Breast Cancer

Concern over a relationship between in vitro fertilization (IVF) and subsequent breast cancer has been ameliorated by a large study conducted in Australia. The authors report no overall increase in the rate of breast cancer in women who undergo IVF. However, there does seem to be a higher risk of breast cancer in those who begin IVF treatment when in their mid-20s.

A population-based study from Western Australia studied the incidence rate of breast cancer in a large cohort (n=21,025) aged 20 to 44 years who underwent hospital-based treatment for infertility. Researchers compared the rate of breast cancer in women who had IVF with those who had fertility treatment but not IVF.

The study, published in Fertility and Sterility, reports that there is no overall increase in the risk of breast cancer for women who undergo hospital-based IVF (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88–1.36).

“For younger women,” write the authors, “there is some cause for concern, because it appears that they may face an increased risk of breast cancer after IVF treatment.”

Women who began hospital infertility treatment at 24 years of age and required IVF had an unadjusted HR of breast cancer of 1.59 (95% CI, 1.05–2.42) compared with women of the same age who had infertility treatment but no IVF.

When adjusted for late age at first delivery, which is associated with an increased rate of breast cancer, and delivery of twins and higher-order multiples, which is associated with a decreased rate of breast cancer, the HR remained elevated at 1.56 (95% CI, 1.01–2.40).

“The results of this study will be reassuring to women who commence IVF treatment in their 30s and 40s because, for these women, there appears to be no direct association between IVF treatment and breast cancer risk,” write the authors. Risk was not elevated in women who commenced treatment at age 40 and required IVF (adjusted HR, 0.87; 95% CI, 0.62–1.22).

“Nevertheless, women should be aware that delivering their first child late in reproductive life, whether assisted by IVF or not, is associated with an increased risk of breast cancer.”

Access to the full-text article is available at http://bit.ly/KiLvwh.

Concern over a relationship between in vitro fertilization (IVF) and subsequent breast cancer has been ameliorated by a large study conducted in Australia. The authors report no overall increase in the rate of breast cancer in women who undergo IVF. However, there does seem to be a higher risk of breast cancer in those who begin IVF treatment when in their mid-20s.

A population-based study from Western Australia studied the incidence rate of breast cancer in a large cohort (n=21,025) aged 20 to 44 years who underwent hospital-based treatment for infertility. Researchers compared the rate of breast cancer in women who had IVF with those who had fertility treatment but not IVF.

The study, published in Fertility and Sterility, reports that there is no overall increase in the risk of breast cancer for women who undergo hospital-based IVF (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88–1.36).

“For younger women,” write the authors, “there is some cause for concern, because it appears that they may face an increased risk of breast cancer after IVF treatment.”

Women who began hospital infertility treatment at 24 years of age and required IVF had an unadjusted HR of breast cancer of 1.59 (95% CI, 1.05–2.42) compared with women of the same age who had infertility treatment but no IVF.

When adjusted for late age at first delivery, which is associated with an increased rate of breast cancer, and delivery of twins and higher-order multiples, which is associated with a decreased rate of breast cancer, the HR remained elevated at 1.56 (95% CI, 1.01–2.40).

“The results of this study will be reassuring to women who commence IVF treatment in their 30s and 40s because, for these women, there appears to be no direct association between IVF treatment and breast cancer risk,” write the authors. Risk was not elevated in women who commenced treatment at age 40 and required IVF (adjusted HR, 0.87; 95% CI, 0.62–1.22).

“Nevertheless, women should be aware that delivering their first child late in reproductive life, whether assisted by IVF or not, is associated with an increased risk of breast cancer.”

Access to the full-text article is available at http://bit.ly/KiLvwh.

Concern over a relationship between in vitro fertilization (IVF) and subsequent breast cancer has been ameliorated by a large study conducted in Australia. The authors report no overall increase in the rate of breast cancer in women who undergo IVF. However, there does seem to be a higher risk of breast cancer in those who begin IVF treatment when in their mid-20s.

A population-based study from Western Australia studied the incidence rate of breast cancer in a large cohort (n=21,025) aged 20 to 44 years who underwent hospital-based treatment for infertility. Researchers compared the rate of breast cancer in women who had IVF with those who had fertility treatment but not IVF.

The study, published in Fertility and Sterility, reports that there is no overall increase in the risk of breast cancer for women who undergo hospital-based IVF (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88–1.36).

“For younger women,” write the authors, “there is some cause for concern, because it appears that they may face an increased risk of breast cancer after IVF treatment.”

Women who began hospital infertility treatment at 24 years of age and required IVF had an unadjusted HR of breast cancer of 1.59 (95% CI, 1.05–2.42) compared with women of the same age who had infertility treatment but no IVF.

When adjusted for late age at first delivery, which is associated with an increased rate of breast cancer, and delivery of twins and higher-order multiples, which is associated with a decreased rate of breast cancer, the HR remained elevated at 1.56 (95% CI, 1.01–2.40).

“The results of this study will be reassuring to women who commence IVF treatment in their 30s and 40s because, for these women, there appears to be no direct association between IVF treatment and breast cancer risk,” write the authors. Risk was not elevated in women who commenced treatment at age 40 and required IVF (adjusted HR, 0.87; 95% CI, 0.62–1.22).

“Nevertheless, women should be aware that delivering their first child late in reproductive life, whether assisted by IVF or not, is associated with an increased risk of breast cancer.”

Access to the full-text article is available at http://bit.ly/KiLvwh.

The European Medicines Agency said June 22 that it had recommended an extension of indication for the cancer drug everolimus to treat hormone receptor–positive, HER2–negative advanced breast cancer.

Everolimus (Afinitor, Novartis), already recommended by the EMA to treat pancreatic and renal cell cancers, is now recommended throughout the European Union in combination with exemestane as a second-line treatment in postmenopausal women in whom aromatase inhibitors have failed.

EMA also extended indications of agents used to treat two rheumatic diseases.

Etanercept (Enbrel), marketed by Pfizer and already licensed in Europe to treat rheumatic arthritis in adults, is now recommended as a treatment for polyarthritis (rheumatoid factor positive or negative), extended oligoarthritis, and psoriatic arthritis in children and adolescents in whom methotrexate has failed or is inappropriate. The indication for etanercept also was extended to treatment of enthesitis-related arthritis in adolescents 12 years and older not responding to conventional therapy.

Adalimumab (Humira), marketed by Abbott and licensed in Europe to treat a range of rheumatic diseases, will now be indicated for the treatment of adults with severe axial spondyloarthritis who have had an inadequate response to, or are intolerant of, nonsteroidal anti-inflammatory drugs. The new indication covers patients without radiographic evidence of axial spondyloarthritis but with evidence of inflammation determined by MRI or elevated C-reactive protein.

Also at its June meeting, the agency recommended a new six-in-one combination vaccine developed for use outside the European Union. Hexaxim, marketed by Sanofi Pasteur, will be used in children aged 6 weeks to 2 years old to inoculate against diphtheria, tetanus, pertussis, hepatitis B, polio, and diseases caused by Haemophilus influenzae type B, including meningitis. The vaccine is administered as three doses 4 or more weeks apart.

Five of the active substances in the vaccine have been used in other vaccines and have been previously combined in Pentaxim, also manufactured by Sanofi Pasteur. The new vaccine adds Hansenula polymorpha-derived recombinant hepatitis B surface antigen. Clinical trials in Argentina, Mexico, Peru, Turkey, Thailand, and South Africa found the new vaccine to be as effective and safe as Pentaxim plus a monovalent hepatitis B vaccine, EMA said.

EMA recommended three additional new medications:

• Teduglutide (Revestive, Nycomed), a subcutaneous injection to treat short-bowel syndrome, a condition in which nutrients are not absorbed as a result of severe intestinal disease or the surgical removal of a large portion of the small intestine.

• Glycopyrronium bromide (Enurev, Novartis), a maintenance bronchodilator treatment for symptom relief in adults with chronic obstructive pulmonary disease.

• Ceftaroline fosamil (Zinforo, AstraZeneca), an infusion for treatment of adults with complicated skin and soft-tissue infections and community-acquired pneumonia.

The agency also announced that it was restricting indications for two medications on safety concerns. Following reports from Germany of hypersensitivity reactions, the agency advised clinicians not to prescribe tolperisone for indications other than poststroke spasticity and to use oral formulations in place of injectable ones. Tolperisone is a muscle relaxant used in Europe since the 1960s and only available in a handful of countries.

EMA recommended restricting the use of trimetazidine to second-line, add-on therapy after reports from France of movement disorders including Parkinsonian symptoms, restless leg syndrome, tremors and gait instability associated with the medicine. Trimetazidine-containing medicines have been available since the 1970s in Europe and are used in the treatment of patients with angina pectoris. Clinicians are also advised not to prescribe in patients with these and related movement disorders, or those who have severe renal impairment.

All EMA recommendations require European Commission approval to be final.

The European Medicines Agency said June 22 that it had recommended an extension of indication for the cancer drug everolimus to treat hormone receptor–positive, HER2–negative advanced breast cancer.

Everolimus (Afinitor, Novartis), already recommended by the EMA to treat pancreatic and renal cell cancers, is now recommended throughout the European Union in combination with exemestane as a second-line treatment in postmenopausal women in whom aromatase inhibitors have failed.

EMA also extended indications of agents used to treat two rheumatic diseases.

Etanercept (Enbrel), marketed by Pfizer and already licensed in Europe to treat rheumatic arthritis in adults, is now recommended as a treatment for polyarthritis (rheumatoid factor positive or negative), extended oligoarthritis, and psoriatic arthritis in children and adolescents in whom methotrexate has failed or is inappropriate. The indication for etanercept also was extended to treatment of enthesitis-related arthritis in adolescents 12 years and older not responding to conventional therapy.

Adalimumab (Humira), marketed by Abbott and licensed in Europe to treat a range of rheumatic diseases, will now be indicated for the treatment of adults with severe axial spondyloarthritis who have had an inadequate response to, or are intolerant of, nonsteroidal anti-inflammatory drugs. The new indication covers patients without radiographic evidence of axial spondyloarthritis but with evidence of inflammation determined by MRI or elevated C-reactive protein.

Also at its June meeting, the agency recommended a new six-in-one combination vaccine developed for use outside the European Union. Hexaxim, marketed by Sanofi Pasteur, will be used in children aged 6 weeks to 2 years old to inoculate against diphtheria, tetanus, pertussis, hepatitis B, polio, and diseases caused by Haemophilus influenzae type B, including meningitis. The vaccine is administered as three doses 4 or more weeks apart.

Five of the active substances in the vaccine have been used in other vaccines and have been previously combined in Pentaxim, also manufactured by Sanofi Pasteur. The new vaccine adds Hansenula polymorpha-derived recombinant hepatitis B surface antigen. Clinical trials in Argentina, Mexico, Peru, Turkey, Thailand, and South Africa found the new vaccine to be as effective and safe as Pentaxim plus a monovalent hepatitis B vaccine, EMA said.

EMA recommended three additional new medications:

• Teduglutide (Revestive, Nycomed), a subcutaneous injection to treat short-bowel syndrome, a condition in which nutrients are not absorbed as a result of severe intestinal disease or the surgical removal of a large portion of the small intestine.

• Glycopyrronium bromide (Enurev, Novartis), a maintenance bronchodilator treatment for symptom relief in adults with chronic obstructive pulmonary disease.

• Ceftaroline fosamil (Zinforo, AstraZeneca), an infusion for treatment of adults with complicated skin and soft-tissue infections and community-acquired pneumonia.

The agency also announced that it was restricting indications for two medications on safety concerns. Following reports from Germany of hypersensitivity reactions, the agency advised clinicians not to prescribe tolperisone for indications other than poststroke spasticity and to use oral formulations in place of injectable ones. Tolperisone is a muscle relaxant used in Europe since the 1960s and only available in a handful of countries.

EMA recommended restricting the use of trimetazidine to second-line, add-on therapy after reports from France of movement disorders including Parkinsonian symptoms, restless leg syndrome, tremors and gait instability associated with the medicine. Trimetazidine-containing medicines have been available since the 1970s in Europe and are used in the treatment of patients with angina pectoris. Clinicians are also advised not to prescribe in patients with these and related movement disorders, or those who have severe renal impairment.

All EMA recommendations require European Commission approval to be final.

The European Medicines Agency said June 22 that it had recommended an extension of indication for the cancer drug everolimus to treat hormone receptor–positive, HER2–negative advanced breast cancer.

Everolimus (Afinitor, Novartis), already recommended by the EMA to treat pancreatic and renal cell cancers, is now recommended throughout the European Union in combination with exemestane as a second-line treatment in postmenopausal women in whom aromatase inhibitors have failed.

EMA also extended indications of agents used to treat two rheumatic diseases.

Etanercept (Enbrel), marketed by Pfizer and already licensed in Europe to treat rheumatic arthritis in adults, is now recommended as a treatment for polyarthritis (rheumatoid factor positive or negative), extended oligoarthritis, and psoriatic arthritis in children and adolescents in whom methotrexate has failed or is inappropriate. The indication for etanercept also was extended to treatment of enthesitis-related arthritis in adolescents 12 years and older not responding to conventional therapy.

Adalimumab (Humira), marketed by Abbott and licensed in Europe to treat a range of rheumatic diseases, will now be indicated for the treatment of adults with severe axial spondyloarthritis who have had an inadequate response to, or are intolerant of, nonsteroidal anti-inflammatory drugs. The new indication covers patients without radiographic evidence of axial spondyloarthritis but with evidence of inflammation determined by MRI or elevated C-reactive protein.

Also at its June meeting, the agency recommended a new six-in-one combination vaccine developed for use outside the European Union. Hexaxim, marketed by Sanofi Pasteur, will be used in children aged 6 weeks to 2 years old to inoculate against diphtheria, tetanus, pertussis, hepatitis B, polio, and diseases caused by Haemophilus influenzae type B, including meningitis. The vaccine is administered as three doses 4 or more weeks apart.

Five of the active substances in the vaccine have been used in other vaccines and have been previously combined in Pentaxim, also manufactured by Sanofi Pasteur. The new vaccine adds Hansenula polymorpha-derived recombinant hepatitis B surface antigen. Clinical trials in Argentina, Mexico, Peru, Turkey, Thailand, and South Africa found the new vaccine to be as effective and safe as Pentaxim plus a monovalent hepatitis B vaccine, EMA said.

EMA recommended three additional new medications:

• Teduglutide (Revestive, Nycomed), a subcutaneous injection to treat short-bowel syndrome, a condition in which nutrients are not absorbed as a result of severe intestinal disease or the surgical removal of a large portion of the small intestine.

• Glycopyrronium bromide (Enurev, Novartis), a maintenance bronchodilator treatment for symptom relief in adults with chronic obstructive pulmonary disease.

• Ceftaroline fosamil (Zinforo, AstraZeneca), an infusion for treatment of adults with complicated skin and soft-tissue infections and community-acquired pneumonia.

The agency also announced that it was restricting indications for two medications on safety concerns. Following reports from Germany of hypersensitivity reactions, the agency advised clinicians not to prescribe tolperisone for indications other than poststroke spasticity and to use oral formulations in place of injectable ones. Tolperisone is a muscle relaxant used in Europe since the 1960s and only available in a handful of countries.

EMA recommended restricting the use of trimetazidine to second-line, add-on therapy after reports from France of movement disorders including Parkinsonian symptoms, restless leg syndrome, tremors and gait instability associated with the medicine. Trimetazidine-containing medicines have been available since the 1970s in Europe and are used in the treatment of patients with angina pectoris. Clinicians are also advised not to prescribe in patients with these and related movement disorders, or those who have severe renal impairment.

All EMA recommendations require European Commission approval to be final.

GAITHERSBURG, MD. – A novel radiofrequency probe is one step closer to the operating room to help surgeons ensure that lumpectomy margins are benign.

At a meeting on June 21, the Food and Drug Administration’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee voted 10-1 that the benefits of the MarginProbe system outweigh risks when used as an adjunctive diagnostic tool for the identification of cancerous tissue at the margins of the ex vivo lumpectomy specimen following primary excision in women previously diagnosed with breast cancer.

"I think that it has the potential to be beneficial to women to reduce their chances of going back to the operating room," said panel member Dr. A. Marilyn Leitch, an oncologic surgeon at the University of Texas Southwestern Medical Center in Dallas. "The sponsor has demonstrated that the device can detect tumor in the margins."

The system uses electromagnetic waves to characterize human tissue in real time, providing surgeons with intraoperative information on the malignancy of the margins of an ex vivo lumpectomy specimen. It is intended for use on freshly excised tissue within 20 minutes of excision. The probe is designed to characterize tissue, based on the principles of dielectric spectroscopy, according to a written statement by the company that sponsors the MarginProbe system, Dune Medical Devices Inc.

The sensor generates radiofrequency electromagnetic fields and measures a slice of tissue 7 mm in diameter, a few mm deep and adjacent to the sensor. The resonance characteristics are dependent on tissue properties – malignant tissue has been shown to have different characteristics compared with benign tissue.

The system is intended for intraoperative use in conjunction with standard methods, such as intraoperative imaging and palpation, to increase the likelihood that patients will undergo intraoperative re-excision of the lumpectomy cavity. The locations of re-excision will correspond to the margins of the ex vivo specimen that have less than 1-mm separation of the excision surface of the margin and the primary breast cancer, according to a statement by the company.

Dune Medical Devices is seeking premarket approval of the device based on data from several clinical trials and intended-use trials conducted primarily in Israel but also in the United States.

The FDA asked the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to vote on three questions:

• Is there reasonable assurance that the MarginProbe system is safe for use in patients who meet the criteria specified in the proposed indication?

• Is there reasonable assurance that the MarginProbe is effective for use in for patients who meet the criteria specified in the proposed indication?

• Do the benefits of the MarginProbe for use in patients who meet the specified criteria outweigh the risks for use in this patient populations?

Eleven panel members voted that the device is safe; there was one abstention. Eight panel members voted that the device was effective with regard to the proposed indication; one member voted no and there were two abstentions.

The agency also posed a number of questions to the panel regarding the adequacy of end points of key trials submitted; device sensitivity/specificity; the effect of specimen volume on future cosmesis; the appropriateness of applying the design dataset (based primarily on Israeli patients) to a U.S. population; and suggestions for the sponsor’s proposed postapproval study.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

GAITHERSBURG, MD. – A novel radiofrequency probe is one step closer to the operating room to help surgeons ensure that lumpectomy margins are benign.

At a meeting on June 21, the Food and Drug Administration’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee voted 10-1 that the benefits of the MarginProbe system outweigh risks when used as an adjunctive diagnostic tool for the identification of cancerous tissue at the margins of the ex vivo lumpectomy specimen following primary excision in women previously diagnosed with breast cancer.

"I think that it has the potential to be beneficial to women to reduce their chances of going back to the operating room," said panel member Dr. A. Marilyn Leitch, an oncologic surgeon at the University of Texas Southwestern Medical Center in Dallas. "The sponsor has demonstrated that the device can detect tumor in the margins."

The system uses electromagnetic waves to characterize human tissue in real time, providing surgeons with intraoperative information on the malignancy of the margins of an ex vivo lumpectomy specimen. It is intended for use on freshly excised tissue within 20 minutes of excision. The probe is designed to characterize tissue, based on the principles of dielectric spectroscopy, according to a written statement by the company that sponsors the MarginProbe system, Dune Medical Devices Inc.

The sensor generates radiofrequency electromagnetic fields and measures a slice of tissue 7 mm in diameter, a few mm deep and adjacent to the sensor. The resonance characteristics are dependent on tissue properties – malignant tissue has been shown to have different characteristics compared with benign tissue.

The system is intended for intraoperative use in conjunction with standard methods, such as intraoperative imaging and palpation, to increase the likelihood that patients will undergo intraoperative re-excision of the lumpectomy cavity. The locations of re-excision will correspond to the margins of the ex vivo specimen that have less than 1-mm separation of the excision surface of the margin and the primary breast cancer, according to a statement by the company.

Dune Medical Devices is seeking premarket approval of the device based on data from several clinical trials and intended-use trials conducted primarily in Israel but also in the United States.

The FDA asked the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to vote on three questions:

• Is there reasonable assurance that the MarginProbe system is safe for use in patients who meet the criteria specified in the proposed indication?

• Is there reasonable assurance that the MarginProbe is effective for use in for patients who meet the criteria specified in the proposed indication?

• Do the benefits of the MarginProbe for use in patients who meet the specified criteria outweigh the risks for use in this patient populations?

Eleven panel members voted that the device is safe; there was one abstention. Eight panel members voted that the device was effective with regard to the proposed indication; one member voted no and there were two abstentions.

The agency also posed a number of questions to the panel regarding the adequacy of end points of key trials submitted; device sensitivity/specificity; the effect of specimen volume on future cosmesis; the appropriateness of applying the design dataset (based primarily on Israeli patients) to a U.S. population; and suggestions for the sponsor’s proposed postapproval study.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

GAITHERSBURG, MD. – A novel radiofrequency probe is one step closer to the operating room to help surgeons ensure that lumpectomy margins are benign.

At a meeting on June 21, the Food and Drug Administration’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee voted 10-1 that the benefits of the MarginProbe system outweigh risks when used as an adjunctive diagnostic tool for the identification of cancerous tissue at the margins of the ex vivo lumpectomy specimen following primary excision in women previously diagnosed with breast cancer.

"I think that it has the potential to be beneficial to women to reduce their chances of going back to the operating room," said panel member Dr. A. Marilyn Leitch, an oncologic surgeon at the University of Texas Southwestern Medical Center in Dallas. "The sponsor has demonstrated that the device can detect tumor in the margins."

The system uses electromagnetic waves to characterize human tissue in real time, providing surgeons with intraoperative information on the malignancy of the margins of an ex vivo lumpectomy specimen. It is intended for use on freshly excised tissue within 20 minutes of excision. The probe is designed to characterize tissue, based on the principles of dielectric spectroscopy, according to a written statement by the company that sponsors the MarginProbe system, Dune Medical Devices Inc.

The sensor generates radiofrequency electromagnetic fields and measures a slice of tissue 7 mm in diameter, a few mm deep and adjacent to the sensor. The resonance characteristics are dependent on tissue properties – malignant tissue has been shown to have different characteristics compared with benign tissue.

The system is intended for intraoperative use in conjunction with standard methods, such as intraoperative imaging and palpation, to increase the likelihood that patients will undergo intraoperative re-excision of the lumpectomy cavity. The locations of re-excision will correspond to the margins of the ex vivo specimen that have less than 1-mm separation of the excision surface of the margin and the primary breast cancer, according to a statement by the company.

Dune Medical Devices is seeking premarket approval of the device based on data from several clinical trials and intended-use trials conducted primarily in Israel but also in the United States.

The FDA asked the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to vote on three questions:

• Is there reasonable assurance that the MarginProbe system is safe for use in patients who meet the criteria specified in the proposed indication?

• Is there reasonable assurance that the MarginProbe is effective for use in for patients who meet the criteria specified in the proposed indication?

• Do the benefits of the MarginProbe for use in patients who meet the specified criteria outweigh the risks for use in this patient populations?

Eleven panel members voted that the device is safe; there was one abstention. Eight panel members voted that the device was effective with regard to the proposed indication; one member voted no and there were two abstentions.

The agency also posed a number of questions to the panel regarding the adequacy of end points of key trials submitted; device sensitivity/specificity; the effect of specimen volume on future cosmesis; the appropriateness of applying the design dataset (based primarily on Israeli patients) to a U.S. population; and suggestions for the sponsor’s proposed postapproval study.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

CHICAGO – Vitamin D₃ can relieve the aches and pains associated with aromatase inhibitor therapy for breast cancer, according to the results of a randomized, double-blind, placebo-controlled trial.

Six months of vitamin D at 30,000 IU per week proved safe and was associated with "less worsening" of musculoskeletal events and fewer overall adverse quality of life events in women starting adjuvant letrozole (Femara) for hormone receptor–positive breast cancer, Dr. Qamar J. Khan reported at the annual meeting of the American Society of Clinical Oncology.

© Kaspri/Fotolia.com

Aromatase inhibitors are often discontinued prematurely because of new or worsening musculoskeletal pain reported in as many as half of women and fatigue in 15%-30%, said Dr. Khan of the University of Kansas Medical Center in Kansas City.

Vitamin D deficiency is thought to contribute to musculoskeletal symptoms, he said, explaining the rationale for the study. It is prevalent in breast cancer patients who have these aches and pains, and in women receiving adjuvant chemotherapy, even with supplementation. A similar syndrome is seen in people with severe vitamin D deficiency, he noted.

A prior pilot study conducted by the investigators suggested that vitamin D at 50,000 IU/wk for 12 weeks may be effective in reducing these symptoms (Breast Cancer Res. 2010;119:111-8).

The current double-blind VITAL (Vitamin D for Arthralgias From Letrozole) trial evenly randomized 160 postmenopausal women with stage I-III hormone receptor–positive invasive breast cancer and a serum vitamin D level of 40 ng/mL or less. All patients received letrozole 2.5 mg daily and the standard daily recommended daily allowance (RDA) of vitamin D 600 IU and calcium 1,200 mg. One cohort also received 30,000 IU of oral vitamin D₃ weekly for 24 weeks; the other was given a placebo.

The two arms were well matched with regard to age, race, body mass index, vitamin D level at baseline, adjuvant chemotherapy, and radiation therapy.

The per-protocol primary end point was the incidence of a musculoskeletal event, defined as worsening of pain using a simple pain intensity scale, worsening disability from musculoskeletal pain using the Health Assessment Questionnaire II, or discontinuation of letrozole because of pain at 6 months. The primary end point also was measured, substituting the quantitative Brief Pain Inventory for the simple pain intensity scale, Dr. Khan said.

Thirteen patients did not complete the study for reasons unrelated to study agents and/or musculoskeletal events, leaving 147 evaluable for efficacy.

At 6 months, 37% of women receiving 30,000 IU vitamin D weekly experienced a per-protocol musculoskeletal event, compared with 51% on placebo (P = .069), based on the simple scale. When the more robust Brief Pain Inventory was used, 61% of controls and 38% of those on vitamin D reported a musculoskeletal event, a difference that reached statistical significance (P = .008), he said.

A significantly higher proportion of women on placebo also had an adverse quality of life event, defined as a musculoskeletal event plus worsening of fatigue (72% vs. 42%; P less than .001).

The median vitamin D level at baseline was 25.1 ng/mL in the control arm and 22.5 ng/mL in the vitamin D group. It hovered at 32 ng/mL at 12 weeks and 31 ng/mL at 24 weeks in the control group, but rose to 53 ng/mL at 12 weeks and 57 ng/mL at 24 weeks in the vitamin D arm (P = .001 at both 12 and 24 weeks).

Baseline levels had little influence on the final level achieved. The sharp rise followed by relatively little gain in the active treatment arm suggests a plateau in the effect of continued vitamin D supplementation, Dr. Khan observed.

One patient in the control arm developed mild hypercalcemia, and three patients in the control arm discontinued early because of a musculoskeletal adverse event. There were no severe adverse events.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) Medical Center, said that the trial used well-validated measures and showed no discernable toxicity with 30,000 IU weekly, which is beyond the current RDA. "Therefore it may be promising for helping with these musculoskeletal symptoms and possibly fatigue," she said.

Dr. Mustian asked whether the time needed to achieve a benefit poses a potential problem in terms of patient adherence and whether data are available on the sustainability of the improvements in musculoskeletal symptoms and fatigue.

Dr. Khan said that aromatase inhibitor–induced adverse events tend to peak at about 6 months and that only one study has looked at using higher doses of vitamin D beyond 6 months. The observation that the effect of vitamin D supplementation plateaus at 3-6 months, however, is consistent with other studies.

"After you load the body with vitamin D and ... you keep on giving the same dose, the body just maintains the levels," he said.

Dr. Khan said that additional studies are needed to address long-term sustainability, and that the investigators have proposed a trial to the Southwest Oncology Group for the same intervention for 1-2 years to study a longer-term effect.

Dr. Khan reports honoraria from Abraxis BioScience and Genentech, and research funding from Abraxis and Novartis Roche/Genentech. His coauthors and Dr. Mustian report no disclosures.

CHICAGO – Vitamin D₃ can relieve the aches and pains associated with aromatase inhibitor therapy for breast cancer, according to the results of a randomized, double-blind, placebo-controlled trial.

Six months of vitamin D at 30,000 IU per week proved safe and was associated with "less worsening" of musculoskeletal events and fewer overall adverse quality of life events in women starting adjuvant letrozole (Femara) for hormone receptor–positive breast cancer, Dr. Qamar J. Khan reported at the annual meeting of the American Society of Clinical Oncology.

© Kaspri/Fotolia.com

Aromatase inhibitors are often discontinued prematurely because of new or worsening musculoskeletal pain reported in as many as half of women and fatigue in 15%-30%, said Dr. Khan of the University of Kansas Medical Center in Kansas City.

Vitamin D deficiency is thought to contribute to musculoskeletal symptoms, he said, explaining the rationale for the study. It is prevalent in breast cancer patients who have these aches and pains, and in women receiving adjuvant chemotherapy, even with supplementation. A similar syndrome is seen in people with severe vitamin D deficiency, he noted.

A prior pilot study conducted by the investigators suggested that vitamin D at 50,000 IU/wk for 12 weeks may be effective in reducing these symptoms (Breast Cancer Res. 2010;119:111-8).

The current double-blind VITAL (Vitamin D for Arthralgias From Letrozole) trial evenly randomized 160 postmenopausal women with stage I-III hormone receptor–positive invasive breast cancer and a serum vitamin D level of 40 ng/mL or less. All patients received letrozole 2.5 mg daily and the standard daily recommended daily allowance (RDA) of vitamin D 600 IU and calcium 1,200 mg. One cohort also received 30,000 IU of oral vitamin D₃ weekly for 24 weeks; the other was given a placebo.

The two arms were well matched with regard to age, race, body mass index, vitamin D level at baseline, adjuvant chemotherapy, and radiation therapy.

The per-protocol primary end point was the incidence of a musculoskeletal event, defined as worsening of pain using a simple pain intensity scale, worsening disability from musculoskeletal pain using the Health Assessment Questionnaire II, or discontinuation of letrozole because of pain at 6 months. The primary end point also was measured, substituting the quantitative Brief Pain Inventory for the simple pain intensity scale, Dr. Khan said.

Thirteen patients did not complete the study for reasons unrelated to study agents and/or musculoskeletal events, leaving 147 evaluable for efficacy.

At 6 months, 37% of women receiving 30,000 IU vitamin D weekly experienced a per-protocol musculoskeletal event, compared with 51% on placebo (P = .069), based on the simple scale. When the more robust Brief Pain Inventory was used, 61% of controls and 38% of those on vitamin D reported a musculoskeletal event, a difference that reached statistical significance (P = .008), he said.

A significantly higher proportion of women on placebo also had an adverse quality of life event, defined as a musculoskeletal event plus worsening of fatigue (72% vs. 42%; P less than .001).

The median vitamin D level at baseline was 25.1 ng/mL in the control arm and 22.5 ng/mL in the vitamin D group. It hovered at 32 ng/mL at 12 weeks and 31 ng/mL at 24 weeks in the control group, but rose to 53 ng/mL at 12 weeks and 57 ng/mL at 24 weeks in the vitamin D arm (P = .001 at both 12 and 24 weeks).

Baseline levels had little influence on the final level achieved. The sharp rise followed by relatively little gain in the active treatment arm suggests a plateau in the effect of continued vitamin D supplementation, Dr. Khan observed.

One patient in the control arm developed mild hypercalcemia, and three patients in the control arm discontinued early because of a musculoskeletal adverse event. There were no severe adverse events.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) Medical Center, said that the trial used well-validated measures and showed no discernable toxicity with 30,000 IU weekly, which is beyond the current RDA. "Therefore it may be promising for helping with these musculoskeletal symptoms and possibly fatigue," she said.

Dr. Mustian asked whether the time needed to achieve a benefit poses a potential problem in terms of patient adherence and whether data are available on the sustainability of the improvements in musculoskeletal symptoms and fatigue.

Dr. Khan said that aromatase inhibitor–induced adverse events tend to peak at about 6 months and that only one study has looked at using higher doses of vitamin D beyond 6 months. The observation that the effect of vitamin D supplementation plateaus at 3-6 months, however, is consistent with other studies.

"After you load the body with vitamin D and ... you keep on giving the same dose, the body just maintains the levels," he said.

Dr. Khan said that additional studies are needed to address long-term sustainability, and that the investigators have proposed a trial to the Southwest Oncology Group for the same intervention for 1-2 years to study a longer-term effect.

Dr. Khan reports honoraria from Abraxis BioScience and Genentech, and research funding from Abraxis and Novartis Roche/Genentech. His coauthors and Dr. Mustian report no disclosures.

CHICAGO – Vitamin D₃ can relieve the aches and pains associated with aromatase inhibitor therapy for breast cancer, according to the results of a randomized, double-blind, placebo-controlled trial.

Six months of vitamin D at 30,000 IU per week proved safe and was associated with "less worsening" of musculoskeletal events and fewer overall adverse quality of life events in women starting adjuvant letrozole (Femara) for hormone receptor–positive breast cancer, Dr. Qamar J. Khan reported at the annual meeting of the American Society of Clinical Oncology.

© Kaspri/Fotolia.com

Aromatase inhibitors are often discontinued prematurely because of new or worsening musculoskeletal pain reported in as many as half of women and fatigue in 15%-30%, said Dr. Khan of the University of Kansas Medical Center in Kansas City.

Vitamin D deficiency is thought to contribute to musculoskeletal symptoms, he said, explaining the rationale for the study. It is prevalent in breast cancer patients who have these aches and pains, and in women receiving adjuvant chemotherapy, even with supplementation. A similar syndrome is seen in people with severe vitamin D deficiency, he noted.

A prior pilot study conducted by the investigators suggested that vitamin D at 50,000 IU/wk for 12 weeks may be effective in reducing these symptoms (Breast Cancer Res. 2010;119:111-8).

The current double-blind VITAL (Vitamin D for Arthralgias From Letrozole) trial evenly randomized 160 postmenopausal women with stage I-III hormone receptor–positive invasive breast cancer and a serum vitamin D level of 40 ng/mL or less. All patients received letrozole 2.5 mg daily and the standard daily recommended daily allowance (RDA) of vitamin D 600 IU and calcium 1,200 mg. One cohort also received 30,000 IU of oral vitamin D₃ weekly for 24 weeks; the other was given a placebo.

The two arms were well matched with regard to age, race, body mass index, vitamin D level at baseline, adjuvant chemotherapy, and radiation therapy.

The per-protocol primary end point was the incidence of a musculoskeletal event, defined as worsening of pain using a simple pain intensity scale, worsening disability from musculoskeletal pain using the Health Assessment Questionnaire II, or discontinuation of letrozole because of pain at 6 months. The primary end point also was measured, substituting the quantitative Brief Pain Inventory for the simple pain intensity scale, Dr. Khan said.

Thirteen patients did not complete the study for reasons unrelated to study agents and/or musculoskeletal events, leaving 147 evaluable for efficacy.

At 6 months, 37% of women receiving 30,000 IU vitamin D weekly experienced a per-protocol musculoskeletal event, compared with 51% on placebo (P = .069), based on the simple scale. When the more robust Brief Pain Inventory was used, 61% of controls and 38% of those on vitamin D reported a musculoskeletal event, a difference that reached statistical significance (P = .008), he said.

A significantly higher proportion of women on placebo also had an adverse quality of life event, defined as a musculoskeletal event plus worsening of fatigue (72% vs. 42%; P less than .001).

The median vitamin D level at baseline was 25.1 ng/mL in the control arm and 22.5 ng/mL in the vitamin D group. It hovered at 32 ng/mL at 12 weeks and 31 ng/mL at 24 weeks in the control group, but rose to 53 ng/mL at 12 weeks and 57 ng/mL at 24 weeks in the vitamin D arm (P = .001 at both 12 and 24 weeks).

Baseline levels had little influence on the final level achieved. The sharp rise followed by relatively little gain in the active treatment arm suggests a plateau in the effect of continued vitamin D supplementation, Dr. Khan observed.

One patient in the control arm developed mild hypercalcemia, and three patients in the control arm discontinued early because of a musculoskeletal adverse event. There were no severe adverse events.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) Medical Center, said that the trial used well-validated measures and showed no discernable toxicity with 30,000 IU weekly, which is beyond the current RDA. "Therefore it may be promising for helping with these musculoskeletal symptoms and possibly fatigue," she said.

Dr. Mustian asked whether the time needed to achieve a benefit poses a potential problem in terms of patient adherence and whether data are available on the sustainability of the improvements in musculoskeletal symptoms and fatigue.

Dr. Khan said that aromatase inhibitor–induced adverse events tend to peak at about 6 months and that only one study has looked at using higher doses of vitamin D beyond 6 months. The observation that the effect of vitamin D supplementation plateaus at 3-6 months, however, is consistent with other studies.

"After you load the body with vitamin D and ... you keep on giving the same dose, the body just maintains the levels," he said.

Dr. Khan said that additional studies are needed to address long-term sustainability, and that the investigators have proposed a trial to the Southwest Oncology Group for the same intervention for 1-2 years to study a longer-term effect.

Dr. Khan reports honoraria from Abraxis BioScience and Genentech, and research funding from Abraxis and Novartis Roche/Genentech. His coauthors and Dr. Mustian report no disclosures.

CHICAGO – Lapatinib was not superior to trastuzumab when used as a component of neoadjuvant therapy for operable HER2-positive breast cancer in a randomized cooperative group trial. And neither was a combination of both drugs in the population overall.

About 50%-60% of the 529 patients studied had a pathological complete response (pCR) whether they received trastuzumab (Herceptin) only, lapatinib (Tykerb) only, or lapatinib plus trastuzumab, each in addition to standard chemotherapy in the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-41 trial, investigators reported.

However, patients whose tumors had a high level of HER2 overexpression on immunohistochemistry, scored as 3+ staining, were more likely to have a pCR if they received lapatinib plus trastuzumab than if they received trastuzumab alone, Dr. Andre Robidoux told attendees at the annual meeting of the American Society of Clinical Oncology.

Of note, the rate of grade 3 or worse diarrhea was higher with lapatinib alone or in combination, the investigators found. And patients in those groups were less likely to complete their treatment.

"Combined HER2-targeted therapy produced a numerically higher pCR percentage than single-agent HER2-directed therapy, but the difference was not statistically significant," said Dr. Robidoux of the Centre Hospitalier de l’Université de Montréal

"Unplanned analysis based on immunohistochemical staining intensity suggests that combined HER2-targeted therapy may be of greatest value in patients with tumors with a high degree of protein overexpression," he added.

Dual Blockade Supported

Discussant Dr. Gunter von Minckwitz of the German Breast Group and the University of Frankfurt noted that neoadjuvant trastuzumab therapy increases the likelihood of residual ductal carcinoma in situ (DCIS) at surgery, which is a negative prognostic factor for disease-free survival (J. Clin. Oncol. 2012;30:901-3). "So maybe the NSABP investigators should also analyze their data for an even more pure pCR definition," he proposed.

"We have seen now a series of studies either combining lapatinib and trastuzumab or combining trastuzumab and pertuzumab [Perjeta] showing higher pCR rates compared to patients who got only one of the anti-HER2 treatments," he maintained. "So this is the way we have to go. ... Dual blockade appears to be the most promising approach for the future."

"We have to wait, of course, to see how far the neoadjuvant results are predicting the outcome of adjuvant treatment; therefore, ALTTO and APHINITY are crucial," Dr. von Minckwitz added, referring to two trials.

"However, I believe the results from the neoadjuvant setting are quite consistent with the results that are now obtained in other settings – the adjuvant and metastatic settings. Therefore, this might open a regulatory path for conditional approval of agents in early development," as recently proposed by the Food and Drug Administration (N. Engl. J. Med. 2012 May 30).

Giving background on NSABP B-41, Dr. Robidoux noted that doxorubicin (Adriamycin) plus cyclophosphamide, followed by weekly paclitaxel plus trastuzumab, has been a standard neoadjuvant therapy for HER2-positive breast cancer since 2005. But lapatinib, an oral dual tyrosine kinase inhibitor of HER2 and the epidermal growth factor receptor (EGFR), has a different mechanism of action and shows synergy with trastuzumab.

"The next logical step was to evaluate the addition of a second agent that interrupts HER2 signaling through a different mechanism than trastuzumab," he said.

PCR Rates Indistinguishable

Women enrolled in the trial had a palpable tumor measuring at least 2 cm, a left ventricular ejection fraction of at least 50%, and HER2-positive disease, defined as gene amplification by fluorescence in situ hybridization (FISH) or a score of 3+ by immunohistochemistry.

All women received four cycles of doxorubicin plus cyclophosphamide. Thereafter, they received weekly paclitaxel plus trastuzumab only (as a control), plus lapatinib only, or plus both. They then underwent surgery and received trastuzumab postoperatively.

The main results showed that the rate of clinical complete response with lapatinib alone (69.9%) was lower than that with trastuzumab alone (82%) (P = .014). But it did not differ significantly between trastuzumab and lapatinib plus trastuzumab (76.8%).

The rates of pCR in the breast with lapatinib alone (53.2%) or lapatinib combined with trastuzumab (62%) were statistically indistinguishable from that seen with trastuzumab alone (52.5%).

This pattern was the same in subgroups having hormone receptor–positive and negative disease. However, in a finding that Dr. Robidoux called "intriguing," the pCR rate among those with 3+ immunohistochemical staining for HER2 was higher with lapatinib plus trastuzumab (71%) than with trastuzumab alone (54.7%) (P = .006).

The overall rate of grade 3 or worse toxicity was 50% with trastuzumab alone, 62% with lapatinib alone, and 61% with lapatinib plus trastuzumab. Grade 3 or worse diarrhea was by far more common in both lapatinib groups (P less than .001), but grade 3 or worse febrile neutropenia and hepatotoxicity were similarly common.

The rate of New York Heart Association class III or IV congestive heart failure was 4% with trastuzumab alone, 4% with lapatinib alone, and 1% with the combination, differences that were not statistically significant.

Patients in the trastuzumab group were more likely to complete their therapy (78%) than their counterparts in the lapatinib group (68%) and in the combination group (63%) (P = .01).

About half of patients were able to have breast-conserving surgery, whether they received trastuzumab alone (54%), lapatinib alone (46%), or both drugs (50%).

Dr. Robidoux disclosed that he is a consultant to GlaxoSmithKline and receives honoraria and research funding from GlaxoSmithKline and Roche. Dr. von Minckwitz disclosed no relevant conflicts of interest.

CHICAGO – Lapatinib was not superior to trastuzumab when used as a component of neoadjuvant therapy for operable HER2-positive breast cancer in a randomized cooperative group trial. And neither was a combination of both drugs in the population overall.

About 50%-60% of the 529 patients studied had a pathological complete response (pCR) whether they received trastuzumab (Herceptin) only, lapatinib (Tykerb) only, or lapatinib plus trastuzumab, each in addition to standard chemotherapy in the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-41 trial, investigators reported.

However, patients whose tumors had a high level of HER2 overexpression on immunohistochemistry, scored as 3+ staining, were more likely to have a pCR if they received lapatinib plus trastuzumab than if they received trastuzumab alone, Dr. Andre Robidoux told attendees at the annual meeting of the American Society of Clinical Oncology.

Of note, the rate of grade 3 or worse diarrhea was higher with lapatinib alone or in combination, the investigators found. And patients in those groups were less likely to complete their treatment.

"Combined HER2-targeted therapy produced a numerically higher pCR percentage than single-agent HER2-directed therapy, but the difference was not statistically significant," said Dr. Robidoux of the Centre Hospitalier de l’Université de Montréal

"Unplanned analysis based on immunohistochemical staining intensity suggests that combined HER2-targeted therapy may be of greatest value in patients with tumors with a high degree of protein overexpression," he added.

Dual Blockade Supported

Discussant Dr. Gunter von Minckwitz of the German Breast Group and the University of Frankfurt noted that neoadjuvant trastuzumab therapy increases the likelihood of residual ductal carcinoma in situ (DCIS) at surgery, which is a negative prognostic factor for disease-free survival (J. Clin. Oncol. 2012;30:901-3). "So maybe the NSABP investigators should also analyze their data for an even more pure pCR definition," he proposed.

"We have seen now a series of studies either combining lapatinib and trastuzumab or combining trastuzumab and pertuzumab [Perjeta] showing higher pCR rates compared to patients who got only one of the anti-HER2 treatments," he maintained. "So this is the way we have to go. ... Dual blockade appears to be the most promising approach for the future."

"We have to wait, of course, to see how far the neoadjuvant results are predicting the outcome of adjuvant treatment; therefore, ALTTO and APHINITY are crucial," Dr. von Minckwitz added, referring to two trials.

"However, I believe the results from the neoadjuvant setting are quite consistent with the results that are now obtained in other settings – the adjuvant and metastatic settings. Therefore, this might open a regulatory path for conditional approval of agents in early development," as recently proposed by the Food and Drug Administration (N. Engl. J. Med. 2012 May 30).

Giving background on NSABP B-41, Dr. Robidoux noted that doxorubicin (Adriamycin) plus cyclophosphamide, followed by weekly paclitaxel plus trastuzumab, has been a standard neoadjuvant therapy for HER2-positive breast cancer since 2005. But lapatinib, an oral dual tyrosine kinase inhibitor of HER2 and the epidermal growth factor receptor (EGFR), has a different mechanism of action and shows synergy with trastuzumab.

"The next logical step was to evaluate the addition of a second agent that interrupts HER2 signaling through a different mechanism than trastuzumab," he said.

PCR Rates Indistinguishable

Women enrolled in the trial had a palpable tumor measuring at least 2 cm, a left ventricular ejection fraction of at least 50%, and HER2-positive disease, defined as gene amplification by fluorescence in situ hybridization (FISH) or a score of 3+ by immunohistochemistry.

All women received four cycles of doxorubicin plus cyclophosphamide. Thereafter, they received weekly paclitaxel plus trastuzumab only (as a control), plus lapatinib only, or plus both. They then underwent surgery and received trastuzumab postoperatively.

The main results showed that the rate of clinical complete response with lapatinib alone (69.9%) was lower than that with trastuzumab alone (82%) (P = .014). But it did not differ significantly between trastuzumab and lapatinib plus trastuzumab (76.8%).

The rates of pCR in the breast with lapatinib alone (53.2%) or lapatinib combined with trastuzumab (62%) were statistically indistinguishable from that seen with trastuzumab alone (52.5%).

This pattern was the same in subgroups having hormone receptor–positive and negative disease. However, in a finding that Dr. Robidoux called "intriguing," the pCR rate among those with 3+ immunohistochemical staining for HER2 was higher with lapatinib plus trastuzumab (71%) than with trastuzumab alone (54.7%) (P = .006).

The overall rate of grade 3 or worse toxicity was 50% with trastuzumab alone, 62% with lapatinib alone, and 61% with lapatinib plus trastuzumab. Grade 3 or worse diarrhea was by far more common in both lapatinib groups (P less than .001), but grade 3 or worse febrile neutropenia and hepatotoxicity were similarly common.

The rate of New York Heart Association class III or IV congestive heart failure was 4% with trastuzumab alone, 4% with lapatinib alone, and 1% with the combination, differences that were not statistically significant.

Patients in the trastuzumab group were more likely to complete their therapy (78%) than their counterparts in the lapatinib group (68%) and in the combination group (63%) (P = .01).

About half of patients were able to have breast-conserving surgery, whether they received trastuzumab alone (54%), lapatinib alone (46%), or both drugs (50%).

Dr. Robidoux disclosed that he is a consultant to GlaxoSmithKline and receives honoraria and research funding from GlaxoSmithKline and Roche. Dr. von Minckwitz disclosed no relevant conflicts of interest.

CHICAGO – Lapatinib was not superior to trastuzumab when used as a component of neoadjuvant therapy for operable HER2-positive breast cancer in a randomized cooperative group trial. And neither was a combination of both drugs in the population overall.

About 50%-60% of the 529 patients studied had a pathological complete response (pCR) whether they received trastuzumab (Herceptin) only, lapatinib (Tykerb) only, or lapatinib plus trastuzumab, each in addition to standard chemotherapy in the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-41 trial, investigators reported.

However, patients whose tumors had a high level of HER2 overexpression on immunohistochemistry, scored as 3+ staining, were more likely to have a pCR if they received lapatinib plus trastuzumab than if they received trastuzumab alone, Dr. Andre Robidoux told attendees at the annual meeting of the American Society of Clinical Oncology.

Of note, the rate of grade 3 or worse diarrhea was higher with lapatinib alone or in combination, the investigators found. And patients in those groups were less likely to complete their treatment.

"Combined HER2-targeted therapy produced a numerically higher pCR percentage than single-agent HER2-directed therapy, but the difference was not statistically significant," said Dr. Robidoux of the Centre Hospitalier de l’Université de Montréal

"Unplanned analysis based on immunohistochemical staining intensity suggests that combined HER2-targeted therapy may be of greatest value in patients with tumors with a high degree of protein overexpression," he added.

Dual Blockade Supported

Discussant Dr. Gunter von Minckwitz of the German Breast Group and the University of Frankfurt noted that neoadjuvant trastuzumab therapy increases the likelihood of residual ductal carcinoma in situ (DCIS) at surgery, which is a negative prognostic factor for disease-free survival (J. Clin. Oncol. 2012;30:901-3). "So maybe the NSABP investigators should also analyze their data for an even more pure pCR definition," he proposed.

"We have seen now a series of studies either combining lapatinib and trastuzumab or combining trastuzumab and pertuzumab [Perjeta] showing higher pCR rates compared to patients who got only one of the anti-HER2 treatments," he maintained. "So this is the way we have to go. ... Dual blockade appears to be the most promising approach for the future."

"We have to wait, of course, to see how far the neoadjuvant results are predicting the outcome of adjuvant treatment; therefore, ALTTO and APHINITY are crucial," Dr. von Minckwitz added, referring to two trials.

"However, I believe the results from the neoadjuvant setting are quite consistent with the results that are now obtained in other settings – the adjuvant and metastatic settings. Therefore, this might open a regulatory path for conditional approval of agents in early development," as recently proposed by the Food and Drug Administration (N. Engl. J. Med. 2012 May 30).

Giving background on NSABP B-41, Dr. Robidoux noted that doxorubicin (Adriamycin) plus cyclophosphamide, followed by weekly paclitaxel plus trastuzumab, has been a standard neoadjuvant therapy for HER2-positive breast cancer since 2005. But lapatinib, an oral dual tyrosine kinase inhibitor of HER2 and the epidermal growth factor receptor (EGFR), has a different mechanism of action and shows synergy with trastuzumab.

"The next logical step was to evaluate the addition of a second agent that interrupts HER2 signaling through a different mechanism than trastuzumab," he said.

PCR Rates Indistinguishable

Women enrolled in the trial had a palpable tumor measuring at least 2 cm, a left ventricular ejection fraction of at least 50%, and HER2-positive disease, defined as gene amplification by fluorescence in situ hybridization (FISH) or a score of 3+ by immunohistochemistry.

All women received four cycles of doxorubicin plus cyclophosphamide. Thereafter, they received weekly paclitaxel plus trastuzumab only (as a control), plus lapatinib only, or plus both. They then underwent surgery and received trastuzumab postoperatively.

The main results showed that the rate of clinical complete response with lapatinib alone (69.9%) was lower than that with trastuzumab alone (82%) (P = .014). But it did not differ significantly between trastuzumab and lapatinib plus trastuzumab (76.8%).

The rates of pCR in the breast with lapatinib alone (53.2%) or lapatinib combined with trastuzumab (62%) were statistically indistinguishable from that seen with trastuzumab alone (52.5%).

This pattern was the same in subgroups having hormone receptor–positive and negative disease. However, in a finding that Dr. Robidoux called "intriguing," the pCR rate among those with 3+ immunohistochemical staining for HER2 was higher with lapatinib plus trastuzumab (71%) than with trastuzumab alone (54.7%) (P = .006).

The overall rate of grade 3 or worse toxicity was 50% with trastuzumab alone, 62% with lapatinib alone, and 61% with lapatinib plus trastuzumab. Grade 3 or worse diarrhea was by far more common in both lapatinib groups (P less than .001), but grade 3 or worse febrile neutropenia and hepatotoxicity were similarly common.

The rate of New York Heart Association class III or IV congestive heart failure was 4% with trastuzumab alone, 4% with lapatinib alone, and 1% with the combination, differences that were not statistically significant.

Patients in the trastuzumab group were more likely to complete their therapy (78%) than their counterparts in the lapatinib group (68%) and in the combination group (63%) (P = .01).

About half of patients were able to have breast-conserving surgery, whether they received trastuzumab alone (54%), lapatinib alone (46%), or both drugs (50%).

Dr. Robidoux disclosed that he is a consultant to GlaxoSmithKline and receives honoraria and research funding from GlaxoSmithKline and Roche. Dr. von Minckwitz disclosed no relevant conflicts of interest.

CHICAGO  – Radiation therapy dramatically improves local control in ductal carcinoma in situ, even in cases having favorable features, investigators reported.

The randomized Radiation Therapy Oncology Group (RTOG) 9804 trial was conducted among 585 women who had "good-risk" ductal carcinoma in situ (DCIS), meaning small, asymptomatic tumors of low grade and with adequate resection margins after lumpectomy.

The main results showed that women had a significant 86% relative reduction in the risk of local failure if they received radiation therapy instead of observation. But the absolute 5-year rate of local failure was only about 3%, even without this intervention.

"We were able, using standard pathology methods and our Web-based RTOG pathology tool, to define good-risk or low-risk DCIS patients who had an extremely low event rate even with observation," said lead investigator Dr. Beryl McCormick at the annual meeting of the American Society of Clinical Oncology.

Nonetheless, "for this good-risk disease, the addition of radiation significantly reduced the risk of local failure. Clearly, we are expecting to follow this group out longer," added Dr. McCormick, a radiation oncologist and chief of the external beam radiotherapy service at Memorial Sloan-Kettering Cancer Center in New York.

"The study was a positive study," commented discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C. "The reasons for that are debatable. On this analysis, there was a lower recurrence rate in the excision-only group than had been predicted, but what drove the positive findings was the much lower rate in the radiation therapy group."

Dr. Hwang speculated that the use of tamoxifen by about two-thirds of women may have contributed to the low rate of local recurrence seen even in the absence of radiation therapy.

"Further follow-up is required, because many of these patients [had] a short follow-up that may explain why we saw such low recurrence risks in this study," she proposed.

Women with DCIS who were above age 26 were eligible for RTOG 9804 if they had no symptoms (their tumors had been found mammographically or incidentally), had only low or intermediate tumor grade, had a tumor size of 2.5 cm or less, and had a resection margin width of at least 3 mm.

The 585 study participants were randomly assigned in balanced fashion to observation or radiation therapy, each with or without tamoxifen. (Overall, 62% received the drug.) Radiation therapy began within 12 weeks of final surgery, and consisted of 42.5-50.4 Gy, with no boost.

The main trial results showed that the actuarial 5-year rate of local failure (invasive or noninvasive) in the treated breast was 3.2% in the observation group and 0.4% in the radiation therapy group, corresponding to an 86% reduction in risk (hazard ratio, 0.14; P = .002), Dr. McCormick reported.

In the radiation therapy group, there were no local failures in the same quadrant as the original tumor; in contrast, in the observation group, two-thirds of the failures were in the same quadrant.

The two groups were statistically indistinguishable with respect to the rate of contralateral breast events, disease-free survival, and overall survival.

The rate of acute grade 3 or worse nonhematologic toxicities was similar in the observation group and radiation therapy group (4.0% vs. 4.2%, respectively), although lower-grade toxicities were more common in the latter. The rate of late grade 3 or worse radiation therapy toxicity was 0.7% in the group given this therapy.

Dr. McCormick disclosed no relevant conflicts of interest. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO  – Radiation therapy dramatically improves local control in ductal carcinoma in situ, even in cases having favorable features, investigators reported.

The randomized Radiation Therapy Oncology Group (RTOG) 9804 trial was conducted among 585 women who had "good-risk" ductal carcinoma in situ (DCIS), meaning small, asymptomatic tumors of low grade and with adequate resection margins after lumpectomy.

The main results showed that women had a significant 86% relative reduction in the risk of local failure if they received radiation therapy instead of observation. But the absolute 5-year rate of local failure was only about 3%, even without this intervention.

"We were able, using standard pathology methods and our Web-based RTOG pathology tool, to define good-risk or low-risk DCIS patients who had an extremely low event rate even with observation," said lead investigator Dr. Beryl McCormick at the annual meeting of the American Society of Clinical Oncology.

Nonetheless, "for this good-risk disease, the addition of radiation significantly reduced the risk of local failure. Clearly, we are expecting to follow this group out longer," added Dr. McCormick, a radiation oncologist and chief of the external beam radiotherapy service at Memorial Sloan-Kettering Cancer Center in New York.

"The study was a positive study," commented discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C. "The reasons for that are debatable. On this analysis, there was a lower recurrence rate in the excision-only group than had been predicted, but what drove the positive findings was the much lower rate in the radiation therapy group."

Dr. Hwang speculated that the use of tamoxifen by about two-thirds of women may have contributed to the low rate of local recurrence seen even in the absence of radiation therapy.

"Further follow-up is required, because many of these patients [had] a short follow-up that may explain why we saw such low recurrence risks in this study," she proposed.

Women with DCIS who were above age 26 were eligible for RTOG 9804 if they had no symptoms (their tumors had been found mammographically or incidentally), had only low or intermediate tumor grade, had a tumor size of 2.5 cm or less, and had a resection margin width of at least 3 mm.

The 585 study participants were randomly assigned in balanced fashion to observation or radiation therapy, each with or without tamoxifen. (Overall, 62% received the drug.) Radiation therapy began within 12 weeks of final surgery, and consisted of 42.5-50.4 Gy, with no boost.

The main trial results showed that the actuarial 5-year rate of local failure (invasive or noninvasive) in the treated breast was 3.2% in the observation group and 0.4% in the radiation therapy group, corresponding to an 86% reduction in risk (hazard ratio, 0.14; P = .002), Dr. McCormick reported.

In the radiation therapy group, there were no local failures in the same quadrant as the original tumor; in contrast, in the observation group, two-thirds of the failures were in the same quadrant.

The two groups were statistically indistinguishable with respect to the rate of contralateral breast events, disease-free survival, and overall survival.

The rate of acute grade 3 or worse nonhematologic toxicities was similar in the observation group and radiation therapy group (4.0% vs. 4.2%, respectively), although lower-grade toxicities were more common in the latter. The rate of late grade 3 or worse radiation therapy toxicity was 0.7% in the group given this therapy.

Dr. McCormick disclosed no relevant conflicts of interest. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO  – Radiation therapy dramatically improves local control in ductal carcinoma in situ, even in cases having favorable features, investigators reported.

The randomized Radiation Therapy Oncology Group (RTOG) 9804 trial was conducted among 585 women who had "good-risk" ductal carcinoma in situ (DCIS), meaning small, asymptomatic tumors of low grade and with adequate resection margins after lumpectomy.

The main results showed that women had a significant 86% relative reduction in the risk of local failure if they received radiation therapy instead of observation. But the absolute 5-year rate of local failure was only about 3%, even without this intervention.

"We were able, using standard pathology methods and our Web-based RTOG pathology tool, to define good-risk or low-risk DCIS patients who had an extremely low event rate even with observation," said lead investigator Dr. Beryl McCormick at the annual meeting of the American Society of Clinical Oncology.

Nonetheless, "for this good-risk disease, the addition of radiation significantly reduced the risk of local failure. Clearly, we are expecting to follow this group out longer," added Dr. McCormick, a radiation oncologist and chief of the external beam radiotherapy service at Memorial Sloan-Kettering Cancer Center in New York.

"The study was a positive study," commented discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C. "The reasons for that are debatable. On this analysis, there was a lower recurrence rate in the excision-only group than had been predicted, but what drove the positive findings was the much lower rate in the radiation therapy group."

Dr. Hwang speculated that the use of tamoxifen by about two-thirds of women may have contributed to the low rate of local recurrence seen even in the absence of radiation therapy.

"Further follow-up is required, because many of these patients [had] a short follow-up that may explain why we saw such low recurrence risks in this study," she proposed.

Women with DCIS who were above age 26 were eligible for RTOG 9804 if they had no symptoms (their tumors had been found mammographically or incidentally), had only low or intermediate tumor grade, had a tumor size of 2.5 cm or less, and had a resection margin width of at least 3 mm.

The 585 study participants were randomly assigned in balanced fashion to observation or radiation therapy, each with or without tamoxifen. (Overall, 62% received the drug.) Radiation therapy began within 12 weeks of final surgery, and consisted of 42.5-50.4 Gy, with no boost.

The main trial results showed that the actuarial 5-year rate of local failure (invasive or noninvasive) in the treated breast was 3.2% in the observation group and 0.4% in the radiation therapy group, corresponding to an 86% reduction in risk (hazard ratio, 0.14; P = .002), Dr. McCormick reported.

In the radiation therapy group, there were no local failures in the same quadrant as the original tumor; in contrast, in the observation group, two-thirds of the failures were in the same quadrant.

The two groups were statistically indistinguishable with respect to the rate of contralateral breast events, disease-free survival, and overall survival.

The rate of acute grade 3 or worse nonhematologic toxicities was similar in the observation group and radiation therapy group (4.0% vs. 4.2%, respectively), although lower-grade toxicities were more common in the latter. The rate of late grade 3 or worse radiation therapy toxicity was 0.7% in the group given this therapy.

Dr. McCormick disclosed no relevant conflicts of interest. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO – The new DCIS score, an offshoot of the Oncotype DX recurrence score, independently predicts the risk of ipsilateral recurrence or invasive disease in patients with ductal carcinoma in situ, according to a subgroup analysis from the prospective validation study.

The score correlated only moderately, poorly, or not at all with measures such as menopausal status and histologic grade among 327 patients with ductal carcinoma in situ (DCIS) treated with wide local excision and without radiation therapy, investigators reported.

And even after such measures were taken into account, each 50-point increase in the 100-point score was significantly associated with more than a doubling of the 10-year risk of recurrence or invasive disease in the same breast.

"The DCIS score provides independent information on ipsilateral breast risk beyond clinical and pathologic variables," lead author Dr. Sunil S. Badve said at the annual meeting of the American Society of Clinical Oncology.

"One can use the DCIS score to select patients with ... a clinically good prognosis who may have a higher DCIS score and may have a slightly [greater] risk than one would have estimated by traditional criteria," added Dr. Badve, a professor in the department of pathology and laboratory medicine and the department of internal medicine, and director of the Translational Genomics Core at Indiana University, Indianapolis.

"So particularly for the subset with a clinically good prognosis, we may be able to dissect which patients really might have a better prognosis and which patients may need to be more cautious."

Discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C., called particular attention to the weak association between nuclear grade and DCIS Score.

"This is a very important point to make and a response to the criticism that’s often heard that the DCIS score or the Oncotype score may just be a surrogate – and a very expensive one – for proliferative index or Ki-67," she commented.

Next-generation sequencing and advances in epigenomics, proteomics, and molecular characterization of stroma are likely to make it possible to further risk-stratify DCIS in the future, according to Dr. Hwang.

"But none of this is important unless we can implement it into treatment of patients. So how this is implemented in our everyday practice will be very important to analyze – whether it impacts decision making, and whether it gives patients satisfaction with the decisions they make will also be very important to look at," she added.

"Finally, in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward," she noted.

Study analyses were based on a subset of women from the E5194 trial, a prospective study to validate the DCIS score, which contains 12 of the 21 genes included in the Oncotype DX recurrence score used in estrogen receptor–positive early-stage breast cancer.

All of the women had DCIS treated with wide local excision. They had a median age of 61 years and a median tumor size of 7 mm. Twenty-nine percent received tamoxifen. The median duration of follow-up was 8.8 years.

Results showed that the DCIS score was only moderately correlated with histologic grade (r = 0.41-0.46) and with the percentage of cells showing comedo necrosis (r = 0.49), and was poorly correlated with tumor size (r = 0.18), Dr. Badve reported. And there was no correlation with age, menopausal status, DCIS histologic pattern, or margin status.

In a multivariate analysis, each 50-point increase in DCIS score was associated with more than a doubling of the risk of a recurrence of DCIS or the occurrence of invasive disease in the ipsilateral breast (hazard ratio, 2.41; P = .02).

In addition, tumor size was an independent positive predictor of risk (HR for each 5-mm increase, 1.52; P = .01), and postmenopausal status was an independent negative predictor (HR, 0.49; P = .02).

Dr. Badve disclosed that he is a consultant to Genomic Health, which makes the assay. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO – The new DCIS score, an offshoot of the Oncotype DX recurrence score, independently predicts the risk of ipsilateral recurrence or invasive disease in patients with ductal carcinoma in situ, according to a subgroup analysis from the prospective validation study.

The score correlated only moderately, poorly, or not at all with measures such as menopausal status and histologic grade among 327 patients with ductal carcinoma in situ (DCIS) treated with wide local excision and without radiation therapy, investigators reported.

And even after such measures were taken into account, each 50-point increase in the 100-point score was significantly associated with more than a doubling of the 10-year risk of recurrence or invasive disease in the same breast.

"The DCIS score provides independent information on ipsilateral breast risk beyond clinical and pathologic variables," lead author Dr. Sunil S. Badve said at the annual meeting of the American Society of Clinical Oncology.

"One can use the DCIS score to select patients with ... a clinically good prognosis who may have a higher DCIS score and may have a slightly [greater] risk than one would have estimated by traditional criteria," added Dr. Badve, a professor in the department of pathology and laboratory medicine and the department of internal medicine, and director of the Translational Genomics Core at Indiana University, Indianapolis.

"So particularly for the subset with a clinically good prognosis, we may be able to dissect which patients really might have a better prognosis and which patients may need to be more cautious."

Discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C., called particular attention to the weak association between nuclear grade and DCIS Score.

"This is a very important point to make and a response to the criticism that’s often heard that the DCIS score or the Oncotype score may just be a surrogate – and a very expensive one – for proliferative index or Ki-67," she commented.

Next-generation sequencing and advances in epigenomics, proteomics, and molecular characterization of stroma are likely to make it possible to further risk-stratify DCIS in the future, according to Dr. Hwang.

"But none of this is important unless we can implement it into treatment of patients. So how this is implemented in our everyday practice will be very important to analyze – whether it impacts decision making, and whether it gives patients satisfaction with the decisions they make will also be very important to look at," she added.

"Finally, in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward," she noted.

Study analyses were based on a subset of women from the E5194 trial, a prospective study to validate the DCIS score, which contains 12 of the 21 genes included in the Oncotype DX recurrence score used in estrogen receptor–positive early-stage breast cancer.

All of the women had DCIS treated with wide local excision. They had a median age of 61 years and a median tumor size of 7 mm. Twenty-nine percent received tamoxifen. The median duration of follow-up was 8.8 years.

Results showed that the DCIS score was only moderately correlated with histologic grade (r = 0.41-0.46) and with the percentage of cells showing comedo necrosis (r = 0.49), and was poorly correlated with tumor size (r = 0.18), Dr. Badve reported. And there was no correlation with age, menopausal status, DCIS histologic pattern, or margin status.

In a multivariate analysis, each 50-point increase in DCIS score was associated with more than a doubling of the risk of a recurrence of DCIS or the occurrence of invasive disease in the ipsilateral breast (hazard ratio, 2.41; P = .02).

In addition, tumor size was an independent positive predictor of risk (HR for each 5-mm increase, 1.52; P = .01), and postmenopausal status was an independent negative predictor (HR, 0.49; P = .02).

Dr. Badve disclosed that he is a consultant to Genomic Health, which makes the assay. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO – The new DCIS score, an offshoot of the Oncotype DX recurrence score, independently predicts the risk of ipsilateral recurrence or invasive disease in patients with ductal carcinoma in situ, according to a subgroup analysis from the prospective validation study.

The score correlated only moderately, poorly, or not at all with measures such as menopausal status and histologic grade among 327 patients with ductal carcinoma in situ (DCIS) treated with wide local excision and without radiation therapy, investigators reported.

And even after such measures were taken into account, each 50-point increase in the 100-point score was significantly associated with more than a doubling of the 10-year risk of recurrence or invasive disease in the same breast.

"The DCIS score provides independent information on ipsilateral breast risk beyond clinical and pathologic variables," lead author Dr. Sunil S. Badve said at the annual meeting of the American Society of Clinical Oncology.

"One can use the DCIS score to select patients with ... a clinically good prognosis who may have a higher DCIS score and may have a slightly [greater] risk than one would have estimated by traditional criteria," added Dr. Badve, a professor in the department of pathology and laboratory medicine and the department of internal medicine, and director of the Translational Genomics Core at Indiana University, Indianapolis.

"So particularly for the subset with a clinically good prognosis, we may be able to dissect which patients really might have a better prognosis and which patients may need to be more cautious."

Discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C., called particular attention to the weak association between nuclear grade and DCIS Score.

"This is a very important point to make and a response to the criticism that’s often heard that the DCIS score or the Oncotype score may just be a surrogate – and a very expensive one – for proliferative index or Ki-67," she commented.

Next-generation sequencing and advances in epigenomics, proteomics, and molecular characterization of stroma are likely to make it possible to further risk-stratify DCIS in the future, according to Dr. Hwang.

"But none of this is important unless we can implement it into treatment of patients. So how this is implemented in our everyday practice will be very important to analyze – whether it impacts decision making, and whether it gives patients satisfaction with the decisions they make will also be very important to look at," she added.

"Finally, in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward," she noted.

Study analyses were based on a subset of women from the E5194 trial, a prospective study to validate the DCIS score, which contains 12 of the 21 genes included in the Oncotype DX recurrence score used in estrogen receptor–positive early-stage breast cancer.

All of the women had DCIS treated with wide local excision. They had a median age of 61 years and a median tumor size of 7 mm. Twenty-nine percent received tamoxifen. The median duration of follow-up was 8.8 years.

Results showed that the DCIS score was only moderately correlated with histologic grade (r = 0.41-0.46) and with the percentage of cells showing comedo necrosis (r = 0.49), and was poorly correlated with tumor size (r = 0.18), Dr. Badve reported. And there was no correlation with age, menopausal status, DCIS histologic pattern, or margin status.

In a multivariate analysis, each 50-point increase in DCIS score was associated with more than a doubling of the risk of a recurrence of DCIS or the occurrence of invasive disease in the ipsilateral breast (hazard ratio, 2.41; P = .02).

In addition, tumor size was an independent positive predictor of risk (HR for each 5-mm increase, 1.52; P = .01), and postmenopausal status was an independent negative predictor (HR, 0.49; P = .02).

Dr. Badve disclosed that he is a consultant to Genomic Health, which makes the assay. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO – Delegates to the American Medical Association’s legislative body are not happy with the U.S. Preventive Services Task Force.

They voted overwhelmingly (322 to 93) to express "concern" over the task force’s recommendations on screening mammography and prostate-specific antigen screening. Both recommendations attracted a firestorm of criticism when they were issued – the mammography recommendation in 2009 and those on PSA testing in May.

Many delegates also said they thought that the USPSTF, a quasi-governmental group operating under the auspices of the Agency for Healthcare Research and Quality, had reached its decisions without proper input from specialty societies or experts in each field.

In a second resolution, the delegates voted to encourage the USPSTF to "implement procedures that allow for meaningful input on recommendation development from specialists and stakeholders in the topic area under study."

Alicia Ault/IMNG Medical Media

Dr. Arl Van Moore Jr., a delegate from the American College of Radiology, said that neither the ACR nor any prominent breast imaging or surgical societies were contacted by the USPSTF in creating the screening mammography recommendations.

"None of the recognized experts in the field were contacted, to the best of our knowledge," said Dr. Moore, an interventional radiologist in Charlotte, N.C.

The American Urological Association delegate, Dr. William Gee, did not mince words when it came to the PSA screening guidelines.

"The [USPSTF] did not use an open process and ignored the public in reaching their conclusions," he said.

But Dr. Sally J. Trippel, a preventive medicine specialist at the Mayo Clinic and delegate from Minnesota, defended the USPSTF and its process. The task force is "about as politically independent as any national organization can get," and "about as free of conflict of interest as is possible in any organization developing guidelines for American clinicians," she said.

She quoted from task force documents showing that urologists provided peer review of the PSA evidence review. "So there were experts from urology involved in the development of that guideline," and also for the one on screening mammography.

To further show its consternation with the task force, AMA delegates also approved a report that stated that starting at age 40, women should be "eligible for screening mammography," and encouraging physicians "to regularly discuss with their individual patients the benefits and risks of screening mammography, and whether screening is appropriate for each clinical situation given that the balance of benefits and risks will be viewed differently by each patient."

Primary care delegates from the American Academy of Family Physicians and the American College of Physicians opposed the resolutions of concern against the USPSTF and the mammography report.

The AAFP supported the task force when it issued its mammography recommendations "because it was the most comprehensive pattern and set of preventive guidelines using current methodology with what was available in science at that time," said Dr. Roland Goertz, AAFP delegate.

The task force basically recommends what the AMA report urged: that physicians have discussions with their patients about risks and benefits, he said. The problem is not the USPSTF recommendations, but that they are being used to deny payment, he added.

Alicia Ault/IMNG Medical Media

Dr. Richard Reiling, a delegate from the American College of Surgeons, said that the task force had confused patients with its mammography recommendation, and called for the AMA to convene all interested parties to craft a single guideline. The USPSTF was "wrong in presenting this report without listening to the stakeholders in the past," he said, adding, "let’s get one guideline out there."

Dr. Goertz agreed that there needed to be a common guideline.

ACP Delegate Dr. William Golden expressed the ACP’s view that the House of Delegates was not the appropriate venue for voting on particular guidelines. "The House should not be in the position of voting on what guideline is best," he said.

CHICAGO – Delegates to the American Medical Association’s legislative body are not happy with the U.S. Preventive Services Task Force.

They voted overwhelmingly (322 to 93) to express "concern" over the task force’s recommendations on screening mammography and prostate-specific antigen screening. Both recommendations attracted a firestorm of criticism when they were issued – the mammography recommendation in 2009 and those on PSA testing in May.

Many delegates also said they thought that the USPSTF, a quasi-governmental group operating under the auspices of the Agency for Healthcare Research and Quality, had reached its decisions without proper input from specialty societies or experts in each field.

In a second resolution, the delegates voted to encourage the USPSTF to "implement procedures that allow for meaningful input on recommendation development from specialists and stakeholders in the topic area under study."

Alicia Ault/IMNG Medical Media

Dr. Arl Van Moore Jr., a delegate from the American College of Radiology, said that neither the ACR nor any prominent breast imaging or surgical societies were contacted by the USPSTF in creating the screening mammography recommendations.

"None of the recognized experts in the field were contacted, to the best of our knowledge," said Dr. Moore, an interventional radiologist in Charlotte, N.C.

The American Urological Association delegate, Dr. William Gee, did not mince words when it came to the PSA screening guidelines.

"The [USPSTF] did not use an open process and ignored the public in reaching their conclusions," he said.

But Dr. Sally J. Trippel, a preventive medicine specialist at the Mayo Clinic and delegate from Minnesota, defended the USPSTF and its process. The task force is "about as politically independent as any national organization can get," and "about as free of conflict of interest as is possible in any organization developing guidelines for American clinicians," she said.

She quoted from task force documents showing that urologists provided peer review of the PSA evidence review. "So there were experts from urology involved in the development of that guideline," and also for the one on screening mammography.

To further show its consternation with the task force, AMA delegates also approved a report that stated that starting at age 40, women should be "eligible for screening mammography," and encouraging physicians "to regularly discuss with their individual patients the benefits and risks of screening mammography, and whether screening is appropriate for each clinical situation given that the balance of benefits and risks will be viewed differently by each patient."

Primary care delegates from the American Academy of Family Physicians and the American College of Physicians opposed the resolutions of concern against the USPSTF and the mammography report.

The AAFP supported the task force when it issued its mammography recommendations "because it was the most comprehensive pattern and set of preventive guidelines using current methodology with what was available in science at that time," said Dr. Roland Goertz, AAFP delegate.

The task force basically recommends what the AMA report urged: that physicians have discussions with their patients about risks and benefits, he said. The problem is not the USPSTF recommendations, but that they are being used to deny payment, he added.

Alicia Ault/IMNG Medical Media

Dr. Richard Reiling, a delegate from the American College of Surgeons, said that the task force had confused patients with its mammography recommendation, and called for the AMA to convene all interested parties to craft a single guideline. The USPSTF was "wrong in presenting this report without listening to the stakeholders in the past," he said, adding, "let’s get one guideline out there."

Dr. Goertz agreed that there needed to be a common guideline.

ACP Delegate Dr. William Golden expressed the ACP’s view that the House of Delegates was not the appropriate venue for voting on particular guidelines. "The House should not be in the position of voting on what guideline is best," he said.

CHICAGO – Delegates to the American Medical Association’s legislative body are not happy with the U.S. Preventive Services Task Force.

They voted overwhelmingly (322 to 93) to express "concern" over the task force’s recommendations on screening mammography and prostate-specific antigen screening. Both recommendations attracted a firestorm of criticism when they were issued – the mammography recommendation in 2009 and those on PSA testing in May.

Many delegates also said they thought that the USPSTF, a quasi-governmental group operating under the auspices of the Agency for Healthcare Research and Quality, had reached its decisions without proper input from specialty societies or experts in each field.

In a second resolution, the delegates voted to encourage the USPSTF to "implement procedures that allow for meaningful input on recommendation development from specialists and stakeholders in the topic area under study."

Alicia Ault/IMNG Medical Media

Dr. Arl Van Moore Jr., a delegate from the American College of Radiology, said that neither the ACR nor any prominent breast imaging or surgical societies were contacted by the USPSTF in creating the screening mammography recommendations.

"None of the recognized experts in the field were contacted, to the best of our knowledge," said Dr. Moore, an interventional radiologist in Charlotte, N.C.

The American Urological Association delegate, Dr. William Gee, did not mince words when it came to the PSA screening guidelines.

"The [USPSTF] did not use an open process and ignored the public in reaching their conclusions," he said.

But Dr. Sally J. Trippel, a preventive medicine specialist at the Mayo Clinic and delegate from Minnesota, defended the USPSTF and its process. The task force is "about as politically independent as any national organization can get," and "about as free of conflict of interest as is possible in any organization developing guidelines for American clinicians," she said.

She quoted from task force documents showing that urologists provided peer review of the PSA evidence review. "So there were experts from urology involved in the development of that guideline," and also for the one on screening mammography.

To further show its consternation with the task force, AMA delegates also approved a report that stated that starting at age 40, women should be "eligible for screening mammography," and encouraging physicians "to regularly discuss with their individual patients the benefits and risks of screening mammography, and whether screening is appropriate for each clinical situation given that the balance of benefits and risks will be viewed differently by each patient."

Primary care delegates from the American Academy of Family Physicians and the American College of Physicians opposed the resolutions of concern against the USPSTF and the mammography report.

The AAFP supported the task force when it issued its mammography recommendations "because it was the most comprehensive pattern and set of preventive guidelines using current methodology with what was available in science at that time," said Dr. Roland Goertz, AAFP delegate.

The task force basically recommends what the AMA report urged: that physicians have discussions with their patients about risks and benefits, he said. The problem is not the USPSTF recommendations, but that they are being used to deny payment, he added.

Alicia Ault/IMNG Medical Media

Dr. Richard Reiling, a delegate from the American College of Surgeons, said that the task force had confused patients with its mammography recommendation, and called for the AMA to convene all interested parties to craft a single guideline. The USPSTF was "wrong in presenting this report without listening to the stakeholders in the past," he said, adding, "let’s get one guideline out there."

Dr. Goertz agreed that there needed to be a common guideline.

ACP Delegate Dr. William Golden expressed the ACP’s view that the House of Delegates was not the appropriate venue for voting on particular guidelines. "The House should not be in the position of voting on what guideline is best," he said.

• Glenn J. Lesser, MD

  

  ,
• Doug Case, PhD,
• Nancy Stark, RN, PhD,
• Susan Williford, MD,
• Jeff Giguere, MD,
• L. Astrid Garino, MD,
• Michelle J. Naughton, PhD,
• Mara Z. Vitolins, DrPH, RD,
• Mark O. Lively, PhD,
• Edward G. Shaw, MD, MA,
• Wake Forest University Community Clinical Oncology Program Research Base

• Glenn J. Lesser, MD

  

  ,
• Doug Case, PhD,
• Nancy Stark, RN, PhD,
• Susan Williford, MD,
• Jeff Giguere, MD,
• L. Astrid Garino, MD,
• Michelle J. Naughton, PhD,
• Mara Z. Vitolins, DrPH, RD,
• Mark O. Lively, PhD,
• Edward G. Shaw, MD, MA,
• Wake Forest University Community Clinical Oncology Program Research Base

• Glenn J. Lesser, MD

  

  ,
• Doug Case, PhD,
• Nancy Stark, RN, PhD,
• Susan Williford, MD,
• Jeff Giguere, MD,
• L. Astrid Garino, MD,
• Michelle J. Naughton, PhD,
• Mara Z. Vitolins, DrPH, RD,
• Mark O. Lively, PhD,
• Edward G. Shaw, MD, MA,
• Wake Forest University Community Clinical Oncology Program Research Base