Diana Mahoney

The Food and Drug Administration on Jan. 13 announced that a boxed warning will be added to the label of brentuximab vedotin because of reports of two cases of progressive multifocal leukoencephalopathy associated with the drug’s use in lymphoma patients.

Brentuximab vedotin (Adcetris) was approved in August 2011 for the treatment of Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma. At the time of its approval, the warnings and precautions label described one case of progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal brain infection. These two additional cases prompted the new boxed warning because of the serious nature of the infection, the FDA release stated.

Additionally, a contraindication warning against the use of brentuximab vedotin in combination with the antitumor antibiotic bleomycin (Blenoxane) has been added to the label because of an association with an increased risk of pulmonary toxicity.

Signs and symptoms of PML include mood or behavior changes; confusion; altered cognitive abilities; memory loss; vision, speech, and motor function changes; and unilateral weakness or decreased strength that can develop over several weeks or months, according to the statement.

The new label advises patients who develop signs or symptoms of the condition to notify their health care provider immediately. If PML is suspected, health care professionals are advised to hold dosing pending the diagnosis of PML, and discontinue the drug if the diagnosis is confirmed.

To listen to a podcast concerning the brentuximab warning, click on the "Listen" button below. Podcast courstesy of the FDA.

The Food and Drug Administration on Jan. 13 announced that a boxed warning will be added to the label of brentuximab vedotin because of reports of two cases of progressive multifocal leukoencephalopathy associated with the drug’s use in lymphoma patients.

Brentuximab vedotin (Adcetris) was approved in August 2011 for the treatment of Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma. At the time of its approval, the warnings and precautions label described one case of progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal brain infection. These two additional cases prompted the new boxed warning because of the serious nature of the infection, the FDA release stated.

Additionally, a contraindication warning against the use of brentuximab vedotin in combination with the antitumor antibiotic bleomycin (Blenoxane) has been added to the label because of an association with an increased risk of pulmonary toxicity.

Signs and symptoms of PML include mood or behavior changes; confusion; altered cognitive abilities; memory loss; vision, speech, and motor function changes; and unilateral weakness or decreased strength that can develop over several weeks or months, according to the statement.

The new label advises patients who develop signs or symptoms of the condition to notify their health care provider immediately. If PML is suspected, health care professionals are advised to hold dosing pending the diagnosis of PML, and discontinue the drug if the diagnosis is confirmed.

To listen to a podcast concerning the brentuximab warning, click on the "Listen" button below. Podcast courstesy of the FDA.

The Food and Drug Administration on Jan. 13 announced that a boxed warning will be added to the label of brentuximab vedotin because of reports of two cases of progressive multifocal leukoencephalopathy associated with the drug’s use in lymphoma patients.

Brentuximab vedotin (Adcetris) was approved in August 2011 for the treatment of Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma. At the time of its approval, the warnings and precautions label described one case of progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal brain infection. These two additional cases prompted the new boxed warning because of the serious nature of the infection, the FDA release stated.

Additionally, a contraindication warning against the use of brentuximab vedotin in combination with the antitumor antibiotic bleomycin (Blenoxane) has been added to the label because of an association with an increased risk of pulmonary toxicity.

Signs and symptoms of PML include mood or behavior changes; confusion; altered cognitive abilities; memory loss; vision, speech, and motor function changes; and unilateral weakness or decreased strength that can develop over several weeks or months, according to the statement.

The new label advises patients who develop signs or symptoms of the condition to notify their health care provider immediately. If PML is suspected, health care professionals are advised to hold dosing pending the diagnosis of PML, and discontinue the drug if the diagnosis is confirmed.

To listen to a podcast concerning the brentuximab warning, click on the "Listen" button below. Podcast courstesy of the FDA.

SAN ANTONIO – Total skin-sparing mastectomy with complete preservation of the breast skin envelope was associated with favorable oncologic and ischemic outcomes in a large, high-risk cohort of women who underwent the procedure over a 10-year period in San Francisco, a study has shown.

The findings suggest that the surgery, which produces superior cosmesis and is associated with a high rate of patient satisfaction, is a reasonable option for many women facing therapeutic or prophylactic mastectomy, Dr. Anne G. Warren Peled said at the San Antonio Breast Cancer Symposium.

The total skin-sparing mastectomy (TSSM) allows preservation of the nipple-areola dermal layer when ductal tissue is removed during mastectomy. "The procedure is increasingly offered to women for both therapeutic and prophylactic indications, and when combined with immediate breast reconstruction, can produce excellent aesthetic results," explained Dr. Warren Peled, a surgical resident at the University of California, San Francisco.

Because the oncologic safety of the procedure and the potential for higher rates of postoperative complications continue to be debated, Dr. Warren Peled and her colleagues sought to evaluate both outcomes using data collected in a prospectively maintained database. The investigators analyzed patient and tumor characteristics, treatment details, and the development of any postoperative complications, as well as local or distant recurrences, for 428 patients (mean age, 46.9 years) who underwent 657 TSSMs and immediate breast reconstruction at the UCSF Medical Center in 2001-2010.

"The mastectomy incisions included radial, lateral, periareolar, and inframammary incisions, and the areolar and nipple complex tissue was separated from the dermal layer of skin by sharp dissection with inversion of the nipple skin to ensure the removal of all of the nipple duct tissue," Dr. Warren Peled said during a poster discussion. Of the 657 mastectomies, 412 were therapeutic procedures, and 245 (58 bilateral and 187 contralateral) were prophylactic, she said.

Most of the tumors were stage 0 (111) or stage I (135), although stage II (95), III (48), and IV (7) tumors were also observed, Dr. Warren Peled reported. Some 14 mastectomies were for recurrent cancer, she noted. In addition, 210 patients underwent neoadjuvant chemotherapy, 144 had postmastectomy radiation therapy, and 78 had adjuvant chemotherapy, she said.

With respect to nipple involvement on pathological analysis, 11 specimens had evidence of in situ cancer and 9 had evidence of invasive cancer, leading to re-excision in 7 cases, removal of the nipple-areolar complex (NAC) in 9 cases, and NAC radiation in 4 cases, said Dr. Warren Peled.

The conventional, two-stage, expander-implant method – in which a tissue expander placed under the chest muscle is implanted and gradually inflated to expand the tissue in preparation for the synthetic implant 3-6 months later – was used in 80% of the postmastectomy reconstructions, Dr. Warren Peled said. The remaining 20% of the reconstructions included either the placement of a permanent silicon implant at the time of mastectomy (4.7%) or autologous reconstruction (15.3%), she said.

A review of the oncologic outcomes in the 412 patients who underwent therapeutic mastectomies showed that, at a median follow-up of 28 months, four patients (1%) experienced local recurrence only, eight (1.9%) experienced distant recurrence only, and four experienced both local and distant recurrence (1%), Dr. Warren Peled reported. Among the local recurrences, two each were invasive (0.7%) and in situ cancer (1.8%), and among the distant recurrences, all eight (2.7) were invasive cancers. Among those with both local and distant recurrences, three (1%) and one (0.9%) were invasive and in situ, respectively, she said,

Of the 126 patients who had a minimum 36 months’ follow-up (median, 45 months), 2 patients (1.6%) had local recurrence only, one of which was invasive; 1 patient (0.8%) had distant recurrence only; and 1 (0.8%) had both, Dr. Peled said, noting that the recurrences in the latter two patients were invasive.

An assessment of ischemic complications showed 13 cases (1.9%) of partial nipple loss; 10 cases (1.5%) of complete nipple loss, and 78 cases (11.8%) of skin flap necrosis, Dr. Peled said, noting that the group’s current nipple loss rate is lower than 1%, thanks to serial improvements in surgical technique.

The findings indicate that TSSM "can be performed with low rates of nipple involvement and locoregional recurrence," Dr. Warren Peled stated. Although the short-term findings are encouraging, the study cannot speak to the long-term oncologic safety of the procedure. "Longer term follow-up is needed to confirm the oncologic safety over time," she said.

Dr. Warren Peled had no relevant financial conflicts to disclose.

SAN ANTONIO – Total skin-sparing mastectomy with complete preservation of the breast skin envelope was associated with favorable oncologic and ischemic outcomes in a large, high-risk cohort of women who underwent the procedure over a 10-year period in San Francisco, a study has shown.

The findings suggest that the surgery, which produces superior cosmesis and is associated with a high rate of patient satisfaction, is a reasonable option for many women facing therapeutic or prophylactic mastectomy, Dr. Anne G. Warren Peled said at the San Antonio Breast Cancer Symposium.

The total skin-sparing mastectomy (TSSM) allows preservation of the nipple-areola dermal layer when ductal tissue is removed during mastectomy. "The procedure is increasingly offered to women for both therapeutic and prophylactic indications, and when combined with immediate breast reconstruction, can produce excellent aesthetic results," explained Dr. Warren Peled, a surgical resident at the University of California, San Francisco.

Because the oncologic safety of the procedure and the potential for higher rates of postoperative complications continue to be debated, Dr. Warren Peled and her colleagues sought to evaluate both outcomes using data collected in a prospectively maintained database. The investigators analyzed patient and tumor characteristics, treatment details, and the development of any postoperative complications, as well as local or distant recurrences, for 428 patients (mean age, 46.9 years) who underwent 657 TSSMs and immediate breast reconstruction at the UCSF Medical Center in 2001-2010.

"The mastectomy incisions included radial, lateral, periareolar, and inframammary incisions, and the areolar and nipple complex tissue was separated from the dermal layer of skin by sharp dissection with inversion of the nipple skin to ensure the removal of all of the nipple duct tissue," Dr. Warren Peled said during a poster discussion. Of the 657 mastectomies, 412 were therapeutic procedures, and 245 (58 bilateral and 187 contralateral) were prophylactic, she said.

Most of the tumors were stage 0 (111) or stage I (135), although stage II (95), III (48), and IV (7) tumors were also observed, Dr. Warren Peled reported. Some 14 mastectomies were for recurrent cancer, she noted. In addition, 210 patients underwent neoadjuvant chemotherapy, 144 had postmastectomy radiation therapy, and 78 had adjuvant chemotherapy, she said.

With respect to nipple involvement on pathological analysis, 11 specimens had evidence of in situ cancer and 9 had evidence of invasive cancer, leading to re-excision in 7 cases, removal of the nipple-areolar complex (NAC) in 9 cases, and NAC radiation in 4 cases, said Dr. Warren Peled.

The conventional, two-stage, expander-implant method – in which a tissue expander placed under the chest muscle is implanted and gradually inflated to expand the tissue in preparation for the synthetic implant 3-6 months later – was used in 80% of the postmastectomy reconstructions, Dr. Warren Peled said. The remaining 20% of the reconstructions included either the placement of a permanent silicon implant at the time of mastectomy (4.7%) or autologous reconstruction (15.3%), she said.

A review of the oncologic outcomes in the 412 patients who underwent therapeutic mastectomies showed that, at a median follow-up of 28 months, four patients (1%) experienced local recurrence only, eight (1.9%) experienced distant recurrence only, and four experienced both local and distant recurrence (1%), Dr. Warren Peled reported. Among the local recurrences, two each were invasive (0.7%) and in situ cancer (1.8%), and among the distant recurrences, all eight (2.7) were invasive cancers. Among those with both local and distant recurrences, three (1%) and one (0.9%) were invasive and in situ, respectively, she said,

Of the 126 patients who had a minimum 36 months’ follow-up (median, 45 months), 2 patients (1.6%) had local recurrence only, one of which was invasive; 1 patient (0.8%) had distant recurrence only; and 1 (0.8%) had both, Dr. Peled said, noting that the recurrences in the latter two patients were invasive.

An assessment of ischemic complications showed 13 cases (1.9%) of partial nipple loss; 10 cases (1.5%) of complete nipple loss, and 78 cases (11.8%) of skin flap necrosis, Dr. Peled said, noting that the group’s current nipple loss rate is lower than 1%, thanks to serial improvements in surgical technique.

The findings indicate that TSSM "can be performed with low rates of nipple involvement and locoregional recurrence," Dr. Warren Peled stated. Although the short-term findings are encouraging, the study cannot speak to the long-term oncologic safety of the procedure. "Longer term follow-up is needed to confirm the oncologic safety over time," she said.

Dr. Warren Peled had no relevant financial conflicts to disclose.

SAN ANTONIO – Total skin-sparing mastectomy with complete preservation of the breast skin envelope was associated with favorable oncologic and ischemic outcomes in a large, high-risk cohort of women who underwent the procedure over a 10-year period in San Francisco, a study has shown.

The findings suggest that the surgery, which produces superior cosmesis and is associated with a high rate of patient satisfaction, is a reasonable option for many women facing therapeutic or prophylactic mastectomy, Dr. Anne G. Warren Peled said at the San Antonio Breast Cancer Symposium.

The total skin-sparing mastectomy (TSSM) allows preservation of the nipple-areola dermal layer when ductal tissue is removed during mastectomy. "The procedure is increasingly offered to women for both therapeutic and prophylactic indications, and when combined with immediate breast reconstruction, can produce excellent aesthetic results," explained Dr. Warren Peled, a surgical resident at the University of California, San Francisco.

Because the oncologic safety of the procedure and the potential for higher rates of postoperative complications continue to be debated, Dr. Warren Peled and her colleagues sought to evaluate both outcomes using data collected in a prospectively maintained database. The investigators analyzed patient and tumor characteristics, treatment details, and the development of any postoperative complications, as well as local or distant recurrences, for 428 patients (mean age, 46.9 years) who underwent 657 TSSMs and immediate breast reconstruction at the UCSF Medical Center in 2001-2010.

"The mastectomy incisions included radial, lateral, periareolar, and inframammary incisions, and the areolar and nipple complex tissue was separated from the dermal layer of skin by sharp dissection with inversion of the nipple skin to ensure the removal of all of the nipple duct tissue," Dr. Warren Peled said during a poster discussion. Of the 657 mastectomies, 412 were therapeutic procedures, and 245 (58 bilateral and 187 contralateral) were prophylactic, she said.

Most of the tumors were stage 0 (111) or stage I (135), although stage II (95), III (48), and IV (7) tumors were also observed, Dr. Warren Peled reported. Some 14 mastectomies were for recurrent cancer, she noted. In addition, 210 patients underwent neoadjuvant chemotherapy, 144 had postmastectomy radiation therapy, and 78 had adjuvant chemotherapy, she said.

With respect to nipple involvement on pathological analysis, 11 specimens had evidence of in situ cancer and 9 had evidence of invasive cancer, leading to re-excision in 7 cases, removal of the nipple-areolar complex (NAC) in 9 cases, and NAC radiation in 4 cases, said Dr. Warren Peled.

The conventional, two-stage, expander-implant method – in which a tissue expander placed under the chest muscle is implanted and gradually inflated to expand the tissue in preparation for the synthetic implant 3-6 months later – was used in 80% of the postmastectomy reconstructions, Dr. Warren Peled said. The remaining 20% of the reconstructions included either the placement of a permanent silicon implant at the time of mastectomy (4.7%) or autologous reconstruction (15.3%), she said.

A review of the oncologic outcomes in the 412 patients who underwent therapeutic mastectomies showed that, at a median follow-up of 28 months, four patients (1%) experienced local recurrence only, eight (1.9%) experienced distant recurrence only, and four experienced both local and distant recurrence (1%), Dr. Warren Peled reported. Among the local recurrences, two each were invasive (0.7%) and in situ cancer (1.8%), and among the distant recurrences, all eight (2.7) were invasive cancers. Among those with both local and distant recurrences, three (1%) and one (0.9%) were invasive and in situ, respectively, she said,

Of the 126 patients who had a minimum 36 months’ follow-up (median, 45 months), 2 patients (1.6%) had local recurrence only, one of which was invasive; 1 patient (0.8%) had distant recurrence only; and 1 (0.8%) had both, Dr. Peled said, noting that the recurrences in the latter two patients were invasive.

An assessment of ischemic complications showed 13 cases (1.9%) of partial nipple loss; 10 cases (1.5%) of complete nipple loss, and 78 cases (11.8%) of skin flap necrosis, Dr. Peled said, noting that the group’s current nipple loss rate is lower than 1%, thanks to serial improvements in surgical technique.

The findings indicate that TSSM "can be performed with low rates of nipple involvement and locoregional recurrence," Dr. Warren Peled stated. Although the short-term findings are encouraging, the study cannot speak to the long-term oncologic safety of the procedure. "Longer term follow-up is needed to confirm the oncologic safety over time," she said.

Dr. Warren Peled had no relevant financial conflicts to disclose.

After 13 years of follow-up, men who underwent annual screening for prostate cancer were no less likely to die of prostate cancer than were men who received usual care and opportunistic screening.

Cumulative mortality rates from prostate cancer differed by a statistically insignificant rate of 0.3 deaths per 10,000 person years in the intervention and usual-care arms of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial, published online Jan. 6 in the Journal of the National Cancer Institute. Further, age, comorbidity status, and pretrial prostate-specific antigen (PSA) testing did not influence the results, wrote Dr. Gerald L. Andriole of Washington University, St. Louis, and his colleagues.

The PLCO trial randomly assigned 76,693 men, aged 55-74 years, to either 6 years of annual PSA screening in combination with 4 years of annual digital rectal examination (38,343) or to usual care (38,350), which included screening tests as recommended by physicians.

The goal was to evaluate the effect of adding annual screening and compare outcomes to the opportunistic screening already in place, the researchers said. It was expected that the impacts of earlier diagnosis and a persistent excess of cases because of annual screening in the intervention arm would exceed the impacts of opportunistic screening.

Prior to the study, 44% of all participants had undergone PSA screening. During the trial, 52% of the usual-care group, compared with the entire intervention group, underwent PSA testing.

The researchers had previously reported 7- and 10-year follow-up results. At 7 years of follow-up, yearly screening was associated with an increased incidence of prostate cancer diagnosis as compared with usual care. The rates of prostate cancer mortality and of all-cause mortality, however, were the same for both groups. Similarly, after 10 years of follow-up, no mortality benefit was observed for the intervention, the investigators reported previously (N. Engl. J. Med. 2009;360:1320-1328).

For the current study, Dr. Andriole and his associates ascertained all incident prostate cancer diagnoses and deaths through 13 years of follow-up or through December 31, 2009, and estimated relative risks as the ratio of observed rates of diagnoses and deaths in the intervention and control arms. They examined the interactions between prostate cancer mortality by trial arm and age, comorbidities, and pretrial PSA testing using Poisson regression modeling (J. Natl. Cancer Inst. 6 Jan. 2012 [doi: 10.1093/jnci/djr500]).

At 13 years, 4,250 of the 38,340 participants in the intervention arm had been diagnosed with prostate cancer, compared with 3,815 of the 38,345 control participants. "The cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10,000 person-years, respectively, resulting in a statistically significant 12% relative increase in the intervention arm," the authors wrote. Of the prostate cancer diagnoses, 401 in the intervention arm and 454 in the usual care arm were high-grade prostate cancers with Gleason scores of 8-10.

At 13 years of follow-up, there were 158 deaths in the intervention arm and 145 deaths in the usual-care arm. "The cumulative mortality rates from prostate cancer were 3.7 and 3.4 deaths per 10,000 person-years, respectively, resulting in a non-statistically significant difference between the two arms," according to the authors. The examination of mortality rates per 10,000 person-years and relative risks of prostate cancer mortality by age, comorbidity, and pretrial PSA testing produced no statistically significant interactions.

Deaths from all causes other than prostate, lung, and colorectal cancers differed by a factor of "borderline" statistical significance, with 5,783 deaths in the intervention arm and 5,982 in the usual-care arm, Dr. Andriole and his associates wrote. "Intervention and control arms showed 23% and 22% deaths, respectively, from non-PLCO cancers, and 21% and 19% deaths, respectively, from ischemic heart disease."

The authors acknowledged limitations of the study, including the possibility that a reduction in prostate cancer mortality in the analysis has somehow been masked by "the sticking diagnosis effect." In other words, more deaths were attributed to prostate cancer in the intervention arm. This possibility is supported by the statistically significant lower all-cause mortality in the intervention group as compared with the usual-care group. The percentage of deaths from other causes was higher in the intervention arm, so an error in cause of death attribution likely does not account for the excess prostate cancer deaths in the intervention group, they concluded.

The investigators plan to update the mortality findings through 15 years of follow-up, when those data become available.

Some of the study authors report relationships with Amgen, Augmenix, Bayer, Cambridge Endo, Caris, Envisioneering Medical, France Foundation, GenProbe, GlaxoSmithKline, Human Genome Sciences, Myriad Genetics, Steba Biotech, Ortho Clinical Diagnostics, and Viking Medical.

After 13 years of follow-up, men who underwent annual screening for prostate cancer were no less likely to die of prostate cancer than were men who received usual care and opportunistic screening.

Cumulative mortality rates from prostate cancer differed by a statistically insignificant rate of 0.3 deaths per 10,000 person years in the intervention and usual-care arms of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial, published online Jan. 6 in the Journal of the National Cancer Institute. Further, age, comorbidity status, and pretrial prostate-specific antigen (PSA) testing did not influence the results, wrote Dr. Gerald L. Andriole of Washington University, St. Louis, and his colleagues.

The PLCO trial randomly assigned 76,693 men, aged 55-74 years, to either 6 years of annual PSA screening in combination with 4 years of annual digital rectal examination (38,343) or to usual care (38,350), which included screening tests as recommended by physicians.

The goal was to evaluate the effect of adding annual screening and compare outcomes to the opportunistic screening already in place, the researchers said. It was expected that the impacts of earlier diagnosis and a persistent excess of cases because of annual screening in the intervention arm would exceed the impacts of opportunistic screening.

Prior to the study, 44% of all participants had undergone PSA screening. During the trial, 52% of the usual-care group, compared with the entire intervention group, underwent PSA testing.

The researchers had previously reported 7- and 10-year follow-up results. At 7 years of follow-up, yearly screening was associated with an increased incidence of prostate cancer diagnosis as compared with usual care. The rates of prostate cancer mortality and of all-cause mortality, however, were the same for both groups. Similarly, after 10 years of follow-up, no mortality benefit was observed for the intervention, the investigators reported previously (N. Engl. J. Med. 2009;360:1320-1328).

For the current study, Dr. Andriole and his associates ascertained all incident prostate cancer diagnoses and deaths through 13 years of follow-up or through December 31, 2009, and estimated relative risks as the ratio of observed rates of diagnoses and deaths in the intervention and control arms. They examined the interactions between prostate cancer mortality by trial arm and age, comorbidities, and pretrial PSA testing using Poisson regression modeling (J. Natl. Cancer Inst. 6 Jan. 2012 [doi: 10.1093/jnci/djr500]).

At 13 years, 4,250 of the 38,340 participants in the intervention arm had been diagnosed with prostate cancer, compared with 3,815 of the 38,345 control participants. "The cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10,000 person-years, respectively, resulting in a statistically significant 12% relative increase in the intervention arm," the authors wrote. Of the prostate cancer diagnoses, 401 in the intervention arm and 454 in the usual care arm were high-grade prostate cancers with Gleason scores of 8-10.

At 13 years of follow-up, there were 158 deaths in the intervention arm and 145 deaths in the usual-care arm. "The cumulative mortality rates from prostate cancer were 3.7 and 3.4 deaths per 10,000 person-years, respectively, resulting in a non-statistically significant difference between the two arms," according to the authors. The examination of mortality rates per 10,000 person-years and relative risks of prostate cancer mortality by age, comorbidity, and pretrial PSA testing produced no statistically significant interactions.

Deaths from all causes other than prostate, lung, and colorectal cancers differed by a factor of "borderline" statistical significance, with 5,783 deaths in the intervention arm and 5,982 in the usual-care arm, Dr. Andriole and his associates wrote. "Intervention and control arms showed 23% and 22% deaths, respectively, from non-PLCO cancers, and 21% and 19% deaths, respectively, from ischemic heart disease."

The authors acknowledged limitations of the study, including the possibility that a reduction in prostate cancer mortality in the analysis has somehow been masked by "the sticking diagnosis effect." In other words, more deaths were attributed to prostate cancer in the intervention arm. This possibility is supported by the statistically significant lower all-cause mortality in the intervention group as compared with the usual-care group. The percentage of deaths from other causes was higher in the intervention arm, so an error in cause of death attribution likely does not account for the excess prostate cancer deaths in the intervention group, they concluded.

The investigators plan to update the mortality findings through 15 years of follow-up, when those data become available.

Some of the study authors report relationships with Amgen, Augmenix, Bayer, Cambridge Endo, Caris, Envisioneering Medical, France Foundation, GenProbe, GlaxoSmithKline, Human Genome Sciences, Myriad Genetics, Steba Biotech, Ortho Clinical Diagnostics, and Viking Medical.

After 13 years of follow-up, men who underwent annual screening for prostate cancer were no less likely to die of prostate cancer than were men who received usual care and opportunistic screening.

Cumulative mortality rates from prostate cancer differed by a statistically insignificant rate of 0.3 deaths per 10,000 person years in the intervention and usual-care arms of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial, published online Jan. 6 in the Journal of the National Cancer Institute. Further, age, comorbidity status, and pretrial prostate-specific antigen (PSA) testing did not influence the results, wrote Dr. Gerald L. Andriole of Washington University, St. Louis, and his colleagues.

The PLCO trial randomly assigned 76,693 men, aged 55-74 years, to either 6 years of annual PSA screening in combination with 4 years of annual digital rectal examination (38,343) or to usual care (38,350), which included screening tests as recommended by physicians.

The goal was to evaluate the effect of adding annual screening and compare outcomes to the opportunistic screening already in place, the researchers said. It was expected that the impacts of earlier diagnosis and a persistent excess of cases because of annual screening in the intervention arm would exceed the impacts of opportunistic screening.

Prior to the study, 44% of all participants had undergone PSA screening. During the trial, 52% of the usual-care group, compared with the entire intervention group, underwent PSA testing.

The researchers had previously reported 7- and 10-year follow-up results. At 7 years of follow-up, yearly screening was associated with an increased incidence of prostate cancer diagnosis as compared with usual care. The rates of prostate cancer mortality and of all-cause mortality, however, were the same for both groups. Similarly, after 10 years of follow-up, no mortality benefit was observed for the intervention, the investigators reported previously (N. Engl. J. Med. 2009;360:1320-1328).

For the current study, Dr. Andriole and his associates ascertained all incident prostate cancer diagnoses and deaths through 13 years of follow-up or through December 31, 2009, and estimated relative risks as the ratio of observed rates of diagnoses and deaths in the intervention and control arms. They examined the interactions between prostate cancer mortality by trial arm and age, comorbidities, and pretrial PSA testing using Poisson regression modeling (J. Natl. Cancer Inst. 6 Jan. 2012 [doi: 10.1093/jnci/djr500]).

At 13 years, 4,250 of the 38,340 participants in the intervention arm had been diagnosed with prostate cancer, compared with 3,815 of the 38,345 control participants. "The cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10,000 person-years, respectively, resulting in a statistically significant 12% relative increase in the intervention arm," the authors wrote. Of the prostate cancer diagnoses, 401 in the intervention arm and 454 in the usual care arm were high-grade prostate cancers with Gleason scores of 8-10.

At 13 years of follow-up, there were 158 deaths in the intervention arm and 145 deaths in the usual-care arm. "The cumulative mortality rates from prostate cancer were 3.7 and 3.4 deaths per 10,000 person-years, respectively, resulting in a non-statistically significant difference between the two arms," according to the authors. The examination of mortality rates per 10,000 person-years and relative risks of prostate cancer mortality by age, comorbidity, and pretrial PSA testing produced no statistically significant interactions.

Deaths from all causes other than prostate, lung, and colorectal cancers differed by a factor of "borderline" statistical significance, with 5,783 deaths in the intervention arm and 5,982 in the usual-care arm, Dr. Andriole and his associates wrote. "Intervention and control arms showed 23% and 22% deaths, respectively, from non-PLCO cancers, and 21% and 19% deaths, respectively, from ischemic heart disease."

The authors acknowledged limitations of the study, including the possibility that a reduction in prostate cancer mortality in the analysis has somehow been masked by "the sticking diagnosis effect." In other words, more deaths were attributed to prostate cancer in the intervention arm. This possibility is supported by the statistically significant lower all-cause mortality in the intervention group as compared with the usual-care group. The percentage of deaths from other causes was higher in the intervention arm, so an error in cause of death attribution likely does not account for the excess prostate cancer deaths in the intervention group, they concluded.

The investigators plan to update the mortality findings through 15 years of follow-up, when those data become available.

Some of the study authors report relationships with Amgen, Augmenix, Bayer, Cambridge Endo, Caris, Envisioneering Medical, France Foundation, GenProbe, GlaxoSmithKline, Human Genome Sciences, Myriad Genetics, Steba Biotech, Ortho Clinical Diagnostics, and Viking Medical.

PHILADELPHIA – Early, intensive treatment for type 1 diabetes with conventional therapy halves the long-term risk of developing an impaired glomerular filtration rate, the common pathway leading to end-stage kidney disease, Dr. Ian H. de Boer said at the meeting.

He reported new data from the Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study demonstrating a nearly 50% reduction in the risk of glomerular filtration rate (GRF) impairment – defined as an incident estimated GFR less than 60 mL/min per 1.73 m

In the multicenter DCCT, 1,441 individuals with type 1 diabetes were randomized to 6.5 years of conventional therapy (730 patients), consisting of one or two insulin injections daily designed to prevent hyperglycemic symptoms, or to intensive diabetes treatment (711 patients), consisting of three or more insulin injections daily or the use of an insulin pump in an attempt to achieve a glycated hemoglobin level of less than 6.05%, “as close to the nondiabetic range as possible,” Dr. de Boer reported at the meeting sponsored by the American Society of Nephrology.

The study population included patients in a primary intervention cohort who had diabetes for 1-5 years with an albumin excretion rate of less than 40 mg per 24 hours and no retinopathy and those in a secondary intervention cohort with a 1- to 15-year history of diabetes, an albumin excretion rate of 200 mg or less per 24 hours, and no more than moderate nonproliferative retinopathy, he noted.

Of the DCCT participants, 1,375 agreed to participate in the observational extension EDIC study, including a statistically similar number of patients from the intensive and conventional therapy groups, Dr. de Boer reported. As per the protocol of both studies, serum creatinine levels were measured annually.

The mean hemoglobin A_1c level during the DCCT was 7.3% in the intensive treatment group and 9.1% in the conventional therapy group. “In the EDIC years 1-16, the mean hemoglobin A_1c was nearly 8% in each group, with no clinically or statistically significant difference,” said Dr. de Boer of the University of Washington in Seattle.

During the combined 22 years of follow-up for both studies, “70 patients developed impaired [GFR], including 24 who had been assigned to intensive therapy and 46 who received conventional treatment,” Dr. de Boer stated, noting that most of the cases occurred during the EDIC study period.

The time of the events is important, he said. “Only 4 of the 70 occurred during DCCT, and 66 occurred during EDIC study follow-up. Almost all of the events occurred more than 10 years after randomization.”

The intensive therapy reduced the risk of impaired GFR by 50%, according to statistical analyses, Dr. de Boer said. Twenty years after randomization, “the cumulative incidence of an impaired GFR was 2.0% among those assigned to intensive therapy and 5.5% in those assigned to conventional therapy,” representing an absolute risk reduction of 3.5%, he explained.

The study results were reported concurrently with the online publication of the data (N. Engl. J. Med. 2011;365:2366-76 Nov.

The study was funded by U.S. government grants and through a Genentech Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. Abbott, Animas, Aventis, Bayer, Becton Dickinson, Can Am, Eli Lilly, LifeScan, Medtronic, MiniMed, Omron, OmniPod, Roche, and Sanofi-Aventis provided research supplies or equipment and the University of Washington received support from Abbott Laboratories.

PHILADELPHIA – Early, intensive treatment for type 1 diabetes with conventional therapy halves the long-term risk of developing an impaired glomerular filtration rate, the common pathway leading to end-stage kidney disease, Dr. Ian H. de Boer said at the meeting.

He reported new data from the Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study demonstrating a nearly 50% reduction in the risk of glomerular filtration rate (GRF) impairment – defined as an incident estimated GFR less than 60 mL/min per 1.73 m

In the multicenter DCCT, 1,441 individuals with type 1 diabetes were randomized to 6.5 years of conventional therapy (730 patients), consisting of one or two insulin injections daily designed to prevent hyperglycemic symptoms, or to intensive diabetes treatment (711 patients), consisting of three or more insulin injections daily or the use of an insulin pump in an attempt to achieve a glycated hemoglobin level of less than 6.05%, “as close to the nondiabetic range as possible,” Dr. de Boer reported at the meeting sponsored by the American Society of Nephrology.

The study population included patients in a primary intervention cohort who had diabetes for 1-5 years with an albumin excretion rate of less than 40 mg per 24 hours and no retinopathy and those in a secondary intervention cohort with a 1- to 15-year history of diabetes, an albumin excretion rate of 200 mg or less per 24 hours, and no more than moderate nonproliferative retinopathy, he noted.

Of the DCCT participants, 1,375 agreed to participate in the observational extension EDIC study, including a statistically similar number of patients from the intensive and conventional therapy groups, Dr. de Boer reported. As per the protocol of both studies, serum creatinine levels were measured annually.

The mean hemoglobin A_1c level during the DCCT was 7.3% in the intensive treatment group and 9.1% in the conventional therapy group. “In the EDIC years 1-16, the mean hemoglobin A_1c was nearly 8% in each group, with no clinically or statistically significant difference,” said Dr. de Boer of the University of Washington in Seattle.

During the combined 22 years of follow-up for both studies, “70 patients developed impaired [GFR], including 24 who had been assigned to intensive therapy and 46 who received conventional treatment,” Dr. de Boer stated, noting that most of the cases occurred during the EDIC study period.

The time of the events is important, he said. “Only 4 of the 70 occurred during DCCT, and 66 occurred during EDIC study follow-up. Almost all of the events occurred more than 10 years after randomization.”

The intensive therapy reduced the risk of impaired GFR by 50%, according to statistical analyses, Dr. de Boer said. Twenty years after randomization, “the cumulative incidence of an impaired GFR was 2.0% among those assigned to intensive therapy and 5.5% in those assigned to conventional therapy,” representing an absolute risk reduction of 3.5%, he explained.

The study results were reported concurrently with the online publication of the data (N. Engl. J. Med. 2011;365:2366-76 Nov.

The study was funded by U.S. government grants and through a Genentech Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. Abbott, Animas, Aventis, Bayer, Becton Dickinson, Can Am, Eli Lilly, LifeScan, Medtronic, MiniMed, Omron, OmniPod, Roche, and Sanofi-Aventis provided research supplies or equipment and the University of Washington received support from Abbott Laboratories.

PHILADELPHIA – Early, intensive treatment for type 1 diabetes with conventional therapy halves the long-term risk of developing an impaired glomerular filtration rate, the common pathway leading to end-stage kidney disease, Dr. Ian H. de Boer said at the meeting.

He reported new data from the Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study demonstrating a nearly 50% reduction in the risk of glomerular filtration rate (GRF) impairment – defined as an incident estimated GFR less than 60 mL/min per 1.73 m

In the multicenter DCCT, 1,441 individuals with type 1 diabetes were randomized to 6.5 years of conventional therapy (730 patients), consisting of one or two insulin injections daily designed to prevent hyperglycemic symptoms, or to intensive diabetes treatment (711 patients), consisting of three or more insulin injections daily or the use of an insulin pump in an attempt to achieve a glycated hemoglobin level of less than 6.05%, “as close to the nondiabetic range as possible,” Dr. de Boer reported at the meeting sponsored by the American Society of Nephrology.

The study population included patients in a primary intervention cohort who had diabetes for 1-5 years with an albumin excretion rate of less than 40 mg per 24 hours and no retinopathy and those in a secondary intervention cohort with a 1- to 15-year history of diabetes, an albumin excretion rate of 200 mg or less per 24 hours, and no more than moderate nonproliferative retinopathy, he noted.

Of the DCCT participants, 1,375 agreed to participate in the observational extension EDIC study, including a statistically similar number of patients from the intensive and conventional therapy groups, Dr. de Boer reported. As per the protocol of both studies, serum creatinine levels were measured annually.

The mean hemoglobin A_1c level during the DCCT was 7.3% in the intensive treatment group and 9.1% in the conventional therapy group. “In the EDIC years 1-16, the mean hemoglobin A_1c was nearly 8% in each group, with no clinically or statistically significant difference,” said Dr. de Boer of the University of Washington in Seattle.

During the combined 22 years of follow-up for both studies, “70 patients developed impaired [GFR], including 24 who had been assigned to intensive therapy and 46 who received conventional treatment,” Dr. de Boer stated, noting that most of the cases occurred during the EDIC study period.

The time of the events is important, he said. “Only 4 of the 70 occurred during DCCT, and 66 occurred during EDIC study follow-up. Almost all of the events occurred more than 10 years after randomization.”

The intensive therapy reduced the risk of impaired GFR by 50%, according to statistical analyses, Dr. de Boer said. Twenty years after randomization, “the cumulative incidence of an impaired GFR was 2.0% among those assigned to intensive therapy and 5.5% in those assigned to conventional therapy,” representing an absolute risk reduction of 3.5%, he explained.

The study results were reported concurrently with the online publication of the data (N. Engl. J. Med. 2011;365:2366-76 Nov.

The study was funded by U.S. government grants and through a Genentech Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. Abbott, Animas, Aventis, Bayer, Becton Dickinson, Can Am, Eli Lilly, LifeScan, Medtronic, MiniMed, Omron, OmniPod, Roche, and Sanofi-Aventis provided research supplies or equipment and the University of Washington received support from Abbott Laboratories.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

BOSTON – Combination therapy with raltegravir is more effective than efavirenz-based therapy in treatment-naive HIV-1–infected patients, according to data from the ongoing phase III STARTMRK study.

The only drug in the integrase inhibitor class approved for the treatment of HIV-1 infection as part of combination antiretroviral therapy, raltegravir also appears to be better tolerated than efavirenz and has a more favorable metabolic profile, according to 4 years of follow-up data presented by Dr. Edwin DeJesus at the annual meeting of the Infectious Diseases Society of America.

The double-blind, active-controlled, noninferiority study randomized 563 patients to receive either 400 mg raltegravir (Isentress) twice daily or 600 mg efavirenz (Sustiva) once daily, both in combination with coformulated tenofovir and emtricitabine (Truvada), said Dr. DeJesus of the Orlando Immunology Center. Of the 280 patients randomized to raltegravir, 223 (80%) remained in treatment through week 192, as did 197 (70%) of the 282 randomized to efavirenz, he said.

Previously reported study results showed the percentage of patients with less than 50 copies/mL HIV RNA, the primary efficacy measure, to be 86% and 82% for the raltegravir and efavirenz groups, respectively, at 48 weeks and 81% and 79%, respectively, at 96 weeks, Dr. DeJesus said.

At 192 weeks, the proportion of patients who met that target viral load reduction was 214 of 280 in the raltegravir group (76%) and 189 of 282 in the efavirenz group (67%), he reported.

The immunological effect was more pronounced in the raltegravir group, as evidenced by a mean change from baseline in CD4 cell count of 360.7 cells/mm³, compared with 300.9 cells/mm³ in the efavirenz group, he said.

With respect to metabolic parameters, the mean change from baseline in the total cholesterol-to-high-density lipoprotein (HDL) cholesterol at week 192 was –0.17 for the raltegravir group and 0.02 for the efavirenz group, Dr. DeJesus said. The raltegravir regimen also produced less mean change in the individual parameters of total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose, he said.

The rate of clinical adverse events, which included diarrhea, nausea, fatigue, dizziness, headache, abnormal dreams, insomnia, nightmares, and rash, was similar overall between both groups, however, significantly fewer drug-related adverse events were observed in the raltegravir group, with a total of 141 (50%), compared with 226 (80%) in the efavirenz patients, according to Dr. DeJesus. There was no significant difference between the two groups in the number of patients who discontinued treatment as a consequence of clinical adverse events, he said.

Based on the findings, "the long-term tolerability and metabolic profile of the integrase-based regimen appear favorable," Dr. DeJesus said. The results are also a good gauge of the evolution of HIV management. "For a long time, we were used to studies that gave us 48-week data, but HIV patients are living much longer now, so we need data that show how these treatments work over the long term," he said. The STARTMRK study is unique in that it has maintained its blinding and will continue to be blinded for 5 years, he added.

Dr. DeJesus disclosed financial relationships with Merck, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Tibotec, Pfizer, Hoffman-La Roche, Achillion, Avexa, and Talmed. The study was sponsored by Merck.

BOSTON – Combination therapy with raltegravir is more effective than efavirenz-based therapy in treatment-naive HIV-1–infected patients, according to data from the ongoing phase III STARTMRK study.

The only drug in the integrase inhibitor class approved for the treatment of HIV-1 infection as part of combination antiretroviral therapy, raltegravir also appears to be better tolerated than efavirenz and has a more favorable metabolic profile, according to 4 years of follow-up data presented by Dr. Edwin DeJesus at the annual meeting of the Infectious Diseases Society of America.

The double-blind, active-controlled, noninferiority study randomized 563 patients to receive either 400 mg raltegravir (Isentress) twice daily or 600 mg efavirenz (Sustiva) once daily, both in combination with coformulated tenofovir and emtricitabine (Truvada), said Dr. DeJesus of the Orlando Immunology Center. Of the 280 patients randomized to raltegravir, 223 (80%) remained in treatment through week 192, as did 197 (70%) of the 282 randomized to efavirenz, he said.

Previously reported study results showed the percentage of patients with less than 50 copies/mL HIV RNA, the primary efficacy measure, to be 86% and 82% for the raltegravir and efavirenz groups, respectively, at 48 weeks and 81% and 79%, respectively, at 96 weeks, Dr. DeJesus said.

At 192 weeks, the proportion of patients who met that target viral load reduction was 214 of 280 in the raltegravir group (76%) and 189 of 282 in the efavirenz group (67%), he reported.

The immunological effect was more pronounced in the raltegravir group, as evidenced by a mean change from baseline in CD4 cell count of 360.7 cells/mm³, compared with 300.9 cells/mm³ in the efavirenz group, he said.

With respect to metabolic parameters, the mean change from baseline in the total cholesterol-to-high-density lipoprotein (HDL) cholesterol at week 192 was –0.17 for the raltegravir group and 0.02 for the efavirenz group, Dr. DeJesus said. The raltegravir regimen also produced less mean change in the individual parameters of total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose, he said.

The rate of clinical adverse events, which included diarrhea, nausea, fatigue, dizziness, headache, abnormal dreams, insomnia, nightmares, and rash, was similar overall between both groups, however, significantly fewer drug-related adverse events were observed in the raltegravir group, with a total of 141 (50%), compared with 226 (80%) in the efavirenz patients, according to Dr. DeJesus. There was no significant difference between the two groups in the number of patients who discontinued treatment as a consequence of clinical adverse events, he said.

Based on the findings, "the long-term tolerability and metabolic profile of the integrase-based regimen appear favorable," Dr. DeJesus said. The results are also a good gauge of the evolution of HIV management. "For a long time, we were used to studies that gave us 48-week data, but HIV patients are living much longer now, so we need data that show how these treatments work over the long term," he said. The STARTMRK study is unique in that it has maintained its blinding and will continue to be blinded for 5 years, he added.

Dr. DeJesus disclosed financial relationships with Merck, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Tibotec, Pfizer, Hoffman-La Roche, Achillion, Avexa, and Talmed. The study was sponsored by Merck.

BOSTON – Combination therapy with raltegravir is more effective than efavirenz-based therapy in treatment-naive HIV-1–infected patients, according to data from the ongoing phase III STARTMRK study.

The only drug in the integrase inhibitor class approved for the treatment of HIV-1 infection as part of combination antiretroviral therapy, raltegravir also appears to be better tolerated than efavirenz and has a more favorable metabolic profile, according to 4 years of follow-up data presented by Dr. Edwin DeJesus at the annual meeting of the Infectious Diseases Society of America.

The double-blind, active-controlled, noninferiority study randomized 563 patients to receive either 400 mg raltegravir (Isentress) twice daily or 600 mg efavirenz (Sustiva) once daily, both in combination with coformulated tenofovir and emtricitabine (Truvada), said Dr. DeJesus of the Orlando Immunology Center. Of the 280 patients randomized to raltegravir, 223 (80%) remained in treatment through week 192, as did 197 (70%) of the 282 randomized to efavirenz, he said.

Previously reported study results showed the percentage of patients with less than 50 copies/mL HIV RNA, the primary efficacy measure, to be 86% and 82% for the raltegravir and efavirenz groups, respectively, at 48 weeks and 81% and 79%, respectively, at 96 weeks, Dr. DeJesus said.

At 192 weeks, the proportion of patients who met that target viral load reduction was 214 of 280 in the raltegravir group (76%) and 189 of 282 in the efavirenz group (67%), he reported.

The immunological effect was more pronounced in the raltegravir group, as evidenced by a mean change from baseline in CD4 cell count of 360.7 cells/mm³, compared with 300.9 cells/mm³ in the efavirenz group, he said.

With respect to metabolic parameters, the mean change from baseline in the total cholesterol-to-high-density lipoprotein (HDL) cholesterol at week 192 was –0.17 for the raltegravir group and 0.02 for the efavirenz group, Dr. DeJesus said. The raltegravir regimen also produced less mean change in the individual parameters of total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose, he said.

The rate of clinical adverse events, which included diarrhea, nausea, fatigue, dizziness, headache, abnormal dreams, insomnia, nightmares, and rash, was similar overall between both groups, however, significantly fewer drug-related adverse events were observed in the raltegravir group, with a total of 141 (50%), compared with 226 (80%) in the efavirenz patients, according to Dr. DeJesus. There was no significant difference between the two groups in the number of patients who discontinued treatment as a consequence of clinical adverse events, he said.

Based on the findings, "the long-term tolerability and metabolic profile of the integrase-based regimen appear favorable," Dr. DeJesus said. The results are also a good gauge of the evolution of HIV management. "For a long time, we were used to studies that gave us 48-week data, but HIV patients are living much longer now, so we need data that show how these treatments work over the long term," he said. The STARTMRK study is unique in that it has maintained its blinding and will continue to be blinded for 5 years, he added.

Dr. DeJesus disclosed financial relationships with Merck, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Tibotec, Pfizer, Hoffman-La Roche, Achillion, Avexa, and Talmed. The study was sponsored by Merck.

SAN ANTONIO – Contralateral prophylactic mastectomy – in comparison to unilateral mastectomy – was associated with a significantly increased rate of major postoperative surgical complications in a 470-patient study.

Physicians therefore must provide appropriate information about these risks to patients who are considering the contralateral procedure, according to lead investigator Allison C. Stover, M.P.H. Major complications often require numerous unplanned procedures, which increase patient burden and treatment costs.

To assess the impact of the contralateral procedure on surgical outcomes, Ms. Stover of the University of California, San Francisco, and her colleagues identified patients who underwent unilateral or bilateral mastectomy with immediate reconstruction at her institution between 2005 and 2010. A minimum of 1 year of follow-up data was available for each study participant. Patients with bilateral cancer or bilateral prophylactic surgery were excluded from the analysis.

The investigators grouped the patients by unilateral or contralateral mastectomy status. They also prospectively captured complications, including infection with use of oral or intravenous antibiotics; implant exposure, loss, or removal; seroma; hematoma; delayed wound healing; necrosis; readmission; and return to the operating room.

Among the 470 patients (665 breasts) who met the study criteria, the mean follow-up time was 22 months. There were no differences between the groups in tumor grade, stage, follow-up time, smoking history, or radiation, either prior to or post surgery, Ms. Stover said in a poster presentation at the San Antonio Breast Cancer Symposium.

Significant between-group differences were observed in age and the number of skin-sparing mastectomies, she said, noting that the contralateral group was younger than the unilateral group (mean age 46.04 years vs. 50.55 years, respectively), and had a larger proportion of skin-sparing mastectomies.

The rate of any major complication was 1.5 times higher in the contralateral group compared with the unilateral group, Ms. Stover stated. "There were significant between-group differences in the number of severe infections requiring IV antibiotics and return to the operating room, as well as the overall rate of any major complication," she said.

A comparison of the complication rate by index vs. prophylactic breast within the contralateral group showed a significantly higher rate of implant loss in the index breast, but no significant differences in any other measure, Ms. Stover noted.

Because many contralateral cases are not at sufficiently high risk for a second breast cancer to meet clinical criteria for prophylactic surgery, the increased complication rate should be taken into consideration when counseling women who are contemplating contralateral mastectomy, Ms. Stover said, adding that they should also be incorporated into guidelines and clinical recommendations.

The poster discussant, Dr. Ismail Jatoi of the University of Texas Health Sciences Center in San Antonio, pointed out that the study’s mean follow-up of 22 months may be insufficient to adequately compare the complication rates. "There are long-term implications that may increase the value [of the contralateral procedure]. For example, patients who undergo the procedure no longer undergo mammograms and thus are not subject to false-positive reports and the subsequent associated testing. They may have lower morbidity over time," he said. "The long-term impact may be less dire than the short-term impact."

It is also possible that the results could be attributed to a "multiplicity of testing," Dr. Jatoi said. "When you test for a lot of bad outcomes, you’re likely to find one."

Despite these concerns, "there clearly are some risks, which point to the need for proper, thorough informed consent," said Dr. Jatoi. "The possible increased complication risks are definitely points to be made when we provide informed consent."

Ms. Stover and Dr. Jatoi reported that they had no relevant financial conflicts.

SAN ANTONIO – Contralateral prophylactic mastectomy – in comparison to unilateral mastectomy – was associated with a significantly increased rate of major postoperative surgical complications in a 470-patient study.

Physicians therefore must provide appropriate information about these risks to patients who are considering the contralateral procedure, according to lead investigator Allison C. Stover, M.P.H. Major complications often require numerous unplanned procedures, which increase patient burden and treatment costs.

To assess the impact of the contralateral procedure on surgical outcomes, Ms. Stover of the University of California, San Francisco, and her colleagues identified patients who underwent unilateral or bilateral mastectomy with immediate reconstruction at her institution between 2005 and 2010. A minimum of 1 year of follow-up data was available for each study participant. Patients with bilateral cancer or bilateral prophylactic surgery were excluded from the analysis.

The investigators grouped the patients by unilateral or contralateral mastectomy status. They also prospectively captured complications, including infection with use of oral or intravenous antibiotics; implant exposure, loss, or removal; seroma; hematoma; delayed wound healing; necrosis; readmission; and return to the operating room.

Among the 470 patients (665 breasts) who met the study criteria, the mean follow-up time was 22 months. There were no differences between the groups in tumor grade, stage, follow-up time, smoking history, or radiation, either prior to or post surgery, Ms. Stover said in a poster presentation at the San Antonio Breast Cancer Symposium.

Significant between-group differences were observed in age and the number of skin-sparing mastectomies, she said, noting that the contralateral group was younger than the unilateral group (mean age 46.04 years vs. 50.55 years, respectively), and had a larger proportion of skin-sparing mastectomies.

The rate of any major complication was 1.5 times higher in the contralateral group compared with the unilateral group, Ms. Stover stated. "There were significant between-group differences in the number of severe infections requiring IV antibiotics and return to the operating room, as well as the overall rate of any major complication," she said.

A comparison of the complication rate by index vs. prophylactic breast within the contralateral group showed a significantly higher rate of implant loss in the index breast, but no significant differences in any other measure, Ms. Stover noted.

Because many contralateral cases are not at sufficiently high risk for a second breast cancer to meet clinical criteria for prophylactic surgery, the increased complication rate should be taken into consideration when counseling women who are contemplating contralateral mastectomy, Ms. Stover said, adding that they should also be incorporated into guidelines and clinical recommendations.

The poster discussant, Dr. Ismail Jatoi of the University of Texas Health Sciences Center in San Antonio, pointed out that the study’s mean follow-up of 22 months may be insufficient to adequately compare the complication rates. "There are long-term implications that may increase the value [of the contralateral procedure]. For example, patients who undergo the procedure no longer undergo mammograms and thus are not subject to false-positive reports and the subsequent associated testing. They may have lower morbidity over time," he said. "The long-term impact may be less dire than the short-term impact."

It is also possible that the results could be attributed to a "multiplicity of testing," Dr. Jatoi said. "When you test for a lot of bad outcomes, you’re likely to find one."

Despite these concerns, "there clearly are some risks, which point to the need for proper, thorough informed consent," said Dr. Jatoi. "The possible increased complication risks are definitely points to be made when we provide informed consent."

Ms. Stover and Dr. Jatoi reported that they had no relevant financial conflicts.

SAN ANTONIO – Contralateral prophylactic mastectomy – in comparison to unilateral mastectomy – was associated with a significantly increased rate of major postoperative surgical complications in a 470-patient study.

Physicians therefore must provide appropriate information about these risks to patients who are considering the contralateral procedure, according to lead investigator Allison C. Stover, M.P.H. Major complications often require numerous unplanned procedures, which increase patient burden and treatment costs.

To assess the impact of the contralateral procedure on surgical outcomes, Ms. Stover of the University of California, San Francisco, and her colleagues identified patients who underwent unilateral or bilateral mastectomy with immediate reconstruction at her institution between 2005 and 2010. A minimum of 1 year of follow-up data was available for each study participant. Patients with bilateral cancer or bilateral prophylactic surgery were excluded from the analysis.

The investigators grouped the patients by unilateral or contralateral mastectomy status. They also prospectively captured complications, including infection with use of oral or intravenous antibiotics; implant exposure, loss, or removal; seroma; hematoma; delayed wound healing; necrosis; readmission; and return to the operating room.

Among the 470 patients (665 breasts) who met the study criteria, the mean follow-up time was 22 months. There were no differences between the groups in tumor grade, stage, follow-up time, smoking history, or radiation, either prior to or post surgery, Ms. Stover said in a poster presentation at the San Antonio Breast Cancer Symposium.

Significant between-group differences were observed in age and the number of skin-sparing mastectomies, she said, noting that the contralateral group was younger than the unilateral group (mean age 46.04 years vs. 50.55 years, respectively), and had a larger proportion of skin-sparing mastectomies.

The rate of any major complication was 1.5 times higher in the contralateral group compared with the unilateral group, Ms. Stover stated. "There were significant between-group differences in the number of severe infections requiring IV antibiotics and return to the operating room, as well as the overall rate of any major complication," she said.

A comparison of the complication rate by index vs. prophylactic breast within the contralateral group showed a significantly higher rate of implant loss in the index breast, but no significant differences in any other measure, Ms. Stover noted.

Because many contralateral cases are not at sufficiently high risk for a second breast cancer to meet clinical criteria for prophylactic surgery, the increased complication rate should be taken into consideration when counseling women who are contemplating contralateral mastectomy, Ms. Stover said, adding that they should also be incorporated into guidelines and clinical recommendations.

The poster discussant, Dr. Ismail Jatoi of the University of Texas Health Sciences Center in San Antonio, pointed out that the study’s mean follow-up of 22 months may be insufficient to adequately compare the complication rates. "There are long-term implications that may increase the value [of the contralateral procedure]. For example, patients who undergo the procedure no longer undergo mammograms and thus are not subject to false-positive reports and the subsequent associated testing. They may have lower morbidity over time," he said. "The long-term impact may be less dire than the short-term impact."

It is also possible that the results could be attributed to a "multiplicity of testing," Dr. Jatoi said. "When you test for a lot of bad outcomes, you’re likely to find one."

Despite these concerns, "there clearly are some risks, which point to the need for proper, thorough informed consent," said Dr. Jatoi. "The possible increased complication risks are definitely points to be made when we provide informed consent."

Ms. Stover and Dr. Jatoi reported that they had no relevant financial conflicts.

SAN ANTONIO – Axillary lymph node dissection is not warranted in patients with clinically node-negative breast cancer and micrometastases in the sentinel node, another randomized phase III clinical trial has found.

New 57-month follow-up data from the International Breast Cancer Study Group (IBCSG) trial 23-01 in breast cancer patients with minimal sentinel node involvement show no disease-free or overall survival differences between patients who underwent axillary dissection and those who did not, Dr. Viviana Galimberti reported at the San Antonio Breast Cancer Symposium.

This is consistent with the results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, which reported in February that it found no survival difference between early-stage breast cancer patients who underwent axillary lymph node dissection and those who did not after being found sentinel node positive on biopsy (JAMA 2011;305:569-75).

The IBCSG trial 23-01 randomized 934 patients from 27 centers to axillary dissection or no further axillary surgery. All of the patients had tumors no larger than 5 cm and minimal sentinel node involvement, defined as one or more micrometastatic (less than 2 mm) sentinel node were included in the analysis, said Dr. Galimberti of the European Institute of Oncology in Milan. Disease-free survival was the study’s primary end point, while overall survival and systemic disease-free survival were secondary end points, she said.

Of the 934 patients, 3 were excluded, including 2 patients in whom no tumor was found in the sentinel node and 1 patient who withdrew consent, Dr. Galimberti said. Of the remaining 931 patients in the intent to treat population, 17 of the 464 assigned to axial dissection did not receive it and 14 of the 467 assigned to no dissection did receive it, she said.

At study entry, mean patient age was 54 years, and more than half (56%) of the patients were postmenopausal. Regarding disease characteristics, 67% of the patients had tumors less than 2 cm, 7% had tumors 3 cm or larger, and 26% had grade 3 disease "Most of the tumors [89%] were estrogen receptor–positive and 75% were progesterone receptor–positive," Dr. Galimberti said. In the involved sentinel nodes, 67% of the patients had micrometastasis less than 1.0 mm, 29% had micrometastasis from 1.1-2.0, 2% had metastasis greater than 2.0, and 2% were unknown, she said.

In all, 96% of the patients underwent lymphoscintigraphy and evidence of one or two sentinel nodes was found in 85% of them, Dr. Galimberti reported. Previous excision biopsy was performed in 16% of the patients, and conservative surgery was the definitive treatment in three-quarters of the patients while 25% received mastectomy. Similar rates of adjuvant radiotherapy, hormonal therapy, and chemotherapy were seen in both groups, she said.

Long-term adverse events were more prevalent in the dissection group, with 18% experiencing sensory neuropathy, compared with 12% of those not undergoing dissection. Similarly, the respective rates of lymphedema were 13% and 4% and the respective rates of motor neuropathy were 8% and 3%, Dr. Galimberti reported.

The 5-year disease-free survival rates in the dissection and no dissection groups were 87.3% and 88.4%, respectively, said Dr. Galimberti. The 5-year overall survival rates were similar between both groups as well, at 97.6% in the dissection group and 98% in the no-dissection group.

"In total, there were 17 [3.7%] deaths among the patients who underwent dissection and 12 [2.6%] among those who did not," she said.

The lack of a difference between the groups for the primary end point of disease-free survival fulfilled the protocol-specified criterion for noninferiority. Indeed, Dr. Galimberti noted, "The 5-year disease-free survival of 88% in the patients who did not undergo dissection was much better than the 70% that was anticipated in the original plan," she said. The rate of reappearance of tumor in the undissected axilla was also unexpectedly low, at about 1%, she added.

"It seems likely that the results of the IBCSG Trial 23-01 and Z0011 will change clinical practice, allowing no axillary dissection in early breast cancer, especially when the sentinel node is minimally involved, to reduce [associated] complications with no adverse effect on survival," Dr. Galimberti concluded.

Dr. Galimberti reported having no relevant financial conflicts to disclose.

SAN ANTONIO – Axillary lymph node dissection is not warranted in patients with clinically node-negative breast cancer and micrometastases in the sentinel node, another randomized phase III clinical trial has found.

New 57-month follow-up data from the International Breast Cancer Study Group (IBCSG) trial 23-01 in breast cancer patients with minimal sentinel node involvement show no disease-free or overall survival differences between patients who underwent axillary dissection and those who did not, Dr. Viviana Galimberti reported at the San Antonio Breast Cancer Symposium.

This is consistent with the results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, which reported in February that it found no survival difference between early-stage breast cancer patients who underwent axillary lymph node dissection and those who did not after being found sentinel node positive on biopsy (JAMA 2011;305:569-75).

The IBCSG trial 23-01 randomized 934 patients from 27 centers to axillary dissection or no further axillary surgery. All of the patients had tumors no larger than 5 cm and minimal sentinel node involvement, defined as one or more micrometastatic (less than 2 mm) sentinel node were included in the analysis, said Dr. Galimberti of the European Institute of Oncology in Milan. Disease-free survival was the study’s primary end point, while overall survival and systemic disease-free survival were secondary end points, she said.

Of the 934 patients, 3 were excluded, including 2 patients in whom no tumor was found in the sentinel node and 1 patient who withdrew consent, Dr. Galimberti said. Of the remaining 931 patients in the intent to treat population, 17 of the 464 assigned to axial dissection did not receive it and 14 of the 467 assigned to no dissection did receive it, she said.

At study entry, mean patient age was 54 years, and more than half (56%) of the patients were postmenopausal. Regarding disease characteristics, 67% of the patients had tumors less than 2 cm, 7% had tumors 3 cm or larger, and 26% had grade 3 disease "Most of the tumors [89%] were estrogen receptor–positive and 75% were progesterone receptor–positive," Dr. Galimberti said. In the involved sentinel nodes, 67% of the patients had micrometastasis less than 1.0 mm, 29% had micrometastasis from 1.1-2.0, 2% had metastasis greater than 2.0, and 2% were unknown, she said.

In all, 96% of the patients underwent lymphoscintigraphy and evidence of one or two sentinel nodes was found in 85% of them, Dr. Galimberti reported. Previous excision biopsy was performed in 16% of the patients, and conservative surgery was the definitive treatment in three-quarters of the patients while 25% received mastectomy. Similar rates of adjuvant radiotherapy, hormonal therapy, and chemotherapy were seen in both groups, she said.

Long-term adverse events were more prevalent in the dissection group, with 18% experiencing sensory neuropathy, compared with 12% of those not undergoing dissection. Similarly, the respective rates of lymphedema were 13% and 4% and the respective rates of motor neuropathy were 8% and 3%, Dr. Galimberti reported.

The 5-year disease-free survival rates in the dissection and no dissection groups were 87.3% and 88.4%, respectively, said Dr. Galimberti. The 5-year overall survival rates were similar between both groups as well, at 97.6% in the dissection group and 98% in the no-dissection group.

"In total, there were 17 [3.7%] deaths among the patients who underwent dissection and 12 [2.6%] among those who did not," she said.

The lack of a difference between the groups for the primary end point of disease-free survival fulfilled the protocol-specified criterion for noninferiority. Indeed, Dr. Galimberti noted, "The 5-year disease-free survival of 88% in the patients who did not undergo dissection was much better than the 70% that was anticipated in the original plan," she said. The rate of reappearance of tumor in the undissected axilla was also unexpectedly low, at about 1%, she added.

"It seems likely that the results of the IBCSG Trial 23-01 and Z0011 will change clinical practice, allowing no axillary dissection in early breast cancer, especially when the sentinel node is minimally involved, to reduce [associated] complications with no adverse effect on survival," Dr. Galimberti concluded.

Dr. Galimberti reported having no relevant financial conflicts to disclose.

SAN ANTONIO – Axillary lymph node dissection is not warranted in patients with clinically node-negative breast cancer and micrometastases in the sentinel node, another randomized phase III clinical trial has found.

New 57-month follow-up data from the International Breast Cancer Study Group (IBCSG) trial 23-01 in breast cancer patients with minimal sentinel node involvement show no disease-free or overall survival differences between patients who underwent axillary dissection and those who did not, Dr. Viviana Galimberti reported at the San Antonio Breast Cancer Symposium.

This is consistent with the results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, which reported in February that it found no survival difference between early-stage breast cancer patients who underwent axillary lymph node dissection and those who did not after being found sentinel node positive on biopsy (JAMA 2011;305:569-75).

The IBCSG trial 23-01 randomized 934 patients from 27 centers to axillary dissection or no further axillary surgery. All of the patients had tumors no larger than 5 cm and minimal sentinel node involvement, defined as one or more micrometastatic (less than 2 mm) sentinel node were included in the analysis, said Dr. Galimberti of the European Institute of Oncology in Milan. Disease-free survival was the study’s primary end point, while overall survival and systemic disease-free survival were secondary end points, she said.

Of the 934 patients, 3 were excluded, including 2 patients in whom no tumor was found in the sentinel node and 1 patient who withdrew consent, Dr. Galimberti said. Of the remaining 931 patients in the intent to treat population, 17 of the 464 assigned to axial dissection did not receive it and 14 of the 467 assigned to no dissection did receive it, she said.

At study entry, mean patient age was 54 years, and more than half (56%) of the patients were postmenopausal. Regarding disease characteristics, 67% of the patients had tumors less than 2 cm, 7% had tumors 3 cm or larger, and 26% had grade 3 disease "Most of the tumors [89%] were estrogen receptor–positive and 75% were progesterone receptor–positive," Dr. Galimberti said. In the involved sentinel nodes, 67% of the patients had micrometastasis less than 1.0 mm, 29% had micrometastasis from 1.1-2.0, 2% had metastasis greater than 2.0, and 2% were unknown, she said.

In all, 96% of the patients underwent lymphoscintigraphy and evidence of one or two sentinel nodes was found in 85% of them, Dr. Galimberti reported. Previous excision biopsy was performed in 16% of the patients, and conservative surgery was the definitive treatment in three-quarters of the patients while 25% received mastectomy. Similar rates of adjuvant radiotherapy, hormonal therapy, and chemotherapy were seen in both groups, she said.

Long-term adverse events were more prevalent in the dissection group, with 18% experiencing sensory neuropathy, compared with 12% of those not undergoing dissection. Similarly, the respective rates of lymphedema were 13% and 4% and the respective rates of motor neuropathy were 8% and 3%, Dr. Galimberti reported.

The 5-year disease-free survival rates in the dissection and no dissection groups were 87.3% and 88.4%, respectively, said Dr. Galimberti. The 5-year overall survival rates were similar between both groups as well, at 97.6% in the dissection group and 98% in the no-dissection group.

"In total, there were 17 [3.7%] deaths among the patients who underwent dissection and 12 [2.6%] among those who did not," she said.

The lack of a difference between the groups for the primary end point of disease-free survival fulfilled the protocol-specified criterion for noninferiority. Indeed, Dr. Galimberti noted, "The 5-year disease-free survival of 88% in the patients who did not undergo dissection was much better than the 70% that was anticipated in the original plan," she said. The rate of reappearance of tumor in the undissected axilla was also unexpectedly low, at about 1%, she added.

"It seems likely that the results of the IBCSG Trial 23-01 and Z0011 will change clinical practice, allowing no axillary dissection in early breast cancer, especially when the sentinel node is minimally involved, to reduce [associated] complications with no adverse effect on survival," Dr. Galimberti concluded.

Dr. Galimberti reported having no relevant financial conflicts to disclose.

SAN ANTONIO – Immediate treatment with zoledronic acid in postmenopausal women with hormone receptor–positive breast cancer initiating letrozole therapy was associated with a 34% reduction in recurrence risk and 31% improvement in overall survival, compared with women of similar status who received the bisphosphonate later, according to new data from the ZO-FAST trial.

This study assessed the impact of zoledronic acid (Zometa) on aromatase inhibitor-associated bone loss after surgery for early breast cancer.

Additional disease-free and overall survival benefits were observed among the subgroup of patients who had been postmenopausal for at least 5 years, Dr. Richard de Boer reported yesterday at the San Antonio Breast Cancer Symposium.

The findings update those previously reported by Dr. de Boer of the Royal Melbourne Hospital and colleagues in the ZO-FAST (Zometa-Femara Adjuvant Synergy Trial), demonstrating that early zoledronic acid significantly improved bone mineral density and improved breast cancer disease-free survival.

The new, long-term data confirm the overall survival benefits, and the results of an exploratory subgroup analysis based on menopausal status indicates that the addition of zoledronic acid confers the most benefit to women who are truly menopausal at diagnosis, Dr. de Boer reported.

The study involved 1,065 postmenopausal women with hormone receptor–positive early breast cancer with a bone mineral density T-score of –2. In addition to receiving adjuvant endocrine therapy with 2.5 mg of letrozole (Femara) four times daily for 5 years, the women were randomized to receive 4 mg of zoledronic acid every 6 months either immediately or when their post-baseline T score dipped below –2 or they suffered a nontraumatic/asymptomatic fracture. Patients were included in the analysis if they had established menopause at the time of diagnosis or if they became menopausal as a consequence of chemotherapy or ovarian suppression, Dr. de Boer explained.

At 60 months follow-up, the hazard ratios for recurrence and mortality in the immediate treatment group were 0.66 and 0.69 respectively, with only the former representing a statistically significant improvement over the delayed treatment patients, Dr. de Boer reported. Exploratory analyses of the 670 women who were postmenopausal for more than 5 years or older than 60 years at study entry showed that immediate zoledronic acid treatment significantly improved disease-free survival, with a hazard ratio of 0.63, and significantly prolonged overall survival, with a hazard ratio of 0.50, compared with the delayed treatment group.

With respect to lumbar spine bone mineral density, "the benefits observed in the immediate therapy group early on, when bone loss is at it greatest, continued out over 5 years, with a net difference of 10% favoring the immediate zoledronic acid group," Dr. de Boer said, noting that similar results were observed in total hip bone mineral density, "with an overall change of close to 6% in the immediate group at the 5-year time point."

In a subset analysis comparing the immediate treatment group with the 27% of patients who initiated zoledronic acid, "we observed a hazard ratio 0.62 for recurrence in favor of the up-front zoledronic acid group," Dr. de Boer said. "Bone was the most common site of recurrence, and this favored the immediate group, with 14 events compared with 24 in the delayed group."

In a comparison of patients who did and did not initiate therapy, "the hazard ratio for disease-free survival was in favor of those who did initiate treatment, suggesting a delay in bisphosphonate initiation could still have an impact on disease outcomes," Dr. de Boer said.

In terms of safety, there were three confirmed cases of osteonecrosis of the jaw in the trial, all in the immediate group. "This compares favorably with published results of studies in which zoledronic acid was administered on a 6-month schedule," according to Dr. de Boer. "The AZURE [Adjuvant Zoledronic Acid to Reduce Recurrence] study had a more intensive administration schedule, and thus had more cases of jaw osteonecrosis."

The findings of this study, together with those of other recent studies including the AZURE trial, "support the hypothesis that the anticancer benefits of zoledronic acid may best be realized in a low-estrogen environment," Dr. de Boer concluded.

The additional anticancer benefit observed in the truly vs. recently postmenopausal women in this study warrants additional investigation, according to Dr. James Ingle of the Mayo Clinic in Rochester, Minn., the discussant for the session. "The study met its primary analysis endpoint, which was bone mineral density improvement, but it was not powered nor designed to detect a difference in breast events," he said. "Although the findings demonstrate the value of zoledronic acid, they are based on an unplanned analysis and thus insufficient on their own to support zoledronic acid as standard of care in postmenopausal women."

Dr. de Boer is on the speakers’ bureau for Novartis. Dr. Ingle said he had no financial conflicts to disclose.

SAN ANTONIO – Immediate treatment with zoledronic acid in postmenopausal women with hormone receptor–positive breast cancer initiating letrozole therapy was associated with a 34% reduction in recurrence risk and 31% improvement in overall survival, compared with women of similar status who received the bisphosphonate later, according to new data from the ZO-FAST trial.

This study assessed the impact of zoledronic acid (Zometa) on aromatase inhibitor-associated bone loss after surgery for early breast cancer.

Additional disease-free and overall survival benefits were observed among the subgroup of patients who had been postmenopausal for at least 5 years, Dr. Richard de Boer reported yesterday at the San Antonio Breast Cancer Symposium.

The findings update those previously reported by Dr. de Boer of the Royal Melbourne Hospital and colleagues in the ZO-FAST (Zometa-Femara Adjuvant Synergy Trial), demonstrating that early zoledronic acid significantly improved bone mineral density and improved breast cancer disease-free survival.

The new, long-term data confirm the overall survival benefits, and the results of an exploratory subgroup analysis based on menopausal status indicates that the addition of zoledronic acid confers the most benefit to women who are truly menopausal at diagnosis, Dr. de Boer reported.

The study involved 1,065 postmenopausal women with hormone receptor–positive early breast cancer with a bone mineral density T-score of –2. In addition to receiving adjuvant endocrine therapy with 2.5 mg of letrozole (Femara) four times daily for 5 years, the women were randomized to receive 4 mg of zoledronic acid every 6 months either immediately or when their post-baseline T score dipped below –2 or they suffered a nontraumatic/asymptomatic fracture. Patients were included in the analysis if they had established menopause at the time of diagnosis or if they became menopausal as a consequence of chemotherapy or ovarian suppression, Dr. de Boer explained.

At 60 months follow-up, the hazard ratios for recurrence and mortality in the immediate treatment group were 0.66 and 0.69 respectively, with only the former representing a statistically significant improvement over the delayed treatment patients, Dr. de Boer reported. Exploratory analyses of the 670 women who were postmenopausal for more than 5 years or older than 60 years at study entry showed that immediate zoledronic acid treatment significantly improved disease-free survival, with a hazard ratio of 0.63, and significantly prolonged overall survival, with a hazard ratio of 0.50, compared with the delayed treatment group.

With respect to lumbar spine bone mineral density, "the benefits observed in the immediate therapy group early on, when bone loss is at it greatest, continued out over 5 years, with a net difference of 10% favoring the immediate zoledronic acid group," Dr. de Boer said, noting that similar results were observed in total hip bone mineral density, "with an overall change of close to 6% in the immediate group at the 5-year time point."

In a subset analysis comparing the immediate treatment group with the 27% of patients who initiated zoledronic acid, "we observed a hazard ratio 0.62 for recurrence in favor of the up-front zoledronic acid group," Dr. de Boer said. "Bone was the most common site of recurrence, and this favored the immediate group, with 14 events compared with 24 in the delayed group."

In a comparison of patients who did and did not initiate therapy, "the hazard ratio for disease-free survival was in favor of those who did initiate treatment, suggesting a delay in bisphosphonate initiation could still have an impact on disease outcomes," Dr. de Boer said.

In terms of safety, there were three confirmed cases of osteonecrosis of the jaw in the trial, all in the immediate group. "This compares favorably with published results of studies in which zoledronic acid was administered on a 6-month schedule," according to Dr. de Boer. "The AZURE [Adjuvant Zoledronic Acid to Reduce Recurrence] study had a more intensive administration schedule, and thus had more cases of jaw osteonecrosis."

The findings of this study, together with those of other recent studies including the AZURE trial, "support the hypothesis that the anticancer benefits of zoledronic acid may best be realized in a low-estrogen environment," Dr. de Boer concluded.

The additional anticancer benefit observed in the truly vs. recently postmenopausal women in this study warrants additional investigation, according to Dr. James Ingle of the Mayo Clinic in Rochester, Minn., the discussant for the session. "The study met its primary analysis endpoint, which was bone mineral density improvement, but it was not powered nor designed to detect a difference in breast events," he said. "Although the findings demonstrate the value of zoledronic acid, they are based on an unplanned analysis and thus insufficient on their own to support zoledronic acid as standard of care in postmenopausal women."

Dr. de Boer is on the speakers’ bureau for Novartis. Dr. Ingle said he had no financial conflicts to disclose.

SAN ANTONIO – Immediate treatment with zoledronic acid in postmenopausal women with hormone receptor–positive breast cancer initiating letrozole therapy was associated with a 34% reduction in recurrence risk and 31% improvement in overall survival, compared with women of similar status who received the bisphosphonate later, according to new data from the ZO-FAST trial.

This study assessed the impact of zoledronic acid (Zometa) on aromatase inhibitor-associated bone loss after surgery for early breast cancer.

Additional disease-free and overall survival benefits were observed among the subgroup of patients who had been postmenopausal for at least 5 years, Dr. Richard de Boer reported yesterday at the San Antonio Breast Cancer Symposium.

The findings update those previously reported by Dr. de Boer of the Royal Melbourne Hospital and colleagues in the ZO-FAST (Zometa-Femara Adjuvant Synergy Trial), demonstrating that early zoledronic acid significantly improved bone mineral density and improved breast cancer disease-free survival.

The new, long-term data confirm the overall survival benefits, and the results of an exploratory subgroup analysis based on menopausal status indicates that the addition of zoledronic acid confers the most benefit to women who are truly menopausal at diagnosis, Dr. de Boer reported.

The study involved 1,065 postmenopausal women with hormone receptor–positive early breast cancer with a bone mineral density T-score of –2. In addition to receiving adjuvant endocrine therapy with 2.5 mg of letrozole (Femara) four times daily for 5 years, the women were randomized to receive 4 mg of zoledronic acid every 6 months either immediately or when their post-baseline T score dipped below –2 or they suffered a nontraumatic/asymptomatic fracture. Patients were included in the analysis if they had established menopause at the time of diagnosis or if they became menopausal as a consequence of chemotherapy or ovarian suppression, Dr. de Boer explained.

At 60 months follow-up, the hazard ratios for recurrence and mortality in the immediate treatment group were 0.66 and 0.69 respectively, with only the former representing a statistically significant improvement over the delayed treatment patients, Dr. de Boer reported. Exploratory analyses of the 670 women who were postmenopausal for more than 5 years or older than 60 years at study entry showed that immediate zoledronic acid treatment significantly improved disease-free survival, with a hazard ratio of 0.63, and significantly prolonged overall survival, with a hazard ratio of 0.50, compared with the delayed treatment group.

With respect to lumbar spine bone mineral density, "the benefits observed in the immediate therapy group early on, when bone loss is at it greatest, continued out over 5 years, with a net difference of 10% favoring the immediate zoledronic acid group," Dr. de Boer said, noting that similar results were observed in total hip bone mineral density, "with an overall change of close to 6% in the immediate group at the 5-year time point."

In a subset analysis comparing the immediate treatment group with the 27% of patients who initiated zoledronic acid, "we observed a hazard ratio 0.62 for recurrence in favor of the up-front zoledronic acid group," Dr. de Boer said. "Bone was the most common site of recurrence, and this favored the immediate group, with 14 events compared with 24 in the delayed group."

In a comparison of patients who did and did not initiate therapy, "the hazard ratio for disease-free survival was in favor of those who did initiate treatment, suggesting a delay in bisphosphonate initiation could still have an impact on disease outcomes," Dr. de Boer said.

In terms of safety, there were three confirmed cases of osteonecrosis of the jaw in the trial, all in the immediate group. "This compares favorably with published results of studies in which zoledronic acid was administered on a 6-month schedule," according to Dr. de Boer. "The AZURE [Adjuvant Zoledronic Acid to Reduce Recurrence] study had a more intensive administration schedule, and thus had more cases of jaw osteonecrosis."

The findings of this study, together with those of other recent studies including the AZURE trial, "support the hypothesis that the anticancer benefits of zoledronic acid may best be realized in a low-estrogen environment," Dr. de Boer concluded.

The additional anticancer benefit observed in the truly vs. recently postmenopausal women in this study warrants additional investigation, according to Dr. James Ingle of the Mayo Clinic in Rochester, Minn., the discussant for the session. "The study met its primary analysis endpoint, which was bone mineral density improvement, but it was not powered nor designed to detect a difference in breast events," he said. "Although the findings demonstrate the value of zoledronic acid, they are based on an unplanned analysis and thus insufficient on their own to support zoledronic acid as standard of care in postmenopausal women."

Dr. de Boer is on the speakers’ bureau for Novartis. Dr. Ingle said he had no financial conflicts to disclose.

SAN ANTONIO – A risk score based on a 12-gene assay is expected to help physicians determine whether postsurgical radiation for ductal carcinoma in situ would improve an individual patient’s outcome, Dr. Lawrence J. Solin reported at the San Antonio Breast Cancer Symposium.

In a biomarker validation study, investigators demonstrated that a prespecified score on the Oncotype DX DCIS measure developed by Genomic Health Inc. can predict the risk of an ipsilateral breast event – either the development of a new invasive breast cancer or the recurrence of DCIS in the same breast – in women who have undergone breast-conservation surgery.

The 12-gene assay is a subset of the Oncotype DX 21 gene assay for invasive breast cancer. Dr. Solin, chair of radiation oncology at Albert Einstein Medical Center in Philadelphia, and colleagues in the Eastern Cooperative Oncology Group (ECOG) evaluated its predictive value in 327 patients drawn from the prospective multicenter ECOG E5194 study in which the more extensive assay had been performed, he explained. All of the patients had low/intermediate grade DCIS, defined as 2.5 cm or smaller or high-grade DCIS, defined as 1 cm or smaller, he said (J. Clin. Oncol. 2009;27:5319-24).

Based on the 21-gene assay, central pathology review, and a recurrence algorithm, the investigators calculated a DCIS score from 0-100, with scores less than 39, 39-54, and 55 and higher, respectively, classified as low, intermediate, and high risk for recurrence, Dr. Solin said. During nearly 9 years of follow-up, recurrent DCIS developed in 20 patients and invasive cancer in the ipsilateral breast in 26 patients, he reported. Among patients with low/intermediate DCIS and high-grade DCIS, respectively, the 10-year breast event rates were 15.4% and 15.1%, and the invasive breast event rates were 5.6% and 9.8%, he reported.

By DCIS score, "75% of the patients were in the low-risk category, compared with 14% classified as intermediate risk and 11% as high risk," said Dr. Solin. The rates of both any ipsilateral breast event and invasive breast cancer were directly related to DCIS risk score, with 12.0%, 24.5%, and 27.3% of patients in the low, intermediate, and high DCIS score groups experiencing any ipsilateral breast event and 5.1%, 8.9%, and 19.1% developing invasive breast cancer, he said. In multivariate analysis, DCIS score, menopausal status, and tumor size were all significantly associated with recurrence.

The DCIS score is "groundbreaking," according to Dr. Solin, because it is the first validated molecular marker that clearly differentiates low-risk from high-risk disease in DCIS, Dr. Solin stressed. The tool "will help physicians understand the underlying biology of [DCIS] for the individual patient, accurately gauging the risk for that patient and helping guide treatment," he said. Clinical and pathologic factors are not reliable enough on their own to determine whether radiation following breast-conservation surgery will confer any survival benefit, he explained.

Genomic Health has announced the Oncotype DX DCIS tool will be available by the end of December 2011. In response to questions about the price of the test and insurance coverage, Dr. Solin noted that, in aggregate, the savings associated with avoiding unnecessary additional treatment in patients with a low-risk DCIS score would more than compensate for the price of the test in individual patients.

Dr. Solin reported having no relevant financial disclosures. The study team included employees of Genomic Health.

SAN ANTONIO – A risk score based on a 12-gene assay is expected to help physicians determine whether postsurgical radiation for ductal carcinoma in situ would improve an individual patient’s outcome, Dr. Lawrence J. Solin reported at the San Antonio Breast Cancer Symposium.

In a biomarker validation study, investigators demonstrated that a prespecified score on the Oncotype DX DCIS measure developed by Genomic Health Inc. can predict the risk of an ipsilateral breast event – either the development of a new invasive breast cancer or the recurrence of DCIS in the same breast – in women who have undergone breast-conservation surgery.

The 12-gene assay is a subset of the Oncotype DX 21 gene assay for invasive breast cancer. Dr. Solin, chair of radiation oncology at Albert Einstein Medical Center in Philadelphia, and colleagues in the Eastern Cooperative Oncology Group (ECOG) evaluated its predictive value in 327 patients drawn from the prospective multicenter ECOG E5194 study in which the more extensive assay had been performed, he explained. All of the patients had low/intermediate grade DCIS, defined as 2.5 cm or smaller or high-grade DCIS, defined as 1 cm or smaller, he said (J. Clin. Oncol. 2009;27:5319-24).

Based on the 21-gene assay, central pathology review, and a recurrence algorithm, the investigators calculated a DCIS score from 0-100, with scores less than 39, 39-54, and 55 and higher, respectively, classified as low, intermediate, and high risk for recurrence, Dr. Solin said. During nearly 9 years of follow-up, recurrent DCIS developed in 20 patients and invasive cancer in the ipsilateral breast in 26 patients, he reported. Among patients with low/intermediate DCIS and high-grade DCIS, respectively, the 10-year breast event rates were 15.4% and 15.1%, and the invasive breast event rates were 5.6% and 9.8%, he reported.

By DCIS score, "75% of the patients were in the low-risk category, compared with 14% classified as intermediate risk and 11% as high risk," said Dr. Solin. The rates of both any ipsilateral breast event and invasive breast cancer were directly related to DCIS risk score, with 12.0%, 24.5%, and 27.3% of patients in the low, intermediate, and high DCIS score groups experiencing any ipsilateral breast event and 5.1%, 8.9%, and 19.1% developing invasive breast cancer, he said. In multivariate analysis, DCIS score, menopausal status, and tumor size were all significantly associated with recurrence.

The DCIS score is "groundbreaking," according to Dr. Solin, because it is the first validated molecular marker that clearly differentiates low-risk from high-risk disease in DCIS, Dr. Solin stressed. The tool "will help physicians understand the underlying biology of [DCIS] for the individual patient, accurately gauging the risk for that patient and helping guide treatment," he said. Clinical and pathologic factors are not reliable enough on their own to determine whether radiation following breast-conservation surgery will confer any survival benefit, he explained.

Genomic Health has announced the Oncotype DX DCIS tool will be available by the end of December 2011. In response to questions about the price of the test and insurance coverage, Dr. Solin noted that, in aggregate, the savings associated with avoiding unnecessary additional treatment in patients with a low-risk DCIS score would more than compensate for the price of the test in individual patients.

Dr. Solin reported having no relevant financial disclosures. The study team included employees of Genomic Health.

SAN ANTONIO – A risk score based on a 12-gene assay is expected to help physicians determine whether postsurgical radiation for ductal carcinoma in situ would improve an individual patient’s outcome, Dr. Lawrence J. Solin reported at the San Antonio Breast Cancer Symposium.

In a biomarker validation study, investigators demonstrated that a prespecified score on the Oncotype DX DCIS measure developed by Genomic Health Inc. can predict the risk of an ipsilateral breast event – either the development of a new invasive breast cancer or the recurrence of DCIS in the same breast – in women who have undergone breast-conservation surgery.

The 12-gene assay is a subset of the Oncotype DX 21 gene assay for invasive breast cancer. Dr. Solin, chair of radiation oncology at Albert Einstein Medical Center in Philadelphia, and colleagues in the Eastern Cooperative Oncology Group (ECOG) evaluated its predictive value in 327 patients drawn from the prospective multicenter ECOG E5194 study in which the more extensive assay had been performed, he explained. All of the patients had low/intermediate grade DCIS, defined as 2.5 cm or smaller or high-grade DCIS, defined as 1 cm or smaller, he said (J. Clin. Oncol. 2009;27:5319-24).

Based on the 21-gene assay, central pathology review, and a recurrence algorithm, the investigators calculated a DCIS score from 0-100, with scores less than 39, 39-54, and 55 and higher, respectively, classified as low, intermediate, and high risk for recurrence, Dr. Solin said. During nearly 9 years of follow-up, recurrent DCIS developed in 20 patients and invasive cancer in the ipsilateral breast in 26 patients, he reported. Among patients with low/intermediate DCIS and high-grade DCIS, respectively, the 10-year breast event rates were 15.4% and 15.1%, and the invasive breast event rates were 5.6% and 9.8%, he reported.

By DCIS score, "75% of the patients were in the low-risk category, compared with 14% classified as intermediate risk and 11% as high risk," said Dr. Solin. The rates of both any ipsilateral breast event and invasive breast cancer were directly related to DCIS risk score, with 12.0%, 24.5%, and 27.3% of patients in the low, intermediate, and high DCIS score groups experiencing any ipsilateral breast event and 5.1%, 8.9%, and 19.1% developing invasive breast cancer, he said. In multivariate analysis, DCIS score, menopausal status, and tumor size were all significantly associated with recurrence.

The DCIS score is "groundbreaking," according to Dr. Solin, because it is the first validated molecular marker that clearly differentiates low-risk from high-risk disease in DCIS, Dr. Solin stressed. The tool "will help physicians understand the underlying biology of [DCIS] for the individual patient, accurately gauging the risk for that patient and helping guide treatment," he said. Clinical and pathologic factors are not reliable enough on their own to determine whether radiation following breast-conservation surgery will confer any survival benefit, he explained.

Genomic Health has announced the Oncotype DX DCIS tool will be available by the end of December 2011. In response to questions about the price of the test and insurance coverage, Dr. Solin noted that, in aggregate, the savings associated with avoiding unnecessary additional treatment in patients with a low-risk DCIS score would more than compensate for the price of the test in individual patients.

Dr. Solin reported having no relevant financial disclosures. The study team included employees of Genomic Health.