Elizabeth Gardner

EXTRA VIGILANCE, CAREFUL MANAGEMENT and emphasizing empathy can make treatment for cancer pain more effective during an opioid addiction epidemic, said Judith A. Paice, Ph.D., RN, during a presentation at the 19th Annual Lynn Sage Breast Cancer Symposium, in September.

Although it’s understandable in the current climate that both patients and physicians might approach opioid use with extra caution, this 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, and 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 published in Pain, estimating that 40 percent of cancer survivors live with some degree of pain and that 5 to 10 percent have severe chronic pain that limits their ability to function. One in five childhood cancer survivors reports pain.

Amid the discussion about opioid overuse, Paice is concerned that some patients remain undertreated due to addiction fears that do not match the evidence. “After (the singer) 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. Although long-term opioid addiction often begins with the use of prescription painkillers like oxycodone, Paice cited research showing that three of four such addicts acquired those pills illicitly rather than through a legitimate prescription.

The Centers for Disease Control issued guidelines for opioid treatment last year, and Paice said that both primary care physicians and insurance companies sometimes treat them 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 three-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 from prescription opioids has plateaued (although 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,” she said, “because we only prescribed opioids at the end of life.”

These side effects include constipation, mental clouding, upper gastrointestinal symptoms, hormonal problems, sleep apnea and a poorly understood risk of opioid-induced hyperalgesia, a condition that stimulates additional feelings of pain.

There is even some evidence suggesting that prolonged opioid use hinders healing and may increase risk of cancer recurrence.

Paice recommended that health care practitioners who want to give patients the full benefit of opioid pain relief follow some steps to minimize risks. Under her plan, a doctor or nurse would put patients through a screening process before prescribing them an opioid.

To assess your potential for addiction, members of your care team might ask if you or any of your biologically close relatives smoke, drink, use other drugs or gamble, or have done so in the past. They may also ask whether you’ve been sexually abused (a strong risk factor for addiction), or if you worry about becoming addicted.

Once you’ve been prescribed an opioid, Paice suggests that your doctor monitor your use of the drug with a toxicity screening test at once a year to assess whether you are overusing the medication or abusing other substances. Your care team also may check that you’re using your opioids for pain, and not to relieve anxiety or help you 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 p.m.to make you sleepy, we have a problem.”

Illicit users of prescription opioids may try to get their drugs from legitimate users, so patients need to be on guard. If you come up short on your pills, you may be taking too many — or maybe someone is stealing them from you, 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.

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An ongoing opioid epidemic is making it more challenging to treat cancer pain.

A Delicate Balance: Treating Cancer in the Midst of the Opioid Epidemic

POST-SURGICAL TREATMENT FOR hormone-driven breast cancer in younger women usually takes a similar course as the therapy given to older women, but studies are finding that the suppression of ovarian function may not always be needed in those who are premenopausal.

Those results were discussed by Ruth O’Regan, M.D., in September during the 19th Annual Lynn Sage Breast Cancer Symposium.

Patients tend to experience more side effects when they undergo artificially induced menopause, and some research suggests it may have a negligible effect on the success of treatment, said O’Regan, division chief of hematology and medical oncology at the University of Wisconsin School of Medicine and Carbone Cancer Center.

About one in five new cases of breast cancer between 2009 and 2013 were in women under 50, according to national data. The overall post-surgical regimen recommendations are currently the same for premenopausal and postmenopausal women who have estrogen receptor-positive disease, except that for the younger group, they include ways to preserve fertility and minimize side effects from longer-term use of tamoxifen or other agents.

O’Regan reviewed research for several post-surgical regimens, including tamoxifen alone, tamoxifen with ovarian function suppression (through removal of the ovaries, radiation or the use of luteinizing hormone-releasing hormone agonists), and the combination of another kind of estrogen blocker, exemestane, with ovarian function suppression. Results of the SOFT and TEXT trials showed that the regimens were similar in effectiveness among women who had not had chemotherapy, but that they differed significantly when it came to the number of reported side effects.

Exemestane was associated with more musculoskeletal problems and osteoporosis, two side effects that O’Regan said are particularly problematic for younger women who may be on these treatment regimens for much longer periods of time.

The SOFT study specifically compared tamoxifen with and without ovarian suppression. The five-year freedomfrom- breast cancer rate was 95.8 percent for those treated with tamoxifen alone versus 95.1 and 97.1 percent for those treated with tamoxifen or exemestane plus ovarian suppression.

In the three groups, respectively, there were six, seven and three distant recurrences at five years.

Although there was almost no difference in freedomfrom- breast cancer or freedom-from-distant-recurrence rates among women who had not received chemotherapy, ovarian function suppression significantly increased the risk of hot flashes, sweating, insomnia, osteoporosis and hypertension, among other symptoms.

O’Regan noted that patients who undergo induced menopause might be at risk of developing premature coronary artery disease, as well.

However, for women who had received chemotherapy, both studies showed clear improvement in recurrence rates from including ovarian function suppression as part of the post-surgical regimen.

Those treated with tamoxifen alone had a 78 percent five-year freedomfrom- breast cancer rate compared with 82.5 percent and 85.7 percent for those treated with ovarian suppression and tamoxifen or exemestane, respectively.

The freedom from distant recurrence rate was 83.6 percent with tamoxifen alone and 84.8 and 87.8 percent for those treated with ovarian suppression and tamoxifen or exemestane, respectively. Compared with tamoxifen alone, these results were statistically significant.

“Given the added toxicities (of ovarian function suppression), we need a better way of working out which patients need this approach,” O’Regan said.

Several areas still require additional research, O’Regan pointed out, specifically when it comes to biomarkers for identifying the younger women who will benefit from ovarian function suppression. The progesterone receptor and the Ki-67 protein have both shown some promise as biomarkers, but more work is needed.

Additionally, she noted, 10 years of endocrine therapy, which has been shown to be superior to five years, has not yet been compared to ovarian function suppression plus endocrine therapy, also warranting further study.

After surgery, some young women with hormone-driven breast cancer can use estrogen blockers but opt against induced menopause.

A La Carte Options to Treat Breast Cancer

It is important to consider quality of life and survival calculations when treating older patients with HER2-positive or triple-negative breast cancer (TNBC), according to a recent talk at the 2017 Lynn Sage Breast Cancer Symposium.

"The real question isn't how old the patient is, but what their life expectancy is," said geriatric oncologist Hyman Muss, M.D., of the University of North Carolina School of Medicine, at the symposium, which was sponsored by Northwestern University's Robert H. Lurie Comprehensive Cancer Center. "Then you calculate the risks and benefits of toxicity, and then put it all together with the defining goals of treatment. And the goal is not always longevity."

For example, while younger patients can still function reasonably well during chemotherapy and will have time to recover from side effects, older patients may be debilitated to the point where they need to move from independent to assisted living, or even full nursing home care. Moreover, patients older than 65 have significantly greater risk of being hospitalized for side effects from chemotherapy. One study showed that for some regimens, their risk was triple that of patients younger than 65.

"This is the worst thing for an older patient," Muss said. "It can be the beginning of going to a skilled nursing facility, falling and having numerous other problems." Staying out of the hospital may take priority over gaining the benefits of chemotherapy, which may be marginal any way if the patient's tumor is one cm or smaller, Muss said.

More than 40 percent of new breast cancer diagnoses are in women 65 and older. In the United States, the median age for a breast cancer diagnosis is 62 years and the median age of death is 68 years, Muss said. But there are also 3 million breast cancer survivors who are older than 65, according to the SEER database.

For older patients, Muss said, clinicians must ask two questions that they might not ask for younger ones:

What is the patient's life expectancy without cancer?

Using a life expectancy calculator from the University of California at San Francisco, Muss walked through a comparison of two patients in their late 70s. The first had excellent health according to her own assessment, had no health issues besides cancer, and lived entirely independently. Her five-year all-cause mortality risk was between 4 percent and 23 percent. The second, a former smoker, had diabetes and COPD and one hospitalization in the past year, rated her own health as fair. Her five-year mortality risk was 69 percent.

The first patient should receive the same treatment as a younger patient if her cancer is likely to recur within five years, Muss said. The second one has both a higher likelihood of dying from something else before her cancer recurs, and a higher risk of being debilitated by chemotherapy, making the treatment decision much less straightforward.

a tool from the United Kingdom’s National Health Service that helps clinicians and patients evaluate the benefits of various  treatment options following breast cancer surgery. It presents survival estimates with and without adjuvant therapies. The model takes into account all-cause mortality, and recommends adjuvant therapy only for patients with a 5 percent or greater chance of surviving for 10 years. If it's less than 3 percent, adjuvant therapy is not offered at all because the side effects exceed the potential benefit.

While healthy older patients can make treatment choices similar to younger patients, and truly frail ones may need only palliative care, there's an “in between" group that can be treated successfully with some preparation to address their potential vulnerabilities. For example, Muss strongly recommended a cardiology consult if an older patient has risk factors for congestive heart failure. Proactive beta-blockers or ACE inhibitors may help reduce toxicity during treatment.

Muss said sentinel node biopsies might be worth the time and cost to help an older patient decide whether the benefits of chemotherapy are worth the risks and the quality of life impact, especially in cases of triple-negative breast cancers where the tumor is one cm or two cm. "If they say they are absolutely never going to consider chemo, then don't do it," he said. "But sometimes when people say they will never do chemo, it's before the fact, and when they get the results it changes their mind."

Elizabeth Gardner

A Delicate Balance: Treating Cancer in the Midst of the Opioid Epidemic

A La Carte Options to Treat Breast Cancer

Older Patients With Breast Cancer: Tell Your Doctor This

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