News & Analysis
when a patient has severe enough pain to require daily, around-the-clock, long-term opioid therapy. The new labels will also caution that there is a risk of addiction, abuse, misuse, overdose, and death associated with using these medications, even at recommended doses. Accordingly, the labels will note that these drugs should be reserved for patients who cannot tolerate or get adequate relief from other pain treatments. Douglas Throckmorton, MD, of the FDA Center for Drug Evaluation and Research, said during the briefing that significant risks are associated with improper patient selection or inappropriate use of these medications. “They should be reserved for patients without an alternative,” he said. The FDA also stated that long-acting and extended-release opioids should not be given for “as-needed use.” The new labels will carry a boxed warning alerting physicians about the risk of neonatal abstinence syndrome among infants born to mothers taking opioid pain medications. Throckmorton noted that some pregnant women have a legitimate need for these
medications, but health care teams need to be aware of and work to manage the risks associated with such use. Makers of these long-acting and extended-release opioids are being required to conduct long-term studies to assess the risks associated with using their products for extended periods and to provide information about the relationship between the dose and adverse events, said Throckmorton. He said the FDA expects to have some data about long-term use by the end of 2015, although some studies may take longer. Andrew Kolodny, MD, president of PROP and chief medical officer at Phoenix House, a nonprofit addiction treatment organization, calledtheFDAactionsa“smallstepintheright direction” that would help reduce some inappropriate prescribing. But he cautioned during an interview that the changes “leave the door wide for opioid manufacturers to continuepromotinglong-termandhigh-doseopioid prescribing for conditions where the benefits may not outweigh the risks.” For example, he noted, most opioid prescribing is for chronic noncancer pain con-
ditions, such as fibromyalgia, low back pain, and chronic headache, for which opioids may not be effective or appropriate. Kolodny also noted that the FDA did not make changes to the labels of immediate-acting opioid medications such as hydrocodone or oxycodone, which are among the most prescribed drugs in the United States. Throckmorton said that the FDA is focusing on extended-release and long-acting opioids because the agency believes they play a disproportionate role in overdose and abuse. But Kolodny questioned that, saying, “I don’t think that is true; I don’t think there is any scientific evidence.” Throckmorton said the agency would like to encourage physicians and patients to more thoroughly discuss the benefits and risks of using long-acting or extendedrelease opioid pain medications. “Physicians and patients need to talk about the patient’s individual needs to make sure the patient requires [an extendedrelease or long-acting opioid] product to live and function better,” he said.
Women With Breast Cancer Who Opt for Contralateral Prophylactic Mastectomy May Overestimate Future Risk Jill Jin, MD, MPH
Y
oungerwomendiagnosedwithbreast cancer in a single breast who chose to undergo prophylactic mastectomy of the other breast had skewed perceptions aboutboththeriskofdevelopingcontralateral breastcancerandthebenefitsassociatedwith contralateralprophylacticmastectomy(CPM), according to a new study (Rosenberg S et al. Ann Intern Med. 2013;159[6]:373-381). Over the last 2 decades, the number of womenwithunilateralbreastcancerchoosing to undergo CPM has been increasing. Traditionally, prophylactic surgery has been performedmostlyinwomenwithmutationsinthe BRCA genes, which are known to significantly increaseoveralllifetimeriskofbreastandovarian cancer. In recent years, however, more young women with unilateral breast cancer who lack such mutations have also been requesting CPM. The researchers surveyed 123 women aged 40 years or younger diagnosed with unilateral breast cancer from 2006 to 2010 1548
in Massachusetts who underwent CPM. The women were questioned 2 years after their surgery about their reasons for choosing CPM, perceptions and knowledge of contralateral breast cancer risk and of CPM benefit, and overall satisfaction and confidence in their decision. The most common reasons women chose CPM were desire to decrease their risk of contralateral breast cancer, desire to improve survival, and peace of mind. No definitive data to date have shown a survival benefit for CPM in women without a genetic predisposition. When asked directly whether women who get CPM live longer than women who do not, however, only 18% of women in the study answered “yes.” In other words, there seemed to be cognitive dissonance between knowledge of survival statistics and desire to improve survival. Of the 123 women, 30 (24%) had mutations in a BRCA gene. Those women with no BRCA mutations estimated they would have
JAMA October 16, 2013 Volume 310, Number 15
Downloaded From: http://jama.jamanetwork.com/ by a Otterbein University User on 05/30/2015
faced a 10% risk in developing contralateral breastcancerover5yearswithoutCPM,while those with BRCA mutations estimated a 20% risk. The actual rate for women without BRCA mutations is much lower, approximately 2% to 4% over 5 years. For those with BRCA mutations, the risk is much higher and varies based on the specific mutation and family history. Therefore, the study concluded that women who do not have BRCA mutations in particular tend to overestimate their risk of contralateral breast cancer. Overall satisfaction with their decision to undergo CPM was high: 80% of women were extremely confident about it and 90% would have chosen CPM again. Given that the effect of bilateral mastectomy on quality of life is greater in younger women than in older women, the authors highlighted potential future roles that decision aids and physician counseling may have in helping younger women make more informed decisions regarding CPM. jama.com
when a patient has severe enough pain to require daily, around-the-clock, long-term opioid therapy. The new labels will also caution that there is a risk of addiction, abuse, misuse, overdose, and death associated with using these medications, even at recommended doses. Accordingly, the labels will note that these drugs should be reserved for patients who cannot tolerate or get adequate relief from other pain treatments. Douglas Throckmorton, MD, of the FDA Center for Drug Evaluation and Research, said during the briefing that significant risks are associated with improper patient selection or inappropriate use of these medications. “They should be reserved for patients without an alternative,” he said. The FDA also stated that long-acting and extended-release opioids should not be given for “as-needed use.” The new labels will carry a boxed warning alerting physicians about the risk of neonatal abstinence syndrome among infants born to mothers taking opioid pain medications. Throckmorton noted that some pregnant women have a legitimate need for these
medications, but health care teams need to be aware of and work to manage the risks associated with such use. Makers of these long-acting and extended-release opioids are being required to conduct long-term studies to assess the risks associated with using their products for extended periods and to provide information about the relationship between the dose and adverse events, said Throckmorton. He said the FDA expects to have some data about long-term use by the end of 2015, although some studies may take longer. Andrew Kolodny, MD, president of PROP and chief medical officer at Phoenix House, a nonprofit addiction treatment organization, calledtheFDAactionsa“smallstepintheright direction” that would help reduce some inappropriate prescribing. But he cautioned during an interview that the changes “leave the door wide for opioid manufacturers to continuepromotinglong-termandhigh-doseopioid prescribing for conditions where the benefits may not outweigh the risks.” For example, he noted, most opioid prescribing is for chronic noncancer pain con-
ditions, such as fibromyalgia, low back pain, and chronic headache, for which opioids may not be effective or appropriate. Kolodny also noted that the FDA did not make changes to the labels of immediate-acting opioid medications such as hydrocodone or oxycodone, which are among the most prescribed drugs in the United States. Throckmorton said that the FDA is focusing on extended-release and long-acting opioids because the agency believes they play a disproportionate role in overdose and abuse. But Kolodny questioned that, saying, “I don’t think that is true; I don’t think there is any scientific evidence.” Throckmorton said the agency would like to encourage physicians and patients to more thoroughly discuss the benefits and risks of using long-acting or extendedrelease opioid pain medications. “Physicians and patients need to talk about the patient’s individual needs to make sure the patient requires [an extendedrelease or long-acting opioid] product to live and function better,” he said.
Women With Breast Cancer Who Opt for Contralateral Prophylactic Mastectomy May Overestimate Future Risk Jill Jin, MD, MPH
Y
oungerwomendiagnosedwithbreast cancer in a single breast who chose to undergo prophylactic mastectomy of the other breast had skewed perceptions aboutboththeriskofdevelopingcontralateral breastcancerandthebenefitsassociatedwith contralateralprophylacticmastectomy(CPM), according to a new study (Rosenberg S et al. Ann Intern Med. 2013;159[6]:373-381). Over the last 2 decades, the number of womenwithunilateralbreastcancerchoosing to undergo CPM has been increasing. Traditionally, prophylactic surgery has been performedmostlyinwomenwithmutationsinthe BRCA genes, which are known to significantly increaseoveralllifetimeriskofbreastandovarian cancer. In recent years, however, more young women with unilateral breast cancer who lack such mutations have also been requesting CPM. The researchers surveyed 123 women aged 40 years or younger diagnosed with unilateral breast cancer from 2006 to 2010 1548
in Massachusetts who underwent CPM. The women were questioned 2 years after their surgery about their reasons for choosing CPM, perceptions and knowledge of contralateral breast cancer risk and of CPM benefit, and overall satisfaction and confidence in their decision. The most common reasons women chose CPM were desire to decrease their risk of contralateral breast cancer, desire to improve survival, and peace of mind. No definitive data to date have shown a survival benefit for CPM in women without a genetic predisposition. When asked directly whether women who get CPM live longer than women who do not, however, only 18% of women in the study answered “yes.” In other words, there seemed to be cognitive dissonance between knowledge of survival statistics and desire to improve survival. Of the 123 women, 30 (24%) had mutations in a BRCA gene. Those women with no BRCA mutations estimated they would have
JAMA October 16, 2013 Volume 310, Number 15
Downloaded From: http://jama.jamanetwork.com/ by a Otterbein University User on 05/30/2015
faced a 10% risk in developing contralateral breastcancerover5yearswithoutCPM,while those with BRCA mutations estimated a 20% risk. The actual rate for women without BRCA mutations is much lower, approximately 2% to 4% over 5 years. For those with BRCA mutations, the risk is much higher and varies based on the specific mutation and family history. Therefore, the study concluded that women who do not have BRCA mutations in particular tend to overestimate their risk of contralateral breast cancer. Overall satisfaction with their decision to undergo CPM was high: 80% of women were extremely confident about it and 90% would have chosen CPM again. Given that the effect of bilateral mastectomy on quality of life is greater in younger women than in older women, the authors highlighted potential future roles that decision aids and physician counseling may have in helping younger women make more informed decisions regarding CPM. jama.com
