarian cancer who meet the National Comprehensive Cancer Network criteria for testing have actually undergone genetic testing—and most patients had never discussed genetic testing with a health care provider.

"Genetic testing is becoming the norm for medical care, whether it be cancer susceptibility, susceptibility to 'benign' genetic diseases (such as cardiomyopathy, etc.), risk of genetic diseases in newborns, pharmacogenetics, or somatic mutations in tumors," Hughes told Oncology Times. "Our failure to get the right patients [in oncology] tested requires a major change in our approach."

Here's what else Hughes shared about why this issue is so urgent.

1. Were you surprised by the findings from Childers et al.? Why is addressing this underutilization of genetic testing in cancer so important now?

"They are not surprising. Huge amounts of ink have been spilled on the risks and harms of cancer genetic testing. Little has been written about how poorly we were actually doing bringing this major aspect of medical care to our patients. The end result has been caution and slow uptake of a lifesaving test.

"Tremendous good could be done if everyone who needed cancer genetic testing was tested and managed appropriately. Our current system concentrates so strongly on the possible harms of testing and the complexity of testing that we lose sight of the benefits.

"It is time to do this. The world has changed. DNA sequencing is cheap and getting cheaper. Childers' paper shows how poorly we have done and that, simultaneously, the genetics professionals are about to be bypassed by inexpensive and ubiquitous testing. Tumor sequencing, whole genome sequencing, panel testing, whole exome sequencing, and direct-to-consumer testing are about to wash over the current pre-test counseling system and make it obsolete.

"Testing will be the norm and everyone will have it done. We need to understand that and get ahead of it, not try to stop it."

2. You argue that the benefit of genetic testing is well-proven. What are the main reasons (given its proven efficacy) it has not been more widely utilized?

"We have concentrated on purported harms and tried to block use of the test at the population level. It is obvious that some cases will be managed incorrectly whether tested by a physician or a genetic counselor. The media and the literature concentrate on a hand full of cases where something was done wrong. Tremendous attention was paid [for example] to a case where a woman had her breasts and uterus removed inappropriately. This is a case where education and support of physicians doing testing was sorely needed.

"The vast majority of the hundreds of thousands of patients tested were managed appropriately, but this case is what is used to dissuade patients and doctors from testing.

"[And] requiring every patient see a genetic counselor before testing is a major barrier. In cities like Boston, it [can take] months to see a genetic counselor (if you do not have cancer)—and requires taking more time off from work and making another trip into the hospital. In rural areas, it might take hours to get to a counselor. Phone counseling is available, but is not used extensively. Testing at the point of care would markedly increase uptake. As best I can tell, cancer genetic testing is the only area where seeing a counselor is felt by some to be required before testing. Prenatal testing, neurologic genetic disease testing, cardiac genetic disease testing, tumor sequencing, and pharmacogenomic testing are done mostly by physicians and genetic counselors to help as needed, such as when tests are positive."

3. What are the next steps that help solve this problem?

"Testing at the point of care would markedly increase uptake. We need to educate physicians regarding the benefits of testing and the need for testing. We need to educate physicians in how to test appropriately rather than tell them they are not able to test. We need decision support tools to help physicians and genetic counselors keep up with the rapid changes (see the tool www.Ask2Me.org).

"But we also have to realize that genetic testing is going to become ubiquitous whether we take the lead or not.

"All aspects of the practice of medicine require a knowledge of genetics. Physicians must assure that their patients get the correct genetic test in a timely fashion and that that information is used to benefit them by helping choose the proper screening, the proper preventive measures, and the proper use of medications. This is not a turf issue, it is good medical care."