Mary Jo M. Dales

DENVER – A gene expression profile test was an independent predictor of metastasis of primary cutaneous melanomas in patients with negative sentinel lymph node biopsies.

The DecisionDx-Melanoma test is useful for identifying a high-risk group of patients with negative sentinel lymph node biopsy results, said Dr. Pedram Gerami of the department of dermatology and director of melanoma research at the Northwestern University, Chicago, Skin Cancer Institute. The test "is an independent predictor of metastasis and death, and significantly improves upon sentinel lymph node biopsy for staging melanoma patients."

The results of the DecisionDx-Melanoma test, a noninvasive 31-gene expression profile (GEP) test, were compared with the results of sentinel lymph node biopsy (SLNB) in 134 patients who had stage I, II, or III cutaneous melanoma and underwent a documented sentinel lymph node procedure. Of the 134 patients, 28 had positive sentinel lymph nodes and 91 had positive (class 2, high risk) GEP results.

Metastases developed over a subsequent 5-year period in 18 of the 28 patients with positive SLNB and in 62 of the 91 patients with positive GEP results. Metastases developed in 51 of the 106 patients with negative SLNB and in 7 of 43 patients with negative (class 1, low risk) GEP results.

While the positive predictive value of the two tests were comparable, the ability of GEP to predict negative outcomes was significantly better than that of SLNB (P less than .0001), Dr. Gerami reported at the annual meeting of the American Academy of Dermatology.

The rate of 5-year metastasis-free survival (MFS) was 55% for 106 patients with negative SLNB, compared to 37% for 28 patients with positive SLNB (P = .003). The GEP test results showed improved prognostic accuracy in these same patients with an MFS of 87% for the 43 patients with negative GEP (class 1, low risk) results and of 31% for the 91 patients with positive GEP (class 2, high risk) results (P less than .0001).

Differences in overall survival (OS) paralleled the MFS rates, with SLNB-negative patients having a 5-year OS of 67% and SLNB-positive patients having a 5-year OS of 55% (P = .024). OS for negative GEP (class 1, low risk) patients was 92% and for positive GEP (high risk, class 2) was 49% (P less than .0001).

Use of the GEP test also was analyzed in combination with SLNB status. As expected, the 20% of patients (n = 27) who had high-risk results for both tests (GEP class 2 and SLNB-positive findings) had lower survival rates (MFS, 34%; OS, 53%). Similarly, the 31% of patients (n = 42) who had low-risk results for both tests (GEP class 1 and SLNB-negative findings) had higher survival rates (MFS, 82%; OS, 92%).

Importantly, the MFS was 31% and the OS was 49% at 5 years in the 64 patients who had SLNB-negative results but class 2 GEP test results, Dr. Gerami said. Cox multivariate analysis comparing the GEP test to SLNB showed the GEP test to be the only independent and highly significant prognostic factor in this analysis (P less than .000003).

Dr. Gerami has been a consultant to Castle Biosciences. The DecisionDx-Melanoma test is a product of Castle Biosciences, the sponsor of the study. More information about the test can be found at www.skinmelanoma.com.

[email protected]

On Twitter @maryjodales

DENVER – A gene expression profile test was an independent predictor of metastasis of primary cutaneous melanomas in patients with negative sentinel lymph node biopsies.

The DecisionDx-Melanoma test is useful for identifying a high-risk group of patients with negative sentinel lymph node biopsy results, said Dr. Pedram Gerami of the department of dermatology and director of melanoma research at the Northwestern University, Chicago, Skin Cancer Institute. The test "is an independent predictor of metastasis and death, and significantly improves upon sentinel lymph node biopsy for staging melanoma patients."

The results of the DecisionDx-Melanoma test, a noninvasive 31-gene expression profile (GEP) test, were compared with the results of sentinel lymph node biopsy (SLNB) in 134 patients who had stage I, II, or III cutaneous melanoma and underwent a documented sentinel lymph node procedure. Of the 134 patients, 28 had positive sentinel lymph nodes and 91 had positive (class 2, high risk) GEP results.

Metastases developed over a subsequent 5-year period in 18 of the 28 patients with positive SLNB and in 62 of the 91 patients with positive GEP results. Metastases developed in 51 of the 106 patients with negative SLNB and in 7 of 43 patients with negative (class 1, low risk) GEP results.

While the positive predictive value of the two tests were comparable, the ability of GEP to predict negative outcomes was significantly better than that of SLNB (P less than .0001), Dr. Gerami reported at the annual meeting of the American Academy of Dermatology.

The rate of 5-year metastasis-free survival (MFS) was 55% for 106 patients with negative SLNB, compared to 37% for 28 patients with positive SLNB (P = .003). The GEP test results showed improved prognostic accuracy in these same patients with an MFS of 87% for the 43 patients with negative GEP (class 1, low risk) results and of 31% for the 91 patients with positive GEP (class 2, high risk) results (P less than .0001).

Differences in overall survival (OS) paralleled the MFS rates, with SLNB-negative patients having a 5-year OS of 67% and SLNB-positive patients having a 5-year OS of 55% (P = .024). OS for negative GEP (class 1, low risk) patients was 92% and for positive GEP (high risk, class 2) was 49% (P less than .0001).

Use of the GEP test also was analyzed in combination with SLNB status. As expected, the 20% of patients (n = 27) who had high-risk results for both tests (GEP class 2 and SLNB-positive findings) had lower survival rates (MFS, 34%; OS, 53%). Similarly, the 31% of patients (n = 42) who had low-risk results for both tests (GEP class 1 and SLNB-negative findings) had higher survival rates (MFS, 82%; OS, 92%).

Importantly, the MFS was 31% and the OS was 49% at 5 years in the 64 patients who had SLNB-negative results but class 2 GEP test results, Dr. Gerami said. Cox multivariate analysis comparing the GEP test to SLNB showed the GEP test to be the only independent and highly significant prognostic factor in this analysis (P less than .000003).

Dr. Gerami has been a consultant to Castle Biosciences. The DecisionDx-Melanoma test is a product of Castle Biosciences, the sponsor of the study. More information about the test can be found at www.skinmelanoma.com.

[email protected]

On Twitter @maryjodales

DENVER – A gene expression profile test was an independent predictor of metastasis of primary cutaneous melanomas in patients with negative sentinel lymph node biopsies.

The DecisionDx-Melanoma test is useful for identifying a high-risk group of patients with negative sentinel lymph node biopsy results, said Dr. Pedram Gerami of the department of dermatology and director of melanoma research at the Northwestern University, Chicago, Skin Cancer Institute. The test "is an independent predictor of metastasis and death, and significantly improves upon sentinel lymph node biopsy for staging melanoma patients."

The results of the DecisionDx-Melanoma test, a noninvasive 31-gene expression profile (GEP) test, were compared with the results of sentinel lymph node biopsy (SLNB) in 134 patients who had stage I, II, or III cutaneous melanoma and underwent a documented sentinel lymph node procedure. Of the 134 patients, 28 had positive sentinel lymph nodes and 91 had positive (class 2, high risk) GEP results.

Metastases developed over a subsequent 5-year period in 18 of the 28 patients with positive SLNB and in 62 of the 91 patients with positive GEP results. Metastases developed in 51 of the 106 patients with negative SLNB and in 7 of 43 patients with negative (class 1, low risk) GEP results.

While the positive predictive value of the two tests were comparable, the ability of GEP to predict negative outcomes was significantly better than that of SLNB (P less than .0001), Dr. Gerami reported at the annual meeting of the American Academy of Dermatology.

The rate of 5-year metastasis-free survival (MFS) was 55% for 106 patients with negative SLNB, compared to 37% for 28 patients with positive SLNB (P = .003). The GEP test results showed improved prognostic accuracy in these same patients with an MFS of 87% for the 43 patients with negative GEP (class 1, low risk) results and of 31% for the 91 patients with positive GEP (class 2, high risk) results (P less than .0001).

Differences in overall survival (OS) paralleled the MFS rates, with SLNB-negative patients having a 5-year OS of 67% and SLNB-positive patients having a 5-year OS of 55% (P = .024). OS for negative GEP (class 1, low risk) patients was 92% and for positive GEP (high risk, class 2) was 49% (P less than .0001).

Use of the GEP test also was analyzed in combination with SLNB status. As expected, the 20% of patients (n = 27) who had high-risk results for both tests (GEP class 2 and SLNB-positive findings) had lower survival rates (MFS, 34%; OS, 53%). Similarly, the 31% of patients (n = 42) who had low-risk results for both tests (GEP class 1 and SLNB-negative findings) had higher survival rates (MFS, 82%; OS, 92%).

Importantly, the MFS was 31% and the OS was 49% at 5 years in the 64 patients who had SLNB-negative results but class 2 GEP test results, Dr. Gerami said. Cox multivariate analysis comparing the GEP test to SLNB showed the GEP test to be the only independent and highly significant prognostic factor in this analysis (P less than .000003).

Dr. Gerami has been a consultant to Castle Biosciences. The DecisionDx-Melanoma test is a product of Castle Biosciences, the sponsor of the study. More information about the test can be found at www.skinmelanoma.com.

[email protected]

On Twitter @maryjodales

DENVER – A newly-available test based on the results of a simple blood draw has proved useful for detecting early recurrences of Merkel cell carcinomas in those patients who produce antibodies to the Merkel polyomavirus oncoprotein at initial diagnosis.

Known as AMERK, the test can be used at diagnosis to determine which patients have the oncoprotein antibodies and performed at routine followups as an indicator of recurrence in asymptomatic, antibody-positive patients.

The test already has been shown to alert clinicians to the presence of surgically manageable metastases that would have otherwise gone undetected until symptoms prompted a tomographic scan, Dr. Astrid Blom reported at the annual meeting of the American Academy of Dermatology. She presented two cases of surgically operable metastatic Merkel cell tumors, one metastatic to the kidney and the other to the pancreas; both were detected via increasing titers of oncoprotein antibodies in otherwise asymptomatic patients.

Nearly 40% of Merkel cell carcinomas recur. Performing a predictive blood test at routine followups can be a reassuring measure in those patients with negative findings. It also can be an early indicator of metastasis in otherwise asymptomatic patients who made oncoprotein antibodies at diagnosis and were successfully treated for Merkel call carcinoma, she said.

Merkel cell polyomavirus drives about 80% of the approximately 2,000 Merkel cell carcinomas that are diagnosed each year. About half of affected patients produce oncoprotein antibodies to the polyomavirus, which are detectable at diagnosis. The AMERK test is useful only for followup of those patients with oncoprotein antibodies. Patients who lack initially detectable levels of oncoprotein antibodies at diagnosis do not later produce antibodies should their disease recur, reported Dr. Blom of the University of Washington, Seattle, where the test was developed and is performed.

The clinical utility of AMERK, a 75-step assay that takes nearly 2 days to perform, was verified using 1,342 samples from 104 controls and 519 patients from around the world, with data correlating to 3,018 status updates. The data analysis was limited to the 217 patients with adequate follow-up data.

A simple blood draw was collected and sent for analysis at the University of Washington, Seattle. Oncoprotein antibodies were detected in 52% of 217 patients with incident cases of Merkel cell carcinoma and in 2% of 530 control subjects. The antibody titers in controls were barely detectable, however, unlike the levels seen in the patients. The sensitivity of the test was 82%, and the specificity was 98%; the negative predictive value was 99%, and the positive predictive value was 78%.

Levels decrease by 90% or more over the course of the year after successful surgical treatment of Merkel cell carcinomas. When the cancers recur, at least a 10-fold increase in oncoprotein antibody titers are noted.

Support for the development of the AMERK test came from the National Institutes of Health, the National Cancer Institute, and the American Cancer Society and from private donors and patients.

RESOURCES:

Information about the test is available online at http://www.merkelcell.org/sero/

A video that discusses the antibody test can be viewed here.

Dr. Kelly Paulsen, et.al. published the scientific paper that first described the test (Cancer Res. 70(21): 8388-97).

How to order the Merkel virus serology test

Physicians and staff based outside of the University of Washington system should contact their local laboratory where the patient will have their blood sample collected to initiate the process.

The local laboratory "send out test coordinator" should contact the UW Reference Laboratory Services Call Center at 206-685-6066. UW Reference Laboratory Services will set up an account for the ordering physician or clinic; collect the required billing and reporting information; and provide requirements for sample collection, processing and shipping from the local laboratory. Once this one-time administrative process is complete, patient samples can be collected routinely from that facility for the Merkel antibody test (name of test is "AMERK").

[email protected]

On Twitter @maryjodales

DENVER – A newly-available test based on the results of a simple blood draw has proved useful for detecting early recurrences of Merkel cell carcinomas in those patients who produce antibodies to the Merkel polyomavirus oncoprotein at initial diagnosis.

Known as AMERK, the test can be used at diagnosis to determine which patients have the oncoprotein antibodies and performed at routine followups as an indicator of recurrence in asymptomatic, antibody-positive patients.

The test already has been shown to alert clinicians to the presence of surgically manageable metastases that would have otherwise gone undetected until symptoms prompted a tomographic scan, Dr. Astrid Blom reported at the annual meeting of the American Academy of Dermatology. She presented two cases of surgically operable metastatic Merkel cell tumors, one metastatic to the kidney and the other to the pancreas; both were detected via increasing titers of oncoprotein antibodies in otherwise asymptomatic patients.

Nearly 40% of Merkel cell carcinomas recur. Performing a predictive blood test at routine followups can be a reassuring measure in those patients with negative findings. It also can be an early indicator of metastasis in otherwise asymptomatic patients who made oncoprotein antibodies at diagnosis and were successfully treated for Merkel call carcinoma, she said.

Merkel cell polyomavirus drives about 80% of the approximately 2,000 Merkel cell carcinomas that are diagnosed each year. About half of affected patients produce oncoprotein antibodies to the polyomavirus, which are detectable at diagnosis. The AMERK test is useful only for followup of those patients with oncoprotein antibodies. Patients who lack initially detectable levels of oncoprotein antibodies at diagnosis do not later produce antibodies should their disease recur, reported Dr. Blom of the University of Washington, Seattle, where the test was developed and is performed.

The clinical utility of AMERK, a 75-step assay that takes nearly 2 days to perform, was verified using 1,342 samples from 104 controls and 519 patients from around the world, with data correlating to 3,018 status updates. The data analysis was limited to the 217 patients with adequate follow-up data.

A simple blood draw was collected and sent for analysis at the University of Washington, Seattle. Oncoprotein antibodies were detected in 52% of 217 patients with incident cases of Merkel cell carcinoma and in 2% of 530 control subjects. The antibody titers in controls were barely detectable, however, unlike the levels seen in the patients. The sensitivity of the test was 82%, and the specificity was 98%; the negative predictive value was 99%, and the positive predictive value was 78%.

Levels decrease by 90% or more over the course of the year after successful surgical treatment of Merkel cell carcinomas. When the cancers recur, at least a 10-fold increase in oncoprotein antibody titers are noted.

Support for the development of the AMERK test came from the National Institutes of Health, the National Cancer Institute, and the American Cancer Society and from private donors and patients.

RESOURCES:

Information about the test is available online at http://www.merkelcell.org/sero/

A video that discusses the antibody test can be viewed here.

Dr. Kelly Paulsen, et.al. published the scientific paper that first described the test (Cancer Res. 70(21): 8388-97).

How to order the Merkel virus serology test

Physicians and staff based outside of the University of Washington system should contact their local laboratory where the patient will have their blood sample collected to initiate the process.

The local laboratory "send out test coordinator" should contact the UW Reference Laboratory Services Call Center at 206-685-6066. UW Reference Laboratory Services will set up an account for the ordering physician or clinic; collect the required billing and reporting information; and provide requirements for sample collection, processing and shipping from the local laboratory. Once this one-time administrative process is complete, patient samples can be collected routinely from that facility for the Merkel antibody test (name of test is "AMERK").

[email protected]

On Twitter @maryjodales

DENVER – A newly-available test based on the results of a simple blood draw has proved useful for detecting early recurrences of Merkel cell carcinomas in those patients who produce antibodies to the Merkel polyomavirus oncoprotein at initial diagnosis.

Known as AMERK, the test can be used at diagnosis to determine which patients have the oncoprotein antibodies and performed at routine followups as an indicator of recurrence in asymptomatic, antibody-positive patients.

The test already has been shown to alert clinicians to the presence of surgically manageable metastases that would have otherwise gone undetected until symptoms prompted a tomographic scan, Dr. Astrid Blom reported at the annual meeting of the American Academy of Dermatology. She presented two cases of surgically operable metastatic Merkel cell tumors, one metastatic to the kidney and the other to the pancreas; both were detected via increasing titers of oncoprotein antibodies in otherwise asymptomatic patients.

Nearly 40% of Merkel cell carcinomas recur. Performing a predictive blood test at routine followups can be a reassuring measure in those patients with negative findings. It also can be an early indicator of metastasis in otherwise asymptomatic patients who made oncoprotein antibodies at diagnosis and were successfully treated for Merkel call carcinoma, she said.

Merkel cell polyomavirus drives about 80% of the approximately 2,000 Merkel cell carcinomas that are diagnosed each year. About half of affected patients produce oncoprotein antibodies to the polyomavirus, which are detectable at diagnosis. The AMERK test is useful only for followup of those patients with oncoprotein antibodies. Patients who lack initially detectable levels of oncoprotein antibodies at diagnosis do not later produce antibodies should their disease recur, reported Dr. Blom of the University of Washington, Seattle, where the test was developed and is performed.

The clinical utility of AMERK, a 75-step assay that takes nearly 2 days to perform, was verified using 1,342 samples from 104 controls and 519 patients from around the world, with data correlating to 3,018 status updates. The data analysis was limited to the 217 patients with adequate follow-up data.

A simple blood draw was collected and sent for analysis at the University of Washington, Seattle. Oncoprotein antibodies were detected in 52% of 217 patients with incident cases of Merkel cell carcinoma and in 2% of 530 control subjects. The antibody titers in controls were barely detectable, however, unlike the levels seen in the patients. The sensitivity of the test was 82%, and the specificity was 98%; the negative predictive value was 99%, and the positive predictive value was 78%.

Levels decrease by 90% or more over the course of the year after successful surgical treatment of Merkel cell carcinomas. When the cancers recur, at least a 10-fold increase in oncoprotein antibody titers are noted.

Support for the development of the AMERK test came from the National Institutes of Health, the National Cancer Institute, and the American Cancer Society and from private donors and patients.

RESOURCES:

Information about the test is available online at http://www.merkelcell.org/sero/

A video that discusses the antibody test can be viewed here.

Dr. Kelly Paulsen, et.al. published the scientific paper that first described the test (Cancer Res. 70(21): 8388-97).

How to order the Merkel virus serology test

Physicians and staff based outside of the University of Washington system should contact their local laboratory where the patient will have their blood sample collected to initiate the process.

The local laboratory "send out test coordinator" should contact the UW Reference Laboratory Services Call Center at 206-685-6066. UW Reference Laboratory Services will set up an account for the ordering physician or clinic; collect the required billing and reporting information; and provide requirements for sample collection, processing and shipping from the local laboratory. Once this one-time administrative process is complete, patient samples can be collected routinely from that facility for the Merkel antibody test (name of test is "AMERK").

[email protected]

On Twitter @maryjodales

SAN ANTONIO – Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University Feinberg School of Medicine, Chicago; and Dr. Hope S. Rugo, Director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, discuss the best to come from the San Antonio Breast Cancer Symposium, including:

• The ECOG, Turkish, and Indian trials that examine whether mastectomy results in better outcomes for the 10% of patients who present with de novo metastatic breast cancer and an intact primary tumor, as well as the accrual status of the U.S. trial examining this issue.

• The parameters of the NeoALTTO trial and the implications of dual targeting in early and preoperative HER2-positive breast cancer.

• Trials aiming to find less toxic regimens, and examining whether and when giving less – such as providing weekly paclitaxel for 12 weeks and a year of trastuzumab – is a better approach.

• Reports from a SWOG trial that will examine whether the numeric levels of circulating tumor cell markers can be used to make changes in therapy for patients with metastatic disease, and whether those changes can improve patients’ overall outcomes.

• Studies on novel agents in the neoadjuvant setting, including the CALGB 40603 trial of paclitaxel with and without bevacizumab and with and without carboplatin in patients with triple-negative disease. The findings may have implications for how newer agents are tested in patients with triple-negative disease.

Dr. Gradishar and Dr. Rugo also discuss reports on one of the arms of the I-SPY2 trial examining adaptive randomization of patients with MammaPrint high-risk disease to standard neoadjuvant chemotherapy vs. novel agents with paclitaxel, followed by anthracycline. The results represent the first oral presentation of data on the PARP inhibitor veliparib and carboplatin.

[email protected]

SAN ANTONIO – Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University Feinberg School of Medicine, Chicago; and Dr. Hope S. Rugo, Director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, discuss the best to come from the San Antonio Breast Cancer Symposium, including:

• The ECOG, Turkish, and Indian trials that examine whether mastectomy results in better outcomes for the 10% of patients who present with de novo metastatic breast cancer and an intact primary tumor, as well as the accrual status of the U.S. trial examining this issue.

• The parameters of the NeoALTTO trial and the implications of dual targeting in early and preoperative HER2-positive breast cancer.

• Trials aiming to find less toxic regimens, and examining whether and when giving less – such as providing weekly paclitaxel for 12 weeks and a year of trastuzumab – is a better approach.

• Reports from a SWOG trial that will examine whether the numeric levels of circulating tumor cell markers can be used to make changes in therapy for patients with metastatic disease, and whether those changes can improve patients’ overall outcomes.

• Studies on novel agents in the neoadjuvant setting, including the CALGB 40603 trial of paclitaxel with and without bevacizumab and with and without carboplatin in patients with triple-negative disease. The findings may have implications for how newer agents are tested in patients with triple-negative disease.

Dr. Gradishar and Dr. Rugo also discuss reports on one of the arms of the I-SPY2 trial examining adaptive randomization of patients with MammaPrint high-risk disease to standard neoadjuvant chemotherapy vs. novel agents with paclitaxel, followed by anthracycline. The results represent the first oral presentation of data on the PARP inhibitor veliparib and carboplatin.

[email protected]

SAN ANTONIO – Dr. William J. Gradishar, Betsy Bramsen Professor of Breast Oncology at Northwestern University Feinberg School of Medicine, Chicago; and Dr. Hope S. Rugo, Director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, discuss the best to come from the San Antonio Breast Cancer Symposium, including:

• The ECOG, Turkish, and Indian trials that examine whether mastectomy results in better outcomes for the 10% of patients who present with de novo metastatic breast cancer and an intact primary tumor, as well as the accrual status of the U.S. trial examining this issue.

• The parameters of the NeoALTTO trial and the implications of dual targeting in early and preoperative HER2-positive breast cancer.

• Trials aiming to find less toxic regimens, and examining whether and when giving less – such as providing weekly paclitaxel for 12 weeks and a year of trastuzumab – is a better approach.

• Reports from a SWOG trial that will examine whether the numeric levels of circulating tumor cell markers can be used to make changes in therapy for patients with metastatic disease, and whether those changes can improve patients’ overall outcomes.

• Studies on novel agents in the neoadjuvant setting, including the CALGB 40603 trial of paclitaxel with and without bevacizumab and with and without carboplatin in patients with triple-negative disease. The findings may have implications for how newer agents are tested in patients with triple-negative disease.

Dr. Gradishar and Dr. Rugo also discuss reports on one of the arms of the I-SPY2 trial examining adaptive randomization of patients with MammaPrint high-risk disease to standard neoadjuvant chemotherapy vs. novel agents with paclitaxel, followed by anthracycline. The results represent the first oral presentation of data on the PARP inhibitor veliparib and carboplatin.

[email protected]

Two years of adjuvant treatment with ibandronate after dose-dense chemotherapy did not improve survival in a study of more than 3,000 German patients with early stage, node-positive breast cancer.

The results were published online Aug. 26 in the Journal of Clinical Oncology.

Bisphosphonates have been shown to prevent skeletal-related events in patients with metastatic breast cancer, but their effectiveness has not been demonstrated in early breast cancer.

No differences in disease-free survival or overall survival were noted in the GAIN (German Adjuvant Intergroup Node-Positive) study, an open-label, randomized, controlled phase III trial (NCT00196872), reported Dr. Gunter von Minckwitz of the German Breast Group, along with his colleagues in the German Breast Group/Gynecologic Oncology Working Group/North-Eastern Germany Society of Gynecologic Oncology study groups.

In patients randomly assigned to 2 years of ibandronate or observation, there was no difference in disease-free survival (HR, 0.945; 95% CI, 0.768 to 1.161; P equals .589) or in overall survival (HR, 1.040; 95% CI, 0.763 to 1.419; P equals .803). Metastasis to the bone was documented in 31% in the ibandronate arm and in 38% in the observation arm.

Post hoc subgroup analyses of the study data imply that the benefit of adjuvant bisphosphonates was restricted to patients with low estrogen levels, either because of medical ovarian suppression or definite menopause. Future meta-analyses on an individual patient data level may reliably reveal subgroups of early-stage, high-risk breast cancer patients who might benefit from adjuvant bisphosphonates, the researchers noted (J. Clin. Oncol. 2013 Aug. 26 [doi:10.1200/JCO.2012.47.2167]).

In GAIN, patients with node-positive early breast cancer were randomly assigned within 4 weeks after surgery to two different dose-dense chemotherapy regimens and then in 2:1 fashion to ibandronate 50 mg per day orally starting within 4 weeks after last administration of chemotherapy and continuing for 2 years (2,015 patients) or to observation (1,008 patients).

Randomly assigned chemotherapy consisted of three courses of epirubicin 150 mg/m² followed by three courses of paclitaxel 225 mg/m² followed by three courses of cyclophosphamide 2,500 mg/m² (reduced to 2,000 mg/m² after recruitment of approximately 1,200 patients), all given at 2-week intervals (iddETC regimen) or epirubicin 112.5 mg/m² and cyclophosphamide 600 mg/m² for four 2-week courses followed by 10 courses of paclitaxel 67.5 mg/m² given once per week with capecitabine 2,000 mg/m² given days 1-14 every 3 weeks (EC-TX regimen).

Radiotherapy, endocrine treatment, and trastuzumab were indicated according to AGO guidelines and, if appropriate, were given in parallel with ibandronate after the end of chemotherapy. All patients received radiotherapy to the affected breast if breast-conserving surgery was performed, the researchers wrote.

Patients with endocrine-sensitive disease received endocrine treatment for 5 years with an aromatase inhibitor either alone or in sequence with tamoxifen if they were postmenopausal. Tamoxifen alone was given for 5 years in some patients together with a luteinizing hormone-releasing hormone (LHRH) analog if they were premenopausal after the end of chemotherapy. Patients with human epidermal growth factor receptor 2–overexpressing tumors received 1 year of adjuvant trastuzumab treatment.

Patients were evaluated every 12 weeks during the first 2 years of treatment and then every 6 months.

A total of 1,421 patients (78.2%) completed ibandronate treatment as planned, 5.8% discontinued treatment due to progression or death, and 16% discontinued treatment for various reasons. There were 405 events, including 186 deaths, after a median of 38.7 months (range, 0-73 months) with a completeness of follow-up of 76.8%.

The study was supported by Amgen, Germany; Bristol-Myers Squibb, Germany; and Roche, Germany, which also provided drugs for the study. Dr. von Minckwitz reported ties with Roche. His colleagues noted ties with numerous drug companies.

[email protected]

Two years of adjuvant treatment with ibandronate after dose-dense chemotherapy did not improve survival in a study of more than 3,000 German patients with early stage, node-positive breast cancer.

The results were published online Aug. 26 in the Journal of Clinical Oncology.

Bisphosphonates have been shown to prevent skeletal-related events in patients with metastatic breast cancer, but their effectiveness has not been demonstrated in early breast cancer.

No differences in disease-free survival or overall survival were noted in the GAIN (German Adjuvant Intergroup Node-Positive) study, an open-label, randomized, controlled phase III trial (NCT00196872), reported Dr. Gunter von Minckwitz of the German Breast Group, along with his colleagues in the German Breast Group/Gynecologic Oncology Working Group/North-Eastern Germany Society of Gynecologic Oncology study groups.

In patients randomly assigned to 2 years of ibandronate or observation, there was no difference in disease-free survival (HR, 0.945; 95% CI, 0.768 to 1.161; P equals .589) or in overall survival (HR, 1.040; 95% CI, 0.763 to 1.419; P equals .803). Metastasis to the bone was documented in 31% in the ibandronate arm and in 38% in the observation arm.

Post hoc subgroup analyses of the study data imply that the benefit of adjuvant bisphosphonates was restricted to patients with low estrogen levels, either because of medical ovarian suppression or definite menopause. Future meta-analyses on an individual patient data level may reliably reveal subgroups of early-stage, high-risk breast cancer patients who might benefit from adjuvant bisphosphonates, the researchers noted (J. Clin. Oncol. 2013 Aug. 26 [doi:10.1200/JCO.2012.47.2167]).

In GAIN, patients with node-positive early breast cancer were randomly assigned within 4 weeks after surgery to two different dose-dense chemotherapy regimens and then in 2:1 fashion to ibandronate 50 mg per day orally starting within 4 weeks after last administration of chemotherapy and continuing for 2 years (2,015 patients) or to observation (1,008 patients).

Randomly assigned chemotherapy consisted of three courses of epirubicin 150 mg/m² followed by three courses of paclitaxel 225 mg/m² followed by three courses of cyclophosphamide 2,500 mg/m² (reduced to 2,000 mg/m² after recruitment of approximately 1,200 patients), all given at 2-week intervals (iddETC regimen) or epirubicin 112.5 mg/m² and cyclophosphamide 600 mg/m² for four 2-week courses followed by 10 courses of paclitaxel 67.5 mg/m² given once per week with capecitabine 2,000 mg/m² given days 1-14 every 3 weeks (EC-TX regimen).

Radiotherapy, endocrine treatment, and trastuzumab were indicated according to AGO guidelines and, if appropriate, were given in parallel with ibandronate after the end of chemotherapy. All patients received radiotherapy to the affected breast if breast-conserving surgery was performed, the researchers wrote.

Patients with endocrine-sensitive disease received endocrine treatment for 5 years with an aromatase inhibitor either alone or in sequence with tamoxifen if they were postmenopausal. Tamoxifen alone was given for 5 years in some patients together with a luteinizing hormone-releasing hormone (LHRH) analog if they were premenopausal after the end of chemotherapy. Patients with human epidermal growth factor receptor 2–overexpressing tumors received 1 year of adjuvant trastuzumab treatment.

Patients were evaluated every 12 weeks during the first 2 years of treatment and then every 6 months.

A total of 1,421 patients (78.2%) completed ibandronate treatment as planned, 5.8% discontinued treatment due to progression or death, and 16% discontinued treatment for various reasons. There were 405 events, including 186 deaths, after a median of 38.7 months (range, 0-73 months) with a completeness of follow-up of 76.8%.

The study was supported by Amgen, Germany; Bristol-Myers Squibb, Germany; and Roche, Germany, which also provided drugs for the study. Dr. von Minckwitz reported ties with Roche. His colleagues noted ties with numerous drug companies.

[email protected]

Two years of adjuvant treatment with ibandronate after dose-dense chemotherapy did not improve survival in a study of more than 3,000 German patients with early stage, node-positive breast cancer.

The results were published online Aug. 26 in the Journal of Clinical Oncology.

Bisphosphonates have been shown to prevent skeletal-related events in patients with metastatic breast cancer, but their effectiveness has not been demonstrated in early breast cancer.

No differences in disease-free survival or overall survival were noted in the GAIN (German Adjuvant Intergroup Node-Positive) study, an open-label, randomized, controlled phase III trial (NCT00196872), reported Dr. Gunter von Minckwitz of the German Breast Group, along with his colleagues in the German Breast Group/Gynecologic Oncology Working Group/North-Eastern Germany Society of Gynecologic Oncology study groups.

In patients randomly assigned to 2 years of ibandronate or observation, there was no difference in disease-free survival (HR, 0.945; 95% CI, 0.768 to 1.161; P equals .589) or in overall survival (HR, 1.040; 95% CI, 0.763 to 1.419; P equals .803). Metastasis to the bone was documented in 31% in the ibandronate arm and in 38% in the observation arm.

Post hoc subgroup analyses of the study data imply that the benefit of adjuvant bisphosphonates was restricted to patients with low estrogen levels, either because of medical ovarian suppression or definite menopause. Future meta-analyses on an individual patient data level may reliably reveal subgroups of early-stage, high-risk breast cancer patients who might benefit from adjuvant bisphosphonates, the researchers noted (J. Clin. Oncol. 2013 Aug. 26 [doi:10.1200/JCO.2012.47.2167]).

In GAIN, patients with node-positive early breast cancer were randomly assigned within 4 weeks after surgery to two different dose-dense chemotherapy regimens and then in 2:1 fashion to ibandronate 50 mg per day orally starting within 4 weeks after last administration of chemotherapy and continuing for 2 years (2,015 patients) or to observation (1,008 patients).

Randomly assigned chemotherapy consisted of three courses of epirubicin 150 mg/m² followed by three courses of paclitaxel 225 mg/m² followed by three courses of cyclophosphamide 2,500 mg/m² (reduced to 2,000 mg/m² after recruitment of approximately 1,200 patients), all given at 2-week intervals (iddETC regimen) or epirubicin 112.5 mg/m² and cyclophosphamide 600 mg/m² for four 2-week courses followed by 10 courses of paclitaxel 67.5 mg/m² given once per week with capecitabine 2,000 mg/m² given days 1-14 every 3 weeks (EC-TX regimen).

Radiotherapy, endocrine treatment, and trastuzumab were indicated according to AGO guidelines and, if appropriate, were given in parallel with ibandronate after the end of chemotherapy. All patients received radiotherapy to the affected breast if breast-conserving surgery was performed, the researchers wrote.

Patients with endocrine-sensitive disease received endocrine treatment for 5 years with an aromatase inhibitor either alone or in sequence with tamoxifen if they were postmenopausal. Tamoxifen alone was given for 5 years in some patients together with a luteinizing hormone-releasing hormone (LHRH) analog if they were premenopausal after the end of chemotherapy. Patients with human epidermal growth factor receptor 2–overexpressing tumors received 1 year of adjuvant trastuzumab treatment.

Patients were evaluated every 12 weeks during the first 2 years of treatment and then every 6 months.

A total of 1,421 patients (78.2%) completed ibandronate treatment as planned, 5.8% discontinued treatment due to progression or death, and 16% discontinued treatment for various reasons. There were 405 events, including 186 deaths, after a median of 38.7 months (range, 0-73 months) with a completeness of follow-up of 76.8%.

The study was supported by Amgen, Germany; Bristol-Myers Squibb, Germany; and Roche, Germany, which also provided drugs for the study. Dr. von Minckwitz reported ties with Roche. His colleagues noted ties with numerous drug companies.

[email protected]

The probability of long-term amenorrhea is similarly high in all premenopausal breast cancer patients age 35 years and older who undergo chemotherapy, regardless of whether they carry a BRCA1 or BRCA2 mutation.

Age at treatment and use of tamoxifen were important predictors of chemotherapy-induced amenorrhea in a multicenter survey of 1,954 premenopausal women aged 26-47 with invasive breast cancers and BRCA1 or BRCA2 mutations. In the absence of chemotherapy, however, tamoxifen alone was not associated with the onset of long-term amenorrhea.

The findings indicate that all women are at risk of chemotherapy-induced amenorrhea and BRCA1 or BRCA2 status per se should not be an indication for referral to a fertility clinic, according to Dr. Adriana Valentini of the Women’s College Research Institute, Toronto, and her colleagues in the Hereditary Breast Cancer Clinical Study Group.

Breast cancer patients who wish to preserve fertility should be aware of the synergistic impact of chemotherapy and tamoxifen on inducing long-term amenorrhea and possibly menopause, the researchers said. The study was published online Aug. 26 in the Journal of Clinical Oncology.

The researchers compared age of amenorrhea onset after breast cancer diagnosis for women who were and were not treated with chemotherapy, alone or with tamoxifen. Chemotherapy-induced amenorrhea was defined as 2 or more years of amenorrhea, with no resumption of menses, commencing within 2 years of initiating chemotherapy (J. Clin. Oncol. 2013 Aug. 26 [doi:10.1200/JCO.2012.47.7893]).

Patients were selected from a database of 13,004 BRCA1 and BRCA2 mutation carriers and 2,451 noncarriers at one of 62 participating centers in seven countries. The women sought testing for BRCA1 and BRCA2 mutations because of a personal or family history of breast or ovarian cancer. They were diagnosed with invasive breast cancer between 26 and 47 years of age and were premenopausal at the time of diagnosis.

In total, 1,954 BRCA carriers with breast cancer were eligible; 1,506 (77%) carried a BRCA1 mutation, 436 (22%) carried a BRCA2 mutation, and 12 (0.6%) carried both mutations.

Of the 1,954 carrier patients, 1,426 received chemotherapy and 35% of them experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea.

The study also included 167 noncarrier women with breast cancer as a comparison group; 100 of these women (59%) received chemotherapy, and 49% developed chemotherapy-induced amenorrhea.

The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed at or before age 30 years, 33% for women diagnosed at age 31-44 years, and 79% for women diagnosed after age 45 years (P trend greater than or equal to .001).

Tamoxifen was give to 478 carrier patients, and 410 (86%) received both tamoxifen and chemotherapy. Their probability of induced amenorrhea was 52%, compared with 29% for those who did not receive tamoxifen (P less than or equal to .001).

The probability of chemotherapy-induced amenorrhea was significantly higher for BRCA2 carriers than for BRCA1 carriers (46.8% v 32.7%; P less than or equal to .001). By age 38 years, 50% of BRCA2 carriers were expected to experience amenorrhea after chemotherapy, compared with the age of 40 years expected for BRCA1 carriers.

Among all women who reached age 56 years, the mean age of menopause was 45.4 years for those who received chemotherapy and resumed menses, and 49 years for those who did not receive chemotherapy (P less than or equal to .001), a difference of 3.6 years.

Among women who had a BRCA1 mutation and reached age 56 years, the mean age of menopause was 45.5 years for those who received chemotherapy and 48.7 years for those who did not receive chemotherapy (P less than or equal to .001).

Among women who had a BRCA2 mutation and reached age 56 years, the mean age of menopause was 45.2 years for those who received chemotherapy and 49.9 years for those who did not receive chemotherapy (P less than or equal to .003).

The study was supported by the Canadian Breast Cancer Research Alliance, the Canadian Cancer Research Society Research Initiative, Fonds de Recherche en Sante´ du Que´ bec, and National Institutes of Health Grant No. R01 CA74415. The authors reported having no potential conflicts of interest.

[email protected]

The probability of long-term amenorrhea is similarly high in all premenopausal breast cancer patients age 35 years and older who undergo chemotherapy, regardless of whether they carry a BRCA1 or BRCA2 mutation.

Age at treatment and use of tamoxifen were important predictors of chemotherapy-induced amenorrhea in a multicenter survey of 1,954 premenopausal women aged 26-47 with invasive breast cancers and BRCA1 or BRCA2 mutations. In the absence of chemotherapy, however, tamoxifen alone was not associated with the onset of long-term amenorrhea.

The findings indicate that all women are at risk of chemotherapy-induced amenorrhea and BRCA1 or BRCA2 status per se should not be an indication for referral to a fertility clinic, according to Dr. Adriana Valentini of the Women’s College Research Institute, Toronto, and her colleagues in the Hereditary Breast Cancer Clinical Study Group.

Breast cancer patients who wish to preserve fertility should be aware of the synergistic impact of chemotherapy and tamoxifen on inducing long-term amenorrhea and possibly menopause, the researchers said. The study was published online Aug. 26 in the Journal of Clinical Oncology.

The researchers compared age of amenorrhea onset after breast cancer diagnosis for women who were and were not treated with chemotherapy, alone or with tamoxifen. Chemotherapy-induced amenorrhea was defined as 2 or more years of amenorrhea, with no resumption of menses, commencing within 2 years of initiating chemotherapy (J. Clin. Oncol. 2013 Aug. 26 [doi:10.1200/JCO.2012.47.7893]).

Patients were selected from a database of 13,004 BRCA1 and BRCA2 mutation carriers and 2,451 noncarriers at one of 62 participating centers in seven countries. The women sought testing for BRCA1 and BRCA2 mutations because of a personal or family history of breast or ovarian cancer. They were diagnosed with invasive breast cancer between 26 and 47 years of age and were premenopausal at the time of diagnosis.

In total, 1,954 BRCA carriers with breast cancer were eligible; 1,506 (77%) carried a BRCA1 mutation, 436 (22%) carried a BRCA2 mutation, and 12 (0.6%) carried both mutations.

Of the 1,954 carrier patients, 1,426 received chemotherapy and 35% of them experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea.

The study also included 167 noncarrier women with breast cancer as a comparison group; 100 of these women (59%) received chemotherapy, and 49% developed chemotherapy-induced amenorrhea.

The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed at or before age 30 years, 33% for women diagnosed at age 31-44 years, and 79% for women diagnosed after age 45 years (P trend greater than or equal to .001).

Tamoxifen was give to 478 carrier patients, and 410 (86%) received both tamoxifen and chemotherapy. Their probability of induced amenorrhea was 52%, compared with 29% for those who did not receive tamoxifen (P less than or equal to .001).

The probability of chemotherapy-induced amenorrhea was significantly higher for BRCA2 carriers than for BRCA1 carriers (46.8% v 32.7%; P less than or equal to .001). By age 38 years, 50% of BRCA2 carriers were expected to experience amenorrhea after chemotherapy, compared with the age of 40 years expected for BRCA1 carriers.

Among all women who reached age 56 years, the mean age of menopause was 45.4 years for those who received chemotherapy and resumed menses, and 49 years for those who did not receive chemotherapy (P less than or equal to .001), a difference of 3.6 years.

Among women who had a BRCA1 mutation and reached age 56 years, the mean age of menopause was 45.5 years for those who received chemotherapy and 48.7 years for those who did not receive chemotherapy (P less than or equal to .001).

Among women who had a BRCA2 mutation and reached age 56 years, the mean age of menopause was 45.2 years for those who received chemotherapy and 49.9 years for those who did not receive chemotherapy (P less than or equal to .003).

The study was supported by the Canadian Breast Cancer Research Alliance, the Canadian Cancer Research Society Research Initiative, Fonds de Recherche en Sante´ du Que´ bec, and National Institutes of Health Grant No. R01 CA74415. The authors reported having no potential conflicts of interest.

[email protected]

The probability of long-term amenorrhea is similarly high in all premenopausal breast cancer patients age 35 years and older who undergo chemotherapy, regardless of whether they carry a BRCA1 or BRCA2 mutation.

Age at treatment and use of tamoxifen were important predictors of chemotherapy-induced amenorrhea in a multicenter survey of 1,954 premenopausal women aged 26-47 with invasive breast cancers and BRCA1 or BRCA2 mutations. In the absence of chemotherapy, however, tamoxifen alone was not associated with the onset of long-term amenorrhea.

The findings indicate that all women are at risk of chemotherapy-induced amenorrhea and BRCA1 or BRCA2 status per se should not be an indication for referral to a fertility clinic, according to Dr. Adriana Valentini of the Women’s College Research Institute, Toronto, and her colleagues in the Hereditary Breast Cancer Clinical Study Group.

Breast cancer patients who wish to preserve fertility should be aware of the synergistic impact of chemotherapy and tamoxifen on inducing long-term amenorrhea and possibly menopause, the researchers said. The study was published online Aug. 26 in the Journal of Clinical Oncology.

The researchers compared age of amenorrhea onset after breast cancer diagnosis for women who were and were not treated with chemotherapy, alone or with tamoxifen. Chemotherapy-induced amenorrhea was defined as 2 or more years of amenorrhea, with no resumption of menses, commencing within 2 years of initiating chemotherapy (J. Clin. Oncol. 2013 Aug. 26 [doi:10.1200/JCO.2012.47.7893]).

Patients were selected from a database of 13,004 BRCA1 and BRCA2 mutation carriers and 2,451 noncarriers at one of 62 participating centers in seven countries. The women sought testing for BRCA1 and BRCA2 mutations because of a personal or family history of breast or ovarian cancer. They were diagnosed with invasive breast cancer between 26 and 47 years of age and were premenopausal at the time of diagnosis.

In total, 1,954 BRCA carriers with breast cancer were eligible; 1,506 (77%) carried a BRCA1 mutation, 436 (22%) carried a BRCA2 mutation, and 12 (0.6%) carried both mutations.

Of the 1,954 carrier patients, 1,426 received chemotherapy and 35% of them experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea.

The study also included 167 noncarrier women with breast cancer as a comparison group; 100 of these women (59%) received chemotherapy, and 49% developed chemotherapy-induced amenorrhea.

The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed at or before age 30 years, 33% for women diagnosed at age 31-44 years, and 79% for women diagnosed after age 45 years (P trend greater than or equal to .001).

Tamoxifen was give to 478 carrier patients, and 410 (86%) received both tamoxifen and chemotherapy. Their probability of induced amenorrhea was 52%, compared with 29% for those who did not receive tamoxifen (P less than or equal to .001).

The probability of chemotherapy-induced amenorrhea was significantly higher for BRCA2 carriers than for BRCA1 carriers (46.8% v 32.7%; P less than or equal to .001). By age 38 years, 50% of BRCA2 carriers were expected to experience amenorrhea after chemotherapy, compared with the age of 40 years expected for BRCA1 carriers.

Among all women who reached age 56 years, the mean age of menopause was 45.4 years for those who received chemotherapy and resumed menses, and 49 years for those who did not receive chemotherapy (P less than or equal to .001), a difference of 3.6 years.

Among women who had a BRCA1 mutation and reached age 56 years, the mean age of menopause was 45.5 years for those who received chemotherapy and 48.7 years for those who did not receive chemotherapy (P less than or equal to .001).

Among women who had a BRCA2 mutation and reached age 56 years, the mean age of menopause was 45.2 years for those who received chemotherapy and 49.9 years for those who did not receive chemotherapy (P less than or equal to .003).

The study was supported by the Canadian Breast Cancer Research Alliance, the Canadian Cancer Research Society Research Initiative, Fonds de Recherche en Sante´ du Que´ bec, and National Institutes of Health Grant No. R01 CA74415. The authors reported having no potential conflicts of interest.

[email protected]

Overall survival rates at 10 years after diagnosis were similarly good in women with and without BRCA1 mutations if they had stage I-III node-negative breast cancers that were smaller than 2 cm, based on a retrospective study of Polish women who were under age 50 years at diagnosis.

Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted hazard ratio, 4.1; 95% confidence interval, 1.8-8.9). Among BRCA1 carriers with 2 cm or smaller breast tumors, the 10-year survival rate was 84.1%, compared with 89.9% for the node-negative patients and 68.6% for the node-positive patients, according to Dr. Tomasz Huzarski of Pomeranian Medical University, Szczecin, Poland, and the members of the Polish Hereditary Breast Cancer Consortium.

Their study also showed that mortality rates were lower in BRCA1 carriers who had prophylactic oophorectomies. Compared with BRCA1 carriers who had intact ovaries, carriers who had an oophorectomy had a mortality reduction of 70% (adjusted HR, 0.30; 95% CI, 0.12-0.75).

The findings were gleaned from the medical records of 3,345 Polish women who were age 50 years or less when diagnosed from 1996 to 2006 with stage I-III breast cancer. In Poland, three founder mutations (5382insC, C61G, 4153delA) represent over 90% of the BRCA1 mutations, and young women diagnosed with breast cancers at one of 17 affiliated clinical centers there are screened for those BRCA1 mutations. The records indicated that 233 (7%) of the women with a first cancer diagnosis of stage I-III breast cancer had a BRCA1 mutation.

Based on BRCA1 status alone, the 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4%-86.4%); for noncarriers, it was 82.2% (95% CI, 80.5%-83.7%). The difference was not statistically significant, the authors wrote in an article published online in the Journal of Clinical Oncology (J. Clin. Oncol. 2013 Aug. 12 [doi:10.1200/JCO.2012.45.3571]).

In a multivariate analysis, however, mortality differed significantly for BRCA1 carriers and noncarriers (HR, 1.81; 95% CI, 1.26-2.61; P = .002). Of the 233 BRCA1-positive patients, 101 (43.6%) comprised a high-risk group who had cancers that were node positive and/or at least 5 cm or more in size. Their 10-year survival was 68.2% (95% CI, 58.2%-78.6%).

"The effect of oophorectomy on survival was profound and was statistically significant for BRCA1 carriers," the Dr. Huzarski and his coworkers wrote. A preventive oophorectomy was performed in 115 of the 233 carriers. There were 13 deaths, all resulting from breast cancer, in the 115 women. Among the 113 women (data were missing for 5 women) who did not have an oophorectomy, there were 28 deaths: 22 from breast cancer and 6 from breast or ovarian cancer. Overall, 28 (68%) of the 41 deaths occurred in women with intact ovaries.

As the study was limited to women in Poland, the authors cautioned that the results may not generalizable to women with other BRCA1 mutations or ethnicities. Additionally, these were early-onset cases only and the survival rates may not accurately reflect those of women diagnosed with cancer at a later age.

"It is important that these observations be replicated in other populations; if they are, oophorectomy should be considered a standard of care for women with breast cancer and a BRCA1 mutation," they wrote.

Dr. Huzarski and his associates reported having no financial conflicts of interest.

[email protected]

Overall survival rates at 10 years after diagnosis were similarly good in women with and without BRCA1 mutations if they had stage I-III node-negative breast cancers that were smaller than 2 cm, based on a retrospective study of Polish women who were under age 50 years at diagnosis.

Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted hazard ratio, 4.1; 95% confidence interval, 1.8-8.9). Among BRCA1 carriers with 2 cm or smaller breast tumors, the 10-year survival rate was 84.1%, compared with 89.9% for the node-negative patients and 68.6% for the node-positive patients, according to Dr. Tomasz Huzarski of Pomeranian Medical University, Szczecin, Poland, and the members of the Polish Hereditary Breast Cancer Consortium.

Their study also showed that mortality rates were lower in BRCA1 carriers who had prophylactic oophorectomies. Compared with BRCA1 carriers who had intact ovaries, carriers who had an oophorectomy had a mortality reduction of 70% (adjusted HR, 0.30; 95% CI, 0.12-0.75).

The findings were gleaned from the medical records of 3,345 Polish women who were age 50 years or less when diagnosed from 1996 to 2006 with stage I-III breast cancer. In Poland, three founder mutations (5382insC, C61G, 4153delA) represent over 90% of the BRCA1 mutations, and young women diagnosed with breast cancers at one of 17 affiliated clinical centers there are screened for those BRCA1 mutations. The records indicated that 233 (7%) of the women with a first cancer diagnosis of stage I-III breast cancer had a BRCA1 mutation.

Based on BRCA1 status alone, the 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4%-86.4%); for noncarriers, it was 82.2% (95% CI, 80.5%-83.7%). The difference was not statistically significant, the authors wrote in an article published online in the Journal of Clinical Oncology (J. Clin. Oncol. 2013 Aug. 12 [doi:10.1200/JCO.2012.45.3571]).

In a multivariate analysis, however, mortality differed significantly for BRCA1 carriers and noncarriers (HR, 1.81; 95% CI, 1.26-2.61; P = .002). Of the 233 BRCA1-positive patients, 101 (43.6%) comprised a high-risk group who had cancers that were node positive and/or at least 5 cm or more in size. Their 10-year survival was 68.2% (95% CI, 58.2%-78.6%).

"The effect of oophorectomy on survival was profound and was statistically significant for BRCA1 carriers," the Dr. Huzarski and his coworkers wrote. A preventive oophorectomy was performed in 115 of the 233 carriers. There were 13 deaths, all resulting from breast cancer, in the 115 women. Among the 113 women (data were missing for 5 women) who did not have an oophorectomy, there were 28 deaths: 22 from breast cancer and 6 from breast or ovarian cancer. Overall, 28 (68%) of the 41 deaths occurred in women with intact ovaries.

As the study was limited to women in Poland, the authors cautioned that the results may not generalizable to women with other BRCA1 mutations or ethnicities. Additionally, these were early-onset cases only and the survival rates may not accurately reflect those of women diagnosed with cancer at a later age.

"It is important that these observations be replicated in other populations; if they are, oophorectomy should be considered a standard of care for women with breast cancer and a BRCA1 mutation," they wrote.

Dr. Huzarski and his associates reported having no financial conflicts of interest.

[email protected]

Overall survival rates at 10 years after diagnosis were similarly good in women with and without BRCA1 mutations if they had stage I-III node-negative breast cancers that were smaller than 2 cm, based on a retrospective study of Polish women who were under age 50 years at diagnosis.

Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted hazard ratio, 4.1; 95% confidence interval, 1.8-8.9). Among BRCA1 carriers with 2 cm or smaller breast tumors, the 10-year survival rate was 84.1%, compared with 89.9% for the node-negative patients and 68.6% for the node-positive patients, according to Dr. Tomasz Huzarski of Pomeranian Medical University, Szczecin, Poland, and the members of the Polish Hereditary Breast Cancer Consortium.

Their study also showed that mortality rates were lower in BRCA1 carriers who had prophylactic oophorectomies. Compared with BRCA1 carriers who had intact ovaries, carriers who had an oophorectomy had a mortality reduction of 70% (adjusted HR, 0.30; 95% CI, 0.12-0.75).

The findings were gleaned from the medical records of 3,345 Polish women who were age 50 years or less when diagnosed from 1996 to 2006 with stage I-III breast cancer. In Poland, three founder mutations (5382insC, C61G, 4153delA) represent over 90% of the BRCA1 mutations, and young women diagnosed with breast cancers at one of 17 affiliated clinical centers there are screened for those BRCA1 mutations. The records indicated that 233 (7%) of the women with a first cancer diagnosis of stage I-III breast cancer had a BRCA1 mutation.

Based on BRCA1 status alone, the 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4%-86.4%); for noncarriers, it was 82.2% (95% CI, 80.5%-83.7%). The difference was not statistically significant, the authors wrote in an article published online in the Journal of Clinical Oncology (J. Clin. Oncol. 2013 Aug. 12 [doi:10.1200/JCO.2012.45.3571]).

In a multivariate analysis, however, mortality differed significantly for BRCA1 carriers and noncarriers (HR, 1.81; 95% CI, 1.26-2.61; P = .002). Of the 233 BRCA1-positive patients, 101 (43.6%) comprised a high-risk group who had cancers that were node positive and/or at least 5 cm or more in size. Their 10-year survival was 68.2% (95% CI, 58.2%-78.6%).

"The effect of oophorectomy on survival was profound and was statistically significant for BRCA1 carriers," the Dr. Huzarski and his coworkers wrote. A preventive oophorectomy was performed in 115 of the 233 carriers. There were 13 deaths, all resulting from breast cancer, in the 115 women. Among the 113 women (data were missing for 5 women) who did not have an oophorectomy, there were 28 deaths: 22 from breast cancer and 6 from breast or ovarian cancer. Overall, 28 (68%) of the 41 deaths occurred in women with intact ovaries.

As the study was limited to women in Poland, the authors cautioned that the results may not generalizable to women with other BRCA1 mutations or ethnicities. Additionally, these were early-onset cases only and the survival rates may not accurately reflect those of women diagnosed with cancer at a later age.

"It is important that these observations be replicated in other populations; if they are, oophorectomy should be considered a standard of care for women with breast cancer and a BRCA1 mutation," they wrote.

Dr. Huzarski and his associates reported having no financial conflicts of interest.

[email protected]

CHICAGO – Prostate cancer outcomes were predicted by a test that measures the expression of cell cycle progression genes, according to results from a retrospective analysis of prostate tissue samples from five patient cohorts.

The Prolaris test gives each tissue sample a cell cycle progression (CCP) score based on measures of 31 CCP genes, normalized to 15 "housekeeper" genes. A unit change in the test is defined as a doubling in CCP genes. For each unit increase in the test’s score, there was a two- to threefold increase in the risk of disease progression, Dr. Jack M. Cuzick reported at the annual meeting of the American Society of Clinical Oncology.

The CCP signature of Myriad Genetics’ Prolaris test was a highly significant predictor of outcome, said Dr. Cuzick of the Wolfson Institute of Preventive Medicine, London. In all five studies, the hazard ratio per unit change in the CCP score was similar, ranging from 1.89 to 2.92. The findings indicate that the effect size for the CCP score is robust in multiple patient cohorts and diverse clinical settings.

The test provides information for differentiating aggressive and indolent disease beyond that available from clinicopathologic variables, he said. As the natural history of prostate cancer can be variable and difficult to predict, the Prolaris test could help to match treatment more appropriately to each individual’s risk of progression.

In the study that examined the test’s predictive value, five patient groups were evaluated. Formalin-fixed tissue samples were obtained from two English patient cohorts that were conservatively managed (n = 337 and 349), two U.S. patient cohorts that underwent radical prostatectomy (366 men treated at Scott & White Hospital, Temple, Tex.; and 413 men treated at the University of California, San Francisco), and one U.S. cohort that underwent external beam radiation therapy (141 men treated at the Durham, N.C., VA Medical Center).

The cohort of conservatively managed English patients was from the late 1990s and had more than 15 years of follow up. In the 337-patient cohort diagnosed via transurethral resection of the prostate (TURP) and conservatively managed, there were 57 deaths from prostate cancer. In the 349-patient cohort diagnosed via needle biopsy and conservatively managed, there were 90 deaths from prostate cancer.

For each unit increase in the CCP score, the hazard ratio for the cohort diagnosed via TURP was 2.9 and the hazard ratio for those diagnosed via needle biopsy was 2. The CCP score was the dominant variable for predicting death from prostate cancer in univariate analysis (P = 6.1 x 10^–22 after diagnosis via TURP, and P = 8.6 x 10^–10 after diagnosis via needle biopsy). In both studies, the CCP score remained highly significant in multivariate analysis and was a stronger predictor of disease-specific mortality than other prognostic variables, he said.

In the U.S. prostatectomy cohorts, there were 132 biochemical recurrences (BCRs) in the first cohort and 83 BCRs in the second cohort. With each unit increase in the CCP score, there was a doubling of risk for recurrence. After prostatectomy, the CCP score predicted BCR in univariate analysis (Scott & White: P = 5.6 x 10^–9; University of California: P = 2.23 x 10^–6) and provided additional prognostic information in multivariate analysis (Scott & White: P = 3.3 x 10^–6; University of California: P = 9.5 x10^–5).

After radiation therapy, the CCP score predicted BCR in univariate (P = .0017) and multivariate (P = .034) analysis. In the 141-patient cohort that was diagnosed by needle biopsy and underwent external beam radiation, there were 19 prostate cancer deaths and more than a doubling of risk with each unit increase in CCP score.

CCP scores only modestly correlated with the Gleason score and prostate-specific antigen (PSA) value. The test adds value beyond those measures, Dr. Cuzick said.

CCP scores predict patient outcome in multiple clinical settings, provide independent information beyond clinicopathological variables, and help to further differentiate aggressive from indolent prostate cancer. With low-grade Gleason 6 cancers, the results can aid in telling who is at low risk and who needs aggressive therapy, he concluded.

The study was funded by Myriad Genetics, the maker of the Prolaris test. Dr. Cuzick received honoraria and research support from Myriad.

CHICAGO – Prostate cancer outcomes were predicted by a test that measures the expression of cell cycle progression genes, according to results from a retrospective analysis of prostate tissue samples from five patient cohorts.

The Prolaris test gives each tissue sample a cell cycle progression (CCP) score based on measures of 31 CCP genes, normalized to 15 "housekeeper" genes. A unit change in the test is defined as a doubling in CCP genes. For each unit increase in the test’s score, there was a two- to threefold increase in the risk of disease progression, Dr. Jack M. Cuzick reported at the annual meeting of the American Society of Clinical Oncology.

The CCP signature of Myriad Genetics’ Prolaris test was a highly significant predictor of outcome, said Dr. Cuzick of the Wolfson Institute of Preventive Medicine, London. In all five studies, the hazard ratio per unit change in the CCP score was similar, ranging from 1.89 to 2.92. The findings indicate that the effect size for the CCP score is robust in multiple patient cohorts and diverse clinical settings.

The test provides information for differentiating aggressive and indolent disease beyond that available from clinicopathologic variables, he said. As the natural history of prostate cancer can be variable and difficult to predict, the Prolaris test could help to match treatment more appropriately to each individual’s risk of progression.

In the study that examined the test’s predictive value, five patient groups were evaluated. Formalin-fixed tissue samples were obtained from two English patient cohorts that were conservatively managed (n = 337 and 349), two U.S. patient cohorts that underwent radical prostatectomy (366 men treated at Scott & White Hospital, Temple, Tex.; and 413 men treated at the University of California, San Francisco), and one U.S. cohort that underwent external beam radiation therapy (141 men treated at the Durham, N.C., VA Medical Center).

The cohort of conservatively managed English patients was from the late 1990s and had more than 15 years of follow up. In the 337-patient cohort diagnosed via transurethral resection of the prostate (TURP) and conservatively managed, there were 57 deaths from prostate cancer. In the 349-patient cohort diagnosed via needle biopsy and conservatively managed, there were 90 deaths from prostate cancer.

For each unit increase in the CCP score, the hazard ratio for the cohort diagnosed via TURP was 2.9 and the hazard ratio for those diagnosed via needle biopsy was 2. The CCP score was the dominant variable for predicting death from prostate cancer in univariate analysis (P = 6.1 x 10^–22 after diagnosis via TURP, and P = 8.6 x 10^–10 after diagnosis via needle biopsy). In both studies, the CCP score remained highly significant in multivariate analysis and was a stronger predictor of disease-specific mortality than other prognostic variables, he said.

In the U.S. prostatectomy cohorts, there were 132 biochemical recurrences (BCRs) in the first cohort and 83 BCRs in the second cohort. With each unit increase in the CCP score, there was a doubling of risk for recurrence. After prostatectomy, the CCP score predicted BCR in univariate analysis (Scott & White: P = 5.6 x 10^–9; University of California: P = 2.23 x 10^–6) and provided additional prognostic information in multivariate analysis (Scott & White: P = 3.3 x 10^–6; University of California: P = 9.5 x10^–5).

After radiation therapy, the CCP score predicted BCR in univariate (P = .0017) and multivariate (P = .034) analysis. In the 141-patient cohort that was diagnosed by needle biopsy and underwent external beam radiation, there were 19 prostate cancer deaths and more than a doubling of risk with each unit increase in CCP score.

CCP scores only modestly correlated with the Gleason score and prostate-specific antigen (PSA) value. The test adds value beyond those measures, Dr. Cuzick said.

CCP scores predict patient outcome in multiple clinical settings, provide independent information beyond clinicopathological variables, and help to further differentiate aggressive from indolent prostate cancer. With low-grade Gleason 6 cancers, the results can aid in telling who is at low risk and who needs aggressive therapy, he concluded.

The study was funded by Myriad Genetics, the maker of the Prolaris test. Dr. Cuzick received honoraria and research support from Myriad.

CHICAGO – Prostate cancer outcomes were predicted by a test that measures the expression of cell cycle progression genes, according to results from a retrospective analysis of prostate tissue samples from five patient cohorts.

The Prolaris test gives each tissue sample a cell cycle progression (CCP) score based on measures of 31 CCP genes, normalized to 15 "housekeeper" genes. A unit change in the test is defined as a doubling in CCP genes. For each unit increase in the test’s score, there was a two- to threefold increase in the risk of disease progression, Dr. Jack M. Cuzick reported at the annual meeting of the American Society of Clinical Oncology.

The CCP signature of Myriad Genetics’ Prolaris test was a highly significant predictor of outcome, said Dr. Cuzick of the Wolfson Institute of Preventive Medicine, London. In all five studies, the hazard ratio per unit change in the CCP score was similar, ranging from 1.89 to 2.92. The findings indicate that the effect size for the CCP score is robust in multiple patient cohorts and diverse clinical settings.

The test provides information for differentiating aggressive and indolent disease beyond that available from clinicopathologic variables, he said. As the natural history of prostate cancer can be variable and difficult to predict, the Prolaris test could help to match treatment more appropriately to each individual’s risk of progression.

In the study that examined the test’s predictive value, five patient groups were evaluated. Formalin-fixed tissue samples were obtained from two English patient cohorts that were conservatively managed (n = 337 and 349), two U.S. patient cohorts that underwent radical prostatectomy (366 men treated at Scott & White Hospital, Temple, Tex.; and 413 men treated at the University of California, San Francisco), and one U.S. cohort that underwent external beam radiation therapy (141 men treated at the Durham, N.C., VA Medical Center).

The cohort of conservatively managed English patients was from the late 1990s and had more than 15 years of follow up. In the 337-patient cohort diagnosed via transurethral resection of the prostate (TURP) and conservatively managed, there were 57 deaths from prostate cancer. In the 349-patient cohort diagnosed via needle biopsy and conservatively managed, there were 90 deaths from prostate cancer.

For each unit increase in the CCP score, the hazard ratio for the cohort diagnosed via TURP was 2.9 and the hazard ratio for those diagnosed via needle biopsy was 2. The CCP score was the dominant variable for predicting death from prostate cancer in univariate analysis (P = 6.1 x 10^–22 after diagnosis via TURP, and P = 8.6 x 10^–10 after diagnosis via needle biopsy). In both studies, the CCP score remained highly significant in multivariate analysis and was a stronger predictor of disease-specific mortality than other prognostic variables, he said.

In the U.S. prostatectomy cohorts, there were 132 biochemical recurrences (BCRs) in the first cohort and 83 BCRs in the second cohort. With each unit increase in the CCP score, there was a doubling of risk for recurrence. After prostatectomy, the CCP score predicted BCR in univariate analysis (Scott & White: P = 5.6 x 10^–9; University of California: P = 2.23 x 10^–6) and provided additional prognostic information in multivariate analysis (Scott & White: P = 3.3 x 10^–6; University of California: P = 9.5 x10^–5).

After radiation therapy, the CCP score predicted BCR in univariate (P = .0017) and multivariate (P = .034) analysis. In the 141-patient cohort that was diagnosed by needle biopsy and underwent external beam radiation, there were 19 prostate cancer deaths and more than a doubling of risk with each unit increase in CCP score.

CCP scores only modestly correlated with the Gleason score and prostate-specific antigen (PSA) value. The test adds value beyond those measures, Dr. Cuzick said.

CCP scores predict patient outcome in multiple clinical settings, provide independent information beyond clinicopathological variables, and help to further differentiate aggressive from indolent prostate cancer. With low-grade Gleason 6 cancers, the results can aid in telling who is at low risk and who needs aggressive therapy, he concluded.

The study was funded by Myriad Genetics, the maker of the Prolaris test. Dr. Cuzick received honoraria and research support from Myriad.

Denosumab is approved for the treatment of giant cell tumors of the bone, the Food and Drug Administration announced June 13.

Rare and usually noncancerous, giant cell tumors of the bone generally affect 20- to 40-year-olds. Most of these tumors destroy growing bone, causing pain, limited range of motion, and bone fractures. Rarely, the tumors become cancerous and spread to the lungs.

Denosumab (Xgeva) is indicated for use in patients who are not candidates for surgical resection of their tumors or when surgery is likely to result in severe morbidity, such as loss of limbs or joint removal. It should be used only in adolescents whose bones have matured, the FDA said in a statement.

"Today’s approval of Xgeva provides a needed treatment option for patients with GCTB who are not surgical candidates or who would otherwise have to undergo extensive, life-altering surgery," said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

The FDA reviewed denosumab under its priority review program as the drug was granted orphan product designation because GCTB is a rare disease.

The safety and effectiveness of denosumab for GCTB were established in two clinical trials that enrolled 305 adult or adolescent patients with confirmed GCTB that was recurrent, unresectable, or would be associated with severe morbidity if surgically managed.

After an average of 3 months, tumors reduced in size among 47 of 187 patients whose tumors could be measured. Over an average follow-up of 20 months, GCTBs regrew in three patients whose tumors originally became smaller during treatment.

Common side effects of denosumab included joint pain, headache, nausea, fatigue, back pain, and extremity pain. The most common serious side effects were osteonecrosis of the jaw and osteomyelitis. Women of reproductive potential should use highly effective contraception while taking denosumab because of potential fetal harm, according to the FDA.

Denosumab was approved in 2010 to prevent fractures when cancer has spread to the bones. It is marketed by Amgen.

[email protected]

On Twitter @maryjodales

Denosumab is approved for the treatment of giant cell tumors of the bone, the Food and Drug Administration announced June 13.

Rare and usually noncancerous, giant cell tumors of the bone generally affect 20- to 40-year-olds. Most of these tumors destroy growing bone, causing pain, limited range of motion, and bone fractures. Rarely, the tumors become cancerous and spread to the lungs.

Denosumab (Xgeva) is indicated for use in patients who are not candidates for surgical resection of their tumors or when surgery is likely to result in severe morbidity, such as loss of limbs or joint removal. It should be used only in adolescents whose bones have matured, the FDA said in a statement.

"Today’s approval of Xgeva provides a needed treatment option for patients with GCTB who are not surgical candidates or who would otherwise have to undergo extensive, life-altering surgery," said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

The FDA reviewed denosumab under its priority review program as the drug was granted orphan product designation because GCTB is a rare disease.

The safety and effectiveness of denosumab for GCTB were established in two clinical trials that enrolled 305 adult or adolescent patients with confirmed GCTB that was recurrent, unresectable, or would be associated with severe morbidity if surgically managed.

After an average of 3 months, tumors reduced in size among 47 of 187 patients whose tumors could be measured. Over an average follow-up of 20 months, GCTBs regrew in three patients whose tumors originally became smaller during treatment.

Common side effects of denosumab included joint pain, headache, nausea, fatigue, back pain, and extremity pain. The most common serious side effects were osteonecrosis of the jaw and osteomyelitis. Women of reproductive potential should use highly effective contraception while taking denosumab because of potential fetal harm, according to the FDA.

Denosumab was approved in 2010 to prevent fractures when cancer has spread to the bones. It is marketed by Amgen.

[email protected]

On Twitter @maryjodales

Denosumab is approved for the treatment of giant cell tumors of the bone, the Food and Drug Administration announced June 13.

Rare and usually noncancerous, giant cell tumors of the bone generally affect 20- to 40-year-olds. Most of these tumors destroy growing bone, causing pain, limited range of motion, and bone fractures. Rarely, the tumors become cancerous and spread to the lungs.

Denosumab (Xgeva) is indicated for use in patients who are not candidates for surgical resection of their tumors or when surgery is likely to result in severe morbidity, such as loss of limbs or joint removal. It should be used only in adolescents whose bones have matured, the FDA said in a statement.

"Today’s approval of Xgeva provides a needed treatment option for patients with GCTB who are not surgical candidates or who would otherwise have to undergo extensive, life-altering surgery," said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

The FDA reviewed denosumab under its priority review program as the drug was granted orphan product designation because GCTB is a rare disease.

The safety and effectiveness of denosumab for GCTB were established in two clinical trials that enrolled 305 adult or adolescent patients with confirmed GCTB that was recurrent, unresectable, or would be associated with severe morbidity if surgically managed.

After an average of 3 months, tumors reduced in size among 47 of 187 patients whose tumors could be measured. Over an average follow-up of 20 months, GCTBs regrew in three patients whose tumors originally became smaller during treatment.

Common side effects of denosumab included joint pain, headache, nausea, fatigue, back pain, and extremity pain. The most common serious side effects were osteonecrosis of the jaw and osteomyelitis. Women of reproductive potential should use highly effective contraception while taking denosumab because of potential fetal harm, according to the FDA.

Denosumab was approved in 2010 to prevent fractures when cancer has spread to the bones. It is marketed by Amgen.

[email protected]

On Twitter @maryjodales

CHICAGO – BROCA, a genetic screening panel that combines BRCA1 and BRCA2 testing with screening for all 18 known breast cancer genes, detected at least one loss of function mutation in 56 of 249 unrelated African American women with breast cancer.

African American women are disproportionately affected by early-onset and triple-negative breast cancers, possibly because of a higher frequency of inherited mutations in DNA repair pathways. The finding of abnormalities in 22% of these women represents the first comprehensive screen of all known breast cancer susceptibility genes using next-generation sequencing in African American women, according to Dr. Jane E. Churpek, who reported the results at the annual meeting of the American Society of Clinical Oncology.

These high carrier frequencies suggest the importance of screening for all gene mutations in African American breast cancer patients who are diagnosed at a young age, have a family history, or have triple-negative breast cancer. The results should be used to encourage testing of at-risk family members to identify those who would benefit from lifesaving interventions, said Dr. Churpek of the University of Chicago.

In the 249-patient study, inherited damaging mutations were seen in 44 of 144 patients with a family history and in 12 of 145 women without a family history of breast and ovarian cancer. Of the 67 women who had triple-negative disease, 20 (30%) had mutations; in the 146 women under age 45, 67 (27%) had mutations.

"Even in the absence of triple-negative disease and family history, there are patients with gene mutations," she said.

While the majority of the 56 women with mutations were positive for BRCA1 (26 patients) or BRCA2 (20 patients), other inherited mutations detected in the BROCA panel were found in 10 patients. Those mutations included CHEK2 (n = 3), PALB2 (n = 3), ATM (n = 5), and PTEN (n = 1), she reported. The study population consisted of women who were treated at the University of Chicago cancer risk and breast cancer clinics.

Having an all-encompassing test like BROCA would allow women to undergo a single test, Dr. Churpek said. Further, advances in technology via targeted genomic capture and next generation sequencing allow this test to be performed inexpensively using 3 mcg of peripheral blood. The current clinical approach to testing requires BRCA1 and BRCA2 testing (BRACAnalysis, Myriad) and possible further testing via a genetic panel, which can be expensive and sometimes difficult to get covered by payers, Dr. Churpek said.

She said there are no plans to market the BROCA test, however. Myriad Genetics holds the U.S. patent on the BRCA genes in the context of cancer diagnostics until 2015. The U.S. Supreme Court is considering the legal issues surrounding the gene patent in the case of Association for Molecular Pathology v. Myriad Genetics. Oral arguments in the case were heard in April, and a decision from the court is expected before July.

Dr. Churpek had no financial disclosures.

[email protected]

On Twitter @maryjodales

CHICAGO – BROCA, a genetic screening panel that combines BRCA1 and BRCA2 testing with screening for all 18 known breast cancer genes, detected at least one loss of function mutation in 56 of 249 unrelated African American women with breast cancer.

African American women are disproportionately affected by early-onset and triple-negative breast cancers, possibly because of a higher frequency of inherited mutations in DNA repair pathways. The finding of abnormalities in 22% of these women represents the first comprehensive screen of all known breast cancer susceptibility genes using next-generation sequencing in African American women, according to Dr. Jane E. Churpek, who reported the results at the annual meeting of the American Society of Clinical Oncology.

These high carrier frequencies suggest the importance of screening for all gene mutations in African American breast cancer patients who are diagnosed at a young age, have a family history, or have triple-negative breast cancer. The results should be used to encourage testing of at-risk family members to identify those who would benefit from lifesaving interventions, said Dr. Churpek of the University of Chicago.

In the 249-patient study, inherited damaging mutations were seen in 44 of 144 patients with a family history and in 12 of 145 women without a family history of breast and ovarian cancer. Of the 67 women who had triple-negative disease, 20 (30%) had mutations; in the 146 women under age 45, 67 (27%) had mutations.

"Even in the absence of triple-negative disease and family history, there are patients with gene mutations," she said.

While the majority of the 56 women with mutations were positive for BRCA1 (26 patients) or BRCA2 (20 patients), other inherited mutations detected in the BROCA panel were found in 10 patients. Those mutations included CHEK2 (n = 3), PALB2 (n = 3), ATM (n = 5), and PTEN (n = 1), she reported. The study population consisted of women who were treated at the University of Chicago cancer risk and breast cancer clinics.

Having an all-encompassing test like BROCA would allow women to undergo a single test, Dr. Churpek said. Further, advances in technology via targeted genomic capture and next generation sequencing allow this test to be performed inexpensively using 3 mcg of peripheral blood. The current clinical approach to testing requires BRCA1 and BRCA2 testing (BRACAnalysis, Myriad) and possible further testing via a genetic panel, which can be expensive and sometimes difficult to get covered by payers, Dr. Churpek said.

She said there are no plans to market the BROCA test, however. Myriad Genetics holds the U.S. patent on the BRCA genes in the context of cancer diagnostics until 2015. The U.S. Supreme Court is considering the legal issues surrounding the gene patent in the case of Association for Molecular Pathology v. Myriad Genetics. Oral arguments in the case were heard in April, and a decision from the court is expected before July.

Dr. Churpek had no financial disclosures.

[email protected]

On Twitter @maryjodales

CHICAGO – BROCA, a genetic screening panel that combines BRCA1 and BRCA2 testing with screening for all 18 known breast cancer genes, detected at least one loss of function mutation in 56 of 249 unrelated African American women with breast cancer.

African American women are disproportionately affected by early-onset and triple-negative breast cancers, possibly because of a higher frequency of inherited mutations in DNA repair pathways. The finding of abnormalities in 22% of these women represents the first comprehensive screen of all known breast cancer susceptibility genes using next-generation sequencing in African American women, according to Dr. Jane E. Churpek, who reported the results at the annual meeting of the American Society of Clinical Oncology.

These high carrier frequencies suggest the importance of screening for all gene mutations in African American breast cancer patients who are diagnosed at a young age, have a family history, or have triple-negative breast cancer. The results should be used to encourage testing of at-risk family members to identify those who would benefit from lifesaving interventions, said Dr. Churpek of the University of Chicago.

In the 249-patient study, inherited damaging mutations were seen in 44 of 144 patients with a family history and in 12 of 145 women without a family history of breast and ovarian cancer. Of the 67 women who had triple-negative disease, 20 (30%) had mutations; in the 146 women under age 45, 67 (27%) had mutations.

"Even in the absence of triple-negative disease and family history, there are patients with gene mutations," she said.

While the majority of the 56 women with mutations were positive for BRCA1 (26 patients) or BRCA2 (20 patients), other inherited mutations detected in the BROCA panel were found in 10 patients. Those mutations included CHEK2 (n = 3), PALB2 (n = 3), ATM (n = 5), and PTEN (n = 1), she reported. The study population consisted of women who were treated at the University of Chicago cancer risk and breast cancer clinics.

Having an all-encompassing test like BROCA would allow women to undergo a single test, Dr. Churpek said. Further, advances in technology via targeted genomic capture and next generation sequencing allow this test to be performed inexpensively using 3 mcg of peripheral blood. The current clinical approach to testing requires BRCA1 and BRCA2 testing (BRACAnalysis, Myriad) and possible further testing via a genetic panel, which can be expensive and sometimes difficult to get covered by payers, Dr. Churpek said.

She said there are no plans to market the BROCA test, however. Myriad Genetics holds the U.S. patent on the BRCA genes in the context of cancer diagnostics until 2015. The U.S. Supreme Court is considering the legal issues surrounding the gene patent in the case of Association for Molecular Pathology v. Myriad Genetics. Oral arguments in the case were heard in April, and a decision from the court is expected before July.

Dr. Churpek had no financial disclosures.

[email protected]

On Twitter @maryjodales

CHICAGO – Selumetinib, an investigational MEK 1/2 inhibitor, shrank uveal melanomas in half of all treated patients, with a duration of disease control that was more than twice that achieved with the comparator therapy temozolomide, based on the final analysis of data from 98 patients in a phase II crossover study.

This is the first clinical trial to identify a drug that improves clinical outcome in patients with advanced melanoma of the eye, said Dr. Richard D. Carvajal, who presented the data at the annual meeting of the American Society of Clinical Oncology.

"Selumetinib is a new standard of therapy for uveal metastatic melanoma," he said at a press conference announcing the results. Before this study, there was no evidence that any systemic therapy was truly effective in this disease. In eight different clinical trials conducted in the last decade, 2 of 157 patients have responded to potential new therapies, including chemotherapy, targeted therapy, and immunotherapy.

“Right now, there are no plans for an official compassionate use program; however, we are reopening up our trial without the randomization such that additional patients can receive selumetinib through this mechanism,” he said in an interview after the meeting.

With about 2,000 cases diagnosed each year in the United States, uveal melanoma is an orphan disease that is biologically distinct from cutaneous melanoma. Treatment consists of surgery to remove the tumor or eye, as well as radiation therapy or chemotherapy. About half of cases metastasize, and survival for these patients is 9-12 months.

In this study, 98 patients with metastatic melanoma of the eye were randomly assigned to receive selumetinib or temozolomide (Temodar), with 48 receiving selumetinib and 50 receiving temozolomide. Based on imaging studies using RECIST (Response Evaluation Criteria in Solid Tumors), patients whose disease worsened on temozolomide were permitted to cross over to selumetinib.

Looking at the response patterns, tumors regressed in 11% (RECIST response, 0%) of 46 evaluable patients in the temozolomide arm and in 50% (RECIST response, 15%) of 46 evaluable patients in the selumetinib arm, for a highly significant hazard ratio of 0.46, reported Dr. Carvajal of Memorial Sloan-Kettering Cancer Center in New York.

Progression-free survival was improved to nearly 16 weeks for selumetinib as compared with 7 weeks for temozolomide. Overall survival was 10.8 months for selumetinib and 9.4 months with temozolomide.

More than 90% of patients in both arms of the study had metastatic liver disease and more than 50% had an elevated lactate dehydrogenase, Dr. Carvajal noted. Further, the study allowed for crossover to selumetinib by temozolomide-treated patients with no evidence of response at 4 weeks; 80% of patients in the temozolomide arm crossed over to selumetinib.

Selumetinib blocks the MEK protein, a key component of the MAPK pathway, which is activated by Gnaq and Gna11 gene mutations, found in 84% of the uveal melanoma patients in the study. Selumetinib also is being investigated for the treatment of cancers of the thyroid and lung, and trials are underway with selumetinib in combination with other drugs.

Dr. Carvajal noted that another MEK inhibitor, trametinib (Mekinist, GlaxoSmithKline), recently became the first MEK inhibitor to be approved by the Food and Drug Administration. Trametinib was approved in May 2013 as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations.

AstraZeneca is developing selumetinib under a licensing agreement with Array Biopharma.

The selumetinib study was supported in part by a Conquer Cancer Foundation of ASCO Career Development Award, the National Institutes of Health, Cycle for Survival, and the Fund for Ophthalmic Knowledge. Dr. Carvajal had no relevant financial disclosures.

[email protected]

On Twitter @maryjodales

CHICAGO – Selumetinib, an investigational MEK 1/2 inhibitor, shrank uveal melanomas in half of all treated patients, with a duration of disease control that was more than twice that achieved with the comparator therapy temozolomide, based on the final analysis of data from 98 patients in a phase II crossover study.

This is the first clinical trial to identify a drug that improves clinical outcome in patients with advanced melanoma of the eye, said Dr. Richard D. Carvajal, who presented the data at the annual meeting of the American Society of Clinical Oncology.

"Selumetinib is a new standard of therapy for uveal metastatic melanoma," he said at a press conference announcing the results. Before this study, there was no evidence that any systemic therapy was truly effective in this disease. In eight different clinical trials conducted in the last decade, 2 of 157 patients have responded to potential new therapies, including chemotherapy, targeted therapy, and immunotherapy.

“Right now, there are no plans for an official compassionate use program; however, we are reopening up our trial without the randomization such that additional patients can receive selumetinib through this mechanism,” he said in an interview after the meeting.

With about 2,000 cases diagnosed each year in the United States, uveal melanoma is an orphan disease that is biologically distinct from cutaneous melanoma. Treatment consists of surgery to remove the tumor or eye, as well as radiation therapy or chemotherapy. About half of cases metastasize, and survival for these patients is 9-12 months.

In this study, 98 patients with metastatic melanoma of the eye were randomly assigned to receive selumetinib or temozolomide (Temodar), with 48 receiving selumetinib and 50 receiving temozolomide. Based on imaging studies using RECIST (Response Evaluation Criteria in Solid Tumors), patients whose disease worsened on temozolomide were permitted to cross over to selumetinib.

Looking at the response patterns, tumors regressed in 11% (RECIST response, 0%) of 46 evaluable patients in the temozolomide arm and in 50% (RECIST response, 15%) of 46 evaluable patients in the selumetinib arm, for a highly significant hazard ratio of 0.46, reported Dr. Carvajal of Memorial Sloan-Kettering Cancer Center in New York.

Progression-free survival was improved to nearly 16 weeks for selumetinib as compared with 7 weeks for temozolomide. Overall survival was 10.8 months for selumetinib and 9.4 months with temozolomide.

More than 90% of patients in both arms of the study had metastatic liver disease and more than 50% had an elevated lactate dehydrogenase, Dr. Carvajal noted. Further, the study allowed for crossover to selumetinib by temozolomide-treated patients with no evidence of response at 4 weeks; 80% of patients in the temozolomide arm crossed over to selumetinib.

Selumetinib blocks the MEK protein, a key component of the MAPK pathway, which is activated by Gnaq and Gna11 gene mutations, found in 84% of the uveal melanoma patients in the study. Selumetinib also is being investigated for the treatment of cancers of the thyroid and lung, and trials are underway with selumetinib in combination with other drugs.

Dr. Carvajal noted that another MEK inhibitor, trametinib (Mekinist, GlaxoSmithKline), recently became the first MEK inhibitor to be approved by the Food and Drug Administration. Trametinib was approved in May 2013 as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations.

AstraZeneca is developing selumetinib under a licensing agreement with Array Biopharma.

The selumetinib study was supported in part by a Conquer Cancer Foundation of ASCO Career Development Award, the National Institutes of Health, Cycle for Survival, and the Fund for Ophthalmic Knowledge. Dr. Carvajal had no relevant financial disclosures.

[email protected]

On Twitter @maryjodales

CHICAGO – Selumetinib, an investigational MEK 1/2 inhibitor, shrank uveal melanomas in half of all treated patients, with a duration of disease control that was more than twice that achieved with the comparator therapy temozolomide, based on the final analysis of data from 98 patients in a phase II crossover study.

This is the first clinical trial to identify a drug that improves clinical outcome in patients with advanced melanoma of the eye, said Dr. Richard D. Carvajal, who presented the data at the annual meeting of the American Society of Clinical Oncology.

"Selumetinib is a new standard of therapy for uveal metastatic melanoma," he said at a press conference announcing the results. Before this study, there was no evidence that any systemic therapy was truly effective in this disease. In eight different clinical trials conducted in the last decade, 2 of 157 patients have responded to potential new therapies, including chemotherapy, targeted therapy, and immunotherapy.

“Right now, there are no plans for an official compassionate use program; however, we are reopening up our trial without the randomization such that additional patients can receive selumetinib through this mechanism,” he said in an interview after the meeting.

With about 2,000 cases diagnosed each year in the United States, uveal melanoma is an orphan disease that is biologically distinct from cutaneous melanoma. Treatment consists of surgery to remove the tumor or eye, as well as radiation therapy or chemotherapy. About half of cases metastasize, and survival for these patients is 9-12 months.

In this study, 98 patients with metastatic melanoma of the eye were randomly assigned to receive selumetinib or temozolomide (Temodar), with 48 receiving selumetinib and 50 receiving temozolomide. Based on imaging studies using RECIST (Response Evaluation Criteria in Solid Tumors), patients whose disease worsened on temozolomide were permitted to cross over to selumetinib.

Looking at the response patterns, tumors regressed in 11% (RECIST response, 0%) of 46 evaluable patients in the temozolomide arm and in 50% (RECIST response, 15%) of 46 evaluable patients in the selumetinib arm, for a highly significant hazard ratio of 0.46, reported Dr. Carvajal of Memorial Sloan-Kettering Cancer Center in New York.

Progression-free survival was improved to nearly 16 weeks for selumetinib as compared with 7 weeks for temozolomide. Overall survival was 10.8 months for selumetinib and 9.4 months with temozolomide.

More than 90% of patients in both arms of the study had metastatic liver disease and more than 50% had an elevated lactate dehydrogenase, Dr. Carvajal noted. Further, the study allowed for crossover to selumetinib by temozolomide-treated patients with no evidence of response at 4 weeks; 80% of patients in the temozolomide arm crossed over to selumetinib.

Selumetinib blocks the MEK protein, a key component of the MAPK pathway, which is activated by Gnaq and Gna11 gene mutations, found in 84% of the uveal melanoma patients in the study. Selumetinib also is being investigated for the treatment of cancers of the thyroid and lung, and trials are underway with selumetinib in combination with other drugs.

Dr. Carvajal noted that another MEK inhibitor, trametinib (Mekinist, GlaxoSmithKline), recently became the first MEK inhibitor to be approved by the Food and Drug Administration. Trametinib was approved in May 2013 as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations.

AstraZeneca is developing selumetinib under a licensing agreement with Array Biopharma.

The selumetinib study was supported in part by a Conquer Cancer Foundation of ASCO Career Development Award, the National Institutes of Health, Cycle for Survival, and the Fund for Ophthalmic Knowledge. Dr. Carvajal had no relevant financial disclosures.

[email protected]

On Twitter @maryjodales