Breast Cancer

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

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

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

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

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

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

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

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

Dr. Churpek had no financial disclosures.

mdales@frontlinemedcom.com

On Twitter @maryjodales

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

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

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

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

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

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

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

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

Dr. Churpek had no financial disclosures.

mdales@frontlinemedcom.com

On Twitter @maryjodales

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

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

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

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

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

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

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

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

Dr. Churpek had no financial disclosures.

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – A new approach to treating the axilla in women with early breast cancer has considerably less morbidity than the current approach, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In the randomized phase III trial – After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) – 1,425 women with early breast cancer were randomized roughly evenly to the current standard of surgical axillary lymph node dissection (ALND) or to axillary radiation therapy. Each participant had a positive sentinel node but clinically negative axillary nodes.

After 5 years of follow-up, the groups had a similarly low rates of cancer recurrence in the axilla of roughly 1%, Dr. Emiel J.T. Rutgers reported on behalf of his coinvestigators with the European Organisation for Research and Treatment of Cancer (EORTC). The radiation therapy group, however, was half as likely as the ALND group to develop lymphedema.

"The trial shows that, if treatment of the axillary lymph nodes in breast cancer is deemed necessary due to larger tumor size and sentinel lymph node involvement, radiotherapy to the axilla is a good alternative – maybe for us a better alternative – as compared to surgery because it’s associated with less side effects and has an extremely good regional cancer control," Dr. Rutgers commented in a press briefing.

The incidence of observed side effects in the radiation therapy group has been decreasing with time, and there is no reason to think that trend will reverse, said Dr. Rutgers, a surgical oncologist at the Netherlands Cancer Institute in Amsterdam. Yet, as late effects can emerge over time, the patients will be followed up for at least another 5 years.

Even though they might perceive surgery to be more effective, women can be reassured that radiation therapy will be adequate treatment, for several reasons, he said. First, only a minority of women with a positive sentinel node actually have other affected nodes. Second, the effectiveness of radiation for local control has been established in the breast conservation setting.

The findings are part of a general trend toward less extensive treatment in breast cancer. "We have shifted from 20 or 30 years ago from mastectomy to breast conservation. And now we will shift from complete axillary treatment to axillary-conserving strategies," he noted.

"It’s really incredible how quickly it seems in the last few years we are rethinking the locoregional management of breast cancer, with less surgery, and perhaps now, maybe an increase for the role of radiotherapy for local control," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

He agreed that there is a growing philosophy of less is more in the sentinel-node era. "So I would certainly try to assure patients that we try to rely on high-level evidence-based medicine ... that you can do this safely," he said.

There has been increasing uptake of radiation therapy of the axilla in the Netherlands, although it is not yet the standard of care, according to Dr. Rutgers.

Whether it will become standard of care in the United States "will remain to be seen over the next few months when people have a chance to critically review and absorb the data that will be presented today," Dr. Seidman said. "I do expect it is going to change practice at my institution and widely. Extensive surgery in the axilla can be a particular problem for certain selected medical comorbidities, and I suspect at least initially, radiation therapy will be used selectively and thoughtfully based on these data."

The AMAROS trial was open to patients with early invasive breast cancer who had tumors up to 5 cm in diameter and clinically negative lymph nodes. Those with a positive sentinel node were randomized to ALND (n = 744) or axillary radiation therapy (n = 681).

The radiation therapy was to levels I, II, and III and the supraclavicular area. The investigators used contemporary techniques to minimize exposure of healthy tissue. "There was a heavy quality control program for radiotherapy to spare lung and nerves," Dr. Rutgers said.

In the ALND group, the median number of nodes removed was 15. Two-thirds of patients did not have any additional positive nodes, other than the sentinel node.

After a median follow-up of 6.1 years, the rate of axillary recurrence was "extremely low," Dr. Rutgers reported: 0.54% with ALND and 1.03% with axillary radiation therapy.

"The axillary recurrence rate was to me, happily enough, far below that hypothesized [during the trial’s planning]; hence, the trial was underpowered," he noted in the session where the findings were presented.

The groups were statistically indistinguishable in estimated 5-year rates of overall survival, at about 93%, and disease-free survival, at about 85%.

The 5-year rate of lymphedema – defined in the study as the need for treatment with a sleeve garment, compression therapy, or lymph drainage therapy, or presence of the condition on physical examination – was 28% with ALND and 14% with axillary radiation therapy (P less than .0001), according to Dr. Rutgers.

"The side effects of radiotherapy cannot be neglected but are limited," he commented. "We looked at many other potential side effects of radiotherapy. There was no excess of cardiac problems, a very small excess of radiation pneumonitis; there was no effect on the brachial nerves."

The groups did not differ with respect to overall quality of life, but there were trends toward greater difficulty moving the arm after radiation therapy and greater swelling after ALND.

Dr. Rutgers disclosed no conflicts of interest related to the research.

CHICAGO – A new approach to treating the axilla in women with early breast cancer has considerably less morbidity than the current approach, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In the randomized phase III trial – After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) – 1,425 women with early breast cancer were randomized roughly evenly to the current standard of surgical axillary lymph node dissection (ALND) or to axillary radiation therapy. Each participant had a positive sentinel node but clinically negative axillary nodes.

After 5 years of follow-up, the groups had a similarly low rates of cancer recurrence in the axilla of roughly 1%, Dr. Emiel J.T. Rutgers reported on behalf of his coinvestigators with the European Organisation for Research and Treatment of Cancer (EORTC). The radiation therapy group, however, was half as likely as the ALND group to develop lymphedema.

"The trial shows that, if treatment of the axillary lymph nodes in breast cancer is deemed necessary due to larger tumor size and sentinel lymph node involvement, radiotherapy to the axilla is a good alternative – maybe for us a better alternative – as compared to surgery because it’s associated with less side effects and has an extremely good regional cancer control," Dr. Rutgers commented in a press briefing.

The incidence of observed side effects in the radiation therapy group has been decreasing with time, and there is no reason to think that trend will reverse, said Dr. Rutgers, a surgical oncologist at the Netherlands Cancer Institute in Amsterdam. Yet, as late effects can emerge over time, the patients will be followed up for at least another 5 years.

Even though they might perceive surgery to be more effective, women can be reassured that radiation therapy will be adequate treatment, for several reasons, he said. First, only a minority of women with a positive sentinel node actually have other affected nodes. Second, the effectiveness of radiation for local control has been established in the breast conservation setting.

The findings are part of a general trend toward less extensive treatment in breast cancer. "We have shifted from 20 or 30 years ago from mastectomy to breast conservation. And now we will shift from complete axillary treatment to axillary-conserving strategies," he noted.

"It’s really incredible how quickly it seems in the last few years we are rethinking the locoregional management of breast cancer, with less surgery, and perhaps now, maybe an increase for the role of radiotherapy for local control," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

He agreed that there is a growing philosophy of less is more in the sentinel-node era. "So I would certainly try to assure patients that we try to rely on high-level evidence-based medicine ... that you can do this safely," he said.

There has been increasing uptake of radiation therapy of the axilla in the Netherlands, although it is not yet the standard of care, according to Dr. Rutgers.

Whether it will become standard of care in the United States "will remain to be seen over the next few months when people have a chance to critically review and absorb the data that will be presented today," Dr. Seidman said. "I do expect it is going to change practice at my institution and widely. Extensive surgery in the axilla can be a particular problem for certain selected medical comorbidities, and I suspect at least initially, radiation therapy will be used selectively and thoughtfully based on these data."

The AMAROS trial was open to patients with early invasive breast cancer who had tumors up to 5 cm in diameter and clinically negative lymph nodes. Those with a positive sentinel node were randomized to ALND (n = 744) or axillary radiation therapy (n = 681).

The radiation therapy was to levels I, II, and III and the supraclavicular area. The investigators used contemporary techniques to minimize exposure of healthy tissue. "There was a heavy quality control program for radiotherapy to spare lung and nerves," Dr. Rutgers said.

In the ALND group, the median number of nodes removed was 15. Two-thirds of patients did not have any additional positive nodes, other than the sentinel node.

After a median follow-up of 6.1 years, the rate of axillary recurrence was "extremely low," Dr. Rutgers reported: 0.54% with ALND and 1.03% with axillary radiation therapy.

"The axillary recurrence rate was to me, happily enough, far below that hypothesized [during the trial’s planning]; hence, the trial was underpowered," he noted in the session where the findings were presented.

The groups were statistically indistinguishable in estimated 5-year rates of overall survival, at about 93%, and disease-free survival, at about 85%.

The 5-year rate of lymphedema – defined in the study as the need for treatment with a sleeve garment, compression therapy, or lymph drainage therapy, or presence of the condition on physical examination – was 28% with ALND and 14% with axillary radiation therapy (P less than .0001), according to Dr. Rutgers.

"The side effects of radiotherapy cannot be neglected but are limited," he commented. "We looked at many other potential side effects of radiotherapy. There was no excess of cardiac problems, a very small excess of radiation pneumonitis; there was no effect on the brachial nerves."

The groups did not differ with respect to overall quality of life, but there were trends toward greater difficulty moving the arm after radiation therapy and greater swelling after ALND.

Dr. Rutgers disclosed no conflicts of interest related to the research.

CHICAGO – A new approach to treating the axilla in women with early breast cancer has considerably less morbidity than the current approach, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In the randomized phase III trial – After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) – 1,425 women with early breast cancer were randomized roughly evenly to the current standard of surgical axillary lymph node dissection (ALND) or to axillary radiation therapy. Each participant had a positive sentinel node but clinically negative axillary nodes.

After 5 years of follow-up, the groups had a similarly low rates of cancer recurrence in the axilla of roughly 1%, Dr. Emiel J.T. Rutgers reported on behalf of his coinvestigators with the European Organisation for Research and Treatment of Cancer (EORTC). The radiation therapy group, however, was half as likely as the ALND group to develop lymphedema.

"The trial shows that, if treatment of the axillary lymph nodes in breast cancer is deemed necessary due to larger tumor size and sentinel lymph node involvement, radiotherapy to the axilla is a good alternative – maybe for us a better alternative – as compared to surgery because it’s associated with less side effects and has an extremely good regional cancer control," Dr. Rutgers commented in a press briefing.

The incidence of observed side effects in the radiation therapy group has been decreasing with time, and there is no reason to think that trend will reverse, said Dr. Rutgers, a surgical oncologist at the Netherlands Cancer Institute in Amsterdam. Yet, as late effects can emerge over time, the patients will be followed up for at least another 5 years.

Even though they might perceive surgery to be more effective, women can be reassured that radiation therapy will be adequate treatment, for several reasons, he said. First, only a minority of women with a positive sentinel node actually have other affected nodes. Second, the effectiveness of radiation for local control has been established in the breast conservation setting.

The findings are part of a general trend toward less extensive treatment in breast cancer. "We have shifted from 20 or 30 years ago from mastectomy to breast conservation. And now we will shift from complete axillary treatment to axillary-conserving strategies," he noted.

"It’s really incredible how quickly it seems in the last few years we are rethinking the locoregional management of breast cancer, with less surgery, and perhaps now, maybe an increase for the role of radiotherapy for local control," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

He agreed that there is a growing philosophy of less is more in the sentinel-node era. "So I would certainly try to assure patients that we try to rely on high-level evidence-based medicine ... that you can do this safely," he said.

There has been increasing uptake of radiation therapy of the axilla in the Netherlands, although it is not yet the standard of care, according to Dr. Rutgers.

Whether it will become standard of care in the United States "will remain to be seen over the next few months when people have a chance to critically review and absorb the data that will be presented today," Dr. Seidman said. "I do expect it is going to change practice at my institution and widely. Extensive surgery in the axilla can be a particular problem for certain selected medical comorbidities, and I suspect at least initially, radiation therapy will be used selectively and thoughtfully based on these data."

The AMAROS trial was open to patients with early invasive breast cancer who had tumors up to 5 cm in diameter and clinically negative lymph nodes. Those with a positive sentinel node were randomized to ALND (n = 744) or axillary radiation therapy (n = 681).

The radiation therapy was to levels I, II, and III and the supraclavicular area. The investigators used contemporary techniques to minimize exposure of healthy tissue. "There was a heavy quality control program for radiotherapy to spare lung and nerves," Dr. Rutgers said.

In the ALND group, the median number of nodes removed was 15. Two-thirds of patients did not have any additional positive nodes, other than the sentinel node.

After a median follow-up of 6.1 years, the rate of axillary recurrence was "extremely low," Dr. Rutgers reported: 0.54% with ALND and 1.03% with axillary radiation therapy.

"The axillary recurrence rate was to me, happily enough, far below that hypothesized [during the trial’s planning]; hence, the trial was underpowered," he noted in the session where the findings were presented.

The groups were statistically indistinguishable in estimated 5-year rates of overall survival, at about 93%, and disease-free survival, at about 85%.

The 5-year rate of lymphedema – defined in the study as the need for treatment with a sleeve garment, compression therapy, or lymph drainage therapy, or presence of the condition on physical examination – was 28% with ALND and 14% with axillary radiation therapy (P less than .0001), according to Dr. Rutgers.

"The side effects of radiotherapy cannot be neglected but are limited," he commented. "We looked at many other potential side effects of radiotherapy. There was no excess of cardiac problems, a very small excess of radiation pneumonitis; there was no effect on the brachial nerves."

The groups did not differ with respect to overall quality of life, but there were trends toward greater difficulty moving the arm after radiation therapy and greater swelling after ALND.

Dr. Rutgers disclosed no conflicts of interest related to the research.

Dr. William Gradishar and Dr. Hope Rugo, Associate Editors of The Oncology Report, give their perspectives on how new breast cancer research presented at ASCO 2013 should affect clinical practice.

Dr. William Gradishar and Dr. Hope Rugo, Associate Editors of The Oncology Report, give their perspectives on how new breast cancer research presented at ASCO 2013 should affect clinical practice.

Dr. William Gradishar and Dr. Hope Rugo, Associate Editors of The Oncology Report, give their perspectives on how new breast cancer research presented at ASCO 2013 should affect clinical practice.

CHICAGO – Weekly paclitaxel is just as efficacious as dose-dense paclitaxel when it comes to adjuvant chemotherapy for breast cancer, but the weekly schedule has lower rates of certain important toxicities, according to data presented at the annual meeting of the American Society of Clinical Oncology.

The Southwest Oncology Group’s S0221 randomized trial tested combination chemotherapy regimens among 3,294 patients who had completed local therapy for early breast cancer.

Half of the patients received lower-dose paclitaxel (Taxol) weekly for twelve cycles, while the other half received standard-dose paclitaxel every 2 weeks for six cycles according to a dose-dense schedule. The dose-dense schedule used in the trial was longer than the standard dose-dense schedule (six cycles vs. four cycles) so that the groups would be on treatment for the same total duration (12 weeks).

The 5-year rate of disease-free survival was equally high, about 80%, with each schedule, reported lead study author Dr. G. Thomas Budd, a medical oncologist at the Cleveland Clinic. The weekly schedule, however, yielded significantly lower rates of grade 3/4 musculoskeletal pain, allergy, and neurotoxicity.

"Either schedule of administration can be recommended based on efficacy, so in practice, treatment can be selected based on other considerations such as toxicity. ... It can be individualized by the patient and their physician," he said. "I think there will be a move to more weekly treatment since hematopoietic growth factor support is not required."

Treatment duration and frequency also might tip the decision one way or another for some patients, he added in a related press briefing, as patients given paclitaxel every 2 weeks with the current practice of four cycles will finish chemotherapy sooner, and patients on the weekly schedule will have to travel to the infusion center more often.

"I think that it’s remarkable that after two decades [since paclitaxel’s approval] we are still asking questions on how to teach an old dog new tricks, so to speak," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

"For me, this is actually going to change my practice because I have generally given" paclitaxel every 2 weeks, he said. "These data suggest to me that I can get the same benefit with less toxicity [with the weekly schedule], possibly with less cost. Although there was no formal economic analysis, the cost of growth factor support is not trivial."

In addition, "there are patients for whom fine motor skills are very important to their livelihood, and they will be happy to hear this news" about less neurotoxicity with weekly scheduling, he said.

The S0221 trial enrolled patients with stage I-III breast cancer who had received adequate local therapy (resection and radiation therapy). Investigators randomized them twice with a factorial design.

The first randomization was for a doxorubicin and cyclophosphamide schedule – investigational (weekly) versus standard (every 2 weeks). This randomization was discontinued because the investigational schedule was not more efficacious; all patients thereafter received the standard schedule, according to Dr. Budd.

The second randomization was for the schedule of paclitaxel – either a lower-dose weekly schedule (80 mg/m² every week × 12 weeks) or a dose-dense schedule (175 mg/m² every 2 weeks × 6 weeks) – with granulocytecolony-stimulating factor (pegfilgrastim) support.

Efficacy results showed that the weekly and every-2-week schedules yielded statistically indistinguishable estimated 5-year disease-free survival (82% for the former and 81% for the latter).

"Since this was not conducted as a noninferiority study, we cannot make a conclusion about the lack of difference. However, the Kaplan-Meier curves and the computed hazard ratios suggest little difference in efficacy between these two arms," Dr. Budd commented.

There was also no significant difference between the paclitaxel schedules in overall survival; median values have not been reached.

The findings were generally similar in patient subgroups stratified according to tumor hormone receptor and HER2 status, and, within the HER2-positive group, according to receipt of trastuzumab (Herceptin).

There was no significant difference in the overall rate of grade 3/4 adverse events with the weekly versus every-2-week schedules (35% vs. 36%), but there were differences in rates of individual types of events.

The weekly schedule was associated with significantly lower rates of allergic reaction (0.6% vs. 1.4%), musculoskeletal pain (3% vs. 11%), and neurotoxicity (10% vs. 17%), although the difference in neurotoxicity may have been smaller had the patients in the dose-dense group received only four cycles of every-2-week paclitaxel (as is current practice) rather than six cycles, Dr. Budd acknowledged.

On the flip side, the weekly schedule was associated with significantly higher rates of grade 3/4 hematologic toxicity (17% vs. 6%), leukopenia (6% vs. 1%), and neutropenia (11% vs. 2%). It’s important to remember, however, that "these patients had their counts checked more frequently, they did not receive hematopoietic growth factors, and the rates of infectious complications were not different between the two arms," he said.

The investigators have not performed a formal pharmacoeconomic analysis, according to Dr. Budd, but "the weekly schedule is somewhere between a third and two-thirds less expensive, just on the basis of calculating drug costs."

Dr. Budd disclosed that he is a consultant to Amgen, maker of pegfilgrastim (Neulasta).

CHICAGO – Weekly paclitaxel is just as efficacious as dose-dense paclitaxel when it comes to adjuvant chemotherapy for breast cancer, but the weekly schedule has lower rates of certain important toxicities, according to data presented at the annual meeting of the American Society of Clinical Oncology.

The Southwest Oncology Group’s S0221 randomized trial tested combination chemotherapy regimens among 3,294 patients who had completed local therapy for early breast cancer.

Half of the patients received lower-dose paclitaxel (Taxol) weekly for twelve cycles, while the other half received standard-dose paclitaxel every 2 weeks for six cycles according to a dose-dense schedule. The dose-dense schedule used in the trial was longer than the standard dose-dense schedule (six cycles vs. four cycles) so that the groups would be on treatment for the same total duration (12 weeks).

The 5-year rate of disease-free survival was equally high, about 80%, with each schedule, reported lead study author Dr. G. Thomas Budd, a medical oncologist at the Cleveland Clinic. The weekly schedule, however, yielded significantly lower rates of grade 3/4 musculoskeletal pain, allergy, and neurotoxicity.

"Either schedule of administration can be recommended based on efficacy, so in practice, treatment can be selected based on other considerations such as toxicity. ... It can be individualized by the patient and their physician," he said. "I think there will be a move to more weekly treatment since hematopoietic growth factor support is not required."

Treatment duration and frequency also might tip the decision one way or another for some patients, he added in a related press briefing, as patients given paclitaxel every 2 weeks with the current practice of four cycles will finish chemotherapy sooner, and patients on the weekly schedule will have to travel to the infusion center more often.

"I think that it’s remarkable that after two decades [since paclitaxel’s approval] we are still asking questions on how to teach an old dog new tricks, so to speak," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

"For me, this is actually going to change my practice because I have generally given" paclitaxel every 2 weeks, he said. "These data suggest to me that I can get the same benefit with less toxicity [with the weekly schedule], possibly with less cost. Although there was no formal economic analysis, the cost of growth factor support is not trivial."

In addition, "there are patients for whom fine motor skills are very important to their livelihood, and they will be happy to hear this news" about less neurotoxicity with weekly scheduling, he said.

The S0221 trial enrolled patients with stage I-III breast cancer who had received adequate local therapy (resection and radiation therapy). Investigators randomized them twice with a factorial design.

The first randomization was for a doxorubicin and cyclophosphamide schedule – investigational (weekly) versus standard (every 2 weeks). This randomization was discontinued because the investigational schedule was not more efficacious; all patients thereafter received the standard schedule, according to Dr. Budd.

The second randomization was for the schedule of paclitaxel – either a lower-dose weekly schedule (80 mg/m² every week × 12 weeks) or a dose-dense schedule (175 mg/m² every 2 weeks × 6 weeks) – with granulocytecolony-stimulating factor (pegfilgrastim) support.

Efficacy results showed that the weekly and every-2-week schedules yielded statistically indistinguishable estimated 5-year disease-free survival (82% for the former and 81% for the latter).

"Since this was not conducted as a noninferiority study, we cannot make a conclusion about the lack of difference. However, the Kaplan-Meier curves and the computed hazard ratios suggest little difference in efficacy between these two arms," Dr. Budd commented.

There was also no significant difference between the paclitaxel schedules in overall survival; median values have not been reached.

The findings were generally similar in patient subgroups stratified according to tumor hormone receptor and HER2 status, and, within the HER2-positive group, according to receipt of trastuzumab (Herceptin).

There was no significant difference in the overall rate of grade 3/4 adverse events with the weekly versus every-2-week schedules (35% vs. 36%), but there were differences in rates of individual types of events.

The weekly schedule was associated with significantly lower rates of allergic reaction (0.6% vs. 1.4%), musculoskeletal pain (3% vs. 11%), and neurotoxicity (10% vs. 17%), although the difference in neurotoxicity may have been smaller had the patients in the dose-dense group received only four cycles of every-2-week paclitaxel (as is current practice) rather than six cycles, Dr. Budd acknowledged.

On the flip side, the weekly schedule was associated with significantly higher rates of grade 3/4 hematologic toxicity (17% vs. 6%), leukopenia (6% vs. 1%), and neutropenia (11% vs. 2%). It’s important to remember, however, that "these patients had their counts checked more frequently, they did not receive hematopoietic growth factors, and the rates of infectious complications were not different between the two arms," he said.

The investigators have not performed a formal pharmacoeconomic analysis, according to Dr. Budd, but "the weekly schedule is somewhere between a third and two-thirds less expensive, just on the basis of calculating drug costs."

Dr. Budd disclosed that he is a consultant to Amgen, maker of pegfilgrastim (Neulasta).

CHICAGO – Weekly paclitaxel is just as efficacious as dose-dense paclitaxel when it comes to adjuvant chemotherapy for breast cancer, but the weekly schedule has lower rates of certain important toxicities, according to data presented at the annual meeting of the American Society of Clinical Oncology.

The Southwest Oncology Group’s S0221 randomized trial tested combination chemotherapy regimens among 3,294 patients who had completed local therapy for early breast cancer.

Half of the patients received lower-dose paclitaxel (Taxol) weekly for twelve cycles, while the other half received standard-dose paclitaxel every 2 weeks for six cycles according to a dose-dense schedule. The dose-dense schedule used in the trial was longer than the standard dose-dense schedule (six cycles vs. four cycles) so that the groups would be on treatment for the same total duration (12 weeks).

The 5-year rate of disease-free survival was equally high, about 80%, with each schedule, reported lead study author Dr. G. Thomas Budd, a medical oncologist at the Cleveland Clinic. The weekly schedule, however, yielded significantly lower rates of grade 3/4 musculoskeletal pain, allergy, and neurotoxicity.

"Either schedule of administration can be recommended based on efficacy, so in practice, treatment can be selected based on other considerations such as toxicity. ... It can be individualized by the patient and their physician," he said. "I think there will be a move to more weekly treatment since hematopoietic growth factor support is not required."

Treatment duration and frequency also might tip the decision one way or another for some patients, he added in a related press briefing, as patients given paclitaxel every 2 weeks with the current practice of four cycles will finish chemotherapy sooner, and patients on the weekly schedule will have to travel to the infusion center more often.

"I think that it’s remarkable that after two decades [since paclitaxel’s approval] we are still asking questions on how to teach an old dog new tricks, so to speak," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

"For me, this is actually going to change my practice because I have generally given" paclitaxel every 2 weeks, he said. "These data suggest to me that I can get the same benefit with less toxicity [with the weekly schedule], possibly with less cost. Although there was no formal economic analysis, the cost of growth factor support is not trivial."

In addition, "there are patients for whom fine motor skills are very important to their livelihood, and they will be happy to hear this news" about less neurotoxicity with weekly scheduling, he said.

The S0221 trial enrolled patients with stage I-III breast cancer who had received adequate local therapy (resection and radiation therapy). Investigators randomized them twice with a factorial design.

The first randomization was for a doxorubicin and cyclophosphamide schedule – investigational (weekly) versus standard (every 2 weeks). This randomization was discontinued because the investigational schedule was not more efficacious; all patients thereafter received the standard schedule, according to Dr. Budd.

The second randomization was for the schedule of paclitaxel – either a lower-dose weekly schedule (80 mg/m² every week × 12 weeks) or a dose-dense schedule (175 mg/m² every 2 weeks × 6 weeks) – with granulocytecolony-stimulating factor (pegfilgrastim) support.

Efficacy results showed that the weekly and every-2-week schedules yielded statistically indistinguishable estimated 5-year disease-free survival (82% for the former and 81% for the latter).

"Since this was not conducted as a noninferiority study, we cannot make a conclusion about the lack of difference. However, the Kaplan-Meier curves and the computed hazard ratios suggest little difference in efficacy between these two arms," Dr. Budd commented.

There was also no significant difference between the paclitaxel schedules in overall survival; median values have not been reached.

The findings were generally similar in patient subgroups stratified according to tumor hormone receptor and HER2 status, and, within the HER2-positive group, according to receipt of trastuzumab (Herceptin).

There was no significant difference in the overall rate of grade 3/4 adverse events with the weekly versus every-2-week schedules (35% vs. 36%), but there were differences in rates of individual types of events.

The weekly schedule was associated with significantly lower rates of allergic reaction (0.6% vs. 1.4%), musculoskeletal pain (3% vs. 11%), and neurotoxicity (10% vs. 17%), although the difference in neurotoxicity may have been smaller had the patients in the dose-dense group received only four cycles of every-2-week paclitaxel (as is current practice) rather than six cycles, Dr. Budd acknowledged.

On the flip side, the weekly schedule was associated with significantly higher rates of grade 3/4 hematologic toxicity (17% vs. 6%), leukopenia (6% vs. 1%), and neutropenia (11% vs. 2%). It’s important to remember, however, that "these patients had their counts checked more frequently, they did not receive hematopoietic growth factors, and the rates of infectious complications were not different between the two arms," he said.

The investigators have not performed a formal pharmacoeconomic analysis, according to Dr. Budd, but "the weekly schedule is somewhere between a third and two-thirds less expensive, just on the basis of calculating drug costs."

Dr. Budd disclosed that he is a consultant to Amgen, maker of pegfilgrastim (Neulasta).

CHICAGO – A second study shows that 10 years of adjuvant tamoxifen is superior to the standard five years in women with estrogen receptor-positive early breast cancer.

Among nearly 7,000 women randomized in the aTTom (Adjuvant Tamoxifen Treatment Offers More) study, extended tamoxifen significantly reduced the risk of recurrence from 32% to 28% in the 10 years or more after diagnosis (P = .003).

This translated into a borderline significant difference in breast cancer mortality, reducing it from 24% to 21% (P = .06), Richard Gray, M.Sc., reported in the plenary session at the annual meeting of the American Society of Clinical Oncology.

Just 6 months ago, Prof. Gray reported that recurrences were down 25% and breast cancer deaths down 29% in years 10-14 after diagnosis in women on tamoxifen for 10 years in the companion ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) trial.

The benefits came at a cost, however. Extended exposure to tamoxifen in aTTom more than doubled the number of endometrial cancers (102 vs. 45 cases; rate ratio, 2.20; P less than .0001) and significantly increased the risk of dying from it (37 vs. 20 deaths; RR, 1.83; P = .02).

On a population basis, the benefits in reduced breast cancer mortality outweigh the risks, according to Prof. Gray, professor of medical statistics at the University of Oxford (U.K.).

Monitoring with ultrasound for endometrial changes could improve early detection and reduce the impact of this known toxicity, Dr. Hope S. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco, said in an interview. This risk is also known to vary considerably by age.

"The dramatic findings presented in the aTTom study today will clearly have a significant impact on clinical practice on Monday and are arguably some of the most important data for the treatment of women with early-stage, hormone receptor–positive breast cancer," she said.

The decision to continue tamoxifen beyond the recommended 5 years should be based on the extent of residual risk of recurrence, and must be balanced against tolerability and alternative options, Dr. Rugo said. Extended-duration tamoxifen is a particularly important option for women at risk for late relapse, who are not candidates for aromatase inhibitors because of menopausal status or tolerability.

Great option for premenopausal women

For women who remain premenopausal on tamoxifen, "extended tamoxifen is a great option where there has been no prior standard," said Dr. Ann H. Partridge, who founded the young women with breast cancer program at Boston’s Dana-Farber Cancer Institute and who was invited to discuss the study during the plenary session. These women have a higher risk of disease, and therefore potentially have the greatest risk reduction and lowest risk of serious toxicity, including an almost negligible risk of endometrial cancer.

She went on to say that the personal cost, however, in this population may be the greatest, referring to fertility. Interestingly, ATLAS also reported a significant increase in pulmonary embolism, but it was coupled with a decrease in ischemic heart disease (Lancet 2012 ;805-16 [doi:10.1016/s0140-6736(12)61963-1]). Cardiovascular events have not been reported for aTTOM.

Adherence, which is a challenge in the real world, quality of life, and symptoms such as vasomotor symptoms, alterations in mood, sexual functioning, and musculoskeletal problems also must be considered, Dr. Partridge said.

"We all know that minor side effects can become deeply troubling over time in this setting," she said.

ASCO spokesperson Dr. Sylvia Adams, a breast cancer specialist at New York University Langone Medical Center said in a statement that the results are practice changing for premenopausal women with hormone receptor–positive breast cancer, and especially relevant for women at high risk of recurrence.

A retrospective analysis of combined data from aTTom, ATLAS, and three smaller trials is planned to determine whether certain subgroups of women are most likely to benefit from longer tamoxifen treatment, according to Prof. Gray.

Tamoxifen compliance was about 75%

The aTTom study randomly assigned 6,953 women with estrogen receptor–positive (40%) or ER-untested invasive breast cancer (80% estimated to be ER+) who had been taking tamoxifen for 5 years to continue tamoxifen for another 5 years or stop immediately. Tamoxifen compliance in the continuation arm was about 75%.

Breast cancer recurred in 580 women allocated to continue tamoxifen and 672 randomized to stop (RR, 0.85; P = .003). There was no benefit in years 5-6 after diagnosis (odds ratio, 1.17), but began to emerge later on, in years 7-9 (OR, 0.99), years 10-14 (OR, 0.79) and 15 years or later (0.75), Prof. Gray said.

Breast cancer deaths were reported in 404 patients on extended tamoxifen and 452 patients in the 5-year group (RR, 0.88; P = .06).

Tamoxifen had little effect on all-cause mortality in the extended and 5-year groups (885 vs. 939 deaths; P = .2).

The aTTom study was funded by Cancer Research UK and the UK Medical Research Council. Prof. Gray reported having no financial conflicts. Dr. Partridge said she had no relevant disclosures.

pwendling@frontlinemedcom.com

CHICAGO – A second study shows that 10 years of adjuvant tamoxifen is superior to the standard five years in women with estrogen receptor-positive early breast cancer.

Among nearly 7,000 women randomized in the aTTom (Adjuvant Tamoxifen Treatment Offers More) study, extended tamoxifen significantly reduced the risk of recurrence from 32% to 28% in the 10 years or more after diagnosis (P = .003).

This translated into a borderline significant difference in breast cancer mortality, reducing it from 24% to 21% (P = .06), Richard Gray, M.Sc., reported in the plenary session at the annual meeting of the American Society of Clinical Oncology.

Just 6 months ago, Prof. Gray reported that recurrences were down 25% and breast cancer deaths down 29% in years 10-14 after diagnosis in women on tamoxifen for 10 years in the companion ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) trial.

The benefits came at a cost, however. Extended exposure to tamoxifen in aTTom more than doubled the number of endometrial cancers (102 vs. 45 cases; rate ratio, 2.20; P less than .0001) and significantly increased the risk of dying from it (37 vs. 20 deaths; RR, 1.83; P = .02).

On a population basis, the benefits in reduced breast cancer mortality outweigh the risks, according to Prof. Gray, professor of medical statistics at the University of Oxford (U.K.).

Monitoring with ultrasound for endometrial changes could improve early detection and reduce the impact of this known toxicity, Dr. Hope S. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco, said in an interview. This risk is also known to vary considerably by age.

"The dramatic findings presented in the aTTom study today will clearly have a significant impact on clinical practice on Monday and are arguably some of the most important data for the treatment of women with early-stage, hormone receptor–positive breast cancer," she said.

The decision to continue tamoxifen beyond the recommended 5 years should be based on the extent of residual risk of recurrence, and must be balanced against tolerability and alternative options, Dr. Rugo said. Extended-duration tamoxifen is a particularly important option for women at risk for late relapse, who are not candidates for aromatase inhibitors because of menopausal status or tolerability.

Great option for premenopausal women

For women who remain premenopausal on tamoxifen, "extended tamoxifen is a great option where there has been no prior standard," said Dr. Ann H. Partridge, who founded the young women with breast cancer program at Boston’s Dana-Farber Cancer Institute and who was invited to discuss the study during the plenary session. These women have a higher risk of disease, and therefore potentially have the greatest risk reduction and lowest risk of serious toxicity, including an almost negligible risk of endometrial cancer.

She went on to say that the personal cost, however, in this population may be the greatest, referring to fertility. Interestingly, ATLAS also reported a significant increase in pulmonary embolism, but it was coupled with a decrease in ischemic heart disease (Lancet 2012 ;805-16 [doi:10.1016/s0140-6736(12)61963-1]). Cardiovascular events have not been reported for aTTOM.

Adherence, which is a challenge in the real world, quality of life, and symptoms such as vasomotor symptoms, alterations in mood, sexual functioning, and musculoskeletal problems also must be considered, Dr. Partridge said.

"We all know that minor side effects can become deeply troubling over time in this setting," she said.

ASCO spokesperson Dr. Sylvia Adams, a breast cancer specialist at New York University Langone Medical Center said in a statement that the results are practice changing for premenopausal women with hormone receptor–positive breast cancer, and especially relevant for women at high risk of recurrence.

A retrospective analysis of combined data from aTTom, ATLAS, and three smaller trials is planned to determine whether certain subgroups of women are most likely to benefit from longer tamoxifen treatment, according to Prof. Gray.

Tamoxifen compliance was about 75%

The aTTom study randomly assigned 6,953 women with estrogen receptor–positive (40%) or ER-untested invasive breast cancer (80% estimated to be ER+) who had been taking tamoxifen for 5 years to continue tamoxifen for another 5 years or stop immediately. Tamoxifen compliance in the continuation arm was about 75%.

Breast cancer recurred in 580 women allocated to continue tamoxifen and 672 randomized to stop (RR, 0.85; P = .003). There was no benefit in years 5-6 after diagnosis (odds ratio, 1.17), but began to emerge later on, in years 7-9 (OR, 0.99), years 10-14 (OR, 0.79) and 15 years or later (0.75), Prof. Gray said.

Breast cancer deaths were reported in 404 patients on extended tamoxifen and 452 patients in the 5-year group (RR, 0.88; P = .06).

Tamoxifen had little effect on all-cause mortality in the extended and 5-year groups (885 vs. 939 deaths; P = .2).

The aTTom study was funded by Cancer Research UK and the UK Medical Research Council. Prof. Gray reported having no financial conflicts. Dr. Partridge said she had no relevant disclosures.

pwendling@frontlinemedcom.com

CHICAGO – A second study shows that 10 years of adjuvant tamoxifen is superior to the standard five years in women with estrogen receptor-positive early breast cancer.

Among nearly 7,000 women randomized in the aTTom (Adjuvant Tamoxifen Treatment Offers More) study, extended tamoxifen significantly reduced the risk of recurrence from 32% to 28% in the 10 years or more after diagnosis (P = .003).

This translated into a borderline significant difference in breast cancer mortality, reducing it from 24% to 21% (P = .06), Richard Gray, M.Sc., reported in the plenary session at the annual meeting of the American Society of Clinical Oncology.

Just 6 months ago, Prof. Gray reported that recurrences were down 25% and breast cancer deaths down 29% in years 10-14 after diagnosis in women on tamoxifen for 10 years in the companion ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) trial.

The benefits came at a cost, however. Extended exposure to tamoxifen in aTTom more than doubled the number of endometrial cancers (102 vs. 45 cases; rate ratio, 2.20; P less than .0001) and significantly increased the risk of dying from it (37 vs. 20 deaths; RR, 1.83; P = .02).

On a population basis, the benefits in reduced breast cancer mortality outweigh the risks, according to Prof. Gray, professor of medical statistics at the University of Oxford (U.K.).

Monitoring with ultrasound for endometrial changes could improve early detection and reduce the impact of this known toxicity, Dr. Hope S. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco, said in an interview. This risk is also known to vary considerably by age.

"The dramatic findings presented in the aTTom study today will clearly have a significant impact on clinical practice on Monday and are arguably some of the most important data for the treatment of women with early-stage, hormone receptor–positive breast cancer," she said.

The decision to continue tamoxifen beyond the recommended 5 years should be based on the extent of residual risk of recurrence, and must be balanced against tolerability and alternative options, Dr. Rugo said. Extended-duration tamoxifen is a particularly important option for women at risk for late relapse, who are not candidates for aromatase inhibitors because of menopausal status or tolerability.

Great option for premenopausal women

For women who remain premenopausal on tamoxifen, "extended tamoxifen is a great option where there has been no prior standard," said Dr. Ann H. Partridge, who founded the young women with breast cancer program at Boston’s Dana-Farber Cancer Institute and who was invited to discuss the study during the plenary session. These women have a higher risk of disease, and therefore potentially have the greatest risk reduction and lowest risk of serious toxicity, including an almost negligible risk of endometrial cancer.

She went on to say that the personal cost, however, in this population may be the greatest, referring to fertility. Interestingly, ATLAS also reported a significant increase in pulmonary embolism, but it was coupled with a decrease in ischemic heart disease (Lancet 2012 ;805-16 [doi:10.1016/s0140-6736(12)61963-1]). Cardiovascular events have not been reported for aTTOM.

Adherence, which is a challenge in the real world, quality of life, and symptoms such as vasomotor symptoms, alterations in mood, sexual functioning, and musculoskeletal problems also must be considered, Dr. Partridge said.

"We all know that minor side effects can become deeply troubling over time in this setting," she said.

ASCO spokesperson Dr. Sylvia Adams, a breast cancer specialist at New York University Langone Medical Center said in a statement that the results are practice changing for premenopausal women with hormone receptor–positive breast cancer, and especially relevant for women at high risk of recurrence.

A retrospective analysis of combined data from aTTom, ATLAS, and three smaller trials is planned to determine whether certain subgroups of women are most likely to benefit from longer tamoxifen treatment, according to Prof. Gray.

Tamoxifen compliance was about 75%

The aTTom study randomly assigned 6,953 women with estrogen receptor–positive (40%) or ER-untested invasive breast cancer (80% estimated to be ER+) who had been taking tamoxifen for 5 years to continue tamoxifen for another 5 years or stop immediately. Tamoxifen compliance in the continuation arm was about 75%.

Breast cancer recurred in 580 women allocated to continue tamoxifen and 672 randomized to stop (RR, 0.85; P = .003). There was no benefit in years 5-6 after diagnosis (odds ratio, 1.17), but began to emerge later on, in years 7-9 (OR, 0.99), years 10-14 (OR, 0.79) and 15 years or later (0.75), Prof. Gray said.

Breast cancer deaths were reported in 404 patients on extended tamoxifen and 452 patients in the 5-year group (RR, 0.88; P = .06).

Tamoxifen had little effect on all-cause mortality in the extended and 5-year groups (885 vs. 939 deaths; P = .2).

The aTTom study was funded by Cancer Research UK and the UK Medical Research Council. Prof. Gray reported having no financial conflicts. Dr. Partridge said she had no relevant disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Dr. Richard Finn presented an update on palbociclib (an oral and selective inhibitor of cyclin-dependent kinases [CDK] 4 and 6) for treating advanced postmenopausal breast cancer at the annual meeting of the American Society of Clinical Oncology.

A phase III trial, with the primary endpoint of progression free survival, is aiming to validate the positive trial results with palbociclib plus letrozole seen in earlier clinical trials. Palbociclib received Breakthrough Therapy designation from the Food and Drug Administration earlier this year.

CHICAGO – Dr. Richard Finn presented an update on palbociclib (an oral and selective inhibitor of cyclin-dependent kinases [CDK] 4 and 6) for treating advanced postmenopausal breast cancer at the annual meeting of the American Society of Clinical Oncology.

A phase III trial, with the primary endpoint of progression free survival, is aiming to validate the positive trial results with palbociclib plus letrozole seen in earlier clinical trials. Palbociclib received Breakthrough Therapy designation from the Food and Drug Administration earlier this year.

CHICAGO – Dr. Richard Finn presented an update on palbociclib (an oral and selective inhibitor of cyclin-dependent kinases [CDK] 4 and 6) for treating advanced postmenopausal breast cancer at the annual meeting of the American Society of Clinical Oncology.

A phase III trial, with the primary endpoint of progression free survival, is aiming to validate the positive trial results with palbociclib plus letrozole seen in earlier clinical trials. Palbociclib received Breakthrough Therapy designation from the Food and Drug Administration earlier this year.

CHICAGO – Dr. G. T. Budd, of the Cleveland Clinic, discusses the efficacy, side effects, and costs of giving paclitaxel weekly vs. every 2 weeks when treating breast cancer. Dr. Budd discussed trial results comparing the schedules in an interview at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Dr. G. T. Budd, of the Cleveland Clinic, discusses the efficacy, side effects, and costs of giving paclitaxel weekly vs. every 2 weeks when treating breast cancer. Dr. Budd discussed trial results comparing the schedules in an interview at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Dr. G. T. Budd, of the Cleveland Clinic, discusses the efficacy, side effects, and costs of giving paclitaxel weekly vs. every 2 weeks when treating breast cancer. Dr. Budd discussed trial results comparing the schedules in an interview at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – In a plenary session at the ASCO 2013 annual meeting, Dr. Richard Gray of the University of Oxford said that when it comes to treating breast cancer patients with tamoxifen "the evidence is now overwhelming."

He presented data from the aTTom trial showing that 10 years of tamoxifen treatment cut these patients' risk of dying of breast cancer in half, when compared with 5 years of treatment.

CHICAGO – In a plenary session at the ASCO 2013 annual meeting, Dr. Richard Gray of the University of Oxford said that when it comes to treating breast cancer patients with tamoxifen "the evidence is now overwhelming."

He presented data from the aTTom trial showing that 10 years of tamoxifen treatment cut these patients' risk of dying of breast cancer in half, when compared with 5 years of treatment.

CHICAGO – In a plenary session at the ASCO 2013 annual meeting, Dr. Richard Gray of the University of Oxford said that when it comes to treating breast cancer patients with tamoxifen "the evidence is now overwhelming."

He presented data from the aTTom trial showing that 10 years of tamoxifen treatment cut these patients' risk of dying of breast cancer in half, when compared with 5 years of treatment.

Guidelines for fertility preservation in newly diagnosed cancer patients have been updated to include oocyte preservation as a standard practice rather than an experimental option, according to the American Society of Clinical Oncology.

With the exception of the recommendation on oocyte preservation, however, the update is essentially comparable to the one that ASCO issued in 2006. The latest guidelines also include literature updates used to create a framework for physician-patient discussions of fertility preservation. The guidelines appear in the May 28 online edition of the Journal of Clinical Oncology (doi: 10.1200/JCO.2013.49.2678).

The discussion of fertility preservation needs to occur early, as part of education and informed consent before treatment. "Current evidence suggests that discussions about fertility and fertility preservation are of great importance to patients with cancer," wrote Dr. Alison Loren, cochair of the guidelines update panel, and her colleagues. "Discussing infertility and introducing the possibility of fertility preservation lead to improved quality of life and diminished distress in all patient populations."

"It may be difficult for physicians to know how important fertility preservation is to their patients unless they ask, because many patients may not bring up the topic," wrote Dr. Loren of the University of Pennsylvania, Philadelphia, and her colleagues. "They may be overwhelmed by and focused exclusively on the cancer diagnosis, they may be unaware that potential fertility loss may occur, or they may be concerned that pursuing fertility preservation will delay their treatment, leading to increased morbidity or mortality."

"There is evidence to suggest that, at least among women, patients may make cancer treatment decisions based on fertility concerns. ... [In a recent study,] 29% of women with breast cancer reported that infertility concerns influenced their treatment decisions," the panel wrote.

The panel examined 18 recent randomized controlled trials; 6 systematic reviews, meta-analyses, and previous guidelines; and dozens of narrative reviews, case series, case studies, and editorials. From this review, they produced guidelines for fertility preservation in men, women, and post- and prepubertal children.

Such discussions should occur with all cancer patients of reproductive age (and with parents or guardians of children and adolescents) before treatment starts when infertility is a potential risk of therapy. Discussions should address whether fertility preservation might have an impact on successful cancer treatment. Those interested in fertility preservation, including ambivalent patients, should be referred to reproductive specialists and the discussion documented in the medical record. Distress about potential infertility warrants a referral to a psychosocial provider. Those who opt for fertility preservation should be encouraged to participate in registries and clinical studies.

For men

Men who choose to move ahead with sperm cryopreservation can usually do so expeditiously with no cancer treatment delay.

Sperm cryopreservation is the only established fertility preservation method; sperm is usually easy to obtain, and samples can be recovered every 24 hours. Testicular hormone suppression and testicular tissue or spermatogonial freezing for later transplanting – including testis xenografting – are experimental and unproven in humans. Men should be advised of a potentially higher risk of genetic damage in sperm collected after initiation of chemotherapy.

For women

"Fertility preservation options in females depend on patient age, diagnosis, type of treatment, presence or participation of a male partner, and/or patient preferences regarding the use of banked donor sperm, time available, and likelihood that cancer has metastasized to her ovaries," the panel wrote. Timing is an issue: Oocyte and embryo cryopreservation are proven methods, but the ovarian stimulation needed to accomplish these generally takes at least 2-4 weeks. Prior worries about hormonal stimulation and its possible effect on hormone-sensitive cancers have been somewhat allayed.

Letrozole combined with standard fertility drugs can induce ovulation without spiking estrogen; the number of eggs and embryos from these inductions appears no different from those obtained with traditional drugs.

Ovarian transposition (oophoropexy) is an option when pelvic radiation therapy is performed as cancer treatment.

Ovarian suppression with gonadotropin-releasing hormone agonists doesn’t seem to have any significant benefit in fertility preservation, according to the panel. No differences have been noted in post-treatment resumption of menstruation or in hormonal or imaging markers of fertility.

Ovarian tissue cryopreservation for the purpose of future transplantation is still experimental. At least 19 live births have been reported using frozen ovarian tissue transplanted after treatment. "There is a theoretic concern with re-implanting ovarian tissue and the potential for reintroducing cancer cells depending on the type and stage of cancer, although so far there have been no reports of cancer recurrence in humans."

For teens and children

Postpubertal adolescents can choose to freeze eggs or sperm, a process that requires consent from both the teen and the parents.

There are no standard options for preserving the fertility of prepubertal children; all approaches are experimental. There are some reports of oocyte cryopreservation in girls aged 13 years and older, but no reports of live births associated with later re-implantation.

Testicular tissue has also been frozen, but again, there are no reports of re-implantation.

"Efforts to preserve the fertility of children using experimental methods should be attempted only under institutional review board–approved protocols," the panel cautioned.

Data are lacking on the fertility impact of new biologic and targeted treatments, with the exceptions of bevacizumab and tyrosine kinase inhibitors.

In 2011, the Food and Drug Administration reported a 34% rate of ovarian failure in women who got bevacizumab as part of a colorectal cancer treatment regimen; 1 in 5 women regained ovarian function. This possible complication should be addressed with women.

Young patients taking tyrosine kinase inhibitors for chronic myeloid leukemia may also face later fertility problems, the panel noted, including an increased risk of complications in pregnancy or congenital anomalies. Data on these findings are incomplete, but patients should understand the possible risks, the panel wrote.

Supplements and clinical tools and resources can be found at www.asco.org/guidelines/fertility. Patient information is also available at www.cancer.net.

Neither Dr. Loren nor any of the other panel members had any financial disclosures.

msullivan@frontlinemedcom.com

Guidelines for fertility preservation in newly diagnosed cancer patients have been updated to include oocyte preservation as a standard practice rather than an experimental option, according to the American Society of Clinical Oncology.

With the exception of the recommendation on oocyte preservation, however, the update is essentially comparable to the one that ASCO issued in 2006. The latest guidelines also include literature updates used to create a framework for physician-patient discussions of fertility preservation. The guidelines appear in the May 28 online edition of the Journal of Clinical Oncology (doi: 10.1200/JCO.2013.49.2678).

The discussion of fertility preservation needs to occur early, as part of education and informed consent before treatment. "Current evidence suggests that discussions about fertility and fertility preservation are of great importance to patients with cancer," wrote Dr. Alison Loren, cochair of the guidelines update panel, and her colleagues. "Discussing infertility and introducing the possibility of fertility preservation lead to improved quality of life and diminished distress in all patient populations."

"It may be difficult for physicians to know how important fertility preservation is to their patients unless they ask, because many patients may not bring up the topic," wrote Dr. Loren of the University of Pennsylvania, Philadelphia, and her colleagues. "They may be overwhelmed by and focused exclusively on the cancer diagnosis, they may be unaware that potential fertility loss may occur, or they may be concerned that pursuing fertility preservation will delay their treatment, leading to increased morbidity or mortality."

"There is evidence to suggest that, at least among women, patients may make cancer treatment decisions based on fertility concerns. ... [In a recent study,] 29% of women with breast cancer reported that infertility concerns influenced their treatment decisions," the panel wrote.

The panel examined 18 recent randomized controlled trials; 6 systematic reviews, meta-analyses, and previous guidelines; and dozens of narrative reviews, case series, case studies, and editorials. From this review, they produced guidelines for fertility preservation in men, women, and post- and prepubertal children.

Such discussions should occur with all cancer patients of reproductive age (and with parents or guardians of children and adolescents) before treatment starts when infertility is a potential risk of therapy. Discussions should address whether fertility preservation might have an impact on successful cancer treatment. Those interested in fertility preservation, including ambivalent patients, should be referred to reproductive specialists and the discussion documented in the medical record. Distress about potential infertility warrants a referral to a psychosocial provider. Those who opt for fertility preservation should be encouraged to participate in registries and clinical studies.

For men

Men who choose to move ahead with sperm cryopreservation can usually do so expeditiously with no cancer treatment delay.

Sperm cryopreservation is the only established fertility preservation method; sperm is usually easy to obtain, and samples can be recovered every 24 hours. Testicular hormone suppression and testicular tissue or spermatogonial freezing for later transplanting – including testis xenografting – are experimental and unproven in humans. Men should be advised of a potentially higher risk of genetic damage in sperm collected after initiation of chemotherapy.

For women

"Fertility preservation options in females depend on patient age, diagnosis, type of treatment, presence or participation of a male partner, and/or patient preferences regarding the use of banked donor sperm, time available, and likelihood that cancer has metastasized to her ovaries," the panel wrote. Timing is an issue: Oocyte and embryo cryopreservation are proven methods, but the ovarian stimulation needed to accomplish these generally takes at least 2-4 weeks. Prior worries about hormonal stimulation and its possible effect on hormone-sensitive cancers have been somewhat allayed.

Letrozole combined with standard fertility drugs can induce ovulation without spiking estrogen; the number of eggs and embryos from these inductions appears no different from those obtained with traditional drugs.

Ovarian transposition (oophoropexy) is an option when pelvic radiation therapy is performed as cancer treatment.

Ovarian suppression with gonadotropin-releasing hormone agonists doesn’t seem to have any significant benefit in fertility preservation, according to the panel. No differences have been noted in post-treatment resumption of menstruation or in hormonal or imaging markers of fertility.

Ovarian tissue cryopreservation for the purpose of future transplantation is still experimental. At least 19 live births have been reported using frozen ovarian tissue transplanted after treatment. "There is a theoretic concern with re-implanting ovarian tissue and the potential for reintroducing cancer cells depending on the type and stage of cancer, although so far there have been no reports of cancer recurrence in humans."

For teens and children

Postpubertal adolescents can choose to freeze eggs or sperm, a process that requires consent from both the teen and the parents.

There are no standard options for preserving the fertility of prepubertal children; all approaches are experimental. There are some reports of oocyte cryopreservation in girls aged 13 years and older, but no reports of live births associated with later re-implantation.

Testicular tissue has also been frozen, but again, there are no reports of re-implantation.

"Efforts to preserve the fertility of children using experimental methods should be attempted only under institutional review board–approved protocols," the panel cautioned.

Data are lacking on the fertility impact of new biologic and targeted treatments, with the exceptions of bevacizumab and tyrosine kinase inhibitors.

In 2011, the Food and Drug Administration reported a 34% rate of ovarian failure in women who got bevacizumab as part of a colorectal cancer treatment regimen; 1 in 5 women regained ovarian function. This possible complication should be addressed with women.

Young patients taking tyrosine kinase inhibitors for chronic myeloid leukemia may also face later fertility problems, the panel noted, including an increased risk of complications in pregnancy or congenital anomalies. Data on these findings are incomplete, but patients should understand the possible risks, the panel wrote.

Supplements and clinical tools and resources can be found at www.asco.org/guidelines/fertility. Patient information is also available at www.cancer.net.

Neither Dr. Loren nor any of the other panel members had any financial disclosures.

msullivan@frontlinemedcom.com

Guidelines for fertility preservation in newly diagnosed cancer patients have been updated to include oocyte preservation as a standard practice rather than an experimental option, according to the American Society of Clinical Oncology.

With the exception of the recommendation on oocyte preservation, however, the update is essentially comparable to the one that ASCO issued in 2006. The latest guidelines also include literature updates used to create a framework for physician-patient discussions of fertility preservation. The guidelines appear in the May 28 online edition of the Journal of Clinical Oncology (doi: 10.1200/JCO.2013.49.2678).

The discussion of fertility preservation needs to occur early, as part of education and informed consent before treatment. "Current evidence suggests that discussions about fertility and fertility preservation are of great importance to patients with cancer," wrote Dr. Alison Loren, cochair of the guidelines update panel, and her colleagues. "Discussing infertility and introducing the possibility of fertility preservation lead to improved quality of life and diminished distress in all patient populations."

"It may be difficult for physicians to know how important fertility preservation is to their patients unless they ask, because many patients may not bring up the topic," wrote Dr. Loren of the University of Pennsylvania, Philadelphia, and her colleagues. "They may be overwhelmed by and focused exclusively on the cancer diagnosis, they may be unaware that potential fertility loss may occur, or they may be concerned that pursuing fertility preservation will delay their treatment, leading to increased morbidity or mortality."

"There is evidence to suggest that, at least among women, patients may make cancer treatment decisions based on fertility concerns. ... [In a recent study,] 29% of women with breast cancer reported that infertility concerns influenced their treatment decisions," the panel wrote.

The panel examined 18 recent randomized controlled trials; 6 systematic reviews, meta-analyses, and previous guidelines; and dozens of narrative reviews, case series, case studies, and editorials. From this review, they produced guidelines for fertility preservation in men, women, and post- and prepubertal children.

Such discussions should occur with all cancer patients of reproductive age (and with parents or guardians of children and adolescents) before treatment starts when infertility is a potential risk of therapy. Discussions should address whether fertility preservation might have an impact on successful cancer treatment. Those interested in fertility preservation, including ambivalent patients, should be referred to reproductive specialists and the discussion documented in the medical record. Distress about potential infertility warrants a referral to a psychosocial provider. Those who opt for fertility preservation should be encouraged to participate in registries and clinical studies.

For men

Men who choose to move ahead with sperm cryopreservation can usually do so expeditiously with no cancer treatment delay.

Sperm cryopreservation is the only established fertility preservation method; sperm is usually easy to obtain, and samples can be recovered every 24 hours. Testicular hormone suppression and testicular tissue or spermatogonial freezing for later transplanting – including testis xenografting – are experimental and unproven in humans. Men should be advised of a potentially higher risk of genetic damage in sperm collected after initiation of chemotherapy.

For women

"Fertility preservation options in females depend on patient age, diagnosis, type of treatment, presence or participation of a male partner, and/or patient preferences regarding the use of banked donor sperm, time available, and likelihood that cancer has metastasized to her ovaries," the panel wrote. Timing is an issue: Oocyte and embryo cryopreservation are proven methods, but the ovarian stimulation needed to accomplish these generally takes at least 2-4 weeks. Prior worries about hormonal stimulation and its possible effect on hormone-sensitive cancers have been somewhat allayed.

Letrozole combined with standard fertility drugs can induce ovulation without spiking estrogen; the number of eggs and embryos from these inductions appears no different from those obtained with traditional drugs.

Ovarian transposition (oophoropexy) is an option when pelvic radiation therapy is performed as cancer treatment.

Ovarian suppression with gonadotropin-releasing hormone agonists doesn’t seem to have any significant benefit in fertility preservation, according to the panel. No differences have been noted in post-treatment resumption of menstruation or in hormonal or imaging markers of fertility.

Ovarian tissue cryopreservation for the purpose of future transplantation is still experimental. At least 19 live births have been reported using frozen ovarian tissue transplanted after treatment. "There is a theoretic concern with re-implanting ovarian tissue and the potential for reintroducing cancer cells depending on the type and stage of cancer, although so far there have been no reports of cancer recurrence in humans."

For teens and children

Postpubertal adolescents can choose to freeze eggs or sperm, a process that requires consent from both the teen and the parents.

There are no standard options for preserving the fertility of prepubertal children; all approaches are experimental. There are some reports of oocyte cryopreservation in girls aged 13 years and older, but no reports of live births associated with later re-implantation.

Testicular tissue has also been frozen, but again, there are no reports of re-implantation.

"Efforts to preserve the fertility of children using experimental methods should be attempted only under institutional review board–approved protocols," the panel cautioned.

Data are lacking on the fertility impact of new biologic and targeted treatments, with the exceptions of bevacizumab and tyrosine kinase inhibitors.

In 2011, the Food and Drug Administration reported a 34% rate of ovarian failure in women who got bevacizumab as part of a colorectal cancer treatment regimen; 1 in 5 women regained ovarian function. This possible complication should be addressed with women.

Young patients taking tyrosine kinase inhibitors for chronic myeloid leukemia may also face later fertility problems, the panel noted, including an increased risk of complications in pregnancy or congenital anomalies. Data on these findings are incomplete, but patients should understand the possible risks, the panel wrote.

Supplements and clinical tools and resources can be found at www.asco.org/guidelines/fertility. Patient information is also available at www.cancer.net.

Neither Dr. Loren nor any of the other panel members had any financial disclosures.

msullivan@frontlinemedcom.com