Breast Cancer ICYMI

Patients with secondary progressive multiple sclerosis (MS) who are treated with rituximab have significantly lower Expanded Disability Status Scale (EDSS) scores during follow-up and significantly delayed confirmed disability progression, compared with matched controls, according to a retrospective analysis published online Jan. 7 in JAMA Neurology.

The results suggest that “B-cell depletion by rituximab may be therapeutically beneficial in these patients,” said study author Yvonne Naegelin, MD, of the department of neurology at University Hospital Basel, Switzerland, and her colleagues. “A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.”

Research indicates that B cells play a role in the pathogenesis of relapsing-remitting and secondary progressive MS, and rituximab, a monoclonal CD20 antibody, may deplete B cells in the peripheral immune system and CNS. “Owing to the limited treatment options for secondary progressive MS and the extrapolation of results in relapsing-remitting MS and primary progressive MS, rituximab was used off-label for the treatment of secondary progressive MS,” the authors said. They compared disability progression in patients who were treated with rituximab at MS centers in Switzerland with disability of control patients with secondary progressive MS who did not receive rituximab. The control patients were part of an observational cohort study at MS centers in Switzerland and the Netherlands. Data for the present analysis were collected between 2004 and 2017.

The investigators matched rituximab-treated and control patients 1:1 using propensity scores. Matching variables were sex, age, EDSS score, and disease duration at baseline. Rituximab-treated patients had a mean age of 49.7 years, mean disease duration of 18.2 years, and mean EDSS score of 5.9; 59% were women. Controls had a mean age of 51.3 years, mean disease duration of 19.4 years, and mean EDSS score of 5.7; 61% were women.

A covariate-adjusted analysis of the matched set found that rituximab-treated patients had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52). In addition, time to confirmed disability progression was delayed in the rituximab-treated group (hazard ratio, 0.49). “Approximately 75% of untreated and 50% of treated individuals in our cohorts developed clinically significant confirmed progression for the 10-year period,” Dr. Naegelin and her colleagues reported. Complications, mainly related to infections, occurred in five cases during treatment. The researchers did not identify major safety concerns, however.

Dr. Naegelin had no conflict of interest disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.

[email protected]

SOURCE: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.

Patients with secondary progressive multiple sclerosis (MS) who are treated with rituximab have significantly lower Expanded Disability Status Scale (EDSS) scores during follow-up and significantly delayed confirmed disability progression, compared with matched controls, according to a retrospective analysis published online Jan. 7 in JAMA Neurology.

The results suggest that “B-cell depletion by rituximab may be therapeutically beneficial in these patients,” said study author Yvonne Naegelin, MD, of the department of neurology at University Hospital Basel, Switzerland, and her colleagues. “A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.”

Research indicates that B cells play a role in the pathogenesis of relapsing-remitting and secondary progressive MS, and rituximab, a monoclonal CD20 antibody, may deplete B cells in the peripheral immune system and CNS. “Owing to the limited treatment options for secondary progressive MS and the extrapolation of results in relapsing-remitting MS and primary progressive MS, rituximab was used off-label for the treatment of secondary progressive MS,” the authors said. They compared disability progression in patients who were treated with rituximab at MS centers in Switzerland with disability of control patients with secondary progressive MS who did not receive rituximab. The control patients were part of an observational cohort study at MS centers in Switzerland and the Netherlands. Data for the present analysis were collected between 2004 and 2017.

The investigators matched rituximab-treated and control patients 1:1 using propensity scores. Matching variables were sex, age, EDSS score, and disease duration at baseline. Rituximab-treated patients had a mean age of 49.7 years, mean disease duration of 18.2 years, and mean EDSS score of 5.9; 59% were women. Controls had a mean age of 51.3 years, mean disease duration of 19.4 years, and mean EDSS score of 5.7; 61% were women.

A covariate-adjusted analysis of the matched set found that rituximab-treated patients had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52). In addition, time to confirmed disability progression was delayed in the rituximab-treated group (hazard ratio, 0.49). “Approximately 75% of untreated and 50% of treated individuals in our cohorts developed clinically significant confirmed progression for the 10-year period,” Dr. Naegelin and her colleagues reported. Complications, mainly related to infections, occurred in five cases during treatment. The researchers did not identify major safety concerns, however.

Dr. Naegelin had no conflict of interest disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.

[email protected]

SOURCE: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.

Patients with secondary progressive multiple sclerosis (MS) who are treated with rituximab have significantly lower Expanded Disability Status Scale (EDSS) scores during follow-up and significantly delayed confirmed disability progression, compared with matched controls, according to a retrospective analysis published online Jan. 7 in JAMA Neurology.

The results suggest that “B-cell depletion by rituximab may be therapeutically beneficial in these patients,” said study author Yvonne Naegelin, MD, of the department of neurology at University Hospital Basel, Switzerland, and her colleagues. “A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.”

Research indicates that B cells play a role in the pathogenesis of relapsing-remitting and secondary progressive MS, and rituximab, a monoclonal CD20 antibody, may deplete B cells in the peripheral immune system and CNS. “Owing to the limited treatment options for secondary progressive MS and the extrapolation of results in relapsing-remitting MS and primary progressive MS, rituximab was used off-label for the treatment of secondary progressive MS,” the authors said. They compared disability progression in patients who were treated with rituximab at MS centers in Switzerland with disability of control patients with secondary progressive MS who did not receive rituximab. The control patients were part of an observational cohort study at MS centers in Switzerland and the Netherlands. Data for the present analysis were collected between 2004 and 2017.

The investigators matched rituximab-treated and control patients 1:1 using propensity scores. Matching variables were sex, age, EDSS score, and disease duration at baseline. Rituximab-treated patients had a mean age of 49.7 years, mean disease duration of 18.2 years, and mean EDSS score of 5.9; 59% were women. Controls had a mean age of 51.3 years, mean disease duration of 19.4 years, and mean EDSS score of 5.7; 61% were women.

A covariate-adjusted analysis of the matched set found that rituximab-treated patients had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52). In addition, time to confirmed disability progression was delayed in the rituximab-treated group (hazard ratio, 0.49). “Approximately 75% of untreated and 50% of treated individuals in our cohorts developed clinically significant confirmed progression for the 10-year period,” Dr. Naegelin and her colleagues reported. Complications, mainly related to infections, occurred in five cases during treatment. The researchers did not identify major safety concerns, however.

Dr. Naegelin had no conflict of interest disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.

[email protected]

SOURCE: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

Cladribine tablets (3.5 mg/kg) have a favorable adverse event profile and are safe as monotherapy for relapsing remitting multiple sclerosis, according to an integrated analysis of several clinical trials published in Multiple Sclerosis and Related Disorders.

The drug causes transient lymphopenia, as is to be expected from its mechanism of action, but most patients who receive cladribine do not have grade 3 or 4 lymphopenia, the authors wrote. In general, cladribine is not associated with an increased risk of infections or malignancy.

Data indicate that cladribine’s mechanism of action contributes to its durable clinical effect, despite the brief treatment periods. Clinical trials have provided information about the treatment’s safety and tolerability. To examine the treatment’s long-term safety, Stuart Cook, MD, of New Jersey Medical School, Newark, and his colleagues pooled data for patients with multiple sclerosis (MS) treated with cladribine tablets (3.5 mg/kg) as monotherapy or placebo in three phase 3 clinical trials (CLARITY, CLARITY Extension, and ORACLE-MS) and followed up in the PREMIERE registry. The investigators called these patients the monotherapy oral cohort.

To investigate the potential associations between cladribine and rarer adverse events such as malignancies, Dr. Cook and his colleagues examined data from patients with MS who received cladribine, regardless of the formulation or route of administration, or placebo (the all-exposed cohort). This cohort included data from the ONWARD trial, in which patients received cladribine tablets or placebo in combination with interferon-beta, as well as data from five trials in which patients received parenteral cladribine or placebo.

The monotherapy oral cohort included 923 patients who received cladribine and 641 who received placebo. The median age at enrollment in this cohort was approximately 36 years. The majority of patients were women and disease characteristics were balanced between arms. The all-exposed cohort included 1,926 patients who received cladribine and 802 who received placebo. The demographic characteristics of this cohort were similar to those of the monotherapy oral cohort.

In the monotherapy oral cohort, the incidence rate of treatment-emergent adverse events, in adjusted adverse events per 100 patient-years, was 103.29 for the active group versus 94.26 for controls. Lymphopenia (7.94 vs. 1.06) and decreased lymphocyte count (0.78 vs. 0.10) occurred more frequently in the active group than in the placebo group.

Herpes zoster also occurred more frequently in the cladribine group (0.83 vs. 0.20). However, cladribine was not associated with systemic serious disseminated herpes zoster. Furthermore, the investigators found no overall increased risk of infections, including opportunistic infections, with cladribine tablets versus placebo, except for herpes zoster.

In addition, Dr. Cook and his colleagues found no increase in malignancy rates among patients who received cladribine, compared with those who received placebo. They also found no increase in the incidence of malignancies over time in the cladribine group.

The adverse event profile for cladribine tablets (3.5 mg/kg) as monotherapy has been well characterized, the investigators wrote. The results of this analysis are broadly similar to the short-term adverse event results reported in the individual trials.

EMD Serono and Merck Serono, two affiliates of Merck in Darmstadt, Germany, sponsored the study. Merck manufactures cladribine.

[email protected]

SOURCE: Cook S et al. Mult Scler Relat Disord. 2018 Nov 18. doi: 10.1016/j.msard.2018.11.021.

Cladribine tablets (3.5 mg/kg) have a favorable adverse event profile and are safe as monotherapy for relapsing remitting multiple sclerosis, according to an integrated analysis of several clinical trials published in Multiple Sclerosis and Related Disorders.

The drug causes transient lymphopenia, as is to be expected from its mechanism of action, but most patients who receive cladribine do not have grade 3 or 4 lymphopenia, the authors wrote. In general, cladribine is not associated with an increased risk of infections or malignancy.

Data indicate that cladribine’s mechanism of action contributes to its durable clinical effect, despite the brief treatment periods. Clinical trials have provided information about the treatment’s safety and tolerability. To examine the treatment’s long-term safety, Stuart Cook, MD, of New Jersey Medical School, Newark, and his colleagues pooled data for patients with multiple sclerosis (MS) treated with cladribine tablets (3.5 mg/kg) as monotherapy or placebo in three phase 3 clinical trials (CLARITY, CLARITY Extension, and ORACLE-MS) and followed up in the PREMIERE registry. The investigators called these patients the monotherapy oral cohort.

To investigate the potential associations between cladribine and rarer adverse events such as malignancies, Dr. Cook and his colleagues examined data from patients with MS who received cladribine, regardless of the formulation or route of administration, or placebo (the all-exposed cohort). This cohort included data from the ONWARD trial, in which patients received cladribine tablets or placebo in combination with interferon-beta, as well as data from five trials in which patients received parenteral cladribine or placebo.

The monotherapy oral cohort included 923 patients who received cladribine and 641 who received placebo. The median age at enrollment in this cohort was approximately 36 years. The majority of patients were women and disease characteristics were balanced between arms. The all-exposed cohort included 1,926 patients who received cladribine and 802 who received placebo. The demographic characteristics of this cohort were similar to those of the monotherapy oral cohort.

In the monotherapy oral cohort, the incidence rate of treatment-emergent adverse events, in adjusted adverse events per 100 patient-years, was 103.29 for the active group versus 94.26 for controls. Lymphopenia (7.94 vs. 1.06) and decreased lymphocyte count (0.78 vs. 0.10) occurred more frequently in the active group than in the placebo group.

Herpes zoster also occurred more frequently in the cladribine group (0.83 vs. 0.20). However, cladribine was not associated with systemic serious disseminated herpes zoster. Furthermore, the investigators found no overall increased risk of infections, including opportunistic infections, with cladribine tablets versus placebo, except for herpes zoster.

In addition, Dr. Cook and his colleagues found no increase in malignancy rates among patients who received cladribine, compared with those who received placebo. They also found no increase in the incidence of malignancies over time in the cladribine group.

The adverse event profile for cladribine tablets (3.5 mg/kg) as monotherapy has been well characterized, the investigators wrote. The results of this analysis are broadly similar to the short-term adverse event results reported in the individual trials.

EMD Serono and Merck Serono, two affiliates of Merck in Darmstadt, Germany, sponsored the study. Merck manufactures cladribine.

[email protected]

SOURCE: Cook S et al. Mult Scler Relat Disord. 2018 Nov 18. doi: 10.1016/j.msard.2018.11.021.

Cladribine tablets (3.5 mg/kg) have a favorable adverse event profile and are safe as monotherapy for relapsing remitting multiple sclerosis, according to an integrated analysis of several clinical trials published in Multiple Sclerosis and Related Disorders.

The drug causes transient lymphopenia, as is to be expected from its mechanism of action, but most patients who receive cladribine do not have grade 3 or 4 lymphopenia, the authors wrote. In general, cladribine is not associated with an increased risk of infections or malignancy.

Data indicate that cladribine’s mechanism of action contributes to its durable clinical effect, despite the brief treatment periods. Clinical trials have provided information about the treatment’s safety and tolerability. To examine the treatment’s long-term safety, Stuart Cook, MD, of New Jersey Medical School, Newark, and his colleagues pooled data for patients with multiple sclerosis (MS) treated with cladribine tablets (3.5 mg/kg) as monotherapy or placebo in three phase 3 clinical trials (CLARITY, CLARITY Extension, and ORACLE-MS) and followed up in the PREMIERE registry. The investigators called these patients the monotherapy oral cohort.

To investigate the potential associations between cladribine and rarer adverse events such as malignancies, Dr. Cook and his colleagues examined data from patients with MS who received cladribine, regardless of the formulation or route of administration, or placebo (the all-exposed cohort). This cohort included data from the ONWARD trial, in which patients received cladribine tablets or placebo in combination with interferon-beta, as well as data from five trials in which patients received parenteral cladribine or placebo.

The monotherapy oral cohort included 923 patients who received cladribine and 641 who received placebo. The median age at enrollment in this cohort was approximately 36 years. The majority of patients were women and disease characteristics were balanced between arms. The all-exposed cohort included 1,926 patients who received cladribine and 802 who received placebo. The demographic characteristics of this cohort were similar to those of the monotherapy oral cohort.

In the monotherapy oral cohort, the incidence rate of treatment-emergent adverse events, in adjusted adverse events per 100 patient-years, was 103.29 for the active group versus 94.26 for controls. Lymphopenia (7.94 vs. 1.06) and decreased lymphocyte count (0.78 vs. 0.10) occurred more frequently in the active group than in the placebo group.

Herpes zoster also occurred more frequently in the cladribine group (0.83 vs. 0.20). However, cladribine was not associated with systemic serious disseminated herpes zoster. Furthermore, the investigators found no overall increased risk of infections, including opportunistic infections, with cladribine tablets versus placebo, except for herpes zoster.

In addition, Dr. Cook and his colleagues found no increase in malignancy rates among patients who received cladribine, compared with those who received placebo. They also found no increase in the incidence of malignancies over time in the cladribine group.

The adverse event profile for cladribine tablets (3.5 mg/kg) as monotherapy has been well characterized, the investigators wrote. The results of this analysis are broadly similar to the short-term adverse event results reported in the individual trials.

EMD Serono and Merck Serono, two affiliates of Merck in Darmstadt, Germany, sponsored the study. Merck manufactures cladribine.

[email protected]

SOURCE: Cook S et al. Mult Scler Relat Disord. 2018 Nov 18. doi: 10.1016/j.msard.2018.11.021.

Steven M. Baskin, PhD, a clinical psychologist at the New England Institute for Neurology and Headache in Stamford, Connecticut, recently answered the Migraine Resource Center’s questions about the benefits of behavioral therapy in the treatment of migraine and tension-type headache.
 

Alan M. Rapoport, MD: Could you please give a brief description of the 5 best modalities of behavioral therapy for migraine and tension-type headache? 
 

Steven M. Baskin, PhD: The most researched modalities that have a good evidence base for both migraine and tension-type headache (TTHA) are relaxation therapies that often combine abdominal breathing with some form of progressive relaxation, electromyography (EMG) biofeedback therapy where headache patients learn to decrease scalp and neck muscle tension utilizing muscular biofeedback, thermal biofeedback where migraine sufferers learn a way to warm their hands which often creates a low arousal state that may reduce brain hyperexcitability, and cognitive behavioral therapy (CBT) techniques to learn stress management. The combination of behavioral medicine techniques plus preventive pharmacological treatment has been showed to be more efficacious than either treatment alone. (Holroyd KA, et al. Effect of preventive (β blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial. BMJ. 2010;1-12)

CBT to treat insomnia has also been shown to reverse many chronic migraine sufferers back to episodic migraine. (Smitherman TA, et al. Cognitive-Behavioral Therapy for Insomnia to Reduce Chronic Migraine: A Sequential Bayesian Analysis. Headache 2018;58:1052-1059)
 

Dr. Rapoport: How do you identify a patient who may benefit from behavioral therapy over acute medication, and what is the first step that you suggest?
 

Dr. Baskin: Behavioral therapies for migraine management are typically preventive therapies that can and should be combined with medications to control acute attacks. There are behavioral principles that can maximize adherence to abortive agents in order to optimize acute care.
 

Dr. Rapoport: Which tends to work the best for migraine?
 

Dr. Baskin: What works best is to first do a good behavioral assessment of the frequency, duration, intensity, and disability level of their headaches as well as current stress levels, history, and adherence to drug and nondrug therapies, and psychiatric comorbidities. A program should then be developed that includes some combination of pharmacological and behavioral interventions to address these issues. It is important to increase self-efficacy: patients’ belief in the ability to control the headache, belief in the ability to manage emotional reactivity to pain, and belief that they can achieve functionality in the presence of a significant headache disorder.
 

Dr. Rapoport: Who should not have biofeedback therapy?
 

Dr. Baskin: Biofeedback has shown to be effective in treating migraine and TTHA. It has not been shown to be effective in treating trigeminal autonomic cephalgias (TACs) such as cluster headache. Like pharmacological therapies, it is less effective in chronic migraine that is daily and constant. A patient with severe psychiatric disorder should be treated for their psychiatric disorder before beginning biofeedback therapy.
 

Dr. Rapoport: Some doctors see patients twice per week for several months. What is your typical routine for behavioral therapy?
 

Dr. Baskin: We have a variety of programs. For complicated patients, we tend to see them weekly and have a very systematic program of biofeedback and CBT for approximately 12 to 15 sessions. This may include treating psychiatric comorbidities. We see many other patients for 1 or 2 sessions of biofeedback to try to effect physiological learning and for 1 or 2 sessions of CBT to help them manage stressors and learn coping skills that they can use to help manage migraines and life stress.
 

Dr. Rapoport: Does behavioral medicine work best in conjunction with preventive medications, or on its own?

Dr. Baskin: Many patients do well with a behavioral treatment as a preventive therapy and a pharmacologic agent to optimize acute care. I believe that many patients with higher frequency migraine with psychological issues or ongoing stressors do best with a combination of preventive pharmacologic therapy and behavior therapy. Any migraine patient with sleep issues should learn CBT for insomnia. 

Dr. Rapoport: Is there evidence that suggests behavioral therapy can help patients at various ages manage their migraines?

Dr. Baskin: There is both adult and child data on behavioral therapy for migraine.  An excellent study was done in children and adolescents by Powers et al. It showed that adding 10 sessions of CBT to preventive amitriptyline therapy, compared to adding headache education, significantly reduced the number of headache days, level of disability, and kids with a better than 50% decrease in days of headache compared to amitriptyline, plus headache education control in chronic migraine patients.  (Powers SW et al. Cognitive Behavioral Therapy Plus Amitriptyline for Chronic Migraine in Children and Adolescents: A Randomized Clinical Trial. JAMA 2013;310(24):2622-2630)

Dr. Rapoport: A recent MedPage Today article noted that “anxiety may complicate migraine more than depression with greater long-term persistence, greater headache-related disability, and reduced satisfaction with acute therapies.” Could you please elaborate on why this may be the case? 

Dr. Baskin: Anxiety disorders are often based on feeling threat. They are always associated with avoidance behaviors. Headache sufferers with significant anxiety tend to overestimate the probability of danger (migraine) and perceive it as more unmanageable and threatening than objective reality. They are often very sensitive to medication side effects and benign somatic sensations. They sometimes take medications pre-emptively, because of their fear of getting a migraine, which may lead to medication misuse or overuse. The lifetime prevalence of anxiety disorders in migraineurs (ranging from 51-58%) is almost twice that of major depression.

Please write to us at Neurology Reviews Migraine Resource Center ([email protected]) with your opinions.

Alan M. Rapoport, M.D.

Editor-in-Chief

Migraine Resource Center

Clinical Professor of Neurology

The David Geffen School of Medicine at UCLA

Los Angeles, California

Steven M. Baskin, PhD, a clinical psychologist at the New England Institute for Neurology and Headache in Stamford, Connecticut, recently answered the Migraine Resource Center’s questions about the benefits of behavioral therapy in the treatment of migraine and tension-type headache.
 

Alan M. Rapoport, MD: Could you please give a brief description of the 5 best modalities of behavioral therapy for migraine and tension-type headache? 
 

Steven M. Baskin, PhD: The most researched modalities that have a good evidence base for both migraine and tension-type headache (TTHA) are relaxation therapies that often combine abdominal breathing with some form of progressive relaxation, electromyography (EMG) biofeedback therapy where headache patients learn to decrease scalp and neck muscle tension utilizing muscular biofeedback, thermal biofeedback where migraine sufferers learn a way to warm their hands which often creates a low arousal state that may reduce brain hyperexcitability, and cognitive behavioral therapy (CBT) techniques to learn stress management. The combination of behavioral medicine techniques plus preventive pharmacological treatment has been showed to be more efficacious than either treatment alone. (Holroyd KA, et al. Effect of preventive (β blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial. BMJ. 2010;1-12)

CBT to treat insomnia has also been shown to reverse many chronic migraine sufferers back to episodic migraine. (Smitherman TA, et al. Cognitive-Behavioral Therapy for Insomnia to Reduce Chronic Migraine: A Sequential Bayesian Analysis. Headache 2018;58:1052-1059)
 

Dr. Rapoport: How do you identify a patient who may benefit from behavioral therapy over acute medication, and what is the first step that you suggest?
 

Dr. Baskin: Behavioral therapies for migraine management are typically preventive therapies that can and should be combined with medications to control acute attacks. There are behavioral principles that can maximize adherence to abortive agents in order to optimize acute care.
 

Dr. Rapoport: Which tends to work the best for migraine?
 

Dr. Baskin: What works best is to first do a good behavioral assessment of the frequency, duration, intensity, and disability level of their headaches as well as current stress levels, history, and adherence to drug and nondrug therapies, and psychiatric comorbidities. A program should then be developed that includes some combination of pharmacological and behavioral interventions to address these issues. It is important to increase self-efficacy: patients’ belief in the ability to control the headache, belief in the ability to manage emotional reactivity to pain, and belief that they can achieve functionality in the presence of a significant headache disorder.
 

Dr. Rapoport: Who should not have biofeedback therapy?
 

Dr. Baskin: Biofeedback has shown to be effective in treating migraine and TTHA. It has not been shown to be effective in treating trigeminal autonomic cephalgias (TACs) such as cluster headache. Like pharmacological therapies, it is less effective in chronic migraine that is daily and constant. A patient with severe psychiatric disorder should be treated for their psychiatric disorder before beginning biofeedback therapy.
 

Dr. Rapoport: Some doctors see patients twice per week for several months. What is your typical routine for behavioral therapy?
 

Dr. Baskin: We have a variety of programs. For complicated patients, we tend to see them weekly and have a very systematic program of biofeedback and CBT for approximately 12 to 15 sessions. This may include treating psychiatric comorbidities. We see many other patients for 1 or 2 sessions of biofeedback to try to effect physiological learning and for 1 or 2 sessions of CBT to help them manage stressors and learn coping skills that they can use to help manage migraines and life stress.
 

Dr. Rapoport: Does behavioral medicine work best in conjunction with preventive medications, or on its own?

Dr. Baskin: Many patients do well with a behavioral treatment as a preventive therapy and a pharmacologic agent to optimize acute care. I believe that many patients with higher frequency migraine with psychological issues or ongoing stressors do best with a combination of preventive pharmacologic therapy and behavior therapy. Any migraine patient with sleep issues should learn CBT for insomnia. 

Dr. Rapoport: Is there evidence that suggests behavioral therapy can help patients at various ages manage their migraines?

Dr. Baskin: There is both adult and child data on behavioral therapy for migraine.  An excellent study was done in children and adolescents by Powers et al. It showed that adding 10 sessions of CBT to preventive amitriptyline therapy, compared to adding headache education, significantly reduced the number of headache days, level of disability, and kids with a better than 50% decrease in days of headache compared to amitriptyline, plus headache education control in chronic migraine patients.  (Powers SW et al. Cognitive Behavioral Therapy Plus Amitriptyline for Chronic Migraine in Children and Adolescents: A Randomized Clinical Trial. JAMA 2013;310(24):2622-2630)

Dr. Rapoport: A recent MedPage Today article noted that “anxiety may complicate migraine more than depression with greater long-term persistence, greater headache-related disability, and reduced satisfaction with acute therapies.” Could you please elaborate on why this may be the case? 

Dr. Baskin: Anxiety disorders are often based on feeling threat. They are always associated with avoidance behaviors. Headache sufferers with significant anxiety tend to overestimate the probability of danger (migraine) and perceive it as more unmanageable and threatening than objective reality. They are often very sensitive to medication side effects and benign somatic sensations. They sometimes take medications pre-emptively, because of their fear of getting a migraine, which may lead to medication misuse or overuse. The lifetime prevalence of anxiety disorders in migraineurs (ranging from 51-58%) is almost twice that of major depression.

Please write to us at Neurology Reviews Migraine Resource Center ([email protected]) with your opinions.

Alan M. Rapoport, M.D.

Editor-in-Chief

Migraine Resource Center

Clinical Professor of Neurology

The David Geffen School of Medicine at UCLA

Los Angeles, California

Steven M. Baskin, PhD, a clinical psychologist at the New England Institute for Neurology and Headache in Stamford, Connecticut, recently answered the Migraine Resource Center’s questions about the benefits of behavioral therapy in the treatment of migraine and tension-type headache.
 

Alan M. Rapoport, MD: Could you please give a brief description of the 5 best modalities of behavioral therapy for migraine and tension-type headache? 
 

Steven M. Baskin, PhD: The most researched modalities that have a good evidence base for both migraine and tension-type headache (TTHA) are relaxation therapies that often combine abdominal breathing with some form of progressive relaxation, electromyography (EMG) biofeedback therapy where headache patients learn to decrease scalp and neck muscle tension utilizing muscular biofeedback, thermal biofeedback where migraine sufferers learn a way to warm their hands which often creates a low arousal state that may reduce brain hyperexcitability, and cognitive behavioral therapy (CBT) techniques to learn stress management. The combination of behavioral medicine techniques plus preventive pharmacological treatment has been showed to be more efficacious than either treatment alone. (Holroyd KA, et al. Effect of preventive (β blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial. BMJ. 2010;1-12)

CBT to treat insomnia has also been shown to reverse many chronic migraine sufferers back to episodic migraine. (Smitherman TA, et al. Cognitive-Behavioral Therapy for Insomnia to Reduce Chronic Migraine: A Sequential Bayesian Analysis. Headache 2018;58:1052-1059)
 

Dr. Rapoport: How do you identify a patient who may benefit from behavioral therapy over acute medication, and what is the first step that you suggest?
 

Dr. Baskin: Behavioral therapies for migraine management are typically preventive therapies that can and should be combined with medications to control acute attacks. There are behavioral principles that can maximize adherence to abortive agents in order to optimize acute care.
 

Dr. Rapoport: Which tends to work the best for migraine?
 

Dr. Baskin: What works best is to first do a good behavioral assessment of the frequency, duration, intensity, and disability level of their headaches as well as current stress levels, history, and adherence to drug and nondrug therapies, and psychiatric comorbidities. A program should then be developed that includes some combination of pharmacological and behavioral interventions to address these issues. It is important to increase self-efficacy: patients’ belief in the ability to control the headache, belief in the ability to manage emotional reactivity to pain, and belief that they can achieve functionality in the presence of a significant headache disorder.
 

Dr. Rapoport: Who should not have biofeedback therapy?
 

Dr. Baskin: Biofeedback has shown to be effective in treating migraine and TTHA. It has not been shown to be effective in treating trigeminal autonomic cephalgias (TACs) such as cluster headache. Like pharmacological therapies, it is less effective in chronic migraine that is daily and constant. A patient with severe psychiatric disorder should be treated for their psychiatric disorder before beginning biofeedback therapy.
 

Dr. Rapoport: Some doctors see patients twice per week for several months. What is your typical routine for behavioral therapy?
 

Dr. Baskin: We have a variety of programs. For complicated patients, we tend to see them weekly and have a very systematic program of biofeedback and CBT for approximately 12 to 15 sessions. This may include treating psychiatric comorbidities. We see many other patients for 1 or 2 sessions of biofeedback to try to effect physiological learning and for 1 or 2 sessions of CBT to help them manage stressors and learn coping skills that they can use to help manage migraines and life stress.
 

Dr. Rapoport: Does behavioral medicine work best in conjunction with preventive medications, or on its own?

Dr. Baskin: Many patients do well with a behavioral treatment as a preventive therapy and a pharmacologic agent to optimize acute care. I believe that many patients with higher frequency migraine with psychological issues or ongoing stressors do best with a combination of preventive pharmacologic therapy and behavior therapy. Any migraine patient with sleep issues should learn CBT for insomnia. 

Dr. Rapoport: Is there evidence that suggests behavioral therapy can help patients at various ages manage their migraines?

Dr. Baskin: There is both adult and child data on behavioral therapy for migraine.  An excellent study was done in children and adolescents by Powers et al. It showed that adding 10 sessions of CBT to preventive amitriptyline therapy, compared to adding headache education, significantly reduced the number of headache days, level of disability, and kids with a better than 50% decrease in days of headache compared to amitriptyline, plus headache education control in chronic migraine patients.  (Powers SW et al. Cognitive Behavioral Therapy Plus Amitriptyline for Chronic Migraine in Children and Adolescents: A Randomized Clinical Trial. JAMA 2013;310(24):2622-2630)

Dr. Rapoport: A recent MedPage Today article noted that “anxiety may complicate migraine more than depression with greater long-term persistence, greater headache-related disability, and reduced satisfaction with acute therapies.” Could you please elaborate on why this may be the case? 

Dr. Baskin: Anxiety disorders are often based on feeling threat. They are always associated with avoidance behaviors. Headache sufferers with significant anxiety tend to overestimate the probability of danger (migraine) and perceive it as more unmanageable and threatening than objective reality. They are often very sensitive to medication side effects and benign somatic sensations. They sometimes take medications pre-emptively, because of their fear of getting a migraine, which may lead to medication misuse or overuse. The lifetime prevalence of anxiety disorders in migraineurs (ranging from 51-58%) is almost twice that of major depression.

Please write to us at Neurology Reviews Migraine Resource Center ([email protected]) with your opinions.

Alan M. Rapoport, M.D.

Editor-in-Chief

Migraine Resource Center

Clinical Professor of Neurology

The David Geffen School of Medicine at UCLA

Los Angeles, California

SAN ANTONIO – Response to neoadjuvant chemotherapy has little if any influence on the choice of surgery among young women with early-stage breast cancer, suggests a multicenter, prospective cohort study reported at the San Antonio Breast Cancer Symposium.

Randomized, controlled trials have found high levels of mastectomy among patients who are eligible for breast-conserving surgery, according to first author Hee Jeong Kim, MD, PhD, a visiting scholar at the Dana-Farber Cancer Institute, Boston, and an associate professor in the division of breast in the department of surgery at the University of Ulsan, Seoul, South Korea.

“Young women are more likely to present with large tumors and particularly benefit from a neoadjuvant systemic approach,” she noted. “Recent data suggest that response rates, including pathological complete response, are higher in women younger than 40 than in older women, but little is known about how response to neoadjuvant chemotherapy influences surgical decisions in young women.”

The investigators studied 315 women aged 40 years or younger at diagnosis of unilateral stage I-III breast cancer who received neoadjuvant chemotherapy. Results showed that the chemotherapy doubled the proportion who were eligible for breast-conserving surgery, but 41% of all women eligible after neoadjuvant chemotherapy opted to undergo mastectomy, and the value was essentially the same (42%) among the subset who achieved a complete clinical response. The leading reason given in the medical record for this choice was personal preference in the absence of any known high-risk predisposition.

“Surgical decisions among young women with breast cancer appear to be driven by factors beyond the extent of disease and response to neoadjuvant chemotherapy,” she commented. “We should focus our efforts to optimize surgical decisions in these patients.”

The study complements another study undertaken in the same cohort, also reported at the symposium, that assessed longer-term quality of life according to which surgery women chose; this quality-of-life study found poorer measures after mastectomy.



Drivers and explanatory factors

Session moderator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, asked, “Do you think this is really the patient preference, or is this more the surgeon’s preference that is passed on to the patient? Because there is now data showing that breast conservation with radiation is better, even in terms of survival, than mastectomy.”

“Patient preference includes a variety of things. Maybe it is a real patient preference [driven by] fear of recurrence or their peace of mind, but another important factor is maybe the doctor, especially the surgeon. That’s why we should be aware of surgical overtreatment, especially in these young early breast cancer patients,” Dr. Kim replied. “But the good news from this study is that neoadjuvant chemotherapy can give options to the patients, they can choose mastectomy. I think that it’s totally different when the patient has no option other than mastectomy versus the patient can choose mastectomy.”

Two main groups of patients in the United States are being given neoadjuvant chemotherapy, noted session attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York. One group has large tumors, and the goal is to shrink the tumor; the other group is planning to have unilateral or bilateral mastectomy with some type of reconstruction by a plastic surgeon.

“The medical oncologist, having decided the [latter] patient needs chemotherapy, chooses to give the chemotherapy preoperatively, so it’s not delayed by 3-5 months for the wounds to heal,” he elaborated. “How many of your patients were in the second category?”

The study did not tease out that population, Dr. Kim replied.

Study details

The women studied were participants in the Young Women’s Breast Cancer Study (YWS). Some 67% had a clinical complete response (no palpable tumor in the breast) to their neoadjuvant chemotherapy, and 32% had a pathological complete response (no tumor in the breast, with or without ductal carcinoma in situ [DCIS], and no tumor deposit exceeding 0.2 mm in the lymph nodes).

Before neoadjuvant chemotherapy, 26% of the women overall were eligible for breast-conserving surgery, but after neoadjuvant chemotherapy, 42% were eligible, Dr. Kim reported.

However, in the entire cohort, breast-conserving surgery was the initial surgery in just 25% of women and the final (definitive) surgery in just 23%.

Among patients eligible for breast conservation after neoadjuvant chemotherapy, 41% chose mastectomy instead as their initial surgery. Response to the chemotherapy seemingly did not influence this choice given that 42% of the subset with a clinical complete response still chose mastectomy. Furthermore, among those eligible for breast conservation who underwent mastectomy, 35% had a pathologic complete response to the chemotherapy.

Of all patients eligible for breast-conserving surgery who opted for mastectomy (and usually a bilateral procedure), the most common reason for choosing this more extensive surgery was personal preference, documented in 53% of cases, followed by presence of a BRCA or p53 mutation or a strong family history, documented in 40%. Reasons were similar among the breast conservation–eligible women who had a clinical complete response and/or ultimately a pathological complete response but chose mastectomy.

The study did not analyze disease factors that may have influenced choice of surgery, such as multicentricity or presence of DCIS, acknowledged Dr. Kim, who disclosed that she had no relevant conflicts of interest.

In an exploratory analysis, use of neoadjuvant chemotherapy increased over time among YWS participants, from 23% among those with diagnosis in 2006-2007 to 44% among those with diagnosis in 2014-2015. There were concurrent improvements in the proportions who achieved a clinical complete response (from 64% to 77%) and a pathological complete response (from 23% to 34%). Yet the proportion undergoing breast-conserving surgery as their initial surgery fell slightly, from 21% to 19%, during the same period.

SOURCE: Kim HJ et al. SABCS 2018, Abstract GS6-01,
 

SAN ANTONIO – Response to neoadjuvant chemotherapy has little if any influence on the choice of surgery among young women with early-stage breast cancer, suggests a multicenter, prospective cohort study reported at the San Antonio Breast Cancer Symposium.

Randomized, controlled trials have found high levels of mastectomy among patients who are eligible for breast-conserving surgery, according to first author Hee Jeong Kim, MD, PhD, a visiting scholar at the Dana-Farber Cancer Institute, Boston, and an associate professor in the division of breast in the department of surgery at the University of Ulsan, Seoul, South Korea.

“Young women are more likely to present with large tumors and particularly benefit from a neoadjuvant systemic approach,” she noted. “Recent data suggest that response rates, including pathological complete response, are higher in women younger than 40 than in older women, but little is known about how response to neoadjuvant chemotherapy influences surgical decisions in young women.”

The investigators studied 315 women aged 40 years or younger at diagnosis of unilateral stage I-III breast cancer who received neoadjuvant chemotherapy. Results showed that the chemotherapy doubled the proportion who were eligible for breast-conserving surgery, but 41% of all women eligible after neoadjuvant chemotherapy opted to undergo mastectomy, and the value was essentially the same (42%) among the subset who achieved a complete clinical response. The leading reason given in the medical record for this choice was personal preference in the absence of any known high-risk predisposition.

“Surgical decisions among young women with breast cancer appear to be driven by factors beyond the extent of disease and response to neoadjuvant chemotherapy,” she commented. “We should focus our efforts to optimize surgical decisions in these patients.”

The study complements another study undertaken in the same cohort, also reported at the symposium, that assessed longer-term quality of life according to which surgery women chose; this quality-of-life study found poorer measures after mastectomy.



Drivers and explanatory factors

Session moderator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, asked, “Do you think this is really the patient preference, or is this more the surgeon’s preference that is passed on to the patient? Because there is now data showing that breast conservation with radiation is better, even in terms of survival, than mastectomy.”

“Patient preference includes a variety of things. Maybe it is a real patient preference [driven by] fear of recurrence or their peace of mind, but another important factor is maybe the doctor, especially the surgeon. That’s why we should be aware of surgical overtreatment, especially in these young early breast cancer patients,” Dr. Kim replied. “But the good news from this study is that neoadjuvant chemotherapy can give options to the patients, they can choose mastectomy. I think that it’s totally different when the patient has no option other than mastectomy versus the patient can choose mastectomy.”

Two main groups of patients in the United States are being given neoadjuvant chemotherapy, noted session attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York. One group has large tumors, and the goal is to shrink the tumor; the other group is planning to have unilateral or bilateral mastectomy with some type of reconstruction by a plastic surgeon.

“The medical oncologist, having decided the [latter] patient needs chemotherapy, chooses to give the chemotherapy preoperatively, so it’s not delayed by 3-5 months for the wounds to heal,” he elaborated. “How many of your patients were in the second category?”

The study did not tease out that population, Dr. Kim replied.

Study details

The women studied were participants in the Young Women’s Breast Cancer Study (YWS). Some 67% had a clinical complete response (no palpable tumor in the breast) to their neoadjuvant chemotherapy, and 32% had a pathological complete response (no tumor in the breast, with or without ductal carcinoma in situ [DCIS], and no tumor deposit exceeding 0.2 mm in the lymph nodes).

Before neoadjuvant chemotherapy, 26% of the women overall were eligible for breast-conserving surgery, but after neoadjuvant chemotherapy, 42% were eligible, Dr. Kim reported.

However, in the entire cohort, breast-conserving surgery was the initial surgery in just 25% of women and the final (definitive) surgery in just 23%.

Among patients eligible for breast conservation after neoadjuvant chemotherapy, 41% chose mastectomy instead as their initial surgery. Response to the chemotherapy seemingly did not influence this choice given that 42% of the subset with a clinical complete response still chose mastectomy. Furthermore, among those eligible for breast conservation who underwent mastectomy, 35% had a pathologic complete response to the chemotherapy.

Of all patients eligible for breast-conserving surgery who opted for mastectomy (and usually a bilateral procedure), the most common reason for choosing this more extensive surgery was personal preference, documented in 53% of cases, followed by presence of a BRCA or p53 mutation or a strong family history, documented in 40%. Reasons were similar among the breast conservation–eligible women who had a clinical complete response and/or ultimately a pathological complete response but chose mastectomy.

The study did not analyze disease factors that may have influenced choice of surgery, such as multicentricity or presence of DCIS, acknowledged Dr. Kim, who disclosed that she had no relevant conflicts of interest.

In an exploratory analysis, use of neoadjuvant chemotherapy increased over time among YWS participants, from 23% among those with diagnosis in 2006-2007 to 44% among those with diagnosis in 2014-2015. There were concurrent improvements in the proportions who achieved a clinical complete response (from 64% to 77%) and a pathological complete response (from 23% to 34%). Yet the proportion undergoing breast-conserving surgery as their initial surgery fell slightly, from 21% to 19%, during the same period.

SOURCE: Kim HJ et al. SABCS 2018, Abstract GS6-01,
 

SAN ANTONIO – Response to neoadjuvant chemotherapy has little if any influence on the choice of surgery among young women with early-stage breast cancer, suggests a multicenter, prospective cohort study reported at the San Antonio Breast Cancer Symposium.

Randomized, controlled trials have found high levels of mastectomy among patients who are eligible for breast-conserving surgery, according to first author Hee Jeong Kim, MD, PhD, a visiting scholar at the Dana-Farber Cancer Institute, Boston, and an associate professor in the division of breast in the department of surgery at the University of Ulsan, Seoul, South Korea.

“Young women are more likely to present with large tumors and particularly benefit from a neoadjuvant systemic approach,” she noted. “Recent data suggest that response rates, including pathological complete response, are higher in women younger than 40 than in older women, but little is known about how response to neoadjuvant chemotherapy influences surgical decisions in young women.”

The investigators studied 315 women aged 40 years or younger at diagnosis of unilateral stage I-III breast cancer who received neoadjuvant chemotherapy. Results showed that the chemotherapy doubled the proportion who were eligible for breast-conserving surgery, but 41% of all women eligible after neoadjuvant chemotherapy opted to undergo mastectomy, and the value was essentially the same (42%) among the subset who achieved a complete clinical response. The leading reason given in the medical record for this choice was personal preference in the absence of any known high-risk predisposition.

“Surgical decisions among young women with breast cancer appear to be driven by factors beyond the extent of disease and response to neoadjuvant chemotherapy,” she commented. “We should focus our efforts to optimize surgical decisions in these patients.”

The study complements another study undertaken in the same cohort, also reported at the symposium, that assessed longer-term quality of life according to which surgery women chose; this quality-of-life study found poorer measures after mastectomy.



Drivers and explanatory factors

Session moderator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, asked, “Do you think this is really the patient preference, or is this more the surgeon’s preference that is passed on to the patient? Because there is now data showing that breast conservation with radiation is better, even in terms of survival, than mastectomy.”

“Patient preference includes a variety of things. Maybe it is a real patient preference [driven by] fear of recurrence or their peace of mind, but another important factor is maybe the doctor, especially the surgeon. That’s why we should be aware of surgical overtreatment, especially in these young early breast cancer patients,” Dr. Kim replied. “But the good news from this study is that neoadjuvant chemotherapy can give options to the patients, they can choose mastectomy. I think that it’s totally different when the patient has no option other than mastectomy versus the patient can choose mastectomy.”

Two main groups of patients in the United States are being given neoadjuvant chemotherapy, noted session attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York. One group has large tumors, and the goal is to shrink the tumor; the other group is planning to have unilateral or bilateral mastectomy with some type of reconstruction by a plastic surgeon.

“The medical oncologist, having decided the [latter] patient needs chemotherapy, chooses to give the chemotherapy preoperatively, so it’s not delayed by 3-5 months for the wounds to heal,” he elaborated. “How many of your patients were in the second category?”

The study did not tease out that population, Dr. Kim replied.

Study details

The women studied were participants in the Young Women’s Breast Cancer Study (YWS). Some 67% had a clinical complete response (no palpable tumor in the breast) to their neoadjuvant chemotherapy, and 32% had a pathological complete response (no tumor in the breast, with or without ductal carcinoma in situ [DCIS], and no tumor deposit exceeding 0.2 mm in the lymph nodes).

Before neoadjuvant chemotherapy, 26% of the women overall were eligible for breast-conserving surgery, but after neoadjuvant chemotherapy, 42% were eligible, Dr. Kim reported.

However, in the entire cohort, breast-conserving surgery was the initial surgery in just 25% of women and the final (definitive) surgery in just 23%.

Among patients eligible for breast conservation after neoadjuvant chemotherapy, 41% chose mastectomy instead as their initial surgery. Response to the chemotherapy seemingly did not influence this choice given that 42% of the subset with a clinical complete response still chose mastectomy. Furthermore, among those eligible for breast conservation who underwent mastectomy, 35% had a pathologic complete response to the chemotherapy.

Of all patients eligible for breast-conserving surgery who opted for mastectomy (and usually a bilateral procedure), the most common reason for choosing this more extensive surgery was personal preference, documented in 53% of cases, followed by presence of a BRCA or p53 mutation or a strong family history, documented in 40%. Reasons were similar among the breast conservation–eligible women who had a clinical complete response and/or ultimately a pathological complete response but chose mastectomy.

The study did not analyze disease factors that may have influenced choice of surgery, such as multicentricity or presence of DCIS, acknowledged Dr. Kim, who disclosed that she had no relevant conflicts of interest.

In an exploratory analysis, use of neoadjuvant chemotherapy increased over time among YWS participants, from 23% among those with diagnosis in 2006-2007 to 44% among those with diagnosis in 2014-2015. There were concurrent improvements in the proportions who achieved a clinical complete response (from 64% to 77%) and a pathological complete response (from 23% to 34%). Yet the proportion undergoing breast-conserving surgery as their initial surgery fell slightly, from 21% to 19%, during the same period.

SOURCE: Kim HJ et al. SABCS 2018, Abstract GS6-01,
 

SAN ANTONIO – Age alone should not be grounds for skipping adjuvant chemotherapy for early breast cancer, suggests an analysis of more than 160,000 patients aged 65 years or older captured in the National Cancer Database.

“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.

In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.

Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.

“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.

In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.

“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.

He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”

“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”

Study details

The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.

Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.

Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).

Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).

Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.

The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).

“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted

Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.

SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.

SAN ANTONIO – Age alone should not be grounds for skipping adjuvant chemotherapy for early breast cancer, suggests an analysis of more than 160,000 patients aged 65 years or older captured in the National Cancer Database.

“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.

In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.

Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.

“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.

In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.

“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.

He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”

“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”

Study details

The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.

Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.

Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).

Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).

Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.

The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).

“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted

Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.

SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.

SAN ANTONIO – Age alone should not be grounds for skipping adjuvant chemotherapy for early breast cancer, suggests an analysis of more than 160,000 patients aged 65 years or older captured in the National Cancer Database.

“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.

In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.

Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.

“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.

In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.

“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.

He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”

“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”

Study details

The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.

Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.

Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).

Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).

Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.

The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).

“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted

Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.

SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.

Survivors of childhood Hodgkin lymphoma have a 14-fold greater risk for second cancers, compared with the general population, according to newly published data.

The subsequent malignant neoplasms (SMNs) tend to follow specific patterns depending on the patient’s age at treatment, sex, treatment modality, and body region treated.

And although the risk of SMNs appears to be somewhat lower for patients treated in more recent decades, it is still significantly elevated, compared with that of the general population, according to Anna S. Holmqvist, MD, PhD, from Lund University (Sweden), and her colleagues.

“A major goal of the current study was to develop evidence with which to guide the screening of survivors of HL for the development of [solid] SMNs,” the investigators wrote in Cancer.

They examined at data from the Late Effects Study Group, a multinational cohort of patients aged 16 years or younger who were treated for Hodgkin lymphoma and other cancers from 1955 to 1986.

The current report is the third update from an expanded cohort, including data on 1,136 patients with a median follow-up of 26.6 years. The median patient age at diagnosis was 11 years and the patients were followed for 23,212 person-years following the Hodgkin lymphoma diagnosis.

In all, 162 patients developed a total of 196 solid SMNs, including breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30, colorectal cancer in 15, lung cancer in 11, other malignancies in 40, and disease site not available in 12 patients.

The cumulative incidence of any solid SMN 40 years after a diagnosis of Hodgkin lymphoma was 26.4%. The standardized incidence ratio for the entire cohort was 14.0, compared with the general population as derived from the Surveillance, Epidemiology and End Results database.

Predisposing factors for breast cancer in females included a Hodgkin lymphoma diagnosis from the ages of 10-16 years, and treatment with radiotherapy to the chest.

The patients at highest risk for subsequent development of lung cancer were males treated with chest radiotherapy before age 10 years. Those at highest risk for colorectal cancer were males and females who had received abdominal/pelvic radiotherapy and high-dose alkylating agents. Patients at highest risk for thyroid cancers were females who had been treated with radiotherapy to the neck before the age of 10.

The cumulative incidence for breast cancer by age 50 years for those at highest risk was 45.3%. The respective cumulative incidences for lung, colorectal, and thyroid cancers by age 50 were 4.2%, 9.5%, and 17.3%.

The investigators noted that patients treated more recently are likely to have received lower doses and volumes of radiotherapy, compared with patients treated in 1970s and earlier. “However, for the cohort of patients treated between 1955 and 1986, it is clear that continued surveillance for [solid] SMNs is essential because their risk continues to increase as these survivors enter their fourth and subsequent decades of life.”

No specific funding source for the study was reported. The authors made no financial disclosures.
 

SOURCE: Holmqvist AS et al. Cancer. 2018 Dec 17. doi: 10.1002/cncr.31807.

Survivors of childhood Hodgkin lymphoma have a 14-fold greater risk for second cancers, compared with the general population, according to newly published data.

The subsequent malignant neoplasms (SMNs) tend to follow specific patterns depending on the patient’s age at treatment, sex, treatment modality, and body region treated.

And although the risk of SMNs appears to be somewhat lower for patients treated in more recent decades, it is still significantly elevated, compared with that of the general population, according to Anna S. Holmqvist, MD, PhD, from Lund University (Sweden), and her colleagues.

“A major goal of the current study was to develop evidence with which to guide the screening of survivors of HL for the development of [solid] SMNs,” the investigators wrote in Cancer.

They examined at data from the Late Effects Study Group, a multinational cohort of patients aged 16 years or younger who were treated for Hodgkin lymphoma and other cancers from 1955 to 1986.

The current report is the third update from an expanded cohort, including data on 1,136 patients with a median follow-up of 26.6 years. The median patient age at diagnosis was 11 years and the patients were followed for 23,212 person-years following the Hodgkin lymphoma diagnosis.

In all, 162 patients developed a total of 196 solid SMNs, including breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30, colorectal cancer in 15, lung cancer in 11, other malignancies in 40, and disease site not available in 12 patients.

The cumulative incidence of any solid SMN 40 years after a diagnosis of Hodgkin lymphoma was 26.4%. The standardized incidence ratio for the entire cohort was 14.0, compared with the general population as derived from the Surveillance, Epidemiology and End Results database.

Predisposing factors for breast cancer in females included a Hodgkin lymphoma diagnosis from the ages of 10-16 years, and treatment with radiotherapy to the chest.

The patients at highest risk for subsequent development of lung cancer were males treated with chest radiotherapy before age 10 years. Those at highest risk for colorectal cancer were males and females who had received abdominal/pelvic radiotherapy and high-dose alkylating agents. Patients at highest risk for thyroid cancers were females who had been treated with radiotherapy to the neck before the age of 10.

The cumulative incidence for breast cancer by age 50 years for those at highest risk was 45.3%. The respective cumulative incidences for lung, colorectal, and thyroid cancers by age 50 were 4.2%, 9.5%, and 17.3%.

The investigators noted that patients treated more recently are likely to have received lower doses and volumes of radiotherapy, compared with patients treated in 1970s and earlier. “However, for the cohort of patients treated between 1955 and 1986, it is clear that continued surveillance for [solid] SMNs is essential because their risk continues to increase as these survivors enter their fourth and subsequent decades of life.”

No specific funding source for the study was reported. The authors made no financial disclosures.
 

SOURCE: Holmqvist AS et al. Cancer. 2018 Dec 17. doi: 10.1002/cncr.31807.

Survivors of childhood Hodgkin lymphoma have a 14-fold greater risk for second cancers, compared with the general population, according to newly published data.

The subsequent malignant neoplasms (SMNs) tend to follow specific patterns depending on the patient’s age at treatment, sex, treatment modality, and body region treated.

And although the risk of SMNs appears to be somewhat lower for patients treated in more recent decades, it is still significantly elevated, compared with that of the general population, according to Anna S. Holmqvist, MD, PhD, from Lund University (Sweden), and her colleagues.

“A major goal of the current study was to develop evidence with which to guide the screening of survivors of HL for the development of [solid] SMNs,” the investigators wrote in Cancer.

They examined at data from the Late Effects Study Group, a multinational cohort of patients aged 16 years or younger who were treated for Hodgkin lymphoma and other cancers from 1955 to 1986.

The current report is the third update from an expanded cohort, including data on 1,136 patients with a median follow-up of 26.6 years. The median patient age at diagnosis was 11 years and the patients were followed for 23,212 person-years following the Hodgkin lymphoma diagnosis.

In all, 162 patients developed a total of 196 solid SMNs, including breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30, colorectal cancer in 15, lung cancer in 11, other malignancies in 40, and disease site not available in 12 patients.

The cumulative incidence of any solid SMN 40 years after a diagnosis of Hodgkin lymphoma was 26.4%. The standardized incidence ratio for the entire cohort was 14.0, compared with the general population as derived from the Surveillance, Epidemiology and End Results database.

Predisposing factors for breast cancer in females included a Hodgkin lymphoma diagnosis from the ages of 10-16 years, and treatment with radiotherapy to the chest.

The patients at highest risk for subsequent development of lung cancer were males treated with chest radiotherapy before age 10 years. Those at highest risk for colorectal cancer were males and females who had received abdominal/pelvic radiotherapy and high-dose alkylating agents. Patients at highest risk for thyroid cancers were females who had been treated with radiotherapy to the neck before the age of 10.

The cumulative incidence for breast cancer by age 50 years for those at highest risk was 45.3%. The respective cumulative incidences for lung, colorectal, and thyroid cancers by age 50 were 4.2%, 9.5%, and 17.3%.

The investigators noted that patients treated more recently are likely to have received lower doses and volumes of radiotherapy, compared with patients treated in 1970s and earlier. “However, for the cohort of patients treated between 1955 and 1986, it is clear that continued surveillance for [solid] SMNs is essential because their risk continues to increase as these survivors enter their fourth and subsequent decades of life.”

No specific funding source for the study was reported. The authors made no financial disclosures.
 

SOURCE: Holmqvist AS et al. Cancer. 2018 Dec 17. doi: 10.1002/cncr.31807.

The efficacy and side effects of cannabidiol (CBD) in severe pediatric epilepsies are similar to those of other antiepileptic drugs (AEDs), according to a review published in Developmental Medicine & Child Neurology. “Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD,” the authors said.

Although CBD’s antiepileptic mechanisms “are not fully elucidated, it is clear that administration of CBD as adjunct therapy decreases seizure frequency in patients with Dravet syndrome and Lennox-Gastaut syndrome,” wrote Shayma Ali, a doctoral student in the department of pediatrics and child health at the University of Otago in Wellington, New Zealand, and her colleagues. “Contrary to public expectation of miraculous results, CBD has a similar antiepileptic and side effect profile to other AEDs. Nevertheless, as individual children with these developmental and epileptic encephalopathies are often refractory to available AEDs, the addition of another potentially effective therapeutic medicine will be warmly welcomed by families and physicians.”

The FDA approved Epidiolex, a pharmaceutical-grade oral solution that is 98% CBD, in June of 2018. In September of 2018, the Drug Enforcement Administration classified it as a Schedule V controlled substance. Patients’ use of nonpharmaceutical grade CBD products, including those combined with tetrahydrocannabinol (THC), “raises concerns about the use of products with THC on the developing brain,” the review authors said.
 

Randomized trials

Three randomized, controlled, double-blind trials in patients with Dravet syndrome and Lennox-Gastaut syndrome found that CBD, compared with placebo, results in greater median seizure reductions (38%-41% vs. 13%-19%) and responder rates (i.e., the proportion of patients with 50% reductions in convulsive or drop seizures; 39%-46% vs. 14%-27%).

Common adverse effects include somnolence, diarrhea, decreased appetite, fatigue, lethargy, pyrexia, and vomiting. Hepatic transaminases became elevated in some patients, and this result occurred more often in patients taking valproate.

No phase 2 or phase 3 trials have assessed the efficacy of CBD without coadministration of other AEDs, and CBD’s efficacy may relate to its impact on the pharmacokinetics of coadministered AEDs. “The most important clinical interaction is between CBD and clobazam, as [the dose of] clobazam often needs to be lowered because of excessive sedation,” wrote Ms. Ali and her colleagues. CBD inhibits CYP2C19 and CYP3A4 – enzymes that are involved in clobazam metabolism – which results in high plasma concentrations of clobazam’s active metabolite, norclobazam. Plasma levels of topiramate, rufinamide, zonisamide, and eslicarbazepine also may increase when these drugs are taken with CBD.
 

Challenges and opportunities

Of the hundreds of compounds in the marijuana plant, CBD “has the most evidence of antiepileptic efficacy and does not have the psychoactive effects” of THC, the authors said. Little evidence supports the combination of THC and CBD for the treatment of epilepsy. In addition, research indicates that THC can have a proconvulsive effect in animal models and harm the development of the human brain.

Investigators are evaluating alternative routes of CBD delivery to avoid first-pass metabolism, such as oromucosal sprays, transdermal gels, eye drops, intranasal sprays, and rectal suppositories. “Alternative methods of administration ... deserve consideration, particularly for the developmental and epileptic encephalopathies population, as administration of oral medication can be challenging,” they said.

[email protected]

SOURCE: Ali S et al. Dev Med Child Neurol. 2018. doi: 10.1111/dmcn.14087.

The efficacy and side effects of cannabidiol (CBD) in severe pediatric epilepsies are similar to those of other antiepileptic drugs (AEDs), according to a review published in Developmental Medicine & Child Neurology. “Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD,” the authors said.

Although CBD’s antiepileptic mechanisms “are not fully elucidated, it is clear that administration of CBD as adjunct therapy decreases seizure frequency in patients with Dravet syndrome and Lennox-Gastaut syndrome,” wrote Shayma Ali, a doctoral student in the department of pediatrics and child health at the University of Otago in Wellington, New Zealand, and her colleagues. “Contrary to public expectation of miraculous results, CBD has a similar antiepileptic and side effect profile to other AEDs. Nevertheless, as individual children with these developmental and epileptic encephalopathies are often refractory to available AEDs, the addition of another potentially effective therapeutic medicine will be warmly welcomed by families and physicians.”

The FDA approved Epidiolex, a pharmaceutical-grade oral solution that is 98% CBD, in June of 2018. In September of 2018, the Drug Enforcement Administration classified it as a Schedule V controlled substance. Patients’ use of nonpharmaceutical grade CBD products, including those combined with tetrahydrocannabinol (THC), “raises concerns about the use of products with THC on the developing brain,” the review authors said.
 

Randomized trials

Three randomized, controlled, double-blind trials in patients with Dravet syndrome and Lennox-Gastaut syndrome found that CBD, compared with placebo, results in greater median seizure reductions (38%-41% vs. 13%-19%) and responder rates (i.e., the proportion of patients with 50% reductions in convulsive or drop seizures; 39%-46% vs. 14%-27%).

Common adverse effects include somnolence, diarrhea, decreased appetite, fatigue, lethargy, pyrexia, and vomiting. Hepatic transaminases became elevated in some patients, and this result occurred more often in patients taking valproate.

No phase 2 or phase 3 trials have assessed the efficacy of CBD without coadministration of other AEDs, and CBD’s efficacy may relate to its impact on the pharmacokinetics of coadministered AEDs. “The most important clinical interaction is between CBD and clobazam, as [the dose of] clobazam often needs to be lowered because of excessive sedation,” wrote Ms. Ali and her colleagues. CBD inhibits CYP2C19 and CYP3A4 – enzymes that are involved in clobazam metabolism – which results in high plasma concentrations of clobazam’s active metabolite, norclobazam. Plasma levels of topiramate, rufinamide, zonisamide, and eslicarbazepine also may increase when these drugs are taken with CBD.
 

Challenges and opportunities

Of the hundreds of compounds in the marijuana plant, CBD “has the most evidence of antiepileptic efficacy and does not have the psychoactive effects” of THC, the authors said. Little evidence supports the combination of THC and CBD for the treatment of epilepsy. In addition, research indicates that THC can have a proconvulsive effect in animal models and harm the development of the human brain.

Investigators are evaluating alternative routes of CBD delivery to avoid first-pass metabolism, such as oromucosal sprays, transdermal gels, eye drops, intranasal sprays, and rectal suppositories. “Alternative methods of administration ... deserve consideration, particularly for the developmental and epileptic encephalopathies population, as administration of oral medication can be challenging,” they said.

[email protected]

SOURCE: Ali S et al. Dev Med Child Neurol. 2018. doi: 10.1111/dmcn.14087.

The efficacy and side effects of cannabidiol (CBD) in severe pediatric epilepsies are similar to those of other antiepileptic drugs (AEDs), according to a review published in Developmental Medicine & Child Neurology. “Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD,” the authors said.

Although CBD’s antiepileptic mechanisms “are not fully elucidated, it is clear that administration of CBD as adjunct therapy decreases seizure frequency in patients with Dravet syndrome and Lennox-Gastaut syndrome,” wrote Shayma Ali, a doctoral student in the department of pediatrics and child health at the University of Otago in Wellington, New Zealand, and her colleagues. “Contrary to public expectation of miraculous results, CBD has a similar antiepileptic and side effect profile to other AEDs. Nevertheless, as individual children with these developmental and epileptic encephalopathies are often refractory to available AEDs, the addition of another potentially effective therapeutic medicine will be warmly welcomed by families and physicians.”

The FDA approved Epidiolex, a pharmaceutical-grade oral solution that is 98% CBD, in June of 2018. In September of 2018, the Drug Enforcement Administration classified it as a Schedule V controlled substance. Patients’ use of nonpharmaceutical grade CBD products, including those combined with tetrahydrocannabinol (THC), “raises concerns about the use of products with THC on the developing brain,” the review authors said.
 

Randomized trials

Three randomized, controlled, double-blind trials in patients with Dravet syndrome and Lennox-Gastaut syndrome found that CBD, compared with placebo, results in greater median seizure reductions (38%-41% vs. 13%-19%) and responder rates (i.e., the proportion of patients with 50% reductions in convulsive or drop seizures; 39%-46% vs. 14%-27%).

Common adverse effects include somnolence, diarrhea, decreased appetite, fatigue, lethargy, pyrexia, and vomiting. Hepatic transaminases became elevated in some patients, and this result occurred more often in patients taking valproate.

No phase 2 or phase 3 trials have assessed the efficacy of CBD without coadministration of other AEDs, and CBD’s efficacy may relate to its impact on the pharmacokinetics of coadministered AEDs. “The most important clinical interaction is between CBD and clobazam, as [the dose of] clobazam often needs to be lowered because of excessive sedation,” wrote Ms. Ali and her colleagues. CBD inhibits CYP2C19 and CYP3A4 – enzymes that are involved in clobazam metabolism – which results in high plasma concentrations of clobazam’s active metabolite, norclobazam. Plasma levels of topiramate, rufinamide, zonisamide, and eslicarbazepine also may increase when these drugs are taken with CBD.
 

Challenges and opportunities

Of the hundreds of compounds in the marijuana plant, CBD “has the most evidence of antiepileptic efficacy and does not have the psychoactive effects” of THC, the authors said. Little evidence supports the combination of THC and CBD for the treatment of epilepsy. In addition, research indicates that THC can have a proconvulsive effect in animal models and harm the development of the human brain.

Investigators are evaluating alternative routes of CBD delivery to avoid first-pass metabolism, such as oromucosal sprays, transdermal gels, eye drops, intranasal sprays, and rectal suppositories. “Alternative methods of administration ... deserve consideration, particularly for the developmental and epileptic encephalopathies population, as administration of oral medication can be challenging,” they said.

[email protected]

SOURCE: Ali S et al. Dev Med Child Neurol. 2018. doi: 10.1111/dmcn.14087.

Patients with multiple sclerosis (MS) and food allergies had more relapses and gadolinium-enhancing lesions than patients with MS but no food allergies, according to a recent analysis of a longitudinal study.

Patients with food allergies had a 1.3-times higher rate for cumulative number of attacks and a 2.5-times higher likelihood of enhancing lesions on brain MRI in the analysis of patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB).

By contrast, there were no significant differences in relapse or lesion rates for patients with environmental or drug allergies when compared with those without allergies, reported Tanuja Chitnis, MD, of Partners Multiple Sclerosis Center at Brigham and Women’s Hospital, Boston, and her coinvestigators.

“Our findings suggest that MS patients with allergies have more active disease than those without allergies, and that this effect is driven by food allergies,” Dr. Tanuja and her coauthors wrote in their report, which appeared in the Journal of Neurology, Neurosurgery and Psychiatry.

Previous investigations have looked at whether allergy history increases risk of developing MS, with conflicting results, they added, noting a meta-analysis of 10 observational studies suggesting no such link.

By contrast, whether allergies lead to more or less intense MS activity has not been addressed, according to investigators, who said this is the first study tying allergy history to MS disease course using clinical and MRI variables.

Their study was based on a subset of 1,349 patients with a diagnosis of MS who were enrolled in CLIMB and completed a self-administered questionnaire on food, environmental, and drug allergies. Of those patients, 922 reported allergies, while 427 reported no known allergies.

Patients with food allergies had a significantly increased rate of cumulative number of attacks, compared with those with no allergies, according to investigators, even after adjusting the analysis for gender, age at symptom onset, disease category, and time on treatment (relapse rate ratio, 1.274; 95% confidence interval, 1.023-1.587; P = .0305).

Food allergy patients were more than twice as likely as no-allergy patients were to have gadolinium-enhancing lesions on brain MRI after adjusting for other covariates (odds ratio, 2.53; 95% CI, 1.25-5.11; P = .0096), they added.

Patients with environmental and drug allergies also appeared to have more relapses, compared with patients with no allergies, in univariate analysis, but the differences were not significant in the adjusted analysis, investigators said. Likewise, there were trends toward a link between number of lesions and presence of environmental or drug allergies that did not hold up on multivariate analysis.

It is unknown what underlying biological mechanisms might potentially link food allergies to MS disease severity; however, findings of experimental studies support the hypothesis that gut microbiota might affect the risk and course of MS, Dr. Chitnis and her coauthors wrote in their report.

The CLIMB study was supported by Merck Serono and the National MS Society Nancy Davis Center Without Walls. Dr. Chitnis reported consulting fees from Biogen Idec, Novartis, Sanofi, Bayer, and Celgene outside the submitted work. Coauthors provided additional disclosures related to Merck Serono, Genentech, Verily Life Sciences, EMD Serono, Biogen, Teva, Sanofi, and Novartis, among others.

SOURCE: Fakih R et al. J Neurol Neurosurg Psychiatry. 2018 Dec 18. doi: 10.1136/jnnp-2018-319301.

Patients with multiple sclerosis (MS) and food allergies had more relapses and gadolinium-enhancing lesions than patients with MS but no food allergies, according to a recent analysis of a longitudinal study.

Patients with food allergies had a 1.3-times higher rate for cumulative number of attacks and a 2.5-times higher likelihood of enhancing lesions on brain MRI in the analysis of patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB).

By contrast, there were no significant differences in relapse or lesion rates for patients with environmental or drug allergies when compared with those without allergies, reported Tanuja Chitnis, MD, of Partners Multiple Sclerosis Center at Brigham and Women’s Hospital, Boston, and her coinvestigators.

“Our findings suggest that MS patients with allergies have more active disease than those without allergies, and that this effect is driven by food allergies,” Dr. Tanuja and her coauthors wrote in their report, which appeared in the Journal of Neurology, Neurosurgery and Psychiatry.

Previous investigations have looked at whether allergy history increases risk of developing MS, with conflicting results, they added, noting a meta-analysis of 10 observational studies suggesting no such link.

By contrast, whether allergies lead to more or less intense MS activity has not been addressed, according to investigators, who said this is the first study tying allergy history to MS disease course using clinical and MRI variables.

Their study was based on a subset of 1,349 patients with a diagnosis of MS who were enrolled in CLIMB and completed a self-administered questionnaire on food, environmental, and drug allergies. Of those patients, 922 reported allergies, while 427 reported no known allergies.

Patients with food allergies had a significantly increased rate of cumulative number of attacks, compared with those with no allergies, according to investigators, even after adjusting the analysis for gender, age at symptom onset, disease category, and time on treatment (relapse rate ratio, 1.274; 95% confidence interval, 1.023-1.587; P = .0305).

Food allergy patients were more than twice as likely as no-allergy patients were to have gadolinium-enhancing lesions on brain MRI after adjusting for other covariates (odds ratio, 2.53; 95% CI, 1.25-5.11; P = .0096), they added.

Patients with environmental and drug allergies also appeared to have more relapses, compared with patients with no allergies, in univariate analysis, but the differences were not significant in the adjusted analysis, investigators said. Likewise, there were trends toward a link between number of lesions and presence of environmental or drug allergies that did not hold up on multivariate analysis.

It is unknown what underlying biological mechanisms might potentially link food allergies to MS disease severity; however, findings of experimental studies support the hypothesis that gut microbiota might affect the risk and course of MS, Dr. Chitnis and her coauthors wrote in their report.

The CLIMB study was supported by Merck Serono and the National MS Society Nancy Davis Center Without Walls. Dr. Chitnis reported consulting fees from Biogen Idec, Novartis, Sanofi, Bayer, and Celgene outside the submitted work. Coauthors provided additional disclosures related to Merck Serono, Genentech, Verily Life Sciences, EMD Serono, Biogen, Teva, Sanofi, and Novartis, among others.

SOURCE: Fakih R et al. J Neurol Neurosurg Psychiatry. 2018 Dec 18. doi: 10.1136/jnnp-2018-319301.

Patients with multiple sclerosis (MS) and food allergies had more relapses and gadolinium-enhancing lesions than patients with MS but no food allergies, according to a recent analysis of a longitudinal study.

Patients with food allergies had a 1.3-times higher rate for cumulative number of attacks and a 2.5-times higher likelihood of enhancing lesions on brain MRI in the analysis of patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB).

By contrast, there were no significant differences in relapse or lesion rates for patients with environmental or drug allergies when compared with those without allergies, reported Tanuja Chitnis, MD, of Partners Multiple Sclerosis Center at Brigham and Women’s Hospital, Boston, and her coinvestigators.

“Our findings suggest that MS patients with allergies have more active disease than those without allergies, and that this effect is driven by food allergies,” Dr. Tanuja and her coauthors wrote in their report, which appeared in the Journal of Neurology, Neurosurgery and Psychiatry.

Previous investigations have looked at whether allergy history increases risk of developing MS, with conflicting results, they added, noting a meta-analysis of 10 observational studies suggesting no such link.

By contrast, whether allergies lead to more or less intense MS activity has not been addressed, according to investigators, who said this is the first study tying allergy history to MS disease course using clinical and MRI variables.

Their study was based on a subset of 1,349 patients with a diagnosis of MS who were enrolled in CLIMB and completed a self-administered questionnaire on food, environmental, and drug allergies. Of those patients, 922 reported allergies, while 427 reported no known allergies.

Patients with food allergies had a significantly increased rate of cumulative number of attacks, compared with those with no allergies, according to investigators, even after adjusting the analysis for gender, age at symptom onset, disease category, and time on treatment (relapse rate ratio, 1.274; 95% confidence interval, 1.023-1.587; P = .0305).

Food allergy patients were more than twice as likely as no-allergy patients were to have gadolinium-enhancing lesions on brain MRI after adjusting for other covariates (odds ratio, 2.53; 95% CI, 1.25-5.11; P = .0096), they added.

Patients with environmental and drug allergies also appeared to have more relapses, compared with patients with no allergies, in univariate analysis, but the differences were not significant in the adjusted analysis, investigators said. Likewise, there were trends toward a link between number of lesions and presence of environmental or drug allergies that did not hold up on multivariate analysis.

It is unknown what underlying biological mechanisms might potentially link food allergies to MS disease severity; however, findings of experimental studies support the hypothesis that gut microbiota might affect the risk and course of MS, Dr. Chitnis and her coauthors wrote in their report.

The CLIMB study was supported by Merck Serono and the National MS Society Nancy Davis Center Without Walls. Dr. Chitnis reported consulting fees from Biogen Idec, Novartis, Sanofi, Bayer, and Celgene outside the submitted work. Coauthors provided additional disclosures related to Merck Serono, Genentech, Verily Life Sciences, EMD Serono, Biogen, Teva, Sanofi, and Novartis, among others.

SOURCE: Fakih R et al. J Neurol Neurosurg Psychiatry. 2018 Dec 18. doi: 10.1136/jnnp-2018-319301.

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,