Kerri Wachter

The Food and Drug Administration wants manufacturers to add new warnings to the labels of gonadotropin-releasing hormone agonists – used mainly to treat men with prostate cancer – because of concerns about increased risks of diabetes, MI, stroke, and sudden death.

The new warnings are the result of a preliminary and ongoing analysis showing that patients on gonadotropin-releasing hormone (GnRH) agonists are at a small increased risk for diabetes, MI, stroke, and sudden death, according to an agency statement released on Oct. 20.

GnRH agonists are indicated for the palliative treatment of symptoms of advanced prostate cancer. Medications in the GnRH class are marketed under the brand names Eligard, Lupron, Synarel, Trelstar, Vantas, Viadur, and Zoladex. Several generic products are also available.

In May 2010, the agency released the early findings and advised physicians to be aware of these potential risks and carefully weigh the benefits and risks of GnRH agonists when determining a treatment for patients with prostate cancer.

Physicians should periodically monitor blood glucose and/or glycosylated hemoglobin (HbA1c) in patients who are receiving treatment with GnRH agonists. Physicians should also monitor patients for signs and symptoms suggestive of development of cardiovascular disease and manage them, according to current clinical practice.

Adverse events involving GnRH agonists should be reported to the FDA MedWatch program at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm, or by calling 800-332-1088.

The Food and Drug Administration wants manufacturers to add new warnings to the labels of gonadotropin-releasing hormone agonists – used mainly to treat men with prostate cancer – because of concerns about increased risks of diabetes, MI, stroke, and sudden death.

The new warnings are the result of a preliminary and ongoing analysis showing that patients on gonadotropin-releasing hormone (GnRH) agonists are at a small increased risk for diabetes, MI, stroke, and sudden death, according to an agency statement released on Oct. 20.

GnRH agonists are indicated for the palliative treatment of symptoms of advanced prostate cancer. Medications in the GnRH class are marketed under the brand names Eligard, Lupron, Synarel, Trelstar, Vantas, Viadur, and Zoladex. Several generic products are also available.

In May 2010, the agency released the early findings and advised physicians to be aware of these potential risks and carefully weigh the benefits and risks of GnRH agonists when determining a treatment for patients with prostate cancer.

Physicians should periodically monitor blood glucose and/or glycosylated hemoglobin (HbA1c) in patients who are receiving treatment with GnRH agonists. Physicians should also monitor patients for signs and symptoms suggestive of development of cardiovascular disease and manage them, according to current clinical practice.

Adverse events involving GnRH agonists should be reported to the FDA MedWatch program at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm, or by calling 800-332-1088.

The Food and Drug Administration wants manufacturers to add new warnings to the labels of gonadotropin-releasing hormone agonists – used mainly to treat men with prostate cancer – because of concerns about increased risks of diabetes, MI, stroke, and sudden death.

The new warnings are the result of a preliminary and ongoing analysis showing that patients on gonadotropin-releasing hormone (GnRH) agonists are at a small increased risk for diabetes, MI, stroke, and sudden death, according to an agency statement released on Oct. 20.

GnRH agonists are indicated for the palliative treatment of symptoms of advanced prostate cancer. Medications in the GnRH class are marketed under the brand names Eligard, Lupron, Synarel, Trelstar, Vantas, Viadur, and Zoladex. Several generic products are also available.

In May 2010, the agency released the early findings and advised physicians to be aware of these potential risks and carefully weigh the benefits and risks of GnRH agonists when determining a treatment for patients with prostate cancer.

Physicians should periodically monitor blood glucose and/or glycosylated hemoglobin (HbA1c) in patients who are receiving treatment with GnRH agonists. Physicians should also monitor patients for signs and symptoms suggestive of development of cardiovascular disease and manage them, according to current clinical practice.

Adverse events involving GnRH agonists should be reported to the FDA MedWatch program at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm, or by calling 800-332-1088.

NATIONAL HARBOR, MD. – Oophorectomy cut the risk of contralateral breast cancer by almost half in women with a family history of BRCA mutations, according to results of a retrospective study of more than 800 women. The benefit was even greater in women diagnosed with breast cancer before age 50.

“Oophorectomy was the most significant predictor of the development of contralateral breast cancer in this group of women,” investigator Kelly A. Metcalfe, Ph.D., said at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

Removing ovaries reduced the risk of contralateral breast cancer by 47% in the entire cohort (relative risk 0.53, P = .007), she reported. Women younger than age 50 had a 55% reduction (RR 0.45, P = .002), but oophorectomy had no effect on risk of contralateral breast cancer in women 50 and older.

The multicenter cohort study followed women from the date of breast cancer diagnosis until contralateral breast cancer was diagnosed, contralateral mastectomy was performed, death, or date of last follow-up.

Women were included if they were part of a family with known BRCA1 or BRCA2 mutations, had stage I or II breast cancer, were 65 years or younger at the time of diagnosis, were diagnosed in 1975 or later, and had no previous cancer diagnosis. Investigators included living and deceased patients to avoid survivorship bias.

Researchers first performed a pedigree review at participating centers in Canada and the United States to identify eligible patients who had first-degree and second-degree relatives with breast cancer (and their age at diagnosis).

Next, they conducted a medical chart review to assess tumor characteristics (size, nodal status, laterality, grade, and ER/PR status) and treatments (chemotherapy, tamoxifen, surgery, radiotherapy, and oophorectomy). All told, 60% of the women had records of oophorectomy.

Lastly, the investigators determined a patient’s vital status, further treatments, and disease status at follow-up – communicating with the patient or next-of-kin. Deaths were confirmed through medical records.

The researchers reviewed 1,866 cases of breast cancer in 615 families. A total of 846 patients – 79% living – were eligible, gave consent, and had medical charts available for review.

The mean year of birth was 1950, and the mean age at diagnosis was 42 years. The women were followed for an average of 11.5 years. Nearly two-thirds (62%) had BRCA1 mutations, and 88% had undergone genetic testing. Among 177 women who died, breast cancer was the cause of death for 83%.

In the full study cohort, 18% were diagnosed with contralateral breast cancer with a mean time between the two diagnoses of 5.7 years. At 5 years, all women in the cohort had a 13% risk of developing contralateral disease, which rose to 34% at 15 years.

“Age was a very important predictor for these women. Women who were diagnosed with young-onset breast cancer (under the age of 50) had a significantly higher risk of developing contralateral breast cancer within the first 15 years,” said Dr. Metcalfe of the nursing faculty at the University of Toronto. For younger women, the risk was 38% at 15 years, compared with 18% in women 50 and older.

At 15 years post diagnosis, a woman younger than 50 years who had not had an oophorectomy had a roughly 60% risk of developing contralateral breast cancer. The risk was roughly 20% in women 50 years or older with intact ovaries.

Family history also appeared to play an important role. “When we looked at the total number of first-degree relatives diagnosed with breast cancer under the age of 50, we saw increases in risk of contralateral breast cancer,” Dr. Metcalfe said.

Among the whole cohort, the risk of contralateral breast cancer increased by a third with every first-degree relative diagnosed with breast cancer under age 50. “This was particularly evident in BRCA1 carriers and early-onset breast cancer,” said Dr. Metcalfe. Risk was increased by roughly 40% in each of these groups.

For women younger than 50 years at diagnosis who still have intact ovaries, the risk of developing contralateral breast cancer at 15 years was 58%. With the addition of two or more first-degree relatives diagnosed with breast cancer under the age 50, the 15-year risk rose to 68%.

“These are the women that we really need to identify and counsel appropriately, when [they are] considering preventive surgery for the development of contralateral breast cancer,” said Dr. Metcalfe. “We need to think about how these women need to be treated, not only to treat that initial breast cancer but also to prevent contralateral breast cancer.”

The authors reported that they have no relevant financial relationships.

NATIONAL HARBOR, MD. – Oophorectomy cut the risk of contralateral breast cancer by almost half in women with a family history of BRCA mutations, according to results of a retrospective study of more than 800 women. The benefit was even greater in women diagnosed with breast cancer before age 50.

“Oophorectomy was the most significant predictor of the development of contralateral breast cancer in this group of women,” investigator Kelly A. Metcalfe, Ph.D., said at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

Removing ovaries reduced the risk of contralateral breast cancer by 47% in the entire cohort (relative risk 0.53, P = .007), she reported. Women younger than age 50 had a 55% reduction (RR 0.45, P = .002), but oophorectomy had no effect on risk of contralateral breast cancer in women 50 and older.

The multicenter cohort study followed women from the date of breast cancer diagnosis until contralateral breast cancer was diagnosed, contralateral mastectomy was performed, death, or date of last follow-up.

Women were included if they were part of a family with known BRCA1 or BRCA2 mutations, had stage I or II breast cancer, were 65 years or younger at the time of diagnosis, were diagnosed in 1975 or later, and had no previous cancer diagnosis. Investigators included living and deceased patients to avoid survivorship bias.

Researchers first performed a pedigree review at participating centers in Canada and the United States to identify eligible patients who had first-degree and second-degree relatives with breast cancer (and their age at diagnosis).

Next, they conducted a medical chart review to assess tumor characteristics (size, nodal status, laterality, grade, and ER/PR status) and treatments (chemotherapy, tamoxifen, surgery, radiotherapy, and oophorectomy). All told, 60% of the women had records of oophorectomy.

Lastly, the investigators determined a patient’s vital status, further treatments, and disease status at follow-up – communicating with the patient or next-of-kin. Deaths were confirmed through medical records.

The researchers reviewed 1,866 cases of breast cancer in 615 families. A total of 846 patients – 79% living – were eligible, gave consent, and had medical charts available for review.

The mean year of birth was 1950, and the mean age at diagnosis was 42 years. The women were followed for an average of 11.5 years. Nearly two-thirds (62%) had BRCA1 mutations, and 88% had undergone genetic testing. Among 177 women who died, breast cancer was the cause of death for 83%.

In the full study cohort, 18% were diagnosed with contralateral breast cancer with a mean time between the two diagnoses of 5.7 years. At 5 years, all women in the cohort had a 13% risk of developing contralateral disease, which rose to 34% at 15 years.

“Age was a very important predictor for these women. Women who were diagnosed with young-onset breast cancer (under the age of 50) had a significantly higher risk of developing contralateral breast cancer within the first 15 years,” said Dr. Metcalfe of the nursing faculty at the University of Toronto. For younger women, the risk was 38% at 15 years, compared with 18% in women 50 and older.

At 15 years post diagnosis, a woman younger than 50 years who had not had an oophorectomy had a roughly 60% risk of developing contralateral breast cancer. The risk was roughly 20% in women 50 years or older with intact ovaries.

Family history also appeared to play an important role. “When we looked at the total number of first-degree relatives diagnosed with breast cancer under the age of 50, we saw increases in risk of contralateral breast cancer,” Dr. Metcalfe said.

Among the whole cohort, the risk of contralateral breast cancer increased by a third with every first-degree relative diagnosed with breast cancer under age 50. “This was particularly evident in BRCA1 carriers and early-onset breast cancer,” said Dr. Metcalfe. Risk was increased by roughly 40% in each of these groups.

For women younger than 50 years at diagnosis who still have intact ovaries, the risk of developing contralateral breast cancer at 15 years was 58%. With the addition of two or more first-degree relatives diagnosed with breast cancer under the age 50, the 15-year risk rose to 68%.

“These are the women that we really need to identify and counsel appropriately, when [they are] considering preventive surgery for the development of contralateral breast cancer,” said Dr. Metcalfe. “We need to think about how these women need to be treated, not only to treat that initial breast cancer but also to prevent contralateral breast cancer.”

The authors reported that they have no relevant financial relationships.

NATIONAL HARBOR, MD. – Oophorectomy cut the risk of contralateral breast cancer by almost half in women with a family history of BRCA mutations, according to results of a retrospective study of more than 800 women. The benefit was even greater in women diagnosed with breast cancer before age 50.

“Oophorectomy was the most significant predictor of the development of contralateral breast cancer in this group of women,” investigator Kelly A. Metcalfe, Ph.D., said at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

Removing ovaries reduced the risk of contralateral breast cancer by 47% in the entire cohort (relative risk 0.53, P = .007), she reported. Women younger than age 50 had a 55% reduction (RR 0.45, P = .002), but oophorectomy had no effect on risk of contralateral breast cancer in women 50 and older.

The multicenter cohort study followed women from the date of breast cancer diagnosis until contralateral breast cancer was diagnosed, contralateral mastectomy was performed, death, or date of last follow-up.

Women were included if they were part of a family with known BRCA1 or BRCA2 mutations, had stage I or II breast cancer, were 65 years or younger at the time of diagnosis, were diagnosed in 1975 or later, and had no previous cancer diagnosis. Investigators included living and deceased patients to avoid survivorship bias.

Researchers first performed a pedigree review at participating centers in Canada and the United States to identify eligible patients who had first-degree and second-degree relatives with breast cancer (and their age at diagnosis).

Next, they conducted a medical chart review to assess tumor characteristics (size, nodal status, laterality, grade, and ER/PR status) and treatments (chemotherapy, tamoxifen, surgery, radiotherapy, and oophorectomy). All told, 60% of the women had records of oophorectomy.

Lastly, the investigators determined a patient’s vital status, further treatments, and disease status at follow-up – communicating with the patient or next-of-kin. Deaths were confirmed through medical records.

The researchers reviewed 1,866 cases of breast cancer in 615 families. A total of 846 patients – 79% living – were eligible, gave consent, and had medical charts available for review.

The mean year of birth was 1950, and the mean age at diagnosis was 42 years. The women were followed for an average of 11.5 years. Nearly two-thirds (62%) had BRCA1 mutations, and 88% had undergone genetic testing. Among 177 women who died, breast cancer was the cause of death for 83%.

In the full study cohort, 18% were diagnosed with contralateral breast cancer with a mean time between the two diagnoses of 5.7 years. At 5 years, all women in the cohort had a 13% risk of developing contralateral disease, which rose to 34% at 15 years.

“Age was a very important predictor for these women. Women who were diagnosed with young-onset breast cancer (under the age of 50) had a significantly higher risk of developing contralateral breast cancer within the first 15 years,” said Dr. Metcalfe of the nursing faculty at the University of Toronto. For younger women, the risk was 38% at 15 years, compared with 18% in women 50 and older.

At 15 years post diagnosis, a woman younger than 50 years who had not had an oophorectomy had a roughly 60% risk of developing contralateral breast cancer. The risk was roughly 20% in women 50 years or older with intact ovaries.

Family history also appeared to play an important role. “When we looked at the total number of first-degree relatives diagnosed with breast cancer under the age of 50, we saw increases in risk of contralateral breast cancer,” Dr. Metcalfe said.

Among the whole cohort, the risk of contralateral breast cancer increased by a third with every first-degree relative diagnosed with breast cancer under age 50. “This was particularly evident in BRCA1 carriers and early-onset breast cancer,” said Dr. Metcalfe. Risk was increased by roughly 40% in each of these groups.

For women younger than 50 years at diagnosis who still have intact ovaries, the risk of developing contralateral breast cancer at 15 years was 58%. With the addition of two or more first-degree relatives diagnosed with breast cancer under the age 50, the 15-year risk rose to 68%.

“These are the women that we really need to identify and counsel appropriately, when [they are] considering preventive surgery for the development of contralateral breast cancer,” said Dr. Metcalfe. “We need to think about how these women need to be treated, not only to treat that initial breast cancer but also to prevent contralateral breast cancer.”

The authors reported that they have no relevant financial relationships.

Major Finding: Carotid endarterectomy, perioperative stroke, and death rates for symptomatic patients have declined over the last 2 decades.

Data Source: NASCET I and II, ACAS, and CREST trials.

Disclosures: The research was supported by the National Institute of Neurological Disorders and Stroke, with supplemental support from Abbott Vascular Inc. Dr. Lal reported that he has no relevant financial relationships.

BOSTON — Perioperative stroke and death rates associated with carotid endarterectomy have improved for symptomatic patients over the last 20 years, based on a comparison of newly released data.

“The periprocedural stroke and death rate has not changed dramatically in asymptomatic patients, whereas it has almost halved in patients with symptomatic disease,” Dr. Brajesh K. Lal observed at the meeting.

Dr. Lal and his coinvestigators compared periprocedural stroke and death rates associated with carotid endarterectomy (CEA) in CREST (Carotid Endarterectomy vs. Stenting Trial), NASCET I and II (North American Symptomatic Carotid Endarterectomy Trials I and II), and ACAS (Asymptomatic Carotid Atherosclerosis Study).

The perioperative stroke plus death rate for symptomatic patients who underwent CEA was 5.8%, 6.7%, and 3.2% in the NASCET I and II (N. Engl. J. Med. 1991;325:445-53; 1998;339:1415-25) and CREST (N. Engl. J. Med. 2010;363:11-23) trials, respectively. “Operative stroke and death in symptomatic patients [in the CREST trial] were lower than in NASCET and could be related to increased intraoperative shunting, patch angioplasty, antilipid therapy, or antihypertensive therapy,” said Dr. Lal of the division of vascular surgery at the University of Maryland in Baltimore.

Although antiplatelet therapy following CEA was used at similar rates in all of the trials, postprocedure antilipid therapy was used much more frequently in the CREST trial: 76% for both symptomatic and asymptomatic patients in CREST, compared with 14% in NASCET I and 40% in NASCET II. Likewise, postprocedure antihypertensive therapy was used more frequently in CREST than in NASCET I and II: 80%, 54%, and 68%, respectively.

For asymptomatic patients, the perioperative stroke plus death rate was 2.3% and 1.4% in ACAS (JAMA 1995;273:1421-8) and CREST, respectively. However, the ACAS rate included a 1.2% angiography complications rate, Dr. Lal noted. If angiographic complications are excluded from the ACAS results, the perioperative stroke plus death rate for asymptomatic patients was comparable for ACAS and CREST (1.5% for ACAS vs. 1.4% for CREST).

The sesearcherr also compared inclusion criteria, enrollment details, criteria used to credential surgeons, criteria used to define perioperative stroke, surgical technique, and perioperative medical therapy.

Inclusion Criteria

NASCET I was open to patients older than 80 years, and ACAS was open to patients aged 40-79 years. NASCET II and CREST were open to patients of all ages.

NASCET I included symptomatic patients with 70%-99% stenosis; NASCET II was open to symptomatic patients with 50%-69% stenosis. ACAS was open to asymptomatic patients with 60% or greater stenosis. CREST was open to asymptomatic patients with 60% or greater stenosis and symptomatic patients with 50% or greater stenosis.

In patients in both NASCETs and roughly half of the patients in ACAS, the percentage of stenosis was determined by means of preoperative angiograms. In CREST, the percentage of stenosis was determined by ultrasound, CT angiography, MR angiography, and angiogram. There were only slight differences among the trials in terms of the definition of symptomatic status.

Enrollment

Both NASCETs as well as ACAS started enrolling patients in 1987 and stopped enrolling patients in the 1990s, whereas CREST enrolled patients during 2000-2008. Both NASCET I and ACAS were conducted in a smaller number of centers (50 and 39, respectively). NASCET II and CREST were conducted in more than 100 centers each (106 and 117, respectively). There were more patients randomized to CEA in the CREST trial (1,240) than in the other three trials (328 for NASCET I, 430 for NASCET II, and 825 for ACAS).

In terms of baseline characteristics, patients in the trials did not differ by age, sex distribution, or race. The rates of smoking, cardiovascular disease, and preprocedure antiplatelet therapy also did not differ among the trials. However, CREST enrolled more patients with hypertension, diabetes, and dyslipidemia. Also, shunting and patch angioplasty were used more frequently in CREST.

Credentialing

“The credentialing criteria for surgeons were fairly consistent across all of the trials,” said Dr. Lal. Both CREST and ACAS required surgeons to perform at least 12 CEAs each year. However, there were no established surgeon volume requirements in the two NASCETs. All four trials included surgical management committees, site evaluations, and reviews of indications, hospital courses, and outcomes in the 50 most recent CEAs.

The minimum stroke plus death rate was no more than 3% for asymptomatic patients and no more than 5% for symptomatic patients in both CREST and ACAS; both NASCETs had a minimum rate of less than 6% in symptomatic patients.

End Points

The primary end point for both NASCETs as well as ACAS was the number of strokes plus deaths. For CREST, however, the primary end point was the number of strokes, MIs, and deaths. Importantly, the definition of stroke (an acute neurologic ischemic event of at least 24 hours' duration with focal signs and symptoms) was consistent across the trials. In all cases, strokes were adjudicated by neurologists, who were blinded to the treatment.

Major Finding: Carotid endarterectomy, perioperative stroke, and death rates for symptomatic patients have declined over the last 2 decades.

Data Source: NASCET I and II, ACAS, and CREST trials.

Disclosures: The research was supported by the National Institute of Neurological Disorders and Stroke, with supplemental support from Abbott Vascular Inc. Dr. Lal reported that he has no relevant financial relationships.

BOSTON — Perioperative stroke and death rates associated with carotid endarterectomy have improved for symptomatic patients over the last 20 years, based on a comparison of newly released data.

“The periprocedural stroke and death rate has not changed dramatically in asymptomatic patients, whereas it has almost halved in patients with symptomatic disease,” Dr. Brajesh K. Lal observed at the meeting.

Dr. Lal and his coinvestigators compared periprocedural stroke and death rates associated with carotid endarterectomy (CEA) in CREST (Carotid Endarterectomy vs. Stenting Trial), NASCET I and II (North American Symptomatic Carotid Endarterectomy Trials I and II), and ACAS (Asymptomatic Carotid Atherosclerosis Study).

The perioperative stroke plus death rate for symptomatic patients who underwent CEA was 5.8%, 6.7%, and 3.2% in the NASCET I and II (N. Engl. J. Med. 1991;325:445-53; 1998;339:1415-25) and CREST (N. Engl. J. Med. 2010;363:11-23) trials, respectively. “Operative stroke and death in symptomatic patients [in the CREST trial] were lower than in NASCET and could be related to increased intraoperative shunting, patch angioplasty, antilipid therapy, or antihypertensive therapy,” said Dr. Lal of the division of vascular surgery at the University of Maryland in Baltimore.

Although antiplatelet therapy following CEA was used at similar rates in all of the trials, postprocedure antilipid therapy was used much more frequently in the CREST trial: 76% for both symptomatic and asymptomatic patients in CREST, compared with 14% in NASCET I and 40% in NASCET II. Likewise, postprocedure antihypertensive therapy was used more frequently in CREST than in NASCET I and II: 80%, 54%, and 68%, respectively.

For asymptomatic patients, the perioperative stroke plus death rate was 2.3% and 1.4% in ACAS (JAMA 1995;273:1421-8) and CREST, respectively. However, the ACAS rate included a 1.2% angiography complications rate, Dr. Lal noted. If angiographic complications are excluded from the ACAS results, the perioperative stroke plus death rate for asymptomatic patients was comparable for ACAS and CREST (1.5% for ACAS vs. 1.4% for CREST).

The sesearcherr also compared inclusion criteria, enrollment details, criteria used to credential surgeons, criteria used to define perioperative stroke, surgical technique, and perioperative medical therapy.

Inclusion Criteria

NASCET I was open to patients older than 80 years, and ACAS was open to patients aged 40-79 years. NASCET II and CREST were open to patients of all ages.

NASCET I included symptomatic patients with 70%-99% stenosis; NASCET II was open to symptomatic patients with 50%-69% stenosis. ACAS was open to asymptomatic patients with 60% or greater stenosis. CREST was open to asymptomatic patients with 60% or greater stenosis and symptomatic patients with 50% or greater stenosis.

In patients in both NASCETs and roughly half of the patients in ACAS, the percentage of stenosis was determined by means of preoperative angiograms. In CREST, the percentage of stenosis was determined by ultrasound, CT angiography, MR angiography, and angiogram. There were only slight differences among the trials in terms of the definition of symptomatic status.

Enrollment

Both NASCETs as well as ACAS started enrolling patients in 1987 and stopped enrolling patients in the 1990s, whereas CREST enrolled patients during 2000-2008. Both NASCET I and ACAS were conducted in a smaller number of centers (50 and 39, respectively). NASCET II and CREST were conducted in more than 100 centers each (106 and 117, respectively). There were more patients randomized to CEA in the CREST trial (1,240) than in the other three trials (328 for NASCET I, 430 for NASCET II, and 825 for ACAS).

In terms of baseline characteristics, patients in the trials did not differ by age, sex distribution, or race. The rates of smoking, cardiovascular disease, and preprocedure antiplatelet therapy also did not differ among the trials. However, CREST enrolled more patients with hypertension, diabetes, and dyslipidemia. Also, shunting and patch angioplasty were used more frequently in CREST.

Credentialing

“The credentialing criteria for surgeons were fairly consistent across all of the trials,” said Dr. Lal. Both CREST and ACAS required surgeons to perform at least 12 CEAs each year. However, there were no established surgeon volume requirements in the two NASCETs. All four trials included surgical management committees, site evaluations, and reviews of indications, hospital courses, and outcomes in the 50 most recent CEAs.

The minimum stroke plus death rate was no more than 3% for asymptomatic patients and no more than 5% for symptomatic patients in both CREST and ACAS; both NASCETs had a minimum rate of less than 6% in symptomatic patients.

End Points

The primary end point for both NASCETs as well as ACAS was the number of strokes plus deaths. For CREST, however, the primary end point was the number of strokes, MIs, and deaths. Importantly, the definition of stroke (an acute neurologic ischemic event of at least 24 hours' duration with focal signs and symptoms) was consistent across the trials. In all cases, strokes were adjudicated by neurologists, who were blinded to the treatment.

Major Finding: Carotid endarterectomy, perioperative stroke, and death rates for symptomatic patients have declined over the last 2 decades.

Data Source: NASCET I and II, ACAS, and CREST trials.

Disclosures: The research was supported by the National Institute of Neurological Disorders and Stroke, with supplemental support from Abbott Vascular Inc. Dr. Lal reported that he has no relevant financial relationships.

BOSTON — Perioperative stroke and death rates associated with carotid endarterectomy have improved for symptomatic patients over the last 20 years, based on a comparison of newly released data.

“The periprocedural stroke and death rate has not changed dramatically in asymptomatic patients, whereas it has almost halved in patients with symptomatic disease,” Dr. Brajesh K. Lal observed at the meeting.

Dr. Lal and his coinvestigators compared periprocedural stroke and death rates associated with carotid endarterectomy (CEA) in CREST (Carotid Endarterectomy vs. Stenting Trial), NASCET I and II (North American Symptomatic Carotid Endarterectomy Trials I and II), and ACAS (Asymptomatic Carotid Atherosclerosis Study).

The perioperative stroke plus death rate for symptomatic patients who underwent CEA was 5.8%, 6.7%, and 3.2% in the NASCET I and II (N. Engl. J. Med. 1991;325:445-53; 1998;339:1415-25) and CREST (N. Engl. J. Med. 2010;363:11-23) trials, respectively. “Operative stroke and death in symptomatic patients [in the CREST trial] were lower than in NASCET and could be related to increased intraoperative shunting, patch angioplasty, antilipid therapy, or antihypertensive therapy,” said Dr. Lal of the division of vascular surgery at the University of Maryland in Baltimore.

Although antiplatelet therapy following CEA was used at similar rates in all of the trials, postprocedure antilipid therapy was used much more frequently in the CREST trial: 76% for both symptomatic and asymptomatic patients in CREST, compared with 14% in NASCET I and 40% in NASCET II. Likewise, postprocedure antihypertensive therapy was used more frequently in CREST than in NASCET I and II: 80%, 54%, and 68%, respectively.

For asymptomatic patients, the perioperative stroke plus death rate was 2.3% and 1.4% in ACAS (JAMA 1995;273:1421-8) and CREST, respectively. However, the ACAS rate included a 1.2% angiography complications rate, Dr. Lal noted. If angiographic complications are excluded from the ACAS results, the perioperative stroke plus death rate for asymptomatic patients was comparable for ACAS and CREST (1.5% for ACAS vs. 1.4% for CREST).

The sesearcherr also compared inclusion criteria, enrollment details, criteria used to credential surgeons, criteria used to define perioperative stroke, surgical technique, and perioperative medical therapy.

Inclusion Criteria

NASCET I was open to patients older than 80 years, and ACAS was open to patients aged 40-79 years. NASCET II and CREST were open to patients of all ages.

NASCET I included symptomatic patients with 70%-99% stenosis; NASCET II was open to symptomatic patients with 50%-69% stenosis. ACAS was open to asymptomatic patients with 60% or greater stenosis. CREST was open to asymptomatic patients with 60% or greater stenosis and symptomatic patients with 50% or greater stenosis.

In patients in both NASCETs and roughly half of the patients in ACAS, the percentage of stenosis was determined by means of preoperative angiograms. In CREST, the percentage of stenosis was determined by ultrasound, CT angiography, MR angiography, and angiogram. There were only slight differences among the trials in terms of the definition of symptomatic status.

Enrollment

Both NASCETs as well as ACAS started enrolling patients in 1987 and stopped enrolling patients in the 1990s, whereas CREST enrolled patients during 2000-2008. Both NASCET I and ACAS were conducted in a smaller number of centers (50 and 39, respectively). NASCET II and CREST were conducted in more than 100 centers each (106 and 117, respectively). There were more patients randomized to CEA in the CREST trial (1,240) than in the other three trials (328 for NASCET I, 430 for NASCET II, and 825 for ACAS).

In terms of baseline characteristics, patients in the trials did not differ by age, sex distribution, or race. The rates of smoking, cardiovascular disease, and preprocedure antiplatelet therapy also did not differ among the trials. However, CREST enrolled more patients with hypertension, diabetes, and dyslipidemia. Also, shunting and patch angioplasty were used more frequently in CREST.

Credentialing

“The credentialing criteria for surgeons were fairly consistent across all of the trials,” said Dr. Lal. Both CREST and ACAS required surgeons to perform at least 12 CEAs each year. However, there were no established surgeon volume requirements in the two NASCETs. All four trials included surgical management committees, site evaluations, and reviews of indications, hospital courses, and outcomes in the 50 most recent CEAs.

The minimum stroke plus death rate was no more than 3% for asymptomatic patients and no more than 5% for symptomatic patients in both CREST and ACAS; both NASCETs had a minimum rate of less than 6% in symptomatic patients.

End Points

The primary end point for both NASCETs as well as ACAS was the number of strokes plus deaths. For CREST, however, the primary end point was the number of strokes, MIs, and deaths. Importantly, the definition of stroke (an acute neurologic ischemic event of at least 24 hours' duration with focal signs and symptoms) was consistent across the trials. In all cases, strokes were adjudicated by neurologists, who were blinded to the treatment.

The rotavirus vaccine Rotarix may slightly increase the risk of intussusception, based on preliminary data from a postmarketing study in Mexico that prompted the Food and Drug Administration to approve label revisions.

The revisions to the warnings and precautions section and the postmarketing subsection of the adverse reactions section of the label were added to inform physicians of the new findings. An interim analysis of the data suggests an increased risk (1.8) of intussusception within the first 31 days after the first dose.

"For the United States, these findings translate to potentially 0–4 additional cases of intussusception hospitalizations per 100,000 infants within the first 31 days of receiving the first dose of Rotarix," the agency wrote in a Questions and Answers update released Sept. 22, 2010. The study did not look at RotaTeq.

Physicians should be aware of the data but "explain to parents and caregivers of infants that the benefits of vaccination with both Rotarix and RotaTeq outweigh any potential risks," the FDA said.

Parents should be informed of the signs and symptoms of intussusception, which include stomach pain, vomiting, diarrhea, blood in the stool, or change in bowel movements – especially within the first 7 days after the dose of the vaccine. Further analysis of the data revealed that most of the intussusception cases occurred within this time period.

The FDA and the Centers for Disease Control and Prevention encourage physicians to report intussusception or any adverse event after vaccination to the Vaccine Adverse Event Reporting System.

The rotavirus vaccine Rotarix may slightly increase the risk of intussusception, based on preliminary data from a postmarketing study in Mexico that prompted the Food and Drug Administration to approve label revisions.

The revisions to the warnings and precautions section and the postmarketing subsection of the adverse reactions section of the label were added to inform physicians of the new findings. An interim analysis of the data suggests an increased risk (1.8) of intussusception within the first 31 days after the first dose.

"For the United States, these findings translate to potentially 0–4 additional cases of intussusception hospitalizations per 100,000 infants within the first 31 days of receiving the first dose of Rotarix," the agency wrote in a Questions and Answers update released Sept. 22, 2010. The study did not look at RotaTeq.

Physicians should be aware of the data but "explain to parents and caregivers of infants that the benefits of vaccination with both Rotarix and RotaTeq outweigh any potential risks," the FDA said.

Parents should be informed of the signs and symptoms of intussusception, which include stomach pain, vomiting, diarrhea, blood in the stool, or change in bowel movements – especially within the first 7 days after the dose of the vaccine. Further analysis of the data revealed that most of the intussusception cases occurred within this time period.

The FDA and the Centers for Disease Control and Prevention encourage physicians to report intussusception or any adverse event after vaccination to the Vaccine Adverse Event Reporting System.

The rotavirus vaccine Rotarix may slightly increase the risk of intussusception, based on preliminary data from a postmarketing study in Mexico that prompted the Food and Drug Administration to approve label revisions.

The revisions to the warnings and precautions section and the postmarketing subsection of the adverse reactions section of the label were added to inform physicians of the new findings. An interim analysis of the data suggests an increased risk (1.8) of intussusception within the first 31 days after the first dose.

"For the United States, these findings translate to potentially 0–4 additional cases of intussusception hospitalizations per 100,000 infants within the first 31 days of receiving the first dose of Rotarix," the agency wrote in a Questions and Answers update released Sept. 22, 2010. The study did not look at RotaTeq.

Physicians should be aware of the data but "explain to parents and caregivers of infants that the benefits of vaccination with both Rotarix and RotaTeq outweigh any potential risks," the FDA said.

Parents should be informed of the signs and symptoms of intussusception, which include stomach pain, vomiting, diarrhea, blood in the stool, or change in bowel movements – especially within the first 7 days after the dose of the vaccine. Further analysis of the data revealed that most of the intussusception cases occurred within this time period.

The FDA and the Centers for Disease Control and Prevention encourage physicians to report intussusception or any adverse event after vaccination to the Vaccine Adverse Event Reporting System.

Antipsychotics are associated with an almost one-third (32%) greater risk of venous thromboembolism, according to results of a nested case-control study of more than 100,000 primary care patients in the United Kingdom.

Previous research has suggested that these drugs – also commonly used for nausea, vomiting, and vertigo – might be linked with an increased risk of venous thromboembolism (VTE). However, the results have been inconsistent.

In the current study, the association was even greater for new users of antipsychotics. Those with any antipsychotic use in last 3 months had a 56% increased risk of VTE. Patients who started taking an antipsychotic in the past 3 months had a 97% increased risk. However, the absolute risks were low, with an excess of four extra cases of VTE per 10,000 patients treated over 1 year in patients of all ages and 10 for patients aged 65 years and older.

“Our study adds to the accumulating evidence of adverse health events associated with antipsychotic drugs,” the researchers wrote in the study, published online Sept. 21 in the British Medical Journal (BMJ 2010 Sept. 21 [doi:10.1136/bmj.c4245]). “If other studies replicate these findings, antipsychotic drugs should be used more cautiously for nausea and agitation, etc., especially among patients at high risk of thromboembolism.”

The researchers used data from the QResearch database, which includes primary care clinical records for more than 11 million people registered in the past 16 years at more than 500 U.K. general practices. The study population was an open cohort of patients aged 16-100 years, who were registered with participating practices between January 1996 and July 2007. Case patients had a first-ever record of VTE – either deep vein thrombosis or pulmonary embolism – during the study period (including postmortem diagnoses).

Incidence density sampling was used to identify up to four control patients for each case patient. Control patients were matched by age, calendar time, sex, and practice. Control patients had no diagnoses of VTE prior to the date of the first recorded diagnosis of VTE in their matched case patient (index date).

In all, 25,532 eligible case patients – 15,975 with DVT and 9,557 with pulmonary embolism – and 89,491 control patients were included in the study. In terms of mental health disorders, the overall prevalence was 0.4% for schizophrenia, 0.3% for bipolar disorder, and 1.0% for dementia. Eight case patients and 31 control patients had more than one disorder. In all, 8.3% of case patients and 5.3% of control patients had received an antipsychotic in the previous 24 months.

Overall, antipsychotic users had a 32% greater risk of VTE than did nonusers. Among those on antipsychotics, 38% were current users and their increase in risk was 56% compared with 36% for recent users. The risk was not significantly increased for past users. Among current antipsychotic users, 15% had started a new drug within the 3 months prior to the index date. This group of new users showed a greater increase in risk (97%) than did continuing users (29%).

Patients who were prescribed atypical antipsychotic drugs had a greater risk of VTE than did those who were prescribed conventional antipsychotics – 73% compared with 28%.

Patients who had received only one prescription in the previous 12 months had a significantly greater risk (32%) than did those receiving none.

In addition, those who were prescribed two or more different antipsychotics had a greater risk (99%) than did those who received only one (29%).

Disclosures: The authors reported that they have no relevant fnancial relationships.

View on the News

Implications Could Be Far Reaching

The validity of the findings is strengthened by the large sample size and the low potential for exposure and outcome misclassification because of the detailed source of data and adjustment for a large number of confounders, according to Dr. Rosa Liperoti and Dr. Giovanni Gambassi.

It's been demonstrated that “patients with schizophrenia have an increased risk of venous thromboembolism (VTE), and this might be associated with the use of antipsychotics, especially low-potency drugs such as chlorpromazine and thioridazine.

So far, however, the possibility that the underlying psychiatric disorders themselves – and not the antipsychotics – are associated with VTE has never been excluded. This could occur by the increased concentrations of adrenaline seen during psychotic excitation increasing blood coagulation,” they noted.

In this study, in almost all cases the reason for prescription of antipsychotics could not be ascertained. Most of the antipsychotics used were conventional agents, with prochlorperazine – probably given for nausea and vomiting – accounting for almost 80% of all prescriptions, they wrote.

“These findings indicate that VTE is directly linked to the use of an antipsychotic, and that the risk of VTE increases early after starting the drug.”

The implications are potentially far reaching. “Despite their association with serious risks and few data to support their efficacy, antipsychotics are widely used, and in 2008 they became the top selling drug class in the United States,” they wrote.

ROSA LIPEROTI, M.D., is a specialist in geriatrics and GIOVANNI GAMBASSI, M.D., is a professor of geriatrics at Università Cattolica del Sacro Cuore in Rome. Both Dr. Liperoti and Dr. Gambassi reported that they have no relevant financial relationships. These comments were taken from a commentary that accompanied the study (BMJ 2010 Sept. 21 [doi: 10.1136/bmj.c4216]).

Antipsychotics are associated with an almost one-third (32%) greater risk of venous thromboembolism, according to results of a nested case-control study of more than 100,000 primary care patients in the United Kingdom.

Previous research has suggested that these drugs – also commonly used for nausea, vomiting, and vertigo – might be linked with an increased risk of venous thromboembolism (VTE). However, the results have been inconsistent.

In the current study, the association was even greater for new users of antipsychotics. Those with any antipsychotic use in last 3 months had a 56% increased risk of VTE. Patients who started taking an antipsychotic in the past 3 months had a 97% increased risk. However, the absolute risks were low, with an excess of four extra cases of VTE per 10,000 patients treated over 1 year in patients of all ages and 10 for patients aged 65 years and older.

“Our study adds to the accumulating evidence of adverse health events associated with antipsychotic drugs,” the researchers wrote in the study, published online Sept. 21 in the British Medical Journal (BMJ 2010 Sept. 21 [doi:10.1136/bmj.c4245]). “If other studies replicate these findings, antipsychotic drugs should be used more cautiously for nausea and agitation, etc., especially among patients at high risk of thromboembolism.”

The researchers used data from the QResearch database, which includes primary care clinical records for more than 11 million people registered in the past 16 years at more than 500 U.K. general practices. The study population was an open cohort of patients aged 16-100 years, who were registered with participating practices between January 1996 and July 2007. Case patients had a first-ever record of VTE – either deep vein thrombosis or pulmonary embolism – during the study period (including postmortem diagnoses).

Incidence density sampling was used to identify up to four control patients for each case patient. Control patients were matched by age, calendar time, sex, and practice. Control patients had no diagnoses of VTE prior to the date of the first recorded diagnosis of VTE in their matched case patient (index date).

In all, 25,532 eligible case patients – 15,975 with DVT and 9,557 with pulmonary embolism – and 89,491 control patients were included in the study. In terms of mental health disorders, the overall prevalence was 0.4% for schizophrenia, 0.3% for bipolar disorder, and 1.0% for dementia. Eight case patients and 31 control patients had more than one disorder. In all, 8.3% of case patients and 5.3% of control patients had received an antipsychotic in the previous 24 months.

Overall, antipsychotic users had a 32% greater risk of VTE than did nonusers. Among those on antipsychotics, 38% were current users and their increase in risk was 56% compared with 36% for recent users. The risk was not significantly increased for past users. Among current antipsychotic users, 15% had started a new drug within the 3 months prior to the index date. This group of new users showed a greater increase in risk (97%) than did continuing users (29%).

Patients who were prescribed atypical antipsychotic drugs had a greater risk of VTE than did those who were prescribed conventional antipsychotics – 73% compared with 28%.

Patients who had received only one prescription in the previous 12 months had a significantly greater risk (32%) than did those receiving none.

In addition, those who were prescribed two or more different antipsychotics had a greater risk (99%) than did those who received only one (29%).

Disclosures: The authors reported that they have no relevant fnancial relationships.

View on the News

Implications Could Be Far Reaching

The validity of the findings is strengthened by the large sample size and the low potential for exposure and outcome misclassification because of the detailed source of data and adjustment for a large number of confounders, according to Dr. Rosa Liperoti and Dr. Giovanni Gambassi.

It's been demonstrated that “patients with schizophrenia have an increased risk of venous thromboembolism (VTE), and this might be associated with the use of antipsychotics, especially low-potency drugs such as chlorpromazine and thioridazine.

So far, however, the possibility that the underlying psychiatric disorders themselves – and not the antipsychotics – are associated with VTE has never been excluded. This could occur by the increased concentrations of adrenaline seen during psychotic excitation increasing blood coagulation,” they noted.

In this study, in almost all cases the reason for prescription of antipsychotics could not be ascertained. Most of the antipsychotics used were conventional agents, with prochlorperazine – probably given for nausea and vomiting – accounting for almost 80% of all prescriptions, they wrote.

“These findings indicate that VTE is directly linked to the use of an antipsychotic, and that the risk of VTE increases early after starting the drug.”

The implications are potentially far reaching. “Despite their association with serious risks and few data to support their efficacy, antipsychotics are widely used, and in 2008 they became the top selling drug class in the United States,” they wrote.

ROSA LIPEROTI, M.D., is a specialist in geriatrics and GIOVANNI GAMBASSI, M.D., is a professor of geriatrics at Università Cattolica del Sacro Cuore in Rome. Both Dr. Liperoti and Dr. Gambassi reported that they have no relevant financial relationships. These comments were taken from a commentary that accompanied the study (BMJ 2010 Sept. 21 [doi: 10.1136/bmj.c4216]).

Antipsychotics are associated with an almost one-third (32%) greater risk of venous thromboembolism, according to results of a nested case-control study of more than 100,000 primary care patients in the United Kingdom.

Previous research has suggested that these drugs – also commonly used for nausea, vomiting, and vertigo – might be linked with an increased risk of venous thromboembolism (VTE). However, the results have been inconsistent.

In the current study, the association was even greater for new users of antipsychotics. Those with any antipsychotic use in last 3 months had a 56% increased risk of VTE. Patients who started taking an antipsychotic in the past 3 months had a 97% increased risk. However, the absolute risks were low, with an excess of four extra cases of VTE per 10,000 patients treated over 1 year in patients of all ages and 10 for patients aged 65 years and older.

“Our study adds to the accumulating evidence of adverse health events associated with antipsychotic drugs,” the researchers wrote in the study, published online Sept. 21 in the British Medical Journal (BMJ 2010 Sept. 21 [doi:10.1136/bmj.c4245]). “If other studies replicate these findings, antipsychotic drugs should be used more cautiously for nausea and agitation, etc., especially among patients at high risk of thromboembolism.”

The researchers used data from the QResearch database, which includes primary care clinical records for more than 11 million people registered in the past 16 years at more than 500 U.K. general practices. The study population was an open cohort of patients aged 16-100 years, who were registered with participating practices between January 1996 and July 2007. Case patients had a first-ever record of VTE – either deep vein thrombosis or pulmonary embolism – during the study period (including postmortem diagnoses).

Incidence density sampling was used to identify up to four control patients for each case patient. Control patients were matched by age, calendar time, sex, and practice. Control patients had no diagnoses of VTE prior to the date of the first recorded diagnosis of VTE in their matched case patient (index date).

In all, 25,532 eligible case patients – 15,975 with DVT and 9,557 with pulmonary embolism – and 89,491 control patients were included in the study. In terms of mental health disorders, the overall prevalence was 0.4% for schizophrenia, 0.3% for bipolar disorder, and 1.0% for dementia. Eight case patients and 31 control patients had more than one disorder. In all, 8.3% of case patients and 5.3% of control patients had received an antipsychotic in the previous 24 months.

Overall, antipsychotic users had a 32% greater risk of VTE than did nonusers. Among those on antipsychotics, 38% were current users and their increase in risk was 56% compared with 36% for recent users. The risk was not significantly increased for past users. Among current antipsychotic users, 15% had started a new drug within the 3 months prior to the index date. This group of new users showed a greater increase in risk (97%) than did continuing users (29%).

Patients who were prescribed atypical antipsychotic drugs had a greater risk of VTE than did those who were prescribed conventional antipsychotics – 73% compared with 28%.

Patients who had received only one prescription in the previous 12 months had a significantly greater risk (32%) than did those receiving none.

In addition, those who were prescribed two or more different antipsychotics had a greater risk (99%) than did those who received only one (29%).

Disclosures: The authors reported that they have no relevant fnancial relationships.

View on the News

Implications Could Be Far Reaching

The validity of the findings is strengthened by the large sample size and the low potential for exposure and outcome misclassification because of the detailed source of data and adjustment for a large number of confounders, according to Dr. Rosa Liperoti and Dr. Giovanni Gambassi.

It's been demonstrated that “patients with schizophrenia have an increased risk of venous thromboembolism (VTE), and this might be associated with the use of antipsychotics, especially low-potency drugs such as chlorpromazine and thioridazine.

So far, however, the possibility that the underlying psychiatric disorders themselves – and not the antipsychotics – are associated with VTE has never been excluded. This could occur by the increased concentrations of adrenaline seen during psychotic excitation increasing blood coagulation,” they noted.

In this study, in almost all cases the reason for prescription of antipsychotics could not be ascertained. Most of the antipsychotics used were conventional agents, with prochlorperazine – probably given for nausea and vomiting – accounting for almost 80% of all prescriptions, they wrote.

“These findings indicate that VTE is directly linked to the use of an antipsychotic, and that the risk of VTE increases early after starting the drug.”

The implications are potentially far reaching. “Despite their association with serious risks and few data to support their efficacy, antipsychotics are widely used, and in 2008 they became the top selling drug class in the United States,” they wrote.

ROSA LIPEROTI, M.D., is a specialist in geriatrics and GIOVANNI GAMBASSI, M.D., is a professor of geriatrics at Università Cattolica del Sacro Cuore in Rome. Both Dr. Liperoti and Dr. Gambassi reported that they have no relevant financial relationships. These comments were taken from a commentary that accompanied the study (BMJ 2010 Sept. 21 [doi: 10.1136/bmj.c4216]).

New data from a large Swedish cohort suggest that screening mammography in women aged 40-49 years reduced the risk of breast cancer mortality by 26%, compared with women in that age group who were not screened. The results were presented Sept. 29 during a press briefing in advance of the annual Breast Cancer Symposium sponsored by the American Society of Clinical Oncology.

It’s widely accepted that screening mammography significantly reduces mortality in women aged 50-69 years, but the effectiveness of screening in women aged 40-49 years has been less clear.

Late last year, the U.S. Preventive Services Task Force issued new recommendations that women delay routine screening mammograms until age 50 years. The panel said that the risk of screening mammograms in this age group – including false-positive results, anxiety, and unnecessary and invasive treatments – outweighed the potential benefit in mortality reduction.

The recommendations generated controversy, prompting several medical organizations – the American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists, among others – to issue critical responses to the recommendations. These organizations argue that the benefits from screening mammography in this age group should not be underestimated and recommend that women aged 40-49 years continue to receive screening mammograms.

The new findings come from the SCRY cohort (Mammography Screening in Young Women), which may be the largest study of screening mammography in this age group. Currently, there are about Swedish 600,000 women aged 40-49 years. However, over the study period – 1986 to 2005 – more than 1 million women fell within this age group. In 1986, Sweden adopted national breast cancer screening guidelines, under which screening mammography was considered optional for women aged 40-49 years and 70-74 years.

By chance, roughly half of the counties in Sweden opted to invite women in the 40- to 49-year-old age group for screening mammograms, setting up the possibility of a head-to-head comparison of screening and no screening in this age group, according to Håkan Jonsson, Ph.D., of the department of cancer epidemiology at Umeå (Sweden) University.

Women aged 40-49 years living in counties that extended the invitation were included in the study group; eligible women living in the remaining counties that did not invite the women to participate comprised the control group. The average follow-up was 16 years. Women in the study group were followed from the time of their first screening; controls were followed from a corresponding time point.

The researchers refined mortality to include only those women who were diagnosed with breast cancer after the start of screening and who were aged 40-49 at the time of diagnosis.

Women in the study group had a 26% lower risk of dying from breast cancer than did those in the control group, when the researchers included all women who were invited for screening. In this analysis, 619 women in the study group died of breast cancer, compared with 1,205 in the control group.

When only those who actually participated in screening were included, women in the study group had a 29% lower risk of dying from breast cancer. In this analysis, 523 women in the study group died of breast cancer, compared with 1,205 in the control group. The researchers also found that 1,250 women would need to be screened in order to save one life.

They also looked at breast cancer deaths in an earlier “reference” period (1970-1985) when screening was not in effect, in order to ensure that the difference in mortality was because of screening alone. There was a nonsignificant 6% reduction in breast cancer mortality in the study group.

These findings bolster arguments for routine breast cancer screening for women aged 40-49 years, which have recently been challenged. A Norwegian study published in the New England Journal of Medicine in the Sept. 23, 2010, issue reinvigorated the controversy. In the study, the availability of screening mammography accounted for a 10% relative reduction in deaths from breast cancer from 1996 through 2005.

The study included more than 40,000 women with breast cancer; screening mammography was offered to women aged 50-69 years. The 10% number is less than the previous estimates in the United States of 15%-23% reductions in breast cancer mortality to because of mammograms. In addition, Norwegian researchers attributed some of the drop in breast cancer deaths to other factors, such as better treatment and awareness of the disease.

The controversy has left women in this age group – and their physicians – confused about what they should be doing with regard to breast health, according to Dr. Jennifer C. Obel, who moderated the press conference. Dr. Obel is a medical oncologist at NorthShore University HealthSystem and the University of Chicago.

“Many women aged 40-49 [years] want unambiguous recommendations regarding whether to undergo mammography. While the optimal scheduling of regular mammograms continues to be discussed by experts in the field, I think the critical message is that all women, beginning at age 40, should speak with their doctors about mammography to try to understand the potential benefits and risks of the test and to determine what is best for them as individuals,” she said.

Disclosures: The authors noted that they had no relevant financial disclosures.

New data from a large Swedish cohort suggest that screening mammography in women aged 40-49 years reduced the risk of breast cancer mortality by 26%, compared with women in that age group who were not screened. The results were presented Sept. 29 during a press briefing in advance of the annual Breast Cancer Symposium sponsored by the American Society of Clinical Oncology.

It’s widely accepted that screening mammography significantly reduces mortality in women aged 50-69 years, but the effectiveness of screening in women aged 40-49 years has been less clear.

Late last year, the U.S. Preventive Services Task Force issued new recommendations that women delay routine screening mammograms until age 50 years. The panel said that the risk of screening mammograms in this age group – including false-positive results, anxiety, and unnecessary and invasive treatments – outweighed the potential benefit in mortality reduction.

The recommendations generated controversy, prompting several medical organizations – the American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists, among others – to issue critical responses to the recommendations. These organizations argue that the benefits from screening mammography in this age group should not be underestimated and recommend that women aged 40-49 years continue to receive screening mammograms.

The new findings come from the SCRY cohort (Mammography Screening in Young Women), which may be the largest study of screening mammography in this age group. Currently, there are about Swedish 600,000 women aged 40-49 years. However, over the study period – 1986 to 2005 – more than 1 million women fell within this age group. In 1986, Sweden adopted national breast cancer screening guidelines, under which screening mammography was considered optional for women aged 40-49 years and 70-74 years.

By chance, roughly half of the counties in Sweden opted to invite women in the 40- to 49-year-old age group for screening mammograms, setting up the possibility of a head-to-head comparison of screening and no screening in this age group, according to Håkan Jonsson, Ph.D., of the department of cancer epidemiology at Umeå (Sweden) University.

Women aged 40-49 years living in counties that extended the invitation were included in the study group; eligible women living in the remaining counties that did not invite the women to participate comprised the control group. The average follow-up was 16 years. Women in the study group were followed from the time of their first screening; controls were followed from a corresponding time point.

The researchers refined mortality to include only those women who were diagnosed with breast cancer after the start of screening and who were aged 40-49 at the time of diagnosis.

Women in the study group had a 26% lower risk of dying from breast cancer than did those in the control group, when the researchers included all women who were invited for screening. In this analysis, 619 women in the study group died of breast cancer, compared with 1,205 in the control group.

When only those who actually participated in screening were included, women in the study group had a 29% lower risk of dying from breast cancer. In this analysis, 523 women in the study group died of breast cancer, compared with 1,205 in the control group. The researchers also found that 1,250 women would need to be screened in order to save one life.

They also looked at breast cancer deaths in an earlier “reference” period (1970-1985) when screening was not in effect, in order to ensure that the difference in mortality was because of screening alone. There was a nonsignificant 6% reduction in breast cancer mortality in the study group.

These findings bolster arguments for routine breast cancer screening for women aged 40-49 years, which have recently been challenged. A Norwegian study published in the New England Journal of Medicine in the Sept. 23, 2010, issue reinvigorated the controversy. In the study, the availability of screening mammography accounted for a 10% relative reduction in deaths from breast cancer from 1996 through 2005.

The study included more than 40,000 women with breast cancer; screening mammography was offered to women aged 50-69 years. The 10% number is less than the previous estimates in the United States of 15%-23% reductions in breast cancer mortality to because of mammograms. In addition, Norwegian researchers attributed some of the drop in breast cancer deaths to other factors, such as better treatment and awareness of the disease.

The controversy has left women in this age group – and their physicians – confused about what they should be doing with regard to breast health, according to Dr. Jennifer C. Obel, who moderated the press conference. Dr. Obel is a medical oncologist at NorthShore University HealthSystem and the University of Chicago.

“Many women aged 40-49 [years] want unambiguous recommendations regarding whether to undergo mammography. While the optimal scheduling of regular mammograms continues to be discussed by experts in the field, I think the critical message is that all women, beginning at age 40, should speak with their doctors about mammography to try to understand the potential benefits and risks of the test and to determine what is best for them as individuals,” she said.

Disclosures: The authors noted that they had no relevant financial disclosures.

New data from a large Swedish cohort suggest that screening mammography in women aged 40-49 years reduced the risk of breast cancer mortality by 26%, compared with women in that age group who were not screened. The results were presented Sept. 29 during a press briefing in advance of the annual Breast Cancer Symposium sponsored by the American Society of Clinical Oncology.

It’s widely accepted that screening mammography significantly reduces mortality in women aged 50-69 years, but the effectiveness of screening in women aged 40-49 years has been less clear.

Late last year, the U.S. Preventive Services Task Force issued new recommendations that women delay routine screening mammograms until age 50 years. The panel said that the risk of screening mammograms in this age group – including false-positive results, anxiety, and unnecessary and invasive treatments – outweighed the potential benefit in mortality reduction.

The recommendations generated controversy, prompting several medical organizations – the American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists, among others – to issue critical responses to the recommendations. These organizations argue that the benefits from screening mammography in this age group should not be underestimated and recommend that women aged 40-49 years continue to receive screening mammograms.

The new findings come from the SCRY cohort (Mammography Screening in Young Women), which may be the largest study of screening mammography in this age group. Currently, there are about Swedish 600,000 women aged 40-49 years. However, over the study period – 1986 to 2005 – more than 1 million women fell within this age group. In 1986, Sweden adopted national breast cancer screening guidelines, under which screening mammography was considered optional for women aged 40-49 years and 70-74 years.

By chance, roughly half of the counties in Sweden opted to invite women in the 40- to 49-year-old age group for screening mammograms, setting up the possibility of a head-to-head comparison of screening and no screening in this age group, according to Håkan Jonsson, Ph.D., of the department of cancer epidemiology at Umeå (Sweden) University.

Women aged 40-49 years living in counties that extended the invitation were included in the study group; eligible women living in the remaining counties that did not invite the women to participate comprised the control group. The average follow-up was 16 years. Women in the study group were followed from the time of their first screening; controls were followed from a corresponding time point.

The researchers refined mortality to include only those women who were diagnosed with breast cancer after the start of screening and who were aged 40-49 at the time of diagnosis.

Women in the study group had a 26% lower risk of dying from breast cancer than did those in the control group, when the researchers included all women who were invited for screening. In this analysis, 619 women in the study group died of breast cancer, compared with 1,205 in the control group.

When only those who actually participated in screening were included, women in the study group had a 29% lower risk of dying from breast cancer. In this analysis, 523 women in the study group died of breast cancer, compared with 1,205 in the control group. The researchers also found that 1,250 women would need to be screened in order to save one life.

They also looked at breast cancer deaths in an earlier “reference” period (1970-1985) when screening was not in effect, in order to ensure that the difference in mortality was because of screening alone. There was a nonsignificant 6% reduction in breast cancer mortality in the study group.

These findings bolster arguments for routine breast cancer screening for women aged 40-49 years, which have recently been challenged. A Norwegian study published in the New England Journal of Medicine in the Sept. 23, 2010, issue reinvigorated the controversy. In the study, the availability of screening mammography accounted for a 10% relative reduction in deaths from breast cancer from 1996 through 2005.

The study included more than 40,000 women with breast cancer; screening mammography was offered to women aged 50-69 years. The 10% number is less than the previous estimates in the United States of 15%-23% reductions in breast cancer mortality to because of mammograms. In addition, Norwegian researchers attributed some of the drop in breast cancer deaths to other factors, such as better treatment and awareness of the disease.

The controversy has left women in this age group – and their physicians – confused about what they should be doing with regard to breast health, according to Dr. Jennifer C. Obel, who moderated the press conference. Dr. Obel is a medical oncologist at NorthShore University HealthSystem and the University of Chicago.

“Many women aged 40-49 [years] want unambiguous recommendations regarding whether to undergo mammography. While the optimal scheduling of regular mammograms continues to be discussed by experts in the field, I think the critical message is that all women, beginning at age 40, should speak with their doctors about mammography to try to understand the potential benefits and risks of the test and to determine what is best for them as individuals,” she said.

Disclosures: The authors noted that they had no relevant financial disclosures.

The insulin-like growth factor 1 receptor may offer a much-needed therapeutic target for triple-negative breast cancer, which can be notoriously difficult to treat.

High levels of insulin-like growth factor 1 receptor (IGF1-R) expression appears to confer a survival benefit for a subset of patients with this type of cancer, based on the results of a small study.

“In triple-negative breast cancer patients younger than 55, high expression is associated with longer survival,” Dr. Agneiszka W. Witkiewicz said during a press briefing Sept. 28 sponsored by the American Association for Cancer Research (AACR).

Unlike hormone receptor–positive or HER2-positive breast cancers, triple-negative breast cancer has lacked a drug target and is managed with conventional chemotherapy. While triple-negative breast cancer accounts for only 15%-20% of breast cancer cases, it results in half of all breast cancer deaths, said Dr. Witkiewicz, a pathologist at Thomas Jefferson University in Philadelphia and an investigator on the study.

The researchers evaluated tissue from 99 women with triple-negative breast cancer. They stained the samples with anti-IGF1R antibody (Ventana Medical Systems Inc.), and scored IGF1-R protein expression according to standardized criteria originally developed to assess HER 2 expression. Patients were stratified as high expression (a score of 3) or low expression (scores 0-2).

More than a quarter of patients (29%) had high IGF1-R expression – and this was significantly correlated with negative lymph nodes. Among patients older than 55 years, there was no survival difference between those with low and high IGF1-R expression.

IGF1-R belongs to the large class of tyrosine kinase receptors that appear to control proliferation and apoptosis in tumors, and may play a role in resistance to chemotherapy. Importantly, a number of drugs targeting IGF1-R are currently under investigation in clinical trials.

The study was presented in Denver as a poster at the AACR’s International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

Disclosures: One of the coauthors is employed by Ventana Medical Systems, which makes an anti-IGF1-R antibody and is developing an IGF1-R probe.

The insulin-like growth factor 1 receptor may offer a much-needed therapeutic target for triple-negative breast cancer, which can be notoriously difficult to treat.

High levels of insulin-like growth factor 1 receptor (IGF1-R) expression appears to confer a survival benefit for a subset of patients with this type of cancer, based on the results of a small study.

“In triple-negative breast cancer patients younger than 55, high expression is associated with longer survival,” Dr. Agneiszka W. Witkiewicz said during a press briefing Sept. 28 sponsored by the American Association for Cancer Research (AACR).

Unlike hormone receptor–positive or HER2-positive breast cancers, triple-negative breast cancer has lacked a drug target and is managed with conventional chemotherapy. While triple-negative breast cancer accounts for only 15%-20% of breast cancer cases, it results in half of all breast cancer deaths, said Dr. Witkiewicz, a pathologist at Thomas Jefferson University in Philadelphia and an investigator on the study.

The researchers evaluated tissue from 99 women with triple-negative breast cancer. They stained the samples with anti-IGF1R antibody (Ventana Medical Systems Inc.), and scored IGF1-R protein expression according to standardized criteria originally developed to assess HER 2 expression. Patients were stratified as high expression (a score of 3) or low expression (scores 0-2).

More than a quarter of patients (29%) had high IGF1-R expression – and this was significantly correlated with negative lymph nodes. Among patients older than 55 years, there was no survival difference between those with low and high IGF1-R expression.

IGF1-R belongs to the large class of tyrosine kinase receptors that appear to control proliferation and apoptosis in tumors, and may play a role in resistance to chemotherapy. Importantly, a number of drugs targeting IGF1-R are currently under investigation in clinical trials.

The study was presented in Denver as a poster at the AACR’s International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

Disclosures: One of the coauthors is employed by Ventana Medical Systems, which makes an anti-IGF1-R antibody and is developing an IGF1-R probe.

The insulin-like growth factor 1 receptor may offer a much-needed therapeutic target for triple-negative breast cancer, which can be notoriously difficult to treat.

High levels of insulin-like growth factor 1 receptor (IGF1-R) expression appears to confer a survival benefit for a subset of patients with this type of cancer, based on the results of a small study.

“In triple-negative breast cancer patients younger than 55, high expression is associated with longer survival,” Dr. Agneiszka W. Witkiewicz said during a press briefing Sept. 28 sponsored by the American Association for Cancer Research (AACR).

Unlike hormone receptor–positive or HER2-positive breast cancers, triple-negative breast cancer has lacked a drug target and is managed with conventional chemotherapy. While triple-negative breast cancer accounts for only 15%-20% of breast cancer cases, it results in half of all breast cancer deaths, said Dr. Witkiewicz, a pathologist at Thomas Jefferson University in Philadelphia and an investigator on the study.

The researchers evaluated tissue from 99 women with triple-negative breast cancer. They stained the samples with anti-IGF1R antibody (Ventana Medical Systems Inc.), and scored IGF1-R protein expression according to standardized criteria originally developed to assess HER 2 expression. Patients were stratified as high expression (a score of 3) or low expression (scores 0-2).

More than a quarter of patients (29%) had high IGF1-R expression – and this was significantly correlated with negative lymph nodes. Among patients older than 55 years, there was no survival difference between those with low and high IGF1-R expression.

IGF1-R belongs to the large class of tyrosine kinase receptors that appear to control proliferation and apoptosis in tumors, and may play a role in resistance to chemotherapy. Importantly, a number of drugs targeting IGF1-R are currently under investigation in clinical trials.

The study was presented in Denver as a poster at the AACR’s International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

Disclosures: One of the coauthors is employed by Ventana Medical Systems, which makes an anti-IGF1-R antibody and is developing an IGF1-R probe.

Women at high risk of ovarian cancer based on family history and BRCA1 or BRCA2 mutation should undergo risk-reducing prophylactic bilateral salpingo-oophorectomy once childbearing is complete, according to guidelines released by the Society of Gynecologic Oncologists.

“For women at average risk of ovarian cancer who are undergoing a hysterectomy for benign conditions, the decision should be individualized after appropriate informed consent, including a careful analysis of personal risk factors, concomitant disease, presence of gynecologic disease (endometriosis, chronic pain, infection), and age,” wrote members of the SGO’s clinical practice committee. Some evidence suggests that bilateral salpingo-oophorectomy (BSO) has a negative impact on health when performed prior to menopause – including increased risk of cardiovascular disease, lung cancer, and possibly neurologic conditions.

The group also pointed out that there are insufficient data to provide sound counseling on the long-term health impact of BSO for postmenopausal women.

“This paper offers some insight with regard to counseling discussion recommendations, and emphasizes the need for additional research concerning BSO’s long-term impact on a woman’s health, especially as it relates to cardiovascular and neurologic diseases,” lead author Dr. Jonathan S. Berek said in a press release. Dr. Berek is the chair of obstetrics and gynecology at Stanford (Calif.) University.

In the guidelines – released in the September issue of the journal Obstetrics & Gynecology (2010;116:733-43) – the authors also highlighted the lack of an effective screening tool for ovarian cancer: “There is no proven method of screening for ovarian cancer that effectively reduces mortality. CA 125 monitoring and transvaginal ultrasonography have high false-positive rates, especially in premenopausal women.”

Women who are carriers of a germline mutation in BRCA1 or BRCA2 have the greatest risk of ovarian cancer – an estimated 15%-60% risk over a lifetime. For these women, the value of prophylactic salpingo-oophorectomy has been well documented, the committee noted.

Women with a strong family history of either ovarian or breast cancer may carry a deleterious mutation and should be presumed to have higher-than-average risk. This is especially true if there are a number of family members who developed these cancers when they were premenopausal. “These women are potentially at high risk even if they have not been tested because there could be other mutations that are either untested or yet undiscovered that confirm higher-than-average risk of these diseases,” the committee members wrote.

The decision to perform a hysterectomy in conjunction with BSO in the high-risk group should be individualized. The committee members offered several examples. For women receiving tamoxifen, which is associated with an increased risk of polyps and endometrial cancer, hysterectomy may be appropriate. Women who carry mutations in BRCA1 or BRCA2 do not appear to have an increased risk of uterine or cervical cancer, so “routine performance of a prophylactic hysterectomy is discretionary,” according to the guidelines.

Women who do not have a strong family history suggesting the possibility that they carry a germline mutation or who do not have a documented germline mutation were considered by the committee to be at average risk of ovarian and breast cancer. To assess the benefits and risks of BSO, the committee reviewed 11 studies of oophorectomy performed in women who were presumed to be at average risk of ovarian cancer.

It is important that women at average risk of ovarian cancer and their gynecologists consider carefully the indications for hysterectomy and whether BSO also should be performed, despite the potential negative long-term effects, according to the guidelines.

A number of studies have suggested a cardioprotective effect for estrogen because the reduction of endogenous estrogen (as with BSO) correlates with an increase in lipids, a reduction in carotid artery blood flow, and an increase in subclinical atherosclerosis, the authors noted.

In addition to adverse effects on cardiac and bone health, increased risks of Parkinson’s disease and cognitive impairment or dementia have recently been reported among women who underwent bilateral oophorectomy. Importantly, the increased risk of cognitive impairment and Parkinson’s disease did not appear to be altered by estrogen. However, these increased risks appear to be dependent on the age at oophorectomy and the use of estrogen replacement.

“There are clinical situations in which patients should be counseled strongly to undergo elective BSO. As pointed out, patients found to have severe endometriosis, pelvic infection, benign ovarian neoplasms, and chronic pelvic pain have a higher probability of undergoing BSO. This seems warranted given that women with these conditions have a significantly higher risk of repeat surgery,” the committee members wrote.

The authors did not report any potential conflicts of interest.

Women at high risk of ovarian cancer based on family history and BRCA1 or BRCA2 mutation should undergo risk-reducing prophylactic bilateral salpingo-oophorectomy once childbearing is complete, according to guidelines released by the Society of Gynecologic Oncologists.

“For women at average risk of ovarian cancer who are undergoing a hysterectomy for benign conditions, the decision should be individualized after appropriate informed consent, including a careful analysis of personal risk factors, concomitant disease, presence of gynecologic disease (endometriosis, chronic pain, infection), and age,” wrote members of the SGO’s clinical practice committee. Some evidence suggests that bilateral salpingo-oophorectomy (BSO) has a negative impact on health when performed prior to menopause – including increased risk of cardiovascular disease, lung cancer, and possibly neurologic conditions.

The group also pointed out that there are insufficient data to provide sound counseling on the long-term health impact of BSO for postmenopausal women.

“This paper offers some insight with regard to counseling discussion recommendations, and emphasizes the need for additional research concerning BSO’s long-term impact on a woman’s health, especially as it relates to cardiovascular and neurologic diseases,” lead author Dr. Jonathan S. Berek said in a press release. Dr. Berek is the chair of obstetrics and gynecology at Stanford (Calif.) University.

In the guidelines – released in the September issue of the journal Obstetrics & Gynecology (2010;116:733-43) – the authors also highlighted the lack of an effective screening tool for ovarian cancer: “There is no proven method of screening for ovarian cancer that effectively reduces mortality. CA 125 monitoring and transvaginal ultrasonography have high false-positive rates, especially in premenopausal women.”

Women who are carriers of a germline mutation in BRCA1 or BRCA2 have the greatest risk of ovarian cancer – an estimated 15%-60% risk over a lifetime. For these women, the value of prophylactic salpingo-oophorectomy has been well documented, the committee noted.

Women with a strong family history of either ovarian or breast cancer may carry a deleterious mutation and should be presumed to have higher-than-average risk. This is especially true if there are a number of family members who developed these cancers when they were premenopausal. “These women are potentially at high risk even if they have not been tested because there could be other mutations that are either untested or yet undiscovered that confirm higher-than-average risk of these diseases,” the committee members wrote.

The decision to perform a hysterectomy in conjunction with BSO in the high-risk group should be individualized. The committee members offered several examples. For women receiving tamoxifen, which is associated with an increased risk of polyps and endometrial cancer, hysterectomy may be appropriate. Women who carry mutations in BRCA1 or BRCA2 do not appear to have an increased risk of uterine or cervical cancer, so “routine performance of a prophylactic hysterectomy is discretionary,” according to the guidelines.

Women who do not have a strong family history suggesting the possibility that they carry a germline mutation or who do not have a documented germline mutation were considered by the committee to be at average risk of ovarian and breast cancer. To assess the benefits and risks of BSO, the committee reviewed 11 studies of oophorectomy performed in women who were presumed to be at average risk of ovarian cancer.

It is important that women at average risk of ovarian cancer and their gynecologists consider carefully the indications for hysterectomy and whether BSO also should be performed, despite the potential negative long-term effects, according to the guidelines.

A number of studies have suggested a cardioprotective effect for estrogen because the reduction of endogenous estrogen (as with BSO) correlates with an increase in lipids, a reduction in carotid artery blood flow, and an increase in subclinical atherosclerosis, the authors noted.

In addition to adverse effects on cardiac and bone health, increased risks of Parkinson’s disease and cognitive impairment or dementia have recently been reported among women who underwent bilateral oophorectomy. Importantly, the increased risk of cognitive impairment and Parkinson’s disease did not appear to be altered by estrogen. However, these increased risks appear to be dependent on the age at oophorectomy and the use of estrogen replacement.

“There are clinical situations in which patients should be counseled strongly to undergo elective BSO. As pointed out, patients found to have severe endometriosis, pelvic infection, benign ovarian neoplasms, and chronic pelvic pain have a higher probability of undergoing BSO. This seems warranted given that women with these conditions have a significantly higher risk of repeat surgery,” the committee members wrote.

The authors did not report any potential conflicts of interest.

Women at high risk of ovarian cancer based on family history and BRCA1 or BRCA2 mutation should undergo risk-reducing prophylactic bilateral salpingo-oophorectomy once childbearing is complete, according to guidelines released by the Society of Gynecologic Oncologists.

“For women at average risk of ovarian cancer who are undergoing a hysterectomy for benign conditions, the decision should be individualized after appropriate informed consent, including a careful analysis of personal risk factors, concomitant disease, presence of gynecologic disease (endometriosis, chronic pain, infection), and age,” wrote members of the SGO’s clinical practice committee. Some evidence suggests that bilateral salpingo-oophorectomy (BSO) has a negative impact on health when performed prior to menopause – including increased risk of cardiovascular disease, lung cancer, and possibly neurologic conditions.

The group also pointed out that there are insufficient data to provide sound counseling on the long-term health impact of BSO for postmenopausal women.

“This paper offers some insight with regard to counseling discussion recommendations, and emphasizes the need for additional research concerning BSO’s long-term impact on a woman’s health, especially as it relates to cardiovascular and neurologic diseases,” lead author Dr. Jonathan S. Berek said in a press release. Dr. Berek is the chair of obstetrics and gynecology at Stanford (Calif.) University.

In the guidelines – released in the September issue of the journal Obstetrics & Gynecology (2010;116:733-43) – the authors also highlighted the lack of an effective screening tool for ovarian cancer: “There is no proven method of screening for ovarian cancer that effectively reduces mortality. CA 125 monitoring and transvaginal ultrasonography have high false-positive rates, especially in premenopausal women.”

Women who are carriers of a germline mutation in BRCA1 or BRCA2 have the greatest risk of ovarian cancer – an estimated 15%-60% risk over a lifetime. For these women, the value of prophylactic salpingo-oophorectomy has been well documented, the committee noted.

Women with a strong family history of either ovarian or breast cancer may carry a deleterious mutation and should be presumed to have higher-than-average risk. This is especially true if there are a number of family members who developed these cancers when they were premenopausal. “These women are potentially at high risk even if they have not been tested because there could be other mutations that are either untested or yet undiscovered that confirm higher-than-average risk of these diseases,” the committee members wrote.

The decision to perform a hysterectomy in conjunction with BSO in the high-risk group should be individualized. The committee members offered several examples. For women receiving tamoxifen, which is associated with an increased risk of polyps and endometrial cancer, hysterectomy may be appropriate. Women who carry mutations in BRCA1 or BRCA2 do not appear to have an increased risk of uterine or cervical cancer, so “routine performance of a prophylactic hysterectomy is discretionary,” according to the guidelines.

Women who do not have a strong family history suggesting the possibility that they carry a germline mutation or who do not have a documented germline mutation were considered by the committee to be at average risk of ovarian and breast cancer. To assess the benefits and risks of BSO, the committee reviewed 11 studies of oophorectomy performed in women who were presumed to be at average risk of ovarian cancer.

It is important that women at average risk of ovarian cancer and their gynecologists consider carefully the indications for hysterectomy and whether BSO also should be performed, despite the potential negative long-term effects, according to the guidelines.

A number of studies have suggested a cardioprotective effect for estrogen because the reduction of endogenous estrogen (as with BSO) correlates with an increase in lipids, a reduction in carotid artery blood flow, and an increase in subclinical atherosclerosis, the authors noted.

In addition to adverse effects on cardiac and bone health, increased risks of Parkinson’s disease and cognitive impairment or dementia have recently been reported among women who underwent bilateral oophorectomy. Importantly, the increased risk of cognitive impairment and Parkinson’s disease did not appear to be altered by estrogen. However, these increased risks appear to be dependent on the age at oophorectomy and the use of estrogen replacement.

“There are clinical situations in which patients should be counseled strongly to undergo elective BSO. As pointed out, patients found to have severe endometriosis, pelvic infection, benign ovarian neoplasms, and chronic pelvic pain have a higher probability of undergoing BSO. This seems warranted given that women with these conditions have a significantly higher risk of repeat surgery,” the committee members wrote.

The authors did not report any potential conflicts of interest.

Melanocytic nevi – spitz, congenital, and acquired – can pose diagnostic challenges for the pediatric dermatologist.

Dr. Jonathan A. Dyer offered a review of the latest literature on these pediatric melanomas at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation.

Atypical Spitzoid Melanocytic Tumors (ASMT)

Data suggest that a positive sentinel lymph node biopsy (SLNB) in ASMT does not necessarily mean poor prognosis, according to Dr. Dyer, who is an assistant professor of clinical dermatology at the University of Missouri in Columbia.

Positive SLNB is not uncommon in ASMT, occurring in 28%-50% of cases. Nodal lesion morphology appears to be what matters – typical-appearing subcapsular cells versus ugly cells that replace a significant portion of the node (Am. J. Surg. Pathol. 2009;33:1386-95).

In a series of six published studies with more than 100 patients, no patient with ASMT and positive SLNB died of disease, he reported. However, follow-up was limited in many reports (median 10 months). Most malignant melanomas recur within 36 months.

In the Multicenter Selective Lymphadenectomy Trial (MSLT), the 5-year survival rate for patients younger than 19 years with malignant melanoma with a positive SLN was 68%, compared with 59% for adults.

Congenital Melanocytic Nevi (CMN)

A 19-year prospective study at Great Ormond Street Hospital in London provided a plethora of information on CMN (Br. J. Dermatol. 2009;160:143-50). The study included 349 families with CMN and 79 control families. Poor maternal health (threatened miscarriage, maternal hypertension, or severe nausea/vomiting) was associated with an increased incidence of CMN.

The researchers also found a possible positive association between maternal smoking and projected adult size and overall CMN incidence. CMN was more likely in females, while maternal freckling was independently associated with smaller projected adult size. A quarter of those with CMN had a second-degree relative with CMN, noted Dr. Dyer.

Furthermore, it is estimated that 5%-30% of patients with large CMN have asymptomatic neurocutaneous melanosis (NCM). NCM symptoms – increased intracranial pressure or seizures – typically occur in the first 2 years of life, he reported. It is possible for patients to convert from asymptomatic NCM to symptomatic but it is unclear how common it is (J. Clin. Oncol. 2009;27:e136).

Occasionally NCM symptoms are temporary or controllable; however, prognosis of symptomatic NCM is guarded. MRI is sensitive for NCM in the first 4-6 months but small deposits can be missed.

In terms of risk, satellites appear to be a major risk factor for NCM in patients with CMN. If there are no satellites, the risk of NCM is very low, summarized Dr. Dyer. In addition, CMN size appears to matter more than location. Based on several studies, the risk of NCM tends to be about 20%.

It has been suggested that up to two-thirds of pediatric patients with NCM go on to develop leptomeningeal tumors. Some patients may develop symptomatic NCM as a result, reported Dr. Dyer. An estimated 50%-90% of these patients die within 3 years of symptom onset. It is also estimated that 50% develop malignant melanoma of the central nervous system (Clin. Dermatol. 2009;27:529-36) .

Many CMN improve with time, he noted. In the Great Ormond Street study, for example, the majority of untreated lesions lightened during the follow-up period (Br. J. Dermatol. 2009;160:387-92). Surgery and the presence of satellites at birth were independently associated with darkening.

Satisfaction with surgery was high for patients with CMN of less than 20 cm and for those with facial lesions. However, satisfaction was reduced with increasing projected adult size. Girls were more likely to have surgery.

Treatment seemed to increase the darkening of remaining or later-developing nevi, independent of type, timing, or nevus. Tissue expansion appeared to be associated with increased satellite development, noted Dr. Dyer. Projected adult size was associated with satellite number but not treatment type.

Childhood Melanoma

Melanoma accounts for 1%-3% of childhood malignancies. The incidence increased by 2.9% per year from 1973 to 2001 (Clin. Dermatol. 2009;27:529-36). Melanoma is seven times more common in the second decade than in the first, said Dr. Dyer. It is estimated that teens aged 15-19 years account for 73%-79% of cases.

Interestingly, there is a slight male predominance in young children that changes to a slight female predominance in older groups. Adolescent white girls with a history of ultraviolet exposure have the greatest melanoma risk, particularly on the trunk and lower extremities, he pointed out.

Approximately 30% of childhood melanomas arise with giant CMN. Lifetime risk appears to be bimodal, with the first peak in the first decade of life (usually in the first 5 years). It is estimated that 50%-70% arise before puberty. Head and neck melanomas are more common at age 1-4 years, while melanomas on the trunk are more common with increasing age. Early-life melanomas tend to be dermal with poorer outcomes. The second peak occurs in adulthood, reported Dr. Dyer.

Approximately 20% of childhood melanomas occur with other melanocytic lesions. Malignant melanomas from small CMN typically occur after puberty. These are more similar to adult malignant melanomas.

Childhood melanomas are associated with an increased incidence of amelanotic and nodular lesions. Risk factors include the following: intermittent intense sun exposure, tendency to sunburn, tendency to freckle, fair skin, blue/green eyes, blonde/red hair, xeroderma pigmentosum, giant CMN, dysplastic nevus syndrome, atypical nevi, a family history of malignant melanoma, and immunosuppression.

The risk of transformation for CMN is associated with size. Small to medium CMN (less than 20 cm) have a 1%-5% risk of transformation, while large/giant CMN (greater than 20 cm) have at least a 5%-10% risk; however, the risk may be as great as 20%.

Some studies suggest that 30%-75% of pediatric malignant melanoma originated in giant CMN, and one-third are fatal, reported Dr. Dyer. Excision does not completely eliminate the risk. In one study, 8% of patients developed extracutaneous malignant melanoma after CMN excision.

He noted that the risk of childhood melanoma is associated with immunodeficiency. The risk is six times greater if immunodeficiency is genetic in origin; the risk is four times greater if immunodeficiency is acquired.

The indications for sentinel lymph node biopsy in children are the same as in adults, he noted. Children have a higher incidence positive sentinel lymph node. However, this does not predict likelihood of recurrence or prognosis in children.

Surgical excision should use the same margins as in adults whenever possible. Thickness, ulceration, and stage at diagnosis are all prognostic factors.

Disclosures: Dr. Dyer reported having no conflicts of interest. SDEF and this news organization are owned by Elsevier.

Melanocytic nevi – spitz, congenital, and acquired – can pose diagnostic challenges for the pediatric dermatologist.

Dr. Jonathan A. Dyer offered a review of the latest literature on these pediatric melanomas at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation.

Atypical Spitzoid Melanocytic Tumors (ASMT)

Data suggest that a positive sentinel lymph node biopsy (SLNB) in ASMT does not necessarily mean poor prognosis, according to Dr. Dyer, who is an assistant professor of clinical dermatology at the University of Missouri in Columbia.

Positive SLNB is not uncommon in ASMT, occurring in 28%-50% of cases. Nodal lesion morphology appears to be what matters – typical-appearing subcapsular cells versus ugly cells that replace a significant portion of the node (Am. J. Surg. Pathol. 2009;33:1386-95).

In a series of six published studies with more than 100 patients, no patient with ASMT and positive SLNB died of disease, he reported. However, follow-up was limited in many reports (median 10 months). Most malignant melanomas recur within 36 months.

In the Multicenter Selective Lymphadenectomy Trial (MSLT), the 5-year survival rate for patients younger than 19 years with malignant melanoma with a positive SLN was 68%, compared with 59% for adults.

Congenital Melanocytic Nevi (CMN)

A 19-year prospective study at Great Ormond Street Hospital in London provided a plethora of information on CMN (Br. J. Dermatol. 2009;160:143-50). The study included 349 families with CMN and 79 control families. Poor maternal health (threatened miscarriage, maternal hypertension, or severe nausea/vomiting) was associated with an increased incidence of CMN.

The researchers also found a possible positive association between maternal smoking and projected adult size and overall CMN incidence. CMN was more likely in females, while maternal freckling was independently associated with smaller projected adult size. A quarter of those with CMN had a second-degree relative with CMN, noted Dr. Dyer.

Furthermore, it is estimated that 5%-30% of patients with large CMN have asymptomatic neurocutaneous melanosis (NCM). NCM symptoms – increased intracranial pressure or seizures – typically occur in the first 2 years of life, he reported. It is possible for patients to convert from asymptomatic NCM to symptomatic but it is unclear how common it is (J. Clin. Oncol. 2009;27:e136).

Occasionally NCM symptoms are temporary or controllable; however, prognosis of symptomatic NCM is guarded. MRI is sensitive for NCM in the first 4-6 months but small deposits can be missed.

In terms of risk, satellites appear to be a major risk factor for NCM in patients with CMN. If there are no satellites, the risk of NCM is very low, summarized Dr. Dyer. In addition, CMN size appears to matter more than location. Based on several studies, the risk of NCM tends to be about 20%.

It has been suggested that up to two-thirds of pediatric patients with NCM go on to develop leptomeningeal tumors. Some patients may develop symptomatic NCM as a result, reported Dr. Dyer. An estimated 50%-90% of these patients die within 3 years of symptom onset. It is also estimated that 50% develop malignant melanoma of the central nervous system (Clin. Dermatol. 2009;27:529-36) .

Many CMN improve with time, he noted. In the Great Ormond Street study, for example, the majority of untreated lesions lightened during the follow-up period (Br. J. Dermatol. 2009;160:387-92). Surgery and the presence of satellites at birth were independently associated with darkening.

Satisfaction with surgery was high for patients with CMN of less than 20 cm and for those with facial lesions. However, satisfaction was reduced with increasing projected adult size. Girls were more likely to have surgery.

Treatment seemed to increase the darkening of remaining or later-developing nevi, independent of type, timing, or nevus. Tissue expansion appeared to be associated with increased satellite development, noted Dr. Dyer. Projected adult size was associated with satellite number but not treatment type.

Childhood Melanoma

Melanoma accounts for 1%-3% of childhood malignancies. The incidence increased by 2.9% per year from 1973 to 2001 (Clin. Dermatol. 2009;27:529-36). Melanoma is seven times more common in the second decade than in the first, said Dr. Dyer. It is estimated that teens aged 15-19 years account for 73%-79% of cases.

Interestingly, there is a slight male predominance in young children that changes to a slight female predominance in older groups. Adolescent white girls with a history of ultraviolet exposure have the greatest melanoma risk, particularly on the trunk and lower extremities, he pointed out.

Approximately 30% of childhood melanomas arise with giant CMN. Lifetime risk appears to be bimodal, with the first peak in the first decade of life (usually in the first 5 years). It is estimated that 50%-70% arise before puberty. Head and neck melanomas are more common at age 1-4 years, while melanomas on the trunk are more common with increasing age. Early-life melanomas tend to be dermal with poorer outcomes. The second peak occurs in adulthood, reported Dr. Dyer.

Approximately 20% of childhood melanomas occur with other melanocytic lesions. Malignant melanomas from small CMN typically occur after puberty. These are more similar to adult malignant melanomas.

Childhood melanomas are associated with an increased incidence of amelanotic and nodular lesions. Risk factors include the following: intermittent intense sun exposure, tendency to sunburn, tendency to freckle, fair skin, blue/green eyes, blonde/red hair, xeroderma pigmentosum, giant CMN, dysplastic nevus syndrome, atypical nevi, a family history of malignant melanoma, and immunosuppression.

The risk of transformation for CMN is associated with size. Small to medium CMN (less than 20 cm) have a 1%-5% risk of transformation, while large/giant CMN (greater than 20 cm) have at least a 5%-10% risk; however, the risk may be as great as 20%.

Some studies suggest that 30%-75% of pediatric malignant melanoma originated in giant CMN, and one-third are fatal, reported Dr. Dyer. Excision does not completely eliminate the risk. In one study, 8% of patients developed extracutaneous malignant melanoma after CMN excision.

He noted that the risk of childhood melanoma is associated with immunodeficiency. The risk is six times greater if immunodeficiency is genetic in origin; the risk is four times greater if immunodeficiency is acquired.

The indications for sentinel lymph node biopsy in children are the same as in adults, he noted. Children have a higher incidence positive sentinel lymph node. However, this does not predict likelihood of recurrence or prognosis in children.

Surgical excision should use the same margins as in adults whenever possible. Thickness, ulceration, and stage at diagnosis are all prognostic factors.

Disclosures: Dr. Dyer reported having no conflicts of interest. SDEF and this news organization are owned by Elsevier.

Melanocytic nevi – spitz, congenital, and acquired – can pose diagnostic challenges for the pediatric dermatologist.

Dr. Jonathan A. Dyer offered a review of the latest literature on these pediatric melanomas at a seminar on women's and pediatric dermatology sponsored by Skin Disease Education Foundation.

Atypical Spitzoid Melanocytic Tumors (ASMT)

Data suggest that a positive sentinel lymph node biopsy (SLNB) in ASMT does not necessarily mean poor prognosis, according to Dr. Dyer, who is an assistant professor of clinical dermatology at the University of Missouri in Columbia.

Positive SLNB is not uncommon in ASMT, occurring in 28%-50% of cases. Nodal lesion morphology appears to be what matters – typical-appearing subcapsular cells versus ugly cells that replace a significant portion of the node (Am. J. Surg. Pathol. 2009;33:1386-95).

In a series of six published studies with more than 100 patients, no patient with ASMT and positive SLNB died of disease, he reported. However, follow-up was limited in many reports (median 10 months). Most malignant melanomas recur within 36 months.

In the Multicenter Selective Lymphadenectomy Trial (MSLT), the 5-year survival rate for patients younger than 19 years with malignant melanoma with a positive SLN was 68%, compared with 59% for adults.

Congenital Melanocytic Nevi (CMN)

A 19-year prospective study at Great Ormond Street Hospital in London provided a plethora of information on CMN (Br. J. Dermatol. 2009;160:143-50). The study included 349 families with CMN and 79 control families. Poor maternal health (threatened miscarriage, maternal hypertension, or severe nausea/vomiting) was associated with an increased incidence of CMN.

The researchers also found a possible positive association between maternal smoking and projected adult size and overall CMN incidence. CMN was more likely in females, while maternal freckling was independently associated with smaller projected adult size. A quarter of those with CMN had a second-degree relative with CMN, noted Dr. Dyer.

Furthermore, it is estimated that 5%-30% of patients with large CMN have asymptomatic neurocutaneous melanosis (NCM). NCM symptoms – increased intracranial pressure or seizures – typically occur in the first 2 years of life, he reported. It is possible for patients to convert from asymptomatic NCM to symptomatic but it is unclear how common it is (J. Clin. Oncol. 2009;27:e136).

Occasionally NCM symptoms are temporary or controllable; however, prognosis of symptomatic NCM is guarded. MRI is sensitive for NCM in the first 4-6 months but small deposits can be missed.

In terms of risk, satellites appear to be a major risk factor for NCM in patients with CMN. If there are no satellites, the risk of NCM is very low, summarized Dr. Dyer. In addition, CMN size appears to matter more than location. Based on several studies, the risk of NCM tends to be about 20%.

It has been suggested that up to two-thirds of pediatric patients with NCM go on to develop leptomeningeal tumors. Some patients may develop symptomatic NCM as a result, reported Dr. Dyer. An estimated 50%-90% of these patients die within 3 years of symptom onset. It is also estimated that 50% develop malignant melanoma of the central nervous system (Clin. Dermatol. 2009;27:529-36) .

Many CMN improve with time, he noted. In the Great Ormond Street study, for example, the majority of untreated lesions lightened during the follow-up period (Br. J. Dermatol. 2009;160:387-92). Surgery and the presence of satellites at birth were independently associated with darkening.

Satisfaction with surgery was high for patients with CMN of less than 20 cm and for those with facial lesions. However, satisfaction was reduced with increasing projected adult size. Girls were more likely to have surgery.

Treatment seemed to increase the darkening of remaining or later-developing nevi, independent of type, timing, or nevus. Tissue expansion appeared to be associated with increased satellite development, noted Dr. Dyer. Projected adult size was associated with satellite number but not treatment type.

Childhood Melanoma

Melanoma accounts for 1%-3% of childhood malignancies. The incidence increased by 2.9% per year from 1973 to 2001 (Clin. Dermatol. 2009;27:529-36). Melanoma is seven times more common in the second decade than in the first, said Dr. Dyer. It is estimated that teens aged 15-19 years account for 73%-79% of cases.

Interestingly, there is a slight male predominance in young children that changes to a slight female predominance in older groups. Adolescent white girls with a history of ultraviolet exposure have the greatest melanoma risk, particularly on the trunk and lower extremities, he pointed out.

Approximately 30% of childhood melanomas arise with giant CMN. Lifetime risk appears to be bimodal, with the first peak in the first decade of life (usually in the first 5 years). It is estimated that 50%-70% arise before puberty. Head and neck melanomas are more common at age 1-4 years, while melanomas on the trunk are more common with increasing age. Early-life melanomas tend to be dermal with poorer outcomes. The second peak occurs in adulthood, reported Dr. Dyer.

Approximately 20% of childhood melanomas occur with other melanocytic lesions. Malignant melanomas from small CMN typically occur after puberty. These are more similar to adult malignant melanomas.

Childhood melanomas are associated with an increased incidence of amelanotic and nodular lesions. Risk factors include the following: intermittent intense sun exposure, tendency to sunburn, tendency to freckle, fair skin, blue/green eyes, blonde/red hair, xeroderma pigmentosum, giant CMN, dysplastic nevus syndrome, atypical nevi, a family history of malignant melanoma, and immunosuppression.

The risk of transformation for CMN is associated with size. Small to medium CMN (less than 20 cm) have a 1%-5% risk of transformation, while large/giant CMN (greater than 20 cm) have at least a 5%-10% risk; however, the risk may be as great as 20%.

Some studies suggest that 30%-75% of pediatric malignant melanoma originated in giant CMN, and one-third are fatal, reported Dr. Dyer. Excision does not completely eliminate the risk. In one study, 8% of patients developed extracutaneous malignant melanoma after CMN excision.

He noted that the risk of childhood melanoma is associated with immunodeficiency. The risk is six times greater if immunodeficiency is genetic in origin; the risk is four times greater if immunodeficiency is acquired.

The indications for sentinel lymph node biopsy in children are the same as in adults, he noted. Children have a higher incidence positive sentinel lymph node. However, this does not predict likelihood of recurrence or prognosis in children.

Surgical excision should use the same margins as in adults whenever possible. Thickness, ulceration, and stage at diagnosis are all prognostic factors.

Disclosures: Dr. Dyer reported having no conflicts of interest. SDEF and this news organization are owned by Elsevier.

While dermoscopy can enhance the diagnosis of a number of skin conditions, it is especially useful in determining whether neoplasms should undergo biopsy.

“Patients are becoming aware of the technique and more and more are expecting their dermatologists to be skilled in its application,” Dr. David L. Swanson said in an interview.

However, fewer than half of academic dermatologists and less than a quarter of practicing dermatologists use dermoscopy in the United States, according to Dr. Swanson, chief of medical dermatology at the Mayo Clinic in Scottsdale, Ariz. In comparison, dermoscopy is taught to primary care physicians in Europe and Australia.

He discussed methods for assessing whether a lesion should be biopsied.

With the two-step pattern recognition method, the dermoscopist must first determine whether a neoplasm is a melanocytic proliferative one, such as a nevus or melanoma.  “The reason that the first step is to consider nevi or melanomas is the importance of identifying the latter – especially melanomas that are not obvious with the naked eye,” said Dr. Swanson at a seminar on women’s and pediatric dermatology sponsored by Skin Disease Education Foundation.

If the lesion is melanocytic proliferative, the dermoscopist then applies the methods of interpretation for nevi or melanoma – such as pattern recognition or an algorithm. “If it isn’t, then there are other diagnostic features that are used to lead to a clinical impression.”

The dermoscopy three-point rule has a high sensitivity for melanoma, he said. If a pigmented lesion has any two of the three criteria – atypical asymmetry, atypical pigment network, or blue-white structures – there is a likelihood of melanoma, and the lesion should be biopsied.

“The three-point rule is easier to learn and apply but as with all algorithms, there are a lot of exceptions to the rules. So one has to be willing to learn those exceptions and step out of the algorithm if they aren’t certain,” said Dr. Swanson.  “One specific problem with the three-point method is that it doesn’t take into account an atypical vasculature. Any dermoscopist using the three-point rule has to keep that in mind as an additional feature.”

The seven-point algorithm – developed by Dr. Giuseppe Argenziano and others – is aimed at helping the novice dermoscopist.  “It is a fairly reproducible method with very good specificity and sensitivity for making a decision to biopsy a melanocytic lesion.  The three-point algorithm actually was derived from it as a method to simplify,” said Dr. Swanson.  “Most experienced dermoscopists only use algorithms occasionally, because with experience they become comfortable with pattern recognition.”

The seven-point algorithm includes the criteria of the three-point rule, please four minor criteria: streaks, regression pattern, irregular diffuse pigmentation, and irregular dot and globules.

Dr. Swanson reported having no disclosures. SDEF and this news organization are owned by Elsevier.

While dermoscopy can enhance the diagnosis of a number of skin conditions, it is especially useful in determining whether neoplasms should undergo biopsy.

“Patients are becoming aware of the technique and more and more are expecting their dermatologists to be skilled in its application,” Dr. David L. Swanson said in an interview.

However, fewer than half of academic dermatologists and less than a quarter of practicing dermatologists use dermoscopy in the United States, according to Dr. Swanson, chief of medical dermatology at the Mayo Clinic in Scottsdale, Ariz. In comparison, dermoscopy is taught to primary care physicians in Europe and Australia.

He discussed methods for assessing whether a lesion should be biopsied.

With the two-step pattern recognition method, the dermoscopist must first determine whether a neoplasm is a melanocytic proliferative one, such as a nevus or melanoma.  “The reason that the first step is to consider nevi or melanomas is the importance of identifying the latter – especially melanomas that are not obvious with the naked eye,” said Dr. Swanson at a seminar on women’s and pediatric dermatology sponsored by Skin Disease Education Foundation.

If the lesion is melanocytic proliferative, the dermoscopist then applies the methods of interpretation for nevi or melanoma – such as pattern recognition or an algorithm. “If it isn’t, then there are other diagnostic features that are used to lead to a clinical impression.”

The dermoscopy three-point rule has a high sensitivity for melanoma, he said. If a pigmented lesion has any two of the three criteria – atypical asymmetry, atypical pigment network, or blue-white structures – there is a likelihood of melanoma, and the lesion should be biopsied.

“The three-point rule is easier to learn and apply but as with all algorithms, there are a lot of exceptions to the rules. So one has to be willing to learn those exceptions and step out of the algorithm if they aren’t certain,” said Dr. Swanson.  “One specific problem with the three-point method is that it doesn’t take into account an atypical vasculature. Any dermoscopist using the three-point rule has to keep that in mind as an additional feature.”

The seven-point algorithm – developed by Dr. Giuseppe Argenziano and others – is aimed at helping the novice dermoscopist.  “It is a fairly reproducible method with very good specificity and sensitivity for making a decision to biopsy a melanocytic lesion.  The three-point algorithm actually was derived from it as a method to simplify,” said Dr. Swanson.  “Most experienced dermoscopists only use algorithms occasionally, because with experience they become comfortable with pattern recognition.”

The seven-point algorithm includes the criteria of the three-point rule, please four minor criteria: streaks, regression pattern, irregular diffuse pigmentation, and irregular dot and globules.

Dr. Swanson reported having no disclosures. SDEF and this news organization are owned by Elsevier.

While dermoscopy can enhance the diagnosis of a number of skin conditions, it is especially useful in determining whether neoplasms should undergo biopsy.

“Patients are becoming aware of the technique and more and more are expecting their dermatologists to be skilled in its application,” Dr. David L. Swanson said in an interview.

However, fewer than half of academic dermatologists and less than a quarter of practicing dermatologists use dermoscopy in the United States, according to Dr. Swanson, chief of medical dermatology at the Mayo Clinic in Scottsdale, Ariz. In comparison, dermoscopy is taught to primary care physicians in Europe and Australia.

He discussed methods for assessing whether a lesion should be biopsied.

With the two-step pattern recognition method, the dermoscopist must first determine whether a neoplasm is a melanocytic proliferative one, such as a nevus or melanoma.  “The reason that the first step is to consider nevi or melanomas is the importance of identifying the latter – especially melanomas that are not obvious with the naked eye,” said Dr. Swanson at a seminar on women’s and pediatric dermatology sponsored by Skin Disease Education Foundation.

If the lesion is melanocytic proliferative, the dermoscopist then applies the methods of interpretation for nevi or melanoma – such as pattern recognition or an algorithm. “If it isn’t, then there are other diagnostic features that are used to lead to a clinical impression.”

The dermoscopy three-point rule has a high sensitivity for melanoma, he said. If a pigmented lesion has any two of the three criteria – atypical asymmetry, atypical pigment network, or blue-white structures – there is a likelihood of melanoma, and the lesion should be biopsied.

“The three-point rule is easier to learn and apply but as with all algorithms, there are a lot of exceptions to the rules. So one has to be willing to learn those exceptions and step out of the algorithm if they aren’t certain,” said Dr. Swanson.  “One specific problem with the three-point method is that it doesn’t take into account an atypical vasculature. Any dermoscopist using the three-point rule has to keep that in mind as an additional feature.”

The seven-point algorithm – developed by Dr. Giuseppe Argenziano and others – is aimed at helping the novice dermoscopist.  “It is a fairly reproducible method with very good specificity and sensitivity for making a decision to biopsy a melanocytic lesion.  The three-point algorithm actually was derived from it as a method to simplify,” said Dr. Swanson.  “Most experienced dermoscopists only use algorithms occasionally, because with experience they become comfortable with pattern recognition.”

The seven-point algorithm includes the criteria of the three-point rule, please four minor criteria: streaks, regression pattern, irregular diffuse pigmentation, and irregular dot and globules.

Dr. Swanson reported having no disclosures. SDEF and this news organization are owned by Elsevier.