Breast Cancer

A test that measures the number of copies of the HER2 gene in breast tumor tissue has been approved by the Food and Drug Administration, the agency announced on June 14.

If the Inform Dual ISH test is positive, then the patient is a candidate for treatment with trastuzumab, the recombinant monoclonal antibody directed against HER2 that is marketed as Herceptin by Genentech for the treatment of HER-2 overexpressing breast cancer.

The test is manufactured by Tucson, Ariz.–based Ventana Medical Systems, a member of the Roche group, as is Genentech.

"When used with other clinical information and laboratory tests, this test can provide health care professionals with additional insight on treatment decisions for patients with breast cancer," Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health, said in the statement announcing the approval.

The test makes it possible "to see and count copies of chromosome 17 and HER2 genes on the same slide, similar to HER2 amplification measurements that have traditionally only been available using fluorescence microscopes," the statement said. But the new test, "allows lab staff to see the HER2 and chromosome 17 signals directly under a microscope, for longer periods of time."

Approval is based on a study conducted in the United States that evaluated the test in 510 women with breast cancer. The test confirmed that the tumor sample contained more than the normal number of copies of the HER-2 gene, located on chromosome 17, in 96% of the HER-2 positive samples, according to the statement.

The test also excluded the possibility that an excessive number of HER2 genes was present in 92.3% of the HER2-negative samples.

About 20% of women diagnosed with breast cancer are HER2-positive, according to the FDA.

A test that measures the number of copies of the HER2 gene in breast tumor tissue has been approved by the Food and Drug Administration, the agency announced on June 14.

If the Inform Dual ISH test is positive, then the patient is a candidate for treatment with trastuzumab, the recombinant monoclonal antibody directed against HER2 that is marketed as Herceptin by Genentech for the treatment of HER-2 overexpressing breast cancer.

The test is manufactured by Tucson, Ariz.–based Ventana Medical Systems, a member of the Roche group, as is Genentech.

"When used with other clinical information and laboratory tests, this test can provide health care professionals with additional insight on treatment decisions for patients with breast cancer," Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health, said in the statement announcing the approval.

The test makes it possible "to see and count copies of chromosome 17 and HER2 genes on the same slide, similar to HER2 amplification measurements that have traditionally only been available using fluorescence microscopes," the statement said. But the new test, "allows lab staff to see the HER2 and chromosome 17 signals directly under a microscope, for longer periods of time."

Approval is based on a study conducted in the United States that evaluated the test in 510 women with breast cancer. The test confirmed that the tumor sample contained more than the normal number of copies of the HER-2 gene, located on chromosome 17, in 96% of the HER-2 positive samples, according to the statement.

The test also excluded the possibility that an excessive number of HER2 genes was present in 92.3% of the HER2-negative samples.

About 20% of women diagnosed with breast cancer are HER2-positive, according to the FDA.

A test that measures the number of copies of the HER2 gene in breast tumor tissue has been approved by the Food and Drug Administration, the agency announced on June 14.

If the Inform Dual ISH test is positive, then the patient is a candidate for treatment with trastuzumab, the recombinant monoclonal antibody directed against HER2 that is marketed as Herceptin by Genentech for the treatment of HER-2 overexpressing breast cancer.

The test is manufactured by Tucson, Ariz.–based Ventana Medical Systems, a member of the Roche group, as is Genentech.

"When used with other clinical information and laboratory tests, this test can provide health care professionals with additional insight on treatment decisions for patients with breast cancer," Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health, said in the statement announcing the approval.

The test makes it possible "to see and count copies of chromosome 17 and HER2 genes on the same slide, similar to HER2 amplification measurements that have traditionally only been available using fluorescence microscopes," the statement said. But the new test, "allows lab staff to see the HER2 and chromosome 17 signals directly under a microscope, for longer periods of time."

Approval is based on a study conducted in the United States that evaluated the test in 510 women with breast cancer. The test confirmed that the tumor sample contained more than the normal number of copies of the HER-2 gene, located on chromosome 17, in 96% of the HER-2 positive samples, according to the statement.

The test also excluded the possibility that an excessive number of HER2 genes was present in 92.3% of the HER2-negative samples.

About 20% of women diagnosed with breast cancer are HER2-positive, according to the FDA.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Adding bevacizumab to chemotherapy may prolong survival in women with newly diagnosed ovarian, primary peritoneal, or fallopian tube cancer who are at high risk for poor outcomes, suggests an interim analysis from the randomized phase III ICON7 trial.

Trials results, reported at a median follow-up of 28 months, showed that when this antiangiogenic agent was added during and after chemotherapy, the risk of death was reduced by a significant 36% among high-risk patients. There was a nonsignificant 15% risk reduction among the study population as a whole.

"Bevacizumab is the first new active agent for the front-line treatment of ovarian cancer in more than 15 years," lead investigator Dr. Gunnar Kristensen said in a press briefing.

"Based on this interim analysis ... we see there is an overall trend for improvement of overall survival with bevacizumab," he said. "The treatment effect is greater in high-risk patients, which may be of clinical relevance."

Indeed, Dr. Kristensen acknowledged, cost considerations and lack of substantial survival benefit in patients who are not at high risk may ultimately guide use of bevacizumab in this context.

"Here we present our data, and then of course it is up to the doctors how they will use the drug," he said. "Personally, I ... [agree] on restricting it to the high-risk group."

The trial differs from the OCEANS trial, also reported at the meeting, in the dose and duration of bevacizumab used, and the patient population, noted moderator Dr. Andrew Seidman, an attending physician for the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center and professor of medicine at Weill Cornell Medical College, both in New York.

"However, the consistent results of these studies, in addition to a previously reported trial, the GOG-0218 trial, and the already documented efficacy of bevacizumab as a single agent in ovarian cancer, I think do all lend support to a potentially important role for bevacizumab as the first biologic agent to be used in this disease," he said.

The investigators conducted the trial among 1,528 women with newly diagnosed, high-risk early or advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. All underwent debulking surgery.

The patients were assigned in nearly equal numbers to receive six cycles of standard chemotherapy (carboplatin and paclitaxel) at 3-week intervals alone, or the same chemotherapy given concurrently with bevacizumab (Avastin, 7.5 mg/kg) followed by single-agent bevacizumab every 3 weeks for 12 additional cycles or until progression.

"This treatment was tolerated well, without a substantial increase in side effects," Dr. Kristensen reported. "The side effects were mild and manageable."

The mature progression-free survival results, previously reported at the 2010 European Society for Medical Oncology meeting, showed that the median duration of progression-free survival was 19.0 months with bevacizumab and 17.3 months without it (hazard ratio, 0.81; P = .004).

U.S. and European regulatory authorities requested an interim analysis of overall survival, in support of applications to license the drug for this indication, according to Dr. Kristensen, a senior consultant in the department for gynecologic oncology at Norwegian Radium Hospital in Oslo.

The interim analysis of overall survival, which was based on 53% of the number of events needed for the final analysis, showed that the risk of death in the entire trial population was lower with bevacizumab than without it, but not significantly so (hazard ratio, 0.85; P = .11).

However, in a preplanned subgroup analysis among the 30% of patients falling into a high-risk category – those with stage III disease whose debulking surgery was suboptimal (leaving more than 1 cm of residual tumor) and those with stage IV disease – there was a significant 36% reduction in the risk of death (hazard ratio, 0.64; P = .002). In this subgroup, the median duration of survival was 7.8 months longer with bevacizumab (36.6 vs. 28.8 months).

Final overall survival results are expected in 2013, according to Dr. Kristensen. "We have to remember that the data [are] premature. It’s an interim analysis. There are very few events in this group of patients" not at high risk, he cautioned when presenting the results in a session. "So we have to await the final analysis in 2 years before we can make conclusions about this group."

The reason for the apparent greater benefit in the high-risk group is as yet unclear, he said, while agreeing with an attendee that tumors that are more difficult to optimally debulk may be more aggressive and more susceptible to antiangiogenic therapy.

"We have just used clinical parameters here, whether they were optimally debulked or not, and we see that we have the main effect in the suboptimally debulked population. Then come all the questions about the biology," he commented. "We have an ancillary research program along with the study, but it will, of course, take time."

In the updated analysis of progression-free survival, the median duration of progression-free survival in the entire trial population continued to be better with bevacizumab, at 19.8 months, than without it, at 17.4 months (hazard ratio, 0.87; P = .039).

Dr. Kristensen reported that he is a consultant to Roche. Dr. Seidman reported being a consultant to Enzon and Wyeth; receiving honoraria from Abraxis BioScience, Genentech, and Genomic Health; and receiving research funding from Abraxis BioScience.

CHICAGO – Adding bevacizumab to chemotherapy may prolong survival in women with newly diagnosed ovarian, primary peritoneal, or fallopian tube cancer who are at high risk for poor outcomes, suggests an interim analysis from the randomized phase III ICON7 trial.

Trials results, reported at a median follow-up of 28 months, showed that when this antiangiogenic agent was added during and after chemotherapy, the risk of death was reduced by a significant 36% among high-risk patients. There was a nonsignificant 15% risk reduction among the study population as a whole.

"Bevacizumab is the first new active agent for the front-line treatment of ovarian cancer in more than 15 years," lead investigator Dr. Gunnar Kristensen said in a press briefing.

"Based on this interim analysis ... we see there is an overall trend for improvement of overall survival with bevacizumab," he said. "The treatment effect is greater in high-risk patients, which may be of clinical relevance."

Indeed, Dr. Kristensen acknowledged, cost considerations and lack of substantial survival benefit in patients who are not at high risk may ultimately guide use of bevacizumab in this context.

"Here we present our data, and then of course it is up to the doctors how they will use the drug," he said. "Personally, I ... [agree] on restricting it to the high-risk group."

The trial differs from the OCEANS trial, also reported at the meeting, in the dose and duration of bevacizumab used, and the patient population, noted moderator Dr. Andrew Seidman, an attending physician for the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center and professor of medicine at Weill Cornell Medical College, both in New York.

"However, the consistent results of these studies, in addition to a previously reported trial, the GOG-0218 trial, and the already documented efficacy of bevacizumab as a single agent in ovarian cancer, I think do all lend support to a potentially important role for bevacizumab as the first biologic agent to be used in this disease," he said.

The investigators conducted the trial among 1,528 women with newly diagnosed, high-risk early or advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. All underwent debulking surgery.

The patients were assigned in nearly equal numbers to receive six cycles of standard chemotherapy (carboplatin and paclitaxel) at 3-week intervals alone, or the same chemotherapy given concurrently with bevacizumab (Avastin, 7.5 mg/kg) followed by single-agent bevacizumab every 3 weeks for 12 additional cycles or until progression.

"This treatment was tolerated well, without a substantial increase in side effects," Dr. Kristensen reported. "The side effects were mild and manageable."

The mature progression-free survival results, previously reported at the 2010 European Society for Medical Oncology meeting, showed that the median duration of progression-free survival was 19.0 months with bevacizumab and 17.3 months without it (hazard ratio, 0.81; P = .004).

U.S. and European regulatory authorities requested an interim analysis of overall survival, in support of applications to license the drug for this indication, according to Dr. Kristensen, a senior consultant in the department for gynecologic oncology at Norwegian Radium Hospital in Oslo.

The interim analysis of overall survival, which was based on 53% of the number of events needed for the final analysis, showed that the risk of death in the entire trial population was lower with bevacizumab than without it, but not significantly so (hazard ratio, 0.85; P = .11).

However, in a preplanned subgroup analysis among the 30% of patients falling into a high-risk category – those with stage III disease whose debulking surgery was suboptimal (leaving more than 1 cm of residual tumor) and those with stage IV disease – there was a significant 36% reduction in the risk of death (hazard ratio, 0.64; P = .002). In this subgroup, the median duration of survival was 7.8 months longer with bevacizumab (36.6 vs. 28.8 months).

Final overall survival results are expected in 2013, according to Dr. Kristensen. "We have to remember that the data [are] premature. It’s an interim analysis. There are very few events in this group of patients" not at high risk, he cautioned when presenting the results in a session. "So we have to await the final analysis in 2 years before we can make conclusions about this group."

The reason for the apparent greater benefit in the high-risk group is as yet unclear, he said, while agreeing with an attendee that tumors that are more difficult to optimally debulk may be more aggressive and more susceptible to antiangiogenic therapy.

"We have just used clinical parameters here, whether they were optimally debulked or not, and we see that we have the main effect in the suboptimally debulked population. Then come all the questions about the biology," he commented. "We have an ancillary research program along with the study, but it will, of course, take time."

In the updated analysis of progression-free survival, the median duration of progression-free survival in the entire trial population continued to be better with bevacizumab, at 19.8 months, than without it, at 17.4 months (hazard ratio, 0.87; P = .039).

Dr. Kristensen reported that he is a consultant to Roche. Dr. Seidman reported being a consultant to Enzon and Wyeth; receiving honoraria from Abraxis BioScience, Genentech, and Genomic Health; and receiving research funding from Abraxis BioScience.

CHICAGO – Adding bevacizumab to chemotherapy may prolong survival in women with newly diagnosed ovarian, primary peritoneal, or fallopian tube cancer who are at high risk for poor outcomes, suggests an interim analysis from the randomized phase III ICON7 trial.

Trials results, reported at a median follow-up of 28 months, showed that when this antiangiogenic agent was added during and after chemotherapy, the risk of death was reduced by a significant 36% among high-risk patients. There was a nonsignificant 15% risk reduction among the study population as a whole.

"Bevacizumab is the first new active agent for the front-line treatment of ovarian cancer in more than 15 years," lead investigator Dr. Gunnar Kristensen said in a press briefing.

"Based on this interim analysis ... we see there is an overall trend for improvement of overall survival with bevacizumab," he said. "The treatment effect is greater in high-risk patients, which may be of clinical relevance."

Indeed, Dr. Kristensen acknowledged, cost considerations and lack of substantial survival benefit in patients who are not at high risk may ultimately guide use of bevacizumab in this context.

"Here we present our data, and then of course it is up to the doctors how they will use the drug," he said. "Personally, I ... [agree] on restricting it to the high-risk group."

The trial differs from the OCEANS trial, also reported at the meeting, in the dose and duration of bevacizumab used, and the patient population, noted moderator Dr. Andrew Seidman, an attending physician for the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center and professor of medicine at Weill Cornell Medical College, both in New York.

"However, the consistent results of these studies, in addition to a previously reported trial, the GOG-0218 trial, and the already documented efficacy of bevacizumab as a single agent in ovarian cancer, I think do all lend support to a potentially important role for bevacizumab as the first biologic agent to be used in this disease," he said.

The investigators conducted the trial among 1,528 women with newly diagnosed, high-risk early or advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. All underwent debulking surgery.

The patients were assigned in nearly equal numbers to receive six cycles of standard chemotherapy (carboplatin and paclitaxel) at 3-week intervals alone, or the same chemotherapy given concurrently with bevacizumab (Avastin, 7.5 mg/kg) followed by single-agent bevacizumab every 3 weeks for 12 additional cycles or until progression.

"This treatment was tolerated well, without a substantial increase in side effects," Dr. Kristensen reported. "The side effects were mild and manageable."

The mature progression-free survival results, previously reported at the 2010 European Society for Medical Oncology meeting, showed that the median duration of progression-free survival was 19.0 months with bevacizumab and 17.3 months without it (hazard ratio, 0.81; P = .004).

U.S. and European regulatory authorities requested an interim analysis of overall survival, in support of applications to license the drug for this indication, according to Dr. Kristensen, a senior consultant in the department for gynecologic oncology at Norwegian Radium Hospital in Oslo.

The interim analysis of overall survival, which was based on 53% of the number of events needed for the final analysis, showed that the risk of death in the entire trial population was lower with bevacizumab than without it, but not significantly so (hazard ratio, 0.85; P = .11).

However, in a preplanned subgroup analysis among the 30% of patients falling into a high-risk category – those with stage III disease whose debulking surgery was suboptimal (leaving more than 1 cm of residual tumor) and those with stage IV disease – there was a significant 36% reduction in the risk of death (hazard ratio, 0.64; P = .002). In this subgroup, the median duration of survival was 7.8 months longer with bevacizumab (36.6 vs. 28.8 months).

Final overall survival results are expected in 2013, according to Dr. Kristensen. "We have to remember that the data [are] premature. It’s an interim analysis. There are very few events in this group of patients" not at high risk, he cautioned when presenting the results in a session. "So we have to await the final analysis in 2 years before we can make conclusions about this group."

The reason for the apparent greater benefit in the high-risk group is as yet unclear, he said, while agreeing with an attendee that tumors that are more difficult to optimally debulk may be more aggressive and more susceptible to antiangiogenic therapy.

"We have just used clinical parameters here, whether they were optimally debulked or not, and we see that we have the main effect in the suboptimally debulked population. Then come all the questions about the biology," he commented. "We have an ancillary research program along with the study, but it will, of course, take time."

In the updated analysis of progression-free survival, the median duration of progression-free survival in the entire trial population continued to be better with bevacizumab, at 19.8 months, than without it, at 17.4 months (hazard ratio, 0.87; P = .039).

Dr. Kristensen reported that he is a consultant to Roche. Dr. Seidman reported being a consultant to Enzon and Wyeth; receiving honoraria from Abraxis BioScience, Genentech, and Genomic Health; and receiving research funding from Abraxis BioScience.

CHICAGO - A daily dose of the aromatase inhibitor exemestane reduced invasive breast cancers by 65% in a placebo-controlled chemoprevention trial that enrolled 4,560 postmenopausal women considered at increased risk of the disease.

Pre-invasive breast cancers and precancerous lesions also were much less common at a median follow-up of 3 years in the study, which is expected to reopen a stalled conversation between women and their physicians regarding the risks and benefits of chemoprevention.

Two selective estrogen receptor modulator (SERM) drugs – tamoxifen and raloxifene (Evista) – are approved for breast cancer prevention, but they are little used for that purpose. Estimated tamoxifen use runs as low as 4% in high-risk women, who are thought to be deterred by rare but potentially serious side effects.

Exemestane (Aromasin) could become a third option for breast cancer prevention in postmenopausal women, Paul E. Goss, M.D., Ph.D., the lead author, said, announcing the results on behalf of the MAP.3 (Mammary Prevention.3 trial) investigators at the annual meeting of the American Society of Clinical Oncology.

"Because of the significant reduction of breast cancer and the excellent safety profile, exemestane has the potential for wider-scale implementation than the selective estrogen modulators in our view," declared Dr. Goss, a professor of medicine at Harvard Medical School and Massachusetts General Hospital in Boston.

Women had to be age 35 or older and postmenopausal with at least one specified risk factor to enter the trial, he noted. Age greater than or equal to 60 years by itself was considered a risk factor, as were a five-year Gail risk score greater than 1.66%, prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ, or prior ductal carcinoma in situ with prior mastectomy.

Dr. Goss stressed that the results should not be extrapolated to premenopausal women or others who do not meet the trial’s eligibility criteria.

The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) led the study, which enrolled women in Canada, the United States, Spain, and France. The findings at a median follow-up of 35 months were published online by the New England Journal of Medicine (2011 June 4;doi:10.1056/NEJMoa1103507) simultaneously with a press briefing at ASCO. These included:

• A 65% relative reduction in annual incidence of invasive breast cancer, based on 11 breast cancers among 2,285 women in the exemestane arm vs. 32 among 2,275 in the placebo arm. The annual incidence was 0.19% vs. 0.55%, respectively (hazard ratio 0.35, P = .002).

• Annual incidence of invasive plus noninvasive (DCIS) breast cancers of 0.35% with exemestane vs. 0.77% with placebo (HR 0.35, P =.004).

Most cancers in both arms of the trial were estrogen receptor-positive, HER2/neu–negative, and node-negative. The investigators said exemestane was superior in all subgroup studies. They said that the number needed to prevent one case of breast cancer would be 94 at 3 years but projected that it would drop to 26 at 5 years.

Physicians – for the most part, those in primary care, as oncologists are not likely to see women who do not have cancer – need to discuss risks and benefits of the three chemoprevention drugs with their patients, stressed Dr. Goss and Dr. Andrew Seidman, moderator of the press briefing. The three agents have different side effect profiles, they noted.

Dr. Seidman, a breast specialist at Memorial Sloan-Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College in New York, credited "heightened fear of endometrial cancers and thrombotic clotting risks" for the sparse use of SERMs as chemoprevention.

Although 88% of women on exemestane and 85% of those on placebo experienced adverse events in the MAP.3 study, none were life-threatening, and the investigators reported that serious events such as skeletal fractures, cardiovascular events, other cancers, and treatment-related deaths were not significantly different between the two groups. Hot flashes and arthritis were more common with exemestane.

Quality of life differences were minimal, they said, characterizing the dropout rates and noncompliance rates as unexceptional for chemoprevention trials. Indeed, the benefits of exemestane were probably higher in women who stuck with the protocol, Dr. Goss said; the intent-to-treat analysis included women who dropped out early in the trial.

"One of the elephants in the kitchen is prophylactic bilateral mastectomy," added Dr. Seidman. He described himself as "always chagrined" at how some women are more willing to undergo "body-altering surgery" than to try chemoprevention.

The Map.3 study randomized women to 25 mg of exemestane or placebo daily. Initially, the study had a third arm in which celecoxib was added to exemestane, but it was dropped because of concerns for "cardiovascular safety" with celecoxib.

Dr. Goss said the investigators plan to look for clearer data on how to define which women are high-risk and would benefit from exemestane. They also will be looking for biomarkers that can show how well a woman does while on chemoprevention: something comparable to measures used when patients take anti-hypertensives or cholesterol-lowering drugs.

Another unknown is whether Pfizer, Inc. will seek a chemoprevention indication for exemestane. Aromasin lost patent protection in the United States in Apri, and will lose it in Europe in July, according to company spokesman Christopher Loder. "We cannot comment on our regulatory plans at this time," he said in a hallway interview at the convention center where ASCO is being held.

Loss of exclusivity is likely to mean lower prices for Aromasin, which could make Pfizer less inclined to invest in applications for the indication. Whether insurance companies would pay for chemoprevention use without an indication is also a question – but price might not be a barrier.

Pfizer helped pay for the trial. Dr. Goss and several of his coauthors received honoraria and research funding from Pfizer, as well as other companies.

CHICAGO - A daily dose of the aromatase inhibitor exemestane reduced invasive breast cancers by 65% in a placebo-controlled chemoprevention trial that enrolled 4,560 postmenopausal women considered at increased risk of the disease.

Pre-invasive breast cancers and precancerous lesions also were much less common at a median follow-up of 3 years in the study, which is expected to reopen a stalled conversation between women and their physicians regarding the risks and benefits of chemoprevention.

Two selective estrogen receptor modulator (SERM) drugs – tamoxifen and raloxifene (Evista) – are approved for breast cancer prevention, but they are little used for that purpose. Estimated tamoxifen use runs as low as 4% in high-risk women, who are thought to be deterred by rare but potentially serious side effects.

Exemestane (Aromasin) could become a third option for breast cancer prevention in postmenopausal women, Paul E. Goss, M.D., Ph.D., the lead author, said, announcing the results on behalf of the MAP.3 (Mammary Prevention.3 trial) investigators at the annual meeting of the American Society of Clinical Oncology.

"Because of the significant reduction of breast cancer and the excellent safety profile, exemestane has the potential for wider-scale implementation than the selective estrogen modulators in our view," declared Dr. Goss, a professor of medicine at Harvard Medical School and Massachusetts General Hospital in Boston.

Women had to be age 35 or older and postmenopausal with at least one specified risk factor to enter the trial, he noted. Age greater than or equal to 60 years by itself was considered a risk factor, as were a five-year Gail risk score greater than 1.66%, prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ, or prior ductal carcinoma in situ with prior mastectomy.

Dr. Goss stressed that the results should not be extrapolated to premenopausal women or others who do not meet the trial’s eligibility criteria.

The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) led the study, which enrolled women in Canada, the United States, Spain, and France. The findings at a median follow-up of 35 months were published online by the New England Journal of Medicine (2011 June 4;doi:10.1056/NEJMoa1103507) simultaneously with a press briefing at ASCO. These included:

• A 65% relative reduction in annual incidence of invasive breast cancer, based on 11 breast cancers among 2,285 women in the exemestane arm vs. 32 among 2,275 in the placebo arm. The annual incidence was 0.19% vs. 0.55%, respectively (hazard ratio 0.35, P = .002).

• Annual incidence of invasive plus noninvasive (DCIS) breast cancers of 0.35% with exemestane vs. 0.77% with placebo (HR 0.35, P =.004).

Most cancers in both arms of the trial were estrogen receptor-positive, HER2/neu–negative, and node-negative. The investigators said exemestane was superior in all subgroup studies. They said that the number needed to prevent one case of breast cancer would be 94 at 3 years but projected that it would drop to 26 at 5 years.

Physicians – for the most part, those in primary care, as oncologists are not likely to see women who do not have cancer – need to discuss risks and benefits of the three chemoprevention drugs with their patients, stressed Dr. Goss and Dr. Andrew Seidman, moderator of the press briefing. The three agents have different side effect profiles, they noted.

Dr. Seidman, a breast specialist at Memorial Sloan-Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College in New York, credited "heightened fear of endometrial cancers and thrombotic clotting risks" for the sparse use of SERMs as chemoprevention.

Although 88% of women on exemestane and 85% of those on placebo experienced adverse events in the MAP.3 study, none were life-threatening, and the investigators reported that serious events such as skeletal fractures, cardiovascular events, other cancers, and treatment-related deaths were not significantly different between the two groups. Hot flashes and arthritis were more common with exemestane.

Quality of life differences were minimal, they said, characterizing the dropout rates and noncompliance rates as unexceptional for chemoprevention trials. Indeed, the benefits of exemestane were probably higher in women who stuck with the protocol, Dr. Goss said; the intent-to-treat analysis included women who dropped out early in the trial.

"One of the elephants in the kitchen is prophylactic bilateral mastectomy," added Dr. Seidman. He described himself as "always chagrined" at how some women are more willing to undergo "body-altering surgery" than to try chemoprevention.

The Map.3 study randomized women to 25 mg of exemestane or placebo daily. Initially, the study had a third arm in which celecoxib was added to exemestane, but it was dropped because of concerns for "cardiovascular safety" with celecoxib.

Dr. Goss said the investigators plan to look for clearer data on how to define which women are high-risk and would benefit from exemestane. They also will be looking for biomarkers that can show how well a woman does while on chemoprevention: something comparable to measures used when patients take anti-hypertensives or cholesterol-lowering drugs.

Another unknown is whether Pfizer, Inc. will seek a chemoprevention indication for exemestane. Aromasin lost patent protection in the United States in Apri, and will lose it in Europe in July, according to company spokesman Christopher Loder. "We cannot comment on our regulatory plans at this time," he said in a hallway interview at the convention center where ASCO is being held.

Loss of exclusivity is likely to mean lower prices for Aromasin, which could make Pfizer less inclined to invest in applications for the indication. Whether insurance companies would pay for chemoprevention use without an indication is also a question – but price might not be a barrier.

Pfizer helped pay for the trial. Dr. Goss and several of his coauthors received honoraria and research funding from Pfizer, as well as other companies.

CHICAGO - A daily dose of the aromatase inhibitor exemestane reduced invasive breast cancers by 65% in a placebo-controlled chemoprevention trial that enrolled 4,560 postmenopausal women considered at increased risk of the disease.

Pre-invasive breast cancers and precancerous lesions also were much less common at a median follow-up of 3 years in the study, which is expected to reopen a stalled conversation between women and their physicians regarding the risks and benefits of chemoprevention.

Two selective estrogen receptor modulator (SERM) drugs – tamoxifen and raloxifene (Evista) – are approved for breast cancer prevention, but they are little used for that purpose. Estimated tamoxifen use runs as low as 4% in high-risk women, who are thought to be deterred by rare but potentially serious side effects.

Exemestane (Aromasin) could become a third option for breast cancer prevention in postmenopausal women, Paul E. Goss, M.D., Ph.D., the lead author, said, announcing the results on behalf of the MAP.3 (Mammary Prevention.3 trial) investigators at the annual meeting of the American Society of Clinical Oncology.

"Because of the significant reduction of breast cancer and the excellent safety profile, exemestane has the potential for wider-scale implementation than the selective estrogen modulators in our view," declared Dr. Goss, a professor of medicine at Harvard Medical School and Massachusetts General Hospital in Boston.

Women had to be age 35 or older and postmenopausal with at least one specified risk factor to enter the trial, he noted. Age greater than or equal to 60 years by itself was considered a risk factor, as were a five-year Gail risk score greater than 1.66%, prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ, or prior ductal carcinoma in situ with prior mastectomy.

Dr. Goss stressed that the results should not be extrapolated to premenopausal women or others who do not meet the trial’s eligibility criteria.

The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) led the study, which enrolled women in Canada, the United States, Spain, and France. The findings at a median follow-up of 35 months were published online by the New England Journal of Medicine (2011 June 4;doi:10.1056/NEJMoa1103507) simultaneously with a press briefing at ASCO. These included:

• A 65% relative reduction in annual incidence of invasive breast cancer, based on 11 breast cancers among 2,285 women in the exemestane arm vs. 32 among 2,275 in the placebo arm. The annual incidence was 0.19% vs. 0.55%, respectively (hazard ratio 0.35, P = .002).

• Annual incidence of invasive plus noninvasive (DCIS) breast cancers of 0.35% with exemestane vs. 0.77% with placebo (HR 0.35, P =.004).

Most cancers in both arms of the trial were estrogen receptor-positive, HER2/neu–negative, and node-negative. The investigators said exemestane was superior in all subgroup studies. They said that the number needed to prevent one case of breast cancer would be 94 at 3 years but projected that it would drop to 26 at 5 years.

Physicians – for the most part, those in primary care, as oncologists are not likely to see women who do not have cancer – need to discuss risks and benefits of the three chemoprevention drugs with their patients, stressed Dr. Goss and Dr. Andrew Seidman, moderator of the press briefing. The three agents have different side effect profiles, they noted.

Dr. Seidman, a breast specialist at Memorial Sloan-Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College in New York, credited "heightened fear of endometrial cancers and thrombotic clotting risks" for the sparse use of SERMs as chemoprevention.

Although 88% of women on exemestane and 85% of those on placebo experienced adverse events in the MAP.3 study, none were life-threatening, and the investigators reported that serious events such as skeletal fractures, cardiovascular events, other cancers, and treatment-related deaths were not significantly different between the two groups. Hot flashes and arthritis were more common with exemestane.

Quality of life differences were minimal, they said, characterizing the dropout rates and noncompliance rates as unexceptional for chemoprevention trials. Indeed, the benefits of exemestane were probably higher in women who stuck with the protocol, Dr. Goss said; the intent-to-treat analysis included women who dropped out early in the trial.

"One of the elephants in the kitchen is prophylactic bilateral mastectomy," added Dr. Seidman. He described himself as "always chagrined" at how some women are more willing to undergo "body-altering surgery" than to try chemoprevention.

The Map.3 study randomized women to 25 mg of exemestane or placebo daily. Initially, the study had a third arm in which celecoxib was added to exemestane, but it was dropped because of concerns for "cardiovascular safety" with celecoxib.

Dr. Goss said the investigators plan to look for clearer data on how to define which women are high-risk and would benefit from exemestane. They also will be looking for biomarkers that can show how well a woman does while on chemoprevention: something comparable to measures used when patients take anti-hypertensives or cholesterol-lowering drugs.

Another unknown is whether Pfizer, Inc. will seek a chemoprevention indication for exemestane. Aromasin lost patent protection in the United States in Apri, and will lose it in Europe in July, according to company spokesman Christopher Loder. "We cannot comment on our regulatory plans at this time," he said in a hallway interview at the convention center where ASCO is being held.

Loss of exclusivity is likely to mean lower prices for Aromasin, which could make Pfizer less inclined to invest in applications for the indication. Whether insurance companies would pay for chemoprevention use without an indication is also a question – but price might not be a barrier.

Pfizer helped pay for the trial. Dr. Goss and several of his coauthors received honoraria and research funding from Pfizer, as well as other companies.

CHICAGO - A daily dose of the aromatase inhibitor exemestane reduced invasive breast cancers by 65% in a placebo-controlled chemoprevention trial that enrolled 4,560 postmenopausal women considered at increased risk of the disease.

Pre-invasive breast cancers and precancerous lesions also were much less common at a median follow-up of 3 years in the study, which is expected to reopen a stalled conversation between women and their physicians regarding the risks and benefits of chemoprevention.

Two selective estrogen receptor modulator (SERM) drugs – tamoxifen and raloxifene (Evista) – are approved for breast cancer prevention, but they are little used for that purpose. Estimated tamoxifen use runs as low as 4% in high-risk women, who are thought to be deterred by rare but potentially serious side effects.

Exemestane (Aromasin) could become a third option for breast cancer prevention in postmenopausal women, Paul E. Goss, M.D., Ph.D., the lead author, said, announcing the results on behalf of the MAP.3 (Mammary Prevention.3 trial) investigators at the annual meeting of the American Society of Clinical Oncology.

"Because of the significant reduction of breast cancer and the excellent safety profile, exemestane has the potential for wider-scale implementation than the selective estrogen modulators in our view," declared Dr. Goss, a professor of medicine at Harvard Medical School and Massachusetts General Hospital in Boston.

Women had to be age 35 or older and postmenopausal with at least one specified risk factor to enter the trial, he noted. Age greater than or equal to 60 years by itself was considered a risk factor, as were a five-year Gail risk score greater than 1.66%, prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ, or prior ductal carcinoma in situ with prior mastectomy.

Dr. Goss stressed that the results should not be extrapolated to premenopausal women or others who do not meet the trial’s eligibility criteria.

The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) led the study, which enrolled women in Canada, the United States, Spain, and France. The findings at a median follow-up of 35 months were published online by the New England Journal of Medicine (10.1056/NEJMoa1103507) simultaneously with a press briefing at ASCO. These included:

• A 65% relative reduction in annual incidence of invasive breast cancer, based on 11 breast cancers among 2,285 women in the exemestane arm vs. 32 among 2,275 in the placebo arm. The annual incidence was 0.19% vs. 0.55%, respectively (hazard ratio 0.35, P = .002).

• Annual incidence of invasive plus noninvasive (DCIS) breast cancers of 0.35% with exemestane vs. 0.77% with placebo (HR 0.35, P =.004).

Most cancers in both arms of the trial were estrogen receptor-positive, HER2/neu–negative, and node-negative. The investigators said exemestane was superior in all subgroup studies. They said that the number needed to prevent one case of breast cancer would be 94 at 3 years but projected that it would drop to 26 at 5 years.

Physicians – for the most part, those in primary care, as oncologists are not likely to see women who do not have cancer – need to discuss risks and benefits of the three chemoprevention drugs with their patients, stressed Dr. Goss and Dr. Andrew Seidman, moderator of the press briefing. The three agents have different side effect profiles, they noted.

Dr. Seidman, a breast specialist at Memorial Sloan-Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College in New York, credited "heightened fear of endometrial cancers and thrombotic clotting risks" for the sparse use of SERMs as chemoprevention.

Although 88% of women on exemestane and 85% of those on placebo experienced adverse events in the MAP.3 study, none were life-threatening, and the investigators reported that serious events such as skeletal fractures, cardiovascular events, other cancers, and treatment-related deaths were not significantly different between the two groups. Hot flashes and arthritis were more common with exemestane.

Quality of life differences were minimal, they said, characterizing the dropout rates and noncompliance rates as unexceptional for chemoprevention trials. Indeed, the benefits of exemestane were probably higher in women who stuck with the protocol, Dr. Goss said; the intent-to-treat analysis included women who dropped out early in the trial.

"One of the elephants in the kitchen is prophylactic bilateral mastectomy," added Dr. Seidman. He described himself as "always chagrined" at how some women are more willing to undergo "body-altering surgery" than to try chemoprevention.

The Map.3 study randomized women to 25 mg of exemestane or placebo daily. Initially, the study had a third arm in which celecoxib was added to exemestane, but it was dropped because of concerns for "cardiovascular safety" with celecoxib.

Dr. Goss said the investigators plan to look for clearer data on how to define which women are high-risk and would benefit from exemestane. They also will be looking for biomarkers that can show how well a woman does while on chemoprevention: something comparable to measures used when patients take anti-hypertensives or cholesterol-lowering drugs.

Another unknown is whether Pfizer, Inc. will seek a chemoprevention indication for exemestane. Aromasin lost patent protection in the United States in Apri, and will lose it in Europe in July, according to company spokesman Christopher Loder. "We cannot comment on our regulatory plans at this time," he said in a hallway interview at the convention center where ASCO is being held.

Loss of exclusivity is likely to mean lower prices for Aromasin, which could make Pfizer less inclined to invest in applications for the indication. Whether insurance companies would pay for chemoprevention use without an indication is also a question – but price might not be a barrier.

Pfizer helped pay for the trial. Dr. Goss and several of his coauthors received honoraria and research funding from Pfizer, as well as other companies. Dr. Davidson and Dr. Kensler disclosed no relevant conflicts of interest.

CHICAGO - A daily dose of the aromatase inhibitor exemestane reduced invasive breast cancers by 65% in a placebo-controlled chemoprevention trial that enrolled 4,560 postmenopausal women considered at increased risk of the disease.

Pre-invasive breast cancers and precancerous lesions also were much less common at a median follow-up of 3 years in the study, which is expected to reopen a stalled conversation between women and their physicians regarding the risks and benefits of chemoprevention.

Two selective estrogen receptor modulator (SERM) drugs – tamoxifen and raloxifene (Evista) – are approved for breast cancer prevention, but they are little used for that purpose. Estimated tamoxifen use runs as low as 4% in high-risk women, who are thought to be deterred by rare but potentially serious side effects.

Exemestane (Aromasin) could become a third option for breast cancer prevention in postmenopausal women, Paul E. Goss, M.D., Ph.D., the lead author, said, announcing the results on behalf of the MAP.3 (Mammary Prevention.3 trial) investigators at the annual meeting of the American Society of Clinical Oncology.

"Because of the significant reduction of breast cancer and the excellent safety profile, exemestane has the potential for wider-scale implementation than the selective estrogen modulators in our view," declared Dr. Goss, a professor of medicine at Harvard Medical School and Massachusetts General Hospital in Boston.

Women had to be age 35 or older and postmenopausal with at least one specified risk factor to enter the trial, he noted. Age greater than or equal to 60 years by itself was considered a risk factor, as were a five-year Gail risk score greater than 1.66%, prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ, or prior ductal carcinoma in situ with prior mastectomy.

Dr. Goss stressed that the results should not be extrapolated to premenopausal women or others who do not meet the trial’s eligibility criteria.

The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) led the study, which enrolled women in Canada, the United States, Spain, and France. The findings at a median follow-up of 35 months were published online by the New England Journal of Medicine (10.1056/NEJMoa1103507) simultaneously with a press briefing at ASCO. These included:

• A 65% relative reduction in annual incidence of invasive breast cancer, based on 11 breast cancers among 2,285 women in the exemestane arm vs. 32 among 2,275 in the placebo arm. The annual incidence was 0.19% vs. 0.55%, respectively (hazard ratio 0.35, P = .002).

• Annual incidence of invasive plus noninvasive (DCIS) breast cancers of 0.35% with exemestane vs. 0.77% with placebo (HR 0.35, P =.004).

Most cancers in both arms of the trial were estrogen receptor-positive, HER2/neu–negative, and node-negative. The investigators said exemestane was superior in all subgroup studies. They said that the number needed to prevent one case of breast cancer would be 94 at 3 years but projected that it would drop to 26 at 5 years.

Physicians – for the most part, those in primary care, as oncologists are not likely to see women who do not have cancer – need to discuss risks and benefits of the three chemoprevention drugs with their patients, stressed Dr. Goss and Dr. Andrew Seidman, moderator of the press briefing. The three agents have different side effect profiles, they noted.

Dr. Seidman, a breast specialist at Memorial Sloan-Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College in New York, credited "heightened fear of endometrial cancers and thrombotic clotting risks" for the sparse use of SERMs as chemoprevention.

Although 88% of women on exemestane and 85% of those on placebo experienced adverse events in the MAP.3 study, none were life-threatening, and the investigators reported that serious events such as skeletal fractures, cardiovascular events, other cancers, and treatment-related deaths were not significantly different between the two groups. Hot flashes and arthritis were more common with exemestane.

Quality of life differences were minimal, they said, characterizing the dropout rates and noncompliance rates as unexceptional for chemoprevention trials. Indeed, the benefits of exemestane were probably higher in women who stuck with the protocol, Dr. Goss said; the intent-to-treat analysis included women who dropped out early in the trial.

"One of the elephants in the kitchen is prophylactic bilateral mastectomy," added Dr. Seidman. He described himself as "always chagrined" at how some women are more willing to undergo "body-altering surgery" than to try chemoprevention.

The Map.3 study randomized women to 25 mg of exemestane or placebo daily. Initially, the study had a third arm in which celecoxib was added to exemestane, but it was dropped because of concerns for "cardiovascular safety" with celecoxib.

Dr. Goss said the investigators plan to look for clearer data on how to define which women are high-risk and would benefit from exemestane. They also will be looking for biomarkers that can show how well a woman does while on chemoprevention: something comparable to measures used when patients take anti-hypertensives or cholesterol-lowering drugs.

Another unknown is whether Pfizer, Inc. will seek a chemoprevention indication for exemestane. Aromasin lost patent protection in the United States in Apri, and will lose it in Europe in July, according to company spokesman Christopher Loder. "We cannot comment on our regulatory plans at this time," he said in a hallway interview at the convention center where ASCO is being held.

Loss of exclusivity is likely to mean lower prices for Aromasin, which could make Pfizer less inclined to invest in applications for the indication. Whether insurance companies would pay for chemoprevention use without an indication is also a question – but price might not be a barrier.

Pfizer helped pay for the trial. Dr. Goss and several of his coauthors received honoraria and research funding from Pfizer, as well as other companies. Dr. Davidson and Dr. Kensler disclosed no relevant conflicts of interest.

CHICAGO - A daily dose of the aromatase inhibitor exemestane reduced invasive breast cancers by 65% in a placebo-controlled chemoprevention trial that enrolled 4,560 postmenopausal women considered at increased risk of the disease.

Pre-invasive breast cancers and precancerous lesions also were much less common at a median follow-up of 3 years in the study, which is expected to reopen a stalled conversation between women and their physicians regarding the risks and benefits of chemoprevention.

Two selective estrogen receptor modulator (SERM) drugs – tamoxifen and raloxifene (Evista) – are approved for breast cancer prevention, but they are little used for that purpose. Estimated tamoxifen use runs as low as 4% in high-risk women, who are thought to be deterred by rare but potentially serious side effects.

Exemestane (Aromasin) could become a third option for breast cancer prevention in postmenopausal women, Paul E. Goss, M.D., Ph.D., the lead author, said, announcing the results on behalf of the MAP.3 (Mammary Prevention.3 trial) investigators at the annual meeting of the American Society of Clinical Oncology.

"Because of the significant reduction of breast cancer and the excellent safety profile, exemestane has the potential for wider-scale implementation than the selective estrogen modulators in our view," declared Dr. Goss, a professor of medicine at Harvard Medical School and Massachusetts General Hospital in Boston.

Women had to be age 35 or older and postmenopausal with at least one specified risk factor to enter the trial, he noted. Age greater than or equal to 60 years by itself was considered a risk factor, as were a five-year Gail risk score greater than 1.66%, prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ, or prior ductal carcinoma in situ with prior mastectomy.

Dr. Goss stressed that the results should not be extrapolated to premenopausal women or others who do not meet the trial’s eligibility criteria.

The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) led the study, which enrolled women in Canada, the United States, Spain, and France. The findings at a median follow-up of 35 months were published online by the New England Journal of Medicine (10.1056/NEJMoa1103507) simultaneously with a press briefing at ASCO. These included:

• A 65% relative reduction in annual incidence of invasive breast cancer, based on 11 breast cancers among 2,285 women in the exemestane arm vs. 32 among 2,275 in the placebo arm. The annual incidence was 0.19% vs. 0.55%, respectively (hazard ratio 0.35, P = .002).

• Annual incidence of invasive plus noninvasive (DCIS) breast cancers of 0.35% with exemestane vs. 0.77% with placebo (HR 0.35, P =.004).

Most cancers in both arms of the trial were estrogen receptor-positive, HER2/neu–negative, and node-negative. The investigators said exemestane was superior in all subgroup studies. They said that the number needed to prevent one case of breast cancer would be 94 at 3 years but projected that it would drop to 26 at 5 years.

Physicians – for the most part, those in primary care, as oncologists are not likely to see women who do not have cancer – need to discuss risks and benefits of the three chemoprevention drugs with their patients, stressed Dr. Goss and Dr. Andrew Seidman, moderator of the press briefing. The three agents have different side effect profiles, they noted.

Dr. Seidman, a breast specialist at Memorial Sloan-Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College in New York, credited "heightened fear of endometrial cancers and thrombotic clotting risks" for the sparse use of SERMs as chemoprevention.

Although 88% of women on exemestane and 85% of those on placebo experienced adverse events in the MAP.3 study, none were life-threatening, and the investigators reported that serious events such as skeletal fractures, cardiovascular events, other cancers, and treatment-related deaths were not significantly different between the two groups. Hot flashes and arthritis were more common with exemestane.

Quality of life differences were minimal, they said, characterizing the dropout rates and noncompliance rates as unexceptional for chemoprevention trials. Indeed, the benefits of exemestane were probably higher in women who stuck with the protocol, Dr. Goss said; the intent-to-treat analysis included women who dropped out early in the trial.

"One of the elephants in the kitchen is prophylactic bilateral mastectomy," added Dr. Seidman. He described himself as "always chagrined" at how some women are more willing to undergo "body-altering surgery" than to try chemoprevention.

The Map.3 study randomized women to 25 mg of exemestane or placebo daily. Initially, the study had a third arm in which celecoxib was added to exemestane, but it was dropped because of concerns for "cardiovascular safety" with celecoxib.

Dr. Goss said the investigators plan to look for clearer data on how to define which women are high-risk and would benefit from exemestane. They also will be looking for biomarkers that can show how well a woman does while on chemoprevention: something comparable to measures used when patients take anti-hypertensives or cholesterol-lowering drugs.

Another unknown is whether Pfizer, Inc. will seek a chemoprevention indication for exemestane. Aromasin lost patent protection in the United States in Apri, and will lose it in Europe in July, according to company spokesman Christopher Loder. "We cannot comment on our regulatory plans at this time," he said in a hallway interview at the convention center where ASCO is being held.

Loss of exclusivity is likely to mean lower prices for Aromasin, which could make Pfizer less inclined to invest in applications for the indication. Whether insurance companies would pay for chemoprevention use without an indication is also a question – but price might not be a barrier.

Pfizer helped pay for the trial. Dr. Goss and several of his coauthors received honoraria and research funding from Pfizer, as well as other companies. Dr. Davidson and Dr. Kensler disclosed no relevant conflicts of interest.

CHICAGO – Adding regional nodal irradiation to whole-breast irradiation significantly improved disease-free survival, but not overall survival in a randomized multi-center phase III trial of women with node-positive or high-risk node-negative disease treated with breast-conserving surgery and adjuvant therapy.

An interim analysis of 1,832 women with breast cancer found that after a median follow-up of 62 months, whole breast irradiation (WBI) plus regional nodal irradiation (RNI) significantly reduced the risk of locoregional recurrence from 5.5% to 3.2% (P = .02; hazard ratio 0.8) and distant recurrence from 13% to 7.6% (P = .002; HR 0.64), lead investigator Dr. Timothy Whelan reported at the annual meeting of the American Society of Clinical Oncology.

Overall survival in the intergroup trial was 9.3% with WBI vs. 7.7% with the combined radiation regimen, but the difference did not reach statistical significance (P = .07; HR 0.76).

In view of the positive findings, the data safety monitoring committee recommended that the results be released, Dr. Whelan told reporters at a press briefing during the meeting.

He suggested that the findings could expand the pool of women offered RNI. Currently, ASCO and the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines recommend locoregional radiation following mastectomy for tumors greater than 5 cm or with more than three positive axillary nodes.

Of the 1,832 women enrolled in the National Cancer Institute of Canada Clinical Trials Group MA.20 trial, 85% had one to three positive lymph nodes, and 10% had high-risk, node-negative breast cancer. All women were treated with breast-conserving surgery plus adjuvant chemotherapy or endocrine therapy.

"Results from MA.20 suggest that all women with node-positive disease be offered regional node irradiation provided they are made aware of the associated toxicities," said Dr. Whelan, head of radiation oncology at McMaster University and the Juravinski Cancer Centre, Hamilton, Ont.

The addition of RNI to WBI significantly increased the rates of grade 2 or higher dermatitis from 40% to 50% (P less than .001), pneumonitis from 0.2% to 1.3% (P = .01), and lymphedema from 4% to 7% (P = .004). The lymphedema was primarily grade 2, Dr. Whelen pointed out.

Reporters questioned why an earlier unpublished French study did not find a benefit with RNI, while MA.20 did. Dr. Whelan responded that regional radiation in the earlier study was limited to the internal mammary lymph nodes alone, whereas MA.20 expanded the upper radiation field to include the upper internal mammary nodes, supraclavicular nodes, and high axillary nodes. He could not explain why overall survival was not improved.

Radiation dosages for WBI were 50 Gy in 25 fractions plus a boost at the discretion of the cancer center of 10 Gy in 5 fractions. The RNI dosage was 45 Gy in 25 fractions.

WBI and RNI were delivered concurrently, so the added therapy would not require additional office visits for women, and would modestly lengthen the therapy.

The researchers will continue to monitor the patients and evaluate new techniques to reduce potential side effects, he said in an interview.

MA.20 was sponsored by the Canadian Cancer Society Research Institute, National Cancer Institute/Cancer Therapy Evaluation Program, and Canadian Breast Cancer Research Alliance. Dr. Whelan and his coauthors disclosed no conflicts of interest.

CHICAGO – Adding regional nodal irradiation to whole-breast irradiation significantly improved disease-free survival, but not overall survival in a randomized multi-center phase III trial of women with node-positive or high-risk node-negative disease treated with breast-conserving surgery and adjuvant therapy.

An interim analysis of 1,832 women with breast cancer found that after a median follow-up of 62 months, whole breast irradiation (WBI) plus regional nodal irradiation (RNI) significantly reduced the risk of locoregional recurrence from 5.5% to 3.2% (P = .02; hazard ratio 0.8) and distant recurrence from 13% to 7.6% (P = .002; HR 0.64), lead investigator Dr. Timothy Whelan reported at the annual meeting of the American Society of Clinical Oncology.

Overall survival in the intergroup trial was 9.3% with WBI vs. 7.7% with the combined radiation regimen, but the difference did not reach statistical significance (P = .07; HR 0.76).

In view of the positive findings, the data safety monitoring committee recommended that the results be released, Dr. Whelan told reporters at a press briefing during the meeting.

He suggested that the findings could expand the pool of women offered RNI. Currently, ASCO and the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines recommend locoregional radiation following mastectomy for tumors greater than 5 cm or with more than three positive axillary nodes.

Of the 1,832 women enrolled in the National Cancer Institute of Canada Clinical Trials Group MA.20 trial, 85% had one to three positive lymph nodes, and 10% had high-risk, node-negative breast cancer. All women were treated with breast-conserving surgery plus adjuvant chemotherapy or endocrine therapy.

"Results from MA.20 suggest that all women with node-positive disease be offered regional node irradiation provided they are made aware of the associated toxicities," said Dr. Whelan, head of radiation oncology at McMaster University and the Juravinski Cancer Centre, Hamilton, Ont.

The addition of RNI to WBI significantly increased the rates of grade 2 or higher dermatitis from 40% to 50% (P less than .001), pneumonitis from 0.2% to 1.3% (P = .01), and lymphedema from 4% to 7% (P = .004). The lymphedema was primarily grade 2, Dr. Whelen pointed out.

Reporters questioned why an earlier unpublished French study did not find a benefit with RNI, while MA.20 did. Dr. Whelan responded that regional radiation in the earlier study was limited to the internal mammary lymph nodes alone, whereas MA.20 expanded the upper radiation field to include the upper internal mammary nodes, supraclavicular nodes, and high axillary nodes. He could not explain why overall survival was not improved.

Radiation dosages for WBI were 50 Gy in 25 fractions plus a boost at the discretion of the cancer center of 10 Gy in 5 fractions. The RNI dosage was 45 Gy in 25 fractions.

WBI and RNI were delivered concurrently, so the added therapy would not require additional office visits for women, and would modestly lengthen the therapy.

The researchers will continue to monitor the patients and evaluate new techniques to reduce potential side effects, he said in an interview.

MA.20 was sponsored by the Canadian Cancer Society Research Institute, National Cancer Institute/Cancer Therapy Evaluation Program, and Canadian Breast Cancer Research Alliance. Dr. Whelan and his coauthors disclosed no conflicts of interest.

CHICAGO – Adding regional nodal irradiation to whole-breast irradiation significantly improved disease-free survival, but not overall survival in a randomized multi-center phase III trial of women with node-positive or high-risk node-negative disease treated with breast-conserving surgery and adjuvant therapy.

An interim analysis of 1,832 women with breast cancer found that after a median follow-up of 62 months, whole breast irradiation (WBI) plus regional nodal irradiation (RNI) significantly reduced the risk of locoregional recurrence from 5.5% to 3.2% (P = .02; hazard ratio 0.8) and distant recurrence from 13% to 7.6% (P = .002; HR 0.64), lead investigator Dr. Timothy Whelan reported at the annual meeting of the American Society of Clinical Oncology.

Overall survival in the intergroup trial was 9.3% with WBI vs. 7.7% with the combined radiation regimen, but the difference did not reach statistical significance (P = .07; HR 0.76).

In view of the positive findings, the data safety monitoring committee recommended that the results be released, Dr. Whelan told reporters at a press briefing during the meeting.

He suggested that the findings could expand the pool of women offered RNI. Currently, ASCO and the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines recommend locoregional radiation following mastectomy for tumors greater than 5 cm or with more than three positive axillary nodes.

Of the 1,832 women enrolled in the National Cancer Institute of Canada Clinical Trials Group MA.20 trial, 85% had one to three positive lymph nodes, and 10% had high-risk, node-negative breast cancer. All women were treated with breast-conserving surgery plus adjuvant chemotherapy or endocrine therapy.

"Results from MA.20 suggest that all women with node-positive disease be offered regional node irradiation provided they are made aware of the associated toxicities," said Dr. Whelan, head of radiation oncology at McMaster University and the Juravinski Cancer Centre, Hamilton, Ont.

The addition of RNI to WBI significantly increased the rates of grade 2 or higher dermatitis from 40% to 50% (P less than .001), pneumonitis from 0.2% to 1.3% (P = .01), and lymphedema from 4% to 7% (P = .004). The lymphedema was primarily grade 2, Dr. Whelen pointed out.

Reporters questioned why an earlier unpublished French study did not find a benefit with RNI, while MA.20 did. Dr. Whelan responded that regional radiation in the earlier study was limited to the internal mammary lymph nodes alone, whereas MA.20 expanded the upper radiation field to include the upper internal mammary nodes, supraclavicular nodes, and high axillary nodes. He could not explain why overall survival was not improved.

Radiation dosages for WBI were 50 Gy in 25 fractions plus a boost at the discretion of the cancer center of 10 Gy in 5 fractions. The RNI dosage was 45 Gy in 25 fractions.

WBI and RNI were delivered concurrently, so the added therapy would not require additional office visits for women, and would modestly lengthen the therapy.

The researchers will continue to monitor the patients and evaluate new techniques to reduce potential side effects, he said in an interview.

MA.20 was sponsored by the Canadian Cancer Society Research Institute, National Cancer Institute/Cancer Therapy Evaluation Program, and Canadian Breast Cancer Research Alliance. Dr. Whelan and his coauthors disclosed no conflicts of interest.