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Less frequent zoledronic acid an option in metastatic breast cancer
CHICAGO – Women with breast cancer and bone metastases previously treated with bisphosphonates can safely reduce the frequency of their zoledronic acid infusions, according to results from the phase III OPTIMIZE-2 study.
At a median follow-up of 11.9 months, the skeletal-related event (SRE) rate, the study’s primary endpoint, was 23.2% with zoledronic acid (Zometa) every 12 weeks and 22% with zoledronic acid every 4 weeks (P = .724).
The upper limit of the 95% confidence interval for the SRE rate difference was 9.8%, which is below the predefined noninferiority margin of 10%, Dr. Gabriel N. Hortobagyi reported at the annual meeting of the American Society of Clinical Oncology.
Zoledronic acid, a third-generation bisphosphonate, is used to reduce the risk of SREs such as bone fractures and spinal cord compression in patients with bone metastases from solid tumors, and is approved to be administered every 3-4 weeks by intravenous infusion.
It has safety concerns similar to other bisphosphonates such as atypical fractures, chronic kidney impairment, and osteonecrosis of the jaw, and therefore, less frequent dosing could have distinct advantages, Dr. Hortobagyi, professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston, said during a press briefing highlighting the study.
Dr. Patricia Ganz, professor of medicine at the University of California, Los Angeles, told reporters that for women living with advanced breast cancer and bone metastases, the late-breaking abstract results mean they can spend more time with family and friends and less time in their doctor’s office, with less toxicity and less cost.
"Sometimes we have to add things, but sometimes we have to take away to add value to patients’ care," she said.
The noninferiority, double-blind OPTIMIZE-2 trial enrolled 412 patients with breast cancer and bone metastases and randomly assigned 403 patients to 4 mg intravenous zoledronic acid every 4 weeks or every 12 weeks for 1 year. All participants had received at least nine doses of zoledronic acid or pamidronate prior to study entry. Their average age was 59 years.
The mean skeletal morbidity rate was 0.46 with monthly zoledronic acid and 0.50 with quarterly treatment (P = .854), Dr. Hortobagyi said.
Times to first on-study SRE were also similar in the two arms (Hazard ratio, 1.06; P = .792).
The safety profile was similar in both arms, although there were more kidney-related adverse events in the monthly arm than in the quarterly arm (9.6% vs. 7.9%), he said.
Women dosed monthly had more grade 3/4 adverse events (47.5% vs. 42.6%) and were more likely to stop treatment due to these events (11.6% vs. 8.9%).
Two patients treated monthly developed osteonecrosis of the jaw, whereas none did with quarterly treatment.
Bone marker profiles were similar between arms, Dr. Hortobagyi said. Serum bone-specific alkaline phosphatase was not significantly different at any time point and urinary N-telopeptide/creatinine was significantly different at week 36 only.
Because of study limitations, such as its relatively modest size, and statistical concerns, the inferiority claim should be interpreted with caution, he said. The protocol was revised during the course of the trial including a placebo arm that was dropped because of poor accrual. The sample size was also reduced from 705 to 412 patients based on new data that became available from the ZOOM trial.
As previously reported, ZOOM also demonstrated no difference in skeletal morbidity rate, its primary endpoint, between zoledronic acid dosed quarterly or monthly in women with metastatic breast cancer and bone metastases.
Novartis sponsored the trial. Dr. Hortobagyi disclosed serving as a consultant to Antigen Express, Novartis, and Pfizer, and research funds to his institution from Novartis.
CHICAGO – Women with breast cancer and bone metastases previously treated with bisphosphonates can safely reduce the frequency of their zoledronic acid infusions, according to results from the phase III OPTIMIZE-2 study.
At a median follow-up of 11.9 months, the skeletal-related event (SRE) rate, the study’s primary endpoint, was 23.2% with zoledronic acid (Zometa) every 12 weeks and 22% with zoledronic acid every 4 weeks (P = .724).
The upper limit of the 95% confidence interval for the SRE rate difference was 9.8%, which is below the predefined noninferiority margin of 10%, Dr. Gabriel N. Hortobagyi reported at the annual meeting of the American Society of Clinical Oncology.
Zoledronic acid, a third-generation bisphosphonate, is used to reduce the risk of SREs such as bone fractures and spinal cord compression in patients with bone metastases from solid tumors, and is approved to be administered every 3-4 weeks by intravenous infusion.
It has safety concerns similar to other bisphosphonates such as atypical fractures, chronic kidney impairment, and osteonecrosis of the jaw, and therefore, less frequent dosing could have distinct advantages, Dr. Hortobagyi, professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston, said during a press briefing highlighting the study.
Dr. Patricia Ganz, professor of medicine at the University of California, Los Angeles, told reporters that for women living with advanced breast cancer and bone metastases, the late-breaking abstract results mean they can spend more time with family and friends and less time in their doctor’s office, with less toxicity and less cost.
"Sometimes we have to add things, but sometimes we have to take away to add value to patients’ care," she said.
The noninferiority, double-blind OPTIMIZE-2 trial enrolled 412 patients with breast cancer and bone metastases and randomly assigned 403 patients to 4 mg intravenous zoledronic acid every 4 weeks or every 12 weeks for 1 year. All participants had received at least nine doses of zoledronic acid or pamidronate prior to study entry. Their average age was 59 years.
The mean skeletal morbidity rate was 0.46 with monthly zoledronic acid and 0.50 with quarterly treatment (P = .854), Dr. Hortobagyi said.
Times to first on-study SRE were also similar in the two arms (Hazard ratio, 1.06; P = .792).
The safety profile was similar in both arms, although there were more kidney-related adverse events in the monthly arm than in the quarterly arm (9.6% vs. 7.9%), he said.
Women dosed monthly had more grade 3/4 adverse events (47.5% vs. 42.6%) and were more likely to stop treatment due to these events (11.6% vs. 8.9%).
Two patients treated monthly developed osteonecrosis of the jaw, whereas none did with quarterly treatment.
Bone marker profiles were similar between arms, Dr. Hortobagyi said. Serum bone-specific alkaline phosphatase was not significantly different at any time point and urinary N-telopeptide/creatinine was significantly different at week 36 only.
Because of study limitations, such as its relatively modest size, and statistical concerns, the inferiority claim should be interpreted with caution, he said. The protocol was revised during the course of the trial including a placebo arm that was dropped because of poor accrual. The sample size was also reduced from 705 to 412 patients based on new data that became available from the ZOOM trial.
As previously reported, ZOOM also demonstrated no difference in skeletal morbidity rate, its primary endpoint, between zoledronic acid dosed quarterly or monthly in women with metastatic breast cancer and bone metastases.
Novartis sponsored the trial. Dr. Hortobagyi disclosed serving as a consultant to Antigen Express, Novartis, and Pfizer, and research funds to his institution from Novartis.
CHICAGO – Women with breast cancer and bone metastases previously treated with bisphosphonates can safely reduce the frequency of their zoledronic acid infusions, according to results from the phase III OPTIMIZE-2 study.
At a median follow-up of 11.9 months, the skeletal-related event (SRE) rate, the study’s primary endpoint, was 23.2% with zoledronic acid (Zometa) every 12 weeks and 22% with zoledronic acid every 4 weeks (P = .724).
The upper limit of the 95% confidence interval for the SRE rate difference was 9.8%, which is below the predefined noninferiority margin of 10%, Dr. Gabriel N. Hortobagyi reported at the annual meeting of the American Society of Clinical Oncology.
Zoledronic acid, a third-generation bisphosphonate, is used to reduce the risk of SREs such as bone fractures and spinal cord compression in patients with bone metastases from solid tumors, and is approved to be administered every 3-4 weeks by intravenous infusion.
It has safety concerns similar to other bisphosphonates such as atypical fractures, chronic kidney impairment, and osteonecrosis of the jaw, and therefore, less frequent dosing could have distinct advantages, Dr. Hortobagyi, professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston, said during a press briefing highlighting the study.
Dr. Patricia Ganz, professor of medicine at the University of California, Los Angeles, told reporters that for women living with advanced breast cancer and bone metastases, the late-breaking abstract results mean they can spend more time with family and friends and less time in their doctor’s office, with less toxicity and less cost.
"Sometimes we have to add things, but sometimes we have to take away to add value to patients’ care," she said.
The noninferiority, double-blind OPTIMIZE-2 trial enrolled 412 patients with breast cancer and bone metastases and randomly assigned 403 patients to 4 mg intravenous zoledronic acid every 4 weeks or every 12 weeks for 1 year. All participants had received at least nine doses of zoledronic acid or pamidronate prior to study entry. Their average age was 59 years.
The mean skeletal morbidity rate was 0.46 with monthly zoledronic acid and 0.50 with quarterly treatment (P = .854), Dr. Hortobagyi said.
Times to first on-study SRE were also similar in the two arms (Hazard ratio, 1.06; P = .792).
The safety profile was similar in both arms, although there were more kidney-related adverse events in the monthly arm than in the quarterly arm (9.6% vs. 7.9%), he said.
Women dosed monthly had more grade 3/4 adverse events (47.5% vs. 42.6%) and were more likely to stop treatment due to these events (11.6% vs. 8.9%).
Two patients treated monthly developed osteonecrosis of the jaw, whereas none did with quarterly treatment.
Bone marker profiles were similar between arms, Dr. Hortobagyi said. Serum bone-specific alkaline phosphatase was not significantly different at any time point and urinary N-telopeptide/creatinine was significantly different at week 36 only.
Because of study limitations, such as its relatively modest size, and statistical concerns, the inferiority claim should be interpreted with caution, he said. The protocol was revised during the course of the trial including a placebo arm that was dropped because of poor accrual. The sample size was also reduced from 705 to 412 patients based on new data that became available from the ZOOM trial.
As previously reported, ZOOM also demonstrated no difference in skeletal morbidity rate, its primary endpoint, between zoledronic acid dosed quarterly or monthly in women with metastatic breast cancer and bone metastases.
Novartis sponsored the trial. Dr. Hortobagyi disclosed serving as a consultant to Antigen Express, Novartis, and Pfizer, and research funds to his institution from Novartis.
AT THE ASCO ANNUAL MEETING 2014
Major finding: The skeletal-related event rate was 23.2% with zoledronic acid every 12 weeks and 22% with zoledronic acid every 4 weeks (P = .724).
Data source: A phase III, double-blind study in 412 women with bone metastases from breast cancer.
Key clinical point: Women with breast cancer and bone metastases can receive bisphosphonates less often without compromising care.
Disclosures: Novartis sponsored the trial. Dr. Hortobagyi disclosed serving as a consultant to Antigen Express, Novartis, and Pfizer, and research funds to his institution from Novartis.
TEXT/SOFT provide practice-changing results for premenopausal breast cancer
CHICAGO – Adjuvant exemestane is more effective at preventing recurrence than tamoxifen is when either is given with ovarian function suppression in premenopausal women with hormone-sensitive breast cancers, according to a joint analysis of the phase III TEXT and SOFT trials.
"Exemestane plus OFS [ovarian function suppression] significantly improves disease-free survival, breast cancer free–interval, and distant recurrence free–interval and is a new treatment option for premenopausal women with hormone receptor-positive early breast cancer," lead study author Dr. Olivia Pagani said during a plenary session at the annual meeting of the American Society of Clinical Oncology.
The results were consistent in TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial), and in women who did and did not receive chemotherapy, said Dr. Pagani, clinical director of the breast unit at the Oncology Institute of Southern Switzerland, Bellinzona.
Among the 43% of women who did not receive chemotherapy, 97.6% of these women in TEXT and 97.5% in SOFT who received the aromatase inhibitor exemestane (Aromasin) remained free from breast cancer at 5 years.
On average, these women had lower-risk features such as older age and smaller tumors, however, 21% of them in TEXT and 8% in SOFT had node-positive disease, she observed. After 5.7 years median follow-up, there were very few distant recurrences in this subgroup, only 1% in the exemestane group.
"These results suggest that some premenopausal women have an excellent prognosis with highly effective endocrine therapy without chemotherapy," Dr. Pagani said.
Invited discussant Dr. Nancy E. Davidson, director of the University of Pittsburgh Cancer Institute, said, "We should remember the power of endocrine therapy in properly selected patients of all ages. Not every premenopausal patient needs chemotherapy."
Dr. Davidson said the results show that the combination of ovarian suppression and an aromatase inhibitor (AI) is "an evidence-based approach and may provide support to use the combination in women who cannot take tamoxifen or perhaps in those at very high risk, especially if they don’t take chemotherapy."
She went on to say, however, that "For now, I’m waiting for the results of SOFT to finalize my approach."
Currently, the standard adjuvant endocrine therapy for premenopausal women is 5 years of tamoxifen, while aromatase inhibitors are primarily used in postmenopausal women, where they have been shown to improve outcomes over tamoxifen.
Physicians in some countries, typically outside the United States, however, recommend adding OFS to tamoxifen in high-risk younger women, but the benefit of this strategy is uncertain. SOFT included a third treatment arm of tamoxifen alone to address the role of OFS for women receiving tamoxifen, but those results are not expected until late 2014.
Study details
The joint analysis, simultaneously published online in the New England Journal of Medicine, included 4,690 premenopausal women with early hormone-sensitive breast cancer, who were randomly assigned to exemestane 25 mg daily or tamoxifen 20 mg daily for 5 years (2014 [doi:10.1056/NEJMoa1404037]).
Randomization occurred within 12 weeks of surgery for all women in TEXT and women in SOFT who did not receive chemotherapy. Women in SOFT who received prior (neo)adjuvant chemotherapy were randomized within 8 months of chemotherapy completion when premenopausal status was demonstrated.
OFS in both trials was achieved through monthly injections of the gonadotropin-releasing hormone agonist triptorelin pamoate (Trelstar Depot), bilateral oophorectomy, or ovarian radiation.
Routine use of bisphosphonates was not permitted, but adjuvant trastuzumab was allowed, if indicated.
Overall, 42% of women were lymph node–positive, 36% had tumors larger than 2 cm, and 12% had human epidermal growth factor receptor 2–positive breast cancer. Their median age was 43 years.
Outcomes
At 5 years, exemestane plus OFS significantly improved the primary endpoint of disease-free survival from 87.3% with tamoxifen plus OFS to 91.1% (hazard ratio, 0.72; P = .0002), Dr. Pagani said.
No striking heterogeneity of treatment effect was observed in prospectively planned subgroup analyses including the cohorts defined by trial, chemotherapy stratum, and node status.
"The relative and absolute differences at 5 years compare favorably with those reported in the practice-changing BIG 1-98 and ATAC [Arimidex, Tamoxifen, Alone or in Combination] trials of aromatase inhibitors vs. tamoxifen in postmenopausal women," she said.
At 5 years, 92.8% of women assigned to receive exemestane plus ovarian suppression were free from breast cancer vs. 88.8% of those given tamoxifen plus ovarian suppression (HR, 0.66; P less than .0001).
The rate of freedom from distant recurrence at 5 years was also superior in the exemestane group (93.8% vs. 92%; HR, 0.78; P = .02). In all, 60% of first events involved distant sites.
These benefits, however, have yet to translate into a significant overall survival benefit at 5 years for exemestane plus ovarian suppression, compared with tamoxifen plus ovarian suppression (95.9% vs. 96.9%; HR, 1.14; P = .37), said Dr. Pagani, who added that conclusions about long-term survival are premature at this early follow-up.
Where do we go from here?
ASCO immediate past-president Dr. Clifford Hudis said in a press briefing that the joint analysis provides long-awaited and actionable information on how best to treat premenopausal women with hormone-sensitive breast cancer who appear cured after surgery, but that data from the tamoxifen-alone arm in SOFT are needed to change practice for those unconvinced about the need for ovarian suppression.
Dr. Davidson said she’s left pondering how the results will be integrated into practice. Will clinicians use 10 years of tamoxifen, as supported by the ATLAS and aTTOM trials, or will they use an extended adjuvant approach of 5 years of tamoxifen followed by a switch to 5 years of AI for women who become postmenopausal during their tamoxifen, as supported by the MA 17 trial? It’s also possible some will follow the lead set by TEXT/SOFT and use 5 years of ovarian suppression and AI.
"If the benefits of OFS with AI hold up, we may want to revisit the role of oophorectomy in selected patients, who want to avoid injections and have a permanent menopause," she added. "We will need to make sure we maximize bisphosphonates for bone health, but I’m not prepared to use bisphosphonates as a routine form of adjuvant therapy in these women just yet."
Finally, Dr. Davidson said long-term follow-up of TEXT/SOFT is vital for both benefit and toxicity. Though overall compliance was good, she noted earlier in her talk that 16% of women on exemestane plus OFS prematurely stopped therapy vs. 11% on tamoxifen plus OFS. "Financial toxicity" is also an issue, with the wholesale acquisition cost at her institution for 1 year of exemestane 25 mg daily at $7,344 vs. $1,369 for tamoxifen, she said.
Dr. Pagani stressed during the press briefing that the results do not mean all premenopausal women should be given an AI plus ovarian suppression, but that the decision should be individualized with input from the physician and patient.
The research was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute (NCI). Dr. Pagani reported research funding from Ipsen and Pfizer. Dr. Davidson reported research funding from the Breast Cancer Research Foundation and National Institutes of Health (NIH).
CHICAGO – Adjuvant exemestane is more effective at preventing recurrence than tamoxifen is when either is given with ovarian function suppression in premenopausal women with hormone-sensitive breast cancers, according to a joint analysis of the phase III TEXT and SOFT trials.
"Exemestane plus OFS [ovarian function suppression] significantly improves disease-free survival, breast cancer free–interval, and distant recurrence free–interval and is a new treatment option for premenopausal women with hormone receptor-positive early breast cancer," lead study author Dr. Olivia Pagani said during a plenary session at the annual meeting of the American Society of Clinical Oncology.
The results were consistent in TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial), and in women who did and did not receive chemotherapy, said Dr. Pagani, clinical director of the breast unit at the Oncology Institute of Southern Switzerland, Bellinzona.
Among the 43% of women who did not receive chemotherapy, 97.6% of these women in TEXT and 97.5% in SOFT who received the aromatase inhibitor exemestane (Aromasin) remained free from breast cancer at 5 years.
On average, these women had lower-risk features such as older age and smaller tumors, however, 21% of them in TEXT and 8% in SOFT had node-positive disease, she observed. After 5.7 years median follow-up, there were very few distant recurrences in this subgroup, only 1% in the exemestane group.
"These results suggest that some premenopausal women have an excellent prognosis with highly effective endocrine therapy without chemotherapy," Dr. Pagani said.
Invited discussant Dr. Nancy E. Davidson, director of the University of Pittsburgh Cancer Institute, said, "We should remember the power of endocrine therapy in properly selected patients of all ages. Not every premenopausal patient needs chemotherapy."
Dr. Davidson said the results show that the combination of ovarian suppression and an aromatase inhibitor (AI) is "an evidence-based approach and may provide support to use the combination in women who cannot take tamoxifen or perhaps in those at very high risk, especially if they don’t take chemotherapy."
She went on to say, however, that "For now, I’m waiting for the results of SOFT to finalize my approach."
Currently, the standard adjuvant endocrine therapy for premenopausal women is 5 years of tamoxifen, while aromatase inhibitors are primarily used in postmenopausal women, where they have been shown to improve outcomes over tamoxifen.
Physicians in some countries, typically outside the United States, however, recommend adding OFS to tamoxifen in high-risk younger women, but the benefit of this strategy is uncertain. SOFT included a third treatment arm of tamoxifen alone to address the role of OFS for women receiving tamoxifen, but those results are not expected until late 2014.
Study details
The joint analysis, simultaneously published online in the New England Journal of Medicine, included 4,690 premenopausal women with early hormone-sensitive breast cancer, who were randomly assigned to exemestane 25 mg daily or tamoxifen 20 mg daily for 5 years (2014 [doi:10.1056/NEJMoa1404037]).
Randomization occurred within 12 weeks of surgery for all women in TEXT and women in SOFT who did not receive chemotherapy. Women in SOFT who received prior (neo)adjuvant chemotherapy were randomized within 8 months of chemotherapy completion when premenopausal status was demonstrated.
OFS in both trials was achieved through monthly injections of the gonadotropin-releasing hormone agonist triptorelin pamoate (Trelstar Depot), bilateral oophorectomy, or ovarian radiation.
Routine use of bisphosphonates was not permitted, but adjuvant trastuzumab was allowed, if indicated.
Overall, 42% of women were lymph node–positive, 36% had tumors larger than 2 cm, and 12% had human epidermal growth factor receptor 2–positive breast cancer. Their median age was 43 years.
Outcomes
At 5 years, exemestane plus OFS significantly improved the primary endpoint of disease-free survival from 87.3% with tamoxifen plus OFS to 91.1% (hazard ratio, 0.72; P = .0002), Dr. Pagani said.
No striking heterogeneity of treatment effect was observed in prospectively planned subgroup analyses including the cohorts defined by trial, chemotherapy stratum, and node status.
"The relative and absolute differences at 5 years compare favorably with those reported in the practice-changing BIG 1-98 and ATAC [Arimidex, Tamoxifen, Alone or in Combination] trials of aromatase inhibitors vs. tamoxifen in postmenopausal women," she said.
At 5 years, 92.8% of women assigned to receive exemestane plus ovarian suppression were free from breast cancer vs. 88.8% of those given tamoxifen plus ovarian suppression (HR, 0.66; P less than .0001).
The rate of freedom from distant recurrence at 5 years was also superior in the exemestane group (93.8% vs. 92%; HR, 0.78; P = .02). In all, 60% of first events involved distant sites.
These benefits, however, have yet to translate into a significant overall survival benefit at 5 years for exemestane plus ovarian suppression, compared with tamoxifen plus ovarian suppression (95.9% vs. 96.9%; HR, 1.14; P = .37), said Dr. Pagani, who added that conclusions about long-term survival are premature at this early follow-up.
Where do we go from here?
ASCO immediate past-president Dr. Clifford Hudis said in a press briefing that the joint analysis provides long-awaited and actionable information on how best to treat premenopausal women with hormone-sensitive breast cancer who appear cured after surgery, but that data from the tamoxifen-alone arm in SOFT are needed to change practice for those unconvinced about the need for ovarian suppression.
Dr. Davidson said she’s left pondering how the results will be integrated into practice. Will clinicians use 10 years of tamoxifen, as supported by the ATLAS and aTTOM trials, or will they use an extended adjuvant approach of 5 years of tamoxifen followed by a switch to 5 years of AI for women who become postmenopausal during their tamoxifen, as supported by the MA 17 trial? It’s also possible some will follow the lead set by TEXT/SOFT and use 5 years of ovarian suppression and AI.
"If the benefits of OFS with AI hold up, we may want to revisit the role of oophorectomy in selected patients, who want to avoid injections and have a permanent menopause," she added. "We will need to make sure we maximize bisphosphonates for bone health, but I’m not prepared to use bisphosphonates as a routine form of adjuvant therapy in these women just yet."
Finally, Dr. Davidson said long-term follow-up of TEXT/SOFT is vital for both benefit and toxicity. Though overall compliance was good, she noted earlier in her talk that 16% of women on exemestane plus OFS prematurely stopped therapy vs. 11% on tamoxifen plus OFS. "Financial toxicity" is also an issue, with the wholesale acquisition cost at her institution for 1 year of exemestane 25 mg daily at $7,344 vs. $1,369 for tamoxifen, she said.
Dr. Pagani stressed during the press briefing that the results do not mean all premenopausal women should be given an AI plus ovarian suppression, but that the decision should be individualized with input from the physician and patient.
The research was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute (NCI). Dr. Pagani reported research funding from Ipsen and Pfizer. Dr. Davidson reported research funding from the Breast Cancer Research Foundation and National Institutes of Health (NIH).
CHICAGO – Adjuvant exemestane is more effective at preventing recurrence than tamoxifen is when either is given with ovarian function suppression in premenopausal women with hormone-sensitive breast cancers, according to a joint analysis of the phase III TEXT and SOFT trials.
"Exemestane plus OFS [ovarian function suppression] significantly improves disease-free survival, breast cancer free–interval, and distant recurrence free–interval and is a new treatment option for premenopausal women with hormone receptor-positive early breast cancer," lead study author Dr. Olivia Pagani said during a plenary session at the annual meeting of the American Society of Clinical Oncology.
The results were consistent in TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial), and in women who did and did not receive chemotherapy, said Dr. Pagani, clinical director of the breast unit at the Oncology Institute of Southern Switzerland, Bellinzona.
Among the 43% of women who did not receive chemotherapy, 97.6% of these women in TEXT and 97.5% in SOFT who received the aromatase inhibitor exemestane (Aromasin) remained free from breast cancer at 5 years.
On average, these women had lower-risk features such as older age and smaller tumors, however, 21% of them in TEXT and 8% in SOFT had node-positive disease, she observed. After 5.7 years median follow-up, there were very few distant recurrences in this subgroup, only 1% in the exemestane group.
"These results suggest that some premenopausal women have an excellent prognosis with highly effective endocrine therapy without chemotherapy," Dr. Pagani said.
Invited discussant Dr. Nancy E. Davidson, director of the University of Pittsburgh Cancer Institute, said, "We should remember the power of endocrine therapy in properly selected patients of all ages. Not every premenopausal patient needs chemotherapy."
Dr. Davidson said the results show that the combination of ovarian suppression and an aromatase inhibitor (AI) is "an evidence-based approach and may provide support to use the combination in women who cannot take tamoxifen or perhaps in those at very high risk, especially if they don’t take chemotherapy."
She went on to say, however, that "For now, I’m waiting for the results of SOFT to finalize my approach."
Currently, the standard adjuvant endocrine therapy for premenopausal women is 5 years of tamoxifen, while aromatase inhibitors are primarily used in postmenopausal women, where they have been shown to improve outcomes over tamoxifen.
Physicians in some countries, typically outside the United States, however, recommend adding OFS to tamoxifen in high-risk younger women, but the benefit of this strategy is uncertain. SOFT included a third treatment arm of tamoxifen alone to address the role of OFS for women receiving tamoxifen, but those results are not expected until late 2014.
Study details
The joint analysis, simultaneously published online in the New England Journal of Medicine, included 4,690 premenopausal women with early hormone-sensitive breast cancer, who were randomly assigned to exemestane 25 mg daily or tamoxifen 20 mg daily for 5 years (2014 [doi:10.1056/NEJMoa1404037]).
Randomization occurred within 12 weeks of surgery for all women in TEXT and women in SOFT who did not receive chemotherapy. Women in SOFT who received prior (neo)adjuvant chemotherapy were randomized within 8 months of chemotherapy completion when premenopausal status was demonstrated.
OFS in both trials was achieved through monthly injections of the gonadotropin-releasing hormone agonist triptorelin pamoate (Trelstar Depot), bilateral oophorectomy, or ovarian radiation.
Routine use of bisphosphonates was not permitted, but adjuvant trastuzumab was allowed, if indicated.
Overall, 42% of women were lymph node–positive, 36% had tumors larger than 2 cm, and 12% had human epidermal growth factor receptor 2–positive breast cancer. Their median age was 43 years.
Outcomes
At 5 years, exemestane plus OFS significantly improved the primary endpoint of disease-free survival from 87.3% with tamoxifen plus OFS to 91.1% (hazard ratio, 0.72; P = .0002), Dr. Pagani said.
No striking heterogeneity of treatment effect was observed in prospectively planned subgroup analyses including the cohorts defined by trial, chemotherapy stratum, and node status.
"The relative and absolute differences at 5 years compare favorably with those reported in the practice-changing BIG 1-98 and ATAC [Arimidex, Tamoxifen, Alone or in Combination] trials of aromatase inhibitors vs. tamoxifen in postmenopausal women," she said.
At 5 years, 92.8% of women assigned to receive exemestane plus ovarian suppression were free from breast cancer vs. 88.8% of those given tamoxifen plus ovarian suppression (HR, 0.66; P less than .0001).
The rate of freedom from distant recurrence at 5 years was also superior in the exemestane group (93.8% vs. 92%; HR, 0.78; P = .02). In all, 60% of first events involved distant sites.
These benefits, however, have yet to translate into a significant overall survival benefit at 5 years for exemestane plus ovarian suppression, compared with tamoxifen plus ovarian suppression (95.9% vs. 96.9%; HR, 1.14; P = .37), said Dr. Pagani, who added that conclusions about long-term survival are premature at this early follow-up.
Where do we go from here?
ASCO immediate past-president Dr. Clifford Hudis said in a press briefing that the joint analysis provides long-awaited and actionable information on how best to treat premenopausal women with hormone-sensitive breast cancer who appear cured after surgery, but that data from the tamoxifen-alone arm in SOFT are needed to change practice for those unconvinced about the need for ovarian suppression.
Dr. Davidson said she’s left pondering how the results will be integrated into practice. Will clinicians use 10 years of tamoxifen, as supported by the ATLAS and aTTOM trials, or will they use an extended adjuvant approach of 5 years of tamoxifen followed by a switch to 5 years of AI for women who become postmenopausal during their tamoxifen, as supported by the MA 17 trial? It’s also possible some will follow the lead set by TEXT/SOFT and use 5 years of ovarian suppression and AI.
"If the benefits of OFS with AI hold up, we may want to revisit the role of oophorectomy in selected patients, who want to avoid injections and have a permanent menopause," she added. "We will need to make sure we maximize bisphosphonates for bone health, but I’m not prepared to use bisphosphonates as a routine form of adjuvant therapy in these women just yet."
Finally, Dr. Davidson said long-term follow-up of TEXT/SOFT is vital for both benefit and toxicity. Though overall compliance was good, she noted earlier in her talk that 16% of women on exemestane plus OFS prematurely stopped therapy vs. 11% on tamoxifen plus OFS. "Financial toxicity" is also an issue, with the wholesale acquisition cost at her institution for 1 year of exemestane 25 mg daily at $7,344 vs. $1,369 for tamoxifen, she said.
Dr. Pagani stressed during the press briefing that the results do not mean all premenopausal women should be given an AI plus ovarian suppression, but that the decision should be individualized with input from the physician and patient.
The research was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute (NCI). Dr. Pagani reported research funding from Ipsen and Pfizer. Dr. Davidson reported research funding from the Breast Cancer Research Foundation and National Institutes of Health (NIH).
AT THE ASCO ANNUAL MEETING 2014
Key clinical point: Exemestane plus OFS is a new treatment option in the setting of premenopausal hormone-sensitive early breast cancer.
Major finding: Exemestane plus OFS significantly improved disease-free survival from 87.3% with tamoxifen plus OFS to 91.1% (HR, 0.72; P = .0002).
Data source: Joint analysis of two phase III studies in 4,690 premenopausal women with hormone receptor-positive, early breast cancer.
Disclosures: The research was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the NCI. Dr. Pagani reported research funding from Ipsen and Pfizer. Dr. Davidson reported research funding from the Breast Cancer Research Foundation and the NIH.
To screen or not to screen: lung and breast cancer
Although the incidence of lung cancer in the United States has been falling in recent years because of a decrease in cigarette smoking, the disease is still the third most common cancer, and the leading cause of cancer death. In March 2014, the US Preventive Services Task Force (USPSTF) updated its 2004 recommendations for lung cancer screening by commissioning a systematic evidence review of low-dose computed tomography (CT) by focusing on new evidence from randomized clinical trials published since 2004. In addition, a modeling study provided information about the optimum screening age, screening interval, and the risk-benefit ratio for screening.
Click on the PDF icon at the top of this introduction to read the full article.
Although the incidence of lung cancer in the United States has been falling in recent years because of a decrease in cigarette smoking, the disease is still the third most common cancer, and the leading cause of cancer death. In March 2014, the US Preventive Services Task Force (USPSTF) updated its 2004 recommendations for lung cancer screening by commissioning a systematic evidence review of low-dose computed tomography (CT) by focusing on new evidence from randomized clinical trials published since 2004. In addition, a modeling study provided information about the optimum screening age, screening interval, and the risk-benefit ratio for screening.
Click on the PDF icon at the top of this introduction to read the full article.
Although the incidence of lung cancer in the United States has been falling in recent years because of a decrease in cigarette smoking, the disease is still the third most common cancer, and the leading cause of cancer death. In March 2014, the US Preventive Services Task Force (USPSTF) updated its 2004 recommendations for lung cancer screening by commissioning a systematic evidence review of low-dose computed tomography (CT) by focusing on new evidence from randomized clinical trials published since 2004. In addition, a modeling study provided information about the optimum screening age, screening interval, and the risk-benefit ratio for screening.
Click on the PDF icon at the top of this introduction to read the full article.
Short-term outcomes of the implementation of a computer-based breast cancer risk assessment program during screening mammography
Background Barriers to assessing a patient’s risk for breast cancer include the inadequate documentation of family history, the complexity of risk calculation and model selection, and a lack of awareness of risk on the part of the patient and/or provider. We have established computer-based, real-time assessment of a patient’s risk for breast cancer at the time of having a mammogram.
Objective To facilitate identification of high-risk patients who need genetic counseling and testing and magnetic resonance imaging screening based on the results of the risk assessment.
Methods Since November 23, 2010, all mammogram patients have completed questionnaires using a wireless tablet. On the basis of a real-time calculation for a patient’s risk of BRCA1/BRCA2 mutation (Myriad, Tyrer-Cuzick, BRCAPRO) and lifetime risk of breast cancer (Gail, Claus, Tyrer-Cuzick, BRCAPRO) using Hughes riskApps, patients were categorized as high risk (≥ 10% BRCA mutation or ≥ 20% lifetime breast cancer risk) or average risk and received a risk assessment letter. The risk data was integrated into our mammography information system (PenRad) at the same time. High-risk patients were contacted to facilitate evaluation.
Results As of June 30, 2012, a total of 24,213 unaffected patients completed the risk assessment. There were 2,196 patients (9.1%) identified as high risk: 1,051 (4.3%) had a BRCA mutation risk, 1,570 (6.5%) had lifetime breast cancer risk, and 425 (1.8%) had risk for both. Of the high-risk patients, 416 (18.7%) were evaluated by our APN and/or genetic counselor. Of the 231 who were evaluated by a genetic counselor, 97 had genetic testing and 9 (8.3%) were BRCA positive. Annual MRI screening was recommended to 254 patients.
Conclusions We have successfully implemented breast cancer risk assessment through our screening mammography service. Results suggest that 9.1% of our patients can benefit from risk assessment, 4.3% should consider genetic testing, and 6.5% may benefit from screening MRI. We strive to improve compliance through patient education.
Click on the PDF icon at the top of this introduction to read the full article.
Background Barriers to assessing a patient’s risk for breast cancer include the inadequate documentation of family history, the complexity of risk calculation and model selection, and a lack of awareness of risk on the part of the patient and/or provider. We have established computer-based, real-time assessment of a patient’s risk for breast cancer at the time of having a mammogram.
Objective To facilitate identification of high-risk patients who need genetic counseling and testing and magnetic resonance imaging screening based on the results of the risk assessment.
Methods Since November 23, 2010, all mammogram patients have completed questionnaires using a wireless tablet. On the basis of a real-time calculation for a patient’s risk of BRCA1/BRCA2 mutation (Myriad, Tyrer-Cuzick, BRCAPRO) and lifetime risk of breast cancer (Gail, Claus, Tyrer-Cuzick, BRCAPRO) using Hughes riskApps, patients were categorized as high risk (≥ 10% BRCA mutation or ≥ 20% lifetime breast cancer risk) or average risk and received a risk assessment letter. The risk data was integrated into our mammography information system (PenRad) at the same time. High-risk patients were contacted to facilitate evaluation.
Results As of June 30, 2012, a total of 24,213 unaffected patients completed the risk assessment. There were 2,196 patients (9.1%) identified as high risk: 1,051 (4.3%) had a BRCA mutation risk, 1,570 (6.5%) had lifetime breast cancer risk, and 425 (1.8%) had risk for both. Of the high-risk patients, 416 (18.7%) were evaluated by our APN and/or genetic counselor. Of the 231 who were evaluated by a genetic counselor, 97 had genetic testing and 9 (8.3%) were BRCA positive. Annual MRI screening was recommended to 254 patients.
Conclusions We have successfully implemented breast cancer risk assessment through our screening mammography service. Results suggest that 9.1% of our patients can benefit from risk assessment, 4.3% should consider genetic testing, and 6.5% may benefit from screening MRI. We strive to improve compliance through patient education.
Click on the PDF icon at the top of this introduction to read the full article.
Background Barriers to assessing a patient’s risk for breast cancer include the inadequate documentation of family history, the complexity of risk calculation and model selection, and a lack of awareness of risk on the part of the patient and/or provider. We have established computer-based, real-time assessment of a patient’s risk for breast cancer at the time of having a mammogram.
Objective To facilitate identification of high-risk patients who need genetic counseling and testing and magnetic resonance imaging screening based on the results of the risk assessment.
Methods Since November 23, 2010, all mammogram patients have completed questionnaires using a wireless tablet. On the basis of a real-time calculation for a patient’s risk of BRCA1/BRCA2 mutation (Myriad, Tyrer-Cuzick, BRCAPRO) and lifetime risk of breast cancer (Gail, Claus, Tyrer-Cuzick, BRCAPRO) using Hughes riskApps, patients were categorized as high risk (≥ 10% BRCA mutation or ≥ 20% lifetime breast cancer risk) or average risk and received a risk assessment letter. The risk data was integrated into our mammography information system (PenRad) at the same time. High-risk patients were contacted to facilitate evaluation.
Results As of June 30, 2012, a total of 24,213 unaffected patients completed the risk assessment. There were 2,196 patients (9.1%) identified as high risk: 1,051 (4.3%) had a BRCA mutation risk, 1,570 (6.5%) had lifetime breast cancer risk, and 425 (1.8%) had risk for both. Of the high-risk patients, 416 (18.7%) were evaluated by our APN and/or genetic counselor. Of the 231 who were evaluated by a genetic counselor, 97 had genetic testing and 9 (8.3%) were BRCA positive. Annual MRI screening was recommended to 254 patients.
Conclusions We have successfully implemented breast cancer risk assessment through our screening mammography service. Results suggest that 9.1% of our patients can benefit from risk assessment, 4.3% should consider genetic testing, and 6.5% may benefit from screening MRI. We strive to improve compliance through patient education.
Click on the PDF icon at the top of this introduction to read the full article.
Targeted sessions for targeted therapies at ASCO
It’s likely that you have just returned from ASCO 2014 in Chicago with 33,000 of your closest oncology friends, or that you have at least heard all about the meeting and some of the exciting presentations. Either way, you must be wondering how best to sift through the mountain of data and information that came out of the meeting so that you can organize it, absorb it, and here’s the real challenge, apply it in the real-clinic setting going forward.
Click on the PDF icon at the top of this introduction to read the full article.
It’s likely that you have just returned from ASCO 2014 in Chicago with 33,000 of your closest oncology friends, or that you have at least heard all about the meeting and some of the exciting presentations. Either way, you must be wondering how best to sift through the mountain of data and information that came out of the meeting so that you can organize it, absorb it, and here’s the real challenge, apply it in the real-clinic setting going forward.
Click on the PDF icon at the top of this introduction to read the full article.
It’s likely that you have just returned from ASCO 2014 in Chicago with 33,000 of your closest oncology friends, or that you have at least heard all about the meeting and some of the exciting presentations. Either way, you must be wondering how best to sift through the mountain of data and information that came out of the meeting so that you can organize it, absorb it, and here’s the real challenge, apply it in the real-clinic setting going forward.
Click on the PDF icon at the top of this introduction to read the full article.
Adding tomosynthesis improved mammography’s cancer detection
Adding tomosynthesis to screening digital mammography decreases the "recall" rate by 15% while increasing the cancer detection rate by 29%, according to a report published online June 25 in JAMA.
Researchers compared the performance of screening digital mammography alone (281,187 cases) against the performance after tomosynthesis was added to mammography (173,663 cases) at 13 sites in geographically diverse regions across the country. The work was funded primarily by Hologic, maker of the only Food and Drug Administration–approved tomosynthesis equipment at the time of this retrospective study, said Dr. Sarah M. Friedewald of the Caldwell Breast Center, Advocate Lutheran General Hospital, Park Ridge, Ill., and her associates.
The "recall" rate – the proportion of patients requiring additional imaging based on the results of their screening mammography – declined from 107 per 1,000 screens with digital mammography alone to 91 per 1,000 screens when tomosynthesis was added, a relative reduction of 15%. At the same time, the cancer detection rate rose from 4.2 to 5.4 per 1,000 scans, a relative increase of 29%. After tomosynthesis was introduced, the detection rate of invasive cancers rose from 2.9 to 4.1 per 1,000 scans, while that of ductal carcinoma in situ remained unchanged at 1.4 per 1,000, the investigators said (JAMA 2014 June 25 [doi:10.1001/jama.2014.6095]).
It is important to note that this study did not assess clinical outcomes, so it remains to be seen whether these improvements in screening mammography translate into clinically relevant improvements in breast cancer mortality. In addition, this study was limited in that it was retrospective and nonrandomized, they wrote.
This study was funded by tomosynthesis equipment maker Hologic and the National Cancer Institute. Dr. Friedewald and her associates also reported other ties to Hologic.
Tomosynthesis likely represents an advance over digital mammography for breast cancer screening, but only appropriately powered, prospective, randomized, multicenter clinical trials involving all four currently available tomosynthesis systems will answer this question definitively, said Dr. Etta D. Pisano and Martin J. Yaffe, Ph.D.
Despite the promising results of Friedewald et al., it is still uncertain whether women should specifically ask for tomosynthesis or whether screening centers should convert to tomosynthesis. People who believe screening mammography saves lives without undue false-positive results and overdiagnosis will likely advocate the addition of tomosynthesis; those who question the utility of screening mammography will not likely change their views after seeing these results, Dr. Pisano and Dr. Yaffe said.
Dr. Pisano is at the Medical University of South Carolina, Charleston. Dr. Yaffe is at the Ontario Institute for Cancer Research at the University of Toronto. Dr. Pisano reported ties to FujiFilm, Koning Corp., Siemens, Philips, and NextRay Inc.; Dr. Yaffe reported ties to GE Healthcare and Mammographic Physics Inc. These remarks were taken from their editorial accompanying Dr. Friedewald’s report (JAMA 2014;311:2488-9).
Tomosynthesis likely represents an advance over digital mammography for breast cancer screening, but only appropriately powered, prospective, randomized, multicenter clinical trials involving all four currently available tomosynthesis systems will answer this question definitively, said Dr. Etta D. Pisano and Martin J. Yaffe, Ph.D.
Despite the promising results of Friedewald et al., it is still uncertain whether women should specifically ask for tomosynthesis or whether screening centers should convert to tomosynthesis. People who believe screening mammography saves lives without undue false-positive results and overdiagnosis will likely advocate the addition of tomosynthesis; those who question the utility of screening mammography will not likely change their views after seeing these results, Dr. Pisano and Dr. Yaffe said.
Dr. Pisano is at the Medical University of South Carolina, Charleston. Dr. Yaffe is at the Ontario Institute for Cancer Research at the University of Toronto. Dr. Pisano reported ties to FujiFilm, Koning Corp., Siemens, Philips, and NextRay Inc.; Dr. Yaffe reported ties to GE Healthcare and Mammographic Physics Inc. These remarks were taken from their editorial accompanying Dr. Friedewald’s report (JAMA 2014;311:2488-9).
Tomosynthesis likely represents an advance over digital mammography for breast cancer screening, but only appropriately powered, prospective, randomized, multicenter clinical trials involving all four currently available tomosynthesis systems will answer this question definitively, said Dr. Etta D. Pisano and Martin J. Yaffe, Ph.D.
Despite the promising results of Friedewald et al., it is still uncertain whether women should specifically ask for tomosynthesis or whether screening centers should convert to tomosynthesis. People who believe screening mammography saves lives without undue false-positive results and overdiagnosis will likely advocate the addition of tomosynthesis; those who question the utility of screening mammography will not likely change their views after seeing these results, Dr. Pisano and Dr. Yaffe said.
Dr. Pisano is at the Medical University of South Carolina, Charleston. Dr. Yaffe is at the Ontario Institute for Cancer Research at the University of Toronto. Dr. Pisano reported ties to FujiFilm, Koning Corp., Siemens, Philips, and NextRay Inc.; Dr. Yaffe reported ties to GE Healthcare and Mammographic Physics Inc. These remarks were taken from their editorial accompanying Dr. Friedewald’s report (JAMA 2014;311:2488-9).
Adding tomosynthesis to screening digital mammography decreases the "recall" rate by 15% while increasing the cancer detection rate by 29%, according to a report published online June 25 in JAMA.
Researchers compared the performance of screening digital mammography alone (281,187 cases) against the performance after tomosynthesis was added to mammography (173,663 cases) at 13 sites in geographically diverse regions across the country. The work was funded primarily by Hologic, maker of the only Food and Drug Administration–approved tomosynthesis equipment at the time of this retrospective study, said Dr. Sarah M. Friedewald of the Caldwell Breast Center, Advocate Lutheran General Hospital, Park Ridge, Ill., and her associates.
The "recall" rate – the proportion of patients requiring additional imaging based on the results of their screening mammography – declined from 107 per 1,000 screens with digital mammography alone to 91 per 1,000 screens when tomosynthesis was added, a relative reduction of 15%. At the same time, the cancer detection rate rose from 4.2 to 5.4 per 1,000 scans, a relative increase of 29%. After tomosynthesis was introduced, the detection rate of invasive cancers rose from 2.9 to 4.1 per 1,000 scans, while that of ductal carcinoma in situ remained unchanged at 1.4 per 1,000, the investigators said (JAMA 2014 June 25 [doi:10.1001/jama.2014.6095]).
It is important to note that this study did not assess clinical outcomes, so it remains to be seen whether these improvements in screening mammography translate into clinically relevant improvements in breast cancer mortality. In addition, this study was limited in that it was retrospective and nonrandomized, they wrote.
This study was funded by tomosynthesis equipment maker Hologic and the National Cancer Institute. Dr. Friedewald and her associates also reported other ties to Hologic.
Adding tomosynthesis to screening digital mammography decreases the "recall" rate by 15% while increasing the cancer detection rate by 29%, according to a report published online June 25 in JAMA.
Researchers compared the performance of screening digital mammography alone (281,187 cases) against the performance after tomosynthesis was added to mammography (173,663 cases) at 13 sites in geographically diverse regions across the country. The work was funded primarily by Hologic, maker of the only Food and Drug Administration–approved tomosynthesis equipment at the time of this retrospective study, said Dr. Sarah M. Friedewald of the Caldwell Breast Center, Advocate Lutheran General Hospital, Park Ridge, Ill., and her associates.
The "recall" rate – the proportion of patients requiring additional imaging based on the results of their screening mammography – declined from 107 per 1,000 screens with digital mammography alone to 91 per 1,000 screens when tomosynthesis was added, a relative reduction of 15%. At the same time, the cancer detection rate rose from 4.2 to 5.4 per 1,000 scans, a relative increase of 29%. After tomosynthesis was introduced, the detection rate of invasive cancers rose from 2.9 to 4.1 per 1,000 scans, while that of ductal carcinoma in situ remained unchanged at 1.4 per 1,000, the investigators said (JAMA 2014 June 25 [doi:10.1001/jama.2014.6095]).
It is important to note that this study did not assess clinical outcomes, so it remains to be seen whether these improvements in screening mammography translate into clinically relevant improvements in breast cancer mortality. In addition, this study was limited in that it was retrospective and nonrandomized, they wrote.
This study was funded by tomosynthesis equipment maker Hologic and the National Cancer Institute. Dr. Friedewald and her associates also reported other ties to Hologic.
FROM JAMA
Key clinical point: Tomosynthesis may reduce the need for repeat imaging to detect breast cancer.
Major finding: The "recall" rate declined from 107 per 1,000 screens with digital mammography alone to 91 per 1,000 screens when tomosynthesis was added, a relative reduction of 15%; at the same time, the cancer detection rate rose from 4.2 to 5.4 per 1,000 scans, a relative increase of 29%.
Data source: A retrospective multicenter analysis of screening digital mammography’s performance before (281,187 scans) and after (173,663 scans) the introduction of tomosynthesis to improve its accuracy.
Disclosures: This study was funded by Hologic and the National Cancer Institute. Dr. Friedewald and her associates also reported other ties to Hologic, which makes tomosynthesis equipment.
Combined imaging differentiated benign, cancerous breast tumors
Combined imaging techniques using multiparametric 18fluorodeoxyglucose PET-MRI allow differentiation between benign and malignant breast tumors with a diagnostic accuracy of 96%, according to a report published online June 24 in Clinical Cancer Research.
This in turn permits a "remarkable" reduction in breast biopsies, said Dr. Katja Pinker and her associates at the Medical University of Vienna.
In a single-center feasibility study, the investigators compared the prognostic accuracy of several different combinations of breast imaging in 76 consecutive women aged 25-86 years (mean age, 55.7 years) who were seen during a 3-year period and had suspicious findings on mammography or breast ultrasonography. The lesions ranged in size from 5 mm to 77 mm (median, 29.2 mm); 53 proved to be malignant and 23 were benign.
Only one combination of imaging techniques – multiparametric 18fluorodeoxyglucose (FDG) PET-MRI – achieved an overall diagnostic accuracy of 96%, with a sensitivity of 100% and a specificity of 87% in distinguishing cancers from benign tumors.
Multiparametric FDG PET-MRI includes:
• Dynamic contrast-enhanced MRI, which provides high-resolution anatomic information and depicts increased microvascular density and capillary leaks, which are markers of angiogenesis in malignant tumors.
• Diffusion-weighted imaging that shows cellular diffusivity on a molecular level, which typically is restricted in malignant tissue.
• Three-dimensional proton spectroscopic imaging, which detects elevated levels of the metabolite choline, a marker of increased cell-membrane turnover.
• FDG PET that allows assessment of glucose consumption, which typically is increased in neoplastic processes.
Thus, this combination of imaging techniques simultaneously assesses several processes involved in cancer development: angiogenesis, molecular capabilities, glucose consumption, and metabolite concentration, the investigators said (Clin. Cancer Res. 2014 June 24 [doi: 10.1158/1055-9965.EPI-13-1284]).
Fluorodeoxyglucose, "currently the ‘workhorse’ in clinical PET imaging, has a good sensitivity but limited specificity, as several types of benign breast tumors and conditions can be 18FDG-avid and mimic malignancy," Dr. Pinker and her associates wrote. "However, a multitude of new, targeted radiotracers for visualization of processes involved in cancer evolution are being developed and investigated." These tracers should increase the specificity of this combination of imaging techniques, which will soon make multiparametric PET-MRI an important tool in detecting breast cancer, staging the disease, and monitoring treatment response, they said.
This study was funded by the Austrian Society of Senology, the Austrian National Bank "Jubiläumsfond," and the Medical Scientific Fund of the Mayor of Vienna. Dr. Pinker and her associates reported no financial conflicts of interest.
Combined imaging techniques using multiparametric 18fluorodeoxyglucose PET-MRI allow differentiation between benign and malignant breast tumors with a diagnostic accuracy of 96%, according to a report published online June 24 in Clinical Cancer Research.
This in turn permits a "remarkable" reduction in breast biopsies, said Dr. Katja Pinker and her associates at the Medical University of Vienna.
In a single-center feasibility study, the investigators compared the prognostic accuracy of several different combinations of breast imaging in 76 consecutive women aged 25-86 years (mean age, 55.7 years) who were seen during a 3-year period and had suspicious findings on mammography or breast ultrasonography. The lesions ranged in size from 5 mm to 77 mm (median, 29.2 mm); 53 proved to be malignant and 23 were benign.
Only one combination of imaging techniques – multiparametric 18fluorodeoxyglucose (FDG) PET-MRI – achieved an overall diagnostic accuracy of 96%, with a sensitivity of 100% and a specificity of 87% in distinguishing cancers from benign tumors.
Multiparametric FDG PET-MRI includes:
• Dynamic contrast-enhanced MRI, which provides high-resolution anatomic information and depicts increased microvascular density and capillary leaks, which are markers of angiogenesis in malignant tumors.
• Diffusion-weighted imaging that shows cellular diffusivity on a molecular level, which typically is restricted in malignant tissue.
• Three-dimensional proton spectroscopic imaging, which detects elevated levels of the metabolite choline, a marker of increased cell-membrane turnover.
• FDG PET that allows assessment of glucose consumption, which typically is increased in neoplastic processes.
Thus, this combination of imaging techniques simultaneously assesses several processes involved in cancer development: angiogenesis, molecular capabilities, glucose consumption, and metabolite concentration, the investigators said (Clin. Cancer Res. 2014 June 24 [doi: 10.1158/1055-9965.EPI-13-1284]).
Fluorodeoxyglucose, "currently the ‘workhorse’ in clinical PET imaging, has a good sensitivity but limited specificity, as several types of benign breast tumors and conditions can be 18FDG-avid and mimic malignancy," Dr. Pinker and her associates wrote. "However, a multitude of new, targeted radiotracers for visualization of processes involved in cancer evolution are being developed and investigated." These tracers should increase the specificity of this combination of imaging techniques, which will soon make multiparametric PET-MRI an important tool in detecting breast cancer, staging the disease, and monitoring treatment response, they said.
This study was funded by the Austrian Society of Senology, the Austrian National Bank "Jubiläumsfond," and the Medical Scientific Fund of the Mayor of Vienna. Dr. Pinker and her associates reported no financial conflicts of interest.
Combined imaging techniques using multiparametric 18fluorodeoxyglucose PET-MRI allow differentiation between benign and malignant breast tumors with a diagnostic accuracy of 96%, according to a report published online June 24 in Clinical Cancer Research.
This in turn permits a "remarkable" reduction in breast biopsies, said Dr. Katja Pinker and her associates at the Medical University of Vienna.
In a single-center feasibility study, the investigators compared the prognostic accuracy of several different combinations of breast imaging in 76 consecutive women aged 25-86 years (mean age, 55.7 years) who were seen during a 3-year period and had suspicious findings on mammography or breast ultrasonography. The lesions ranged in size from 5 mm to 77 mm (median, 29.2 mm); 53 proved to be malignant and 23 were benign.
Only one combination of imaging techniques – multiparametric 18fluorodeoxyglucose (FDG) PET-MRI – achieved an overall diagnostic accuracy of 96%, with a sensitivity of 100% and a specificity of 87% in distinguishing cancers from benign tumors.
Multiparametric FDG PET-MRI includes:
• Dynamic contrast-enhanced MRI, which provides high-resolution anatomic information and depicts increased microvascular density and capillary leaks, which are markers of angiogenesis in malignant tumors.
• Diffusion-weighted imaging that shows cellular diffusivity on a molecular level, which typically is restricted in malignant tissue.
• Three-dimensional proton spectroscopic imaging, which detects elevated levels of the metabolite choline, a marker of increased cell-membrane turnover.
• FDG PET that allows assessment of glucose consumption, which typically is increased in neoplastic processes.
Thus, this combination of imaging techniques simultaneously assesses several processes involved in cancer development: angiogenesis, molecular capabilities, glucose consumption, and metabolite concentration, the investigators said (Clin. Cancer Res. 2014 June 24 [doi: 10.1158/1055-9965.EPI-13-1284]).
Fluorodeoxyglucose, "currently the ‘workhorse’ in clinical PET imaging, has a good sensitivity but limited specificity, as several types of benign breast tumors and conditions can be 18FDG-avid and mimic malignancy," Dr. Pinker and her associates wrote. "However, a multitude of new, targeted radiotracers for visualization of processes involved in cancer evolution are being developed and investigated." These tracers should increase the specificity of this combination of imaging techniques, which will soon make multiparametric PET-MRI an important tool in detecting breast cancer, staging the disease, and monitoring treatment response, they said.
This study was funded by the Austrian Society of Senology, the Austrian National Bank "Jubiläumsfond," and the Medical Scientific Fund of the Mayor of Vienna. Dr. Pinker and her associates reported no financial conflicts of interest.
FROM CLINICAL CANCER RESEARCH
Key clinical point: A combination of imaging techniques, which simultaneously assesses several processes involved in cancer development, achieved high diagnostic accuracy in distinguishing breast cancers from benign lesions.
Major finding: Only one combination of imaging techniques – 18fluorodeoxyglucose PET-MRI – achieved an overall diagnostic accuracy of 96%, with a sensitivity of 100% and a specificity of 87% in distinguishing malignancies from benign lesions.
Data source: A prospective, single-center feasibility study involving different combinations of breast imaging techniques to assess the likelihood of malignancy in 76 consecutive women who had suspicious findings on mammography or ultrasonography.
Disclosures: This study was funded by the Austrian Society of Senology, the Austrian National Bank "Jubiläumsfond," and the Medical Scientific Fund of the Mayor of Vienna. Dr. Pinker and her associates reported no financial conflicts of interest.
Phone-based intervention helped breast cancer patients lose weight, but key question remains
A telephone-based lifestyle intervention can have a significant effect on weight loss in overweight breast cancer survivors, according to a study that also highlights the dilemmas of funding large lifestyle trials with definitive mortality endpoints.
Mean weight loss at 6 months was greater in women who received telephone-based coaching and were mailed health information vs. women who received mailed information only (5.3% vs. 0.7%; P less than .001), investigators reported online June 16 in the Journal of Clinical Oncology. The study was part of the multicenter LISA(Lifestyle Intervention Study in Adjuvant Treatment of Early Breast Cancer) trial.
At 24 months the weight loss still compared favorably in the intervention group (3.6% loss vs. 0.4% in the mail-only group; P less than .001), reported Dr. Pamela J. Goodwin of the Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, and her associates (J. Clin. Oncol. 2014 June 16 [doi: 10.1200/JCO.2013.53.1517].
But will losing weight improve breast cancer outcomes?
The original aim of LISA was to examine the effect of weight loss on disease-free survival, but patient accrual was terminated early (at 338 of the 2,150 planned participants), because of a loss of funding from sponsor Novartis Pharmaceuticals, leaving that question unanswered.
Patients were eligible to participate in the study if they had been diagnosed in the last 36 months, had a body mass index of 24 kg/m2 or higher, and were receiving letrozole for hormone receptor–positive breast cancer. Study participants were randomly assigned to receive general health information by mail, or to a lifestyle intervention where they received weight loss advice by telephone in addition to the health information by mail.
The telephone-based lifestyle intervention included a dietary goal (500-1,000 kcal per day deficit) and a physical activity goal (150-200 minutes of moderate-intensity physical activity per week) to achieve weight loss.
"Our results support the use of telephone-based delivery of weight-loss interventions in patients with breast cancer, and they suggest that our approach will be generally effective in postmenopausal patients receiving an aromatase inhibitor," the investigators concluded.
The results, combined with the recognition that obesity is associated with poor breast cancer outcomes, provide support for a randomized trial using a telephone-based weight-loss intervention that is adequately powered to detect clinically important effects on breast cancer outcomes, they said.
While the findings add to a growing body of evidence supporting the benefits of weight-loss interventions in overweight breast cancer survivors, questions remain regarding the effect of weight loss on breast cancer recurrence and mortality, said Melinda L. Irwin, Ph.D., M.P.H., in an accompanying editorial (J. Clin. Oncol. 2014 June 16 [doi: 10.1200/JCO.2014.56.4583]).
"How can important lifestyle trials with definitive mortality end points best be funded?" asked Dr. Irwin of Yale University, New Haven, Conn. She suggested that pharmaceutical companies be required to include a lifestyle intervention arm in drug trials.
"Given that pharmaceutical companies primarily fund therapeutic trials, with little incentive to fund lifestyle interventions, and given the scarcity of funding from government agencies for large-scale long-term trials of lifestyle interventions with disease-free survival endpoints, another option may be to require pharmaceutical companies to include lifestyle interventions as an active comparison arm to drug trials, especially in cases when drug options provide modest benefit, or uptake or adherence to particular medications [is] low," she said.
The study was funded by Novartis Pharmaceuticals. Dr. Goodwin and Dr. Irwin reported no disclosures. Two coauthors disclosed honoraria or research funding from Novartis and other companies.
A telephone-based lifestyle intervention can have a significant effect on weight loss in overweight breast cancer survivors, according to a study that also highlights the dilemmas of funding large lifestyle trials with definitive mortality endpoints.
Mean weight loss at 6 months was greater in women who received telephone-based coaching and were mailed health information vs. women who received mailed information only (5.3% vs. 0.7%; P less than .001), investigators reported online June 16 in the Journal of Clinical Oncology. The study was part of the multicenter LISA(Lifestyle Intervention Study in Adjuvant Treatment of Early Breast Cancer) trial.
At 24 months the weight loss still compared favorably in the intervention group (3.6% loss vs. 0.4% in the mail-only group; P less than .001), reported Dr. Pamela J. Goodwin of the Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, and her associates (J. Clin. Oncol. 2014 June 16 [doi: 10.1200/JCO.2013.53.1517].
But will losing weight improve breast cancer outcomes?
The original aim of LISA was to examine the effect of weight loss on disease-free survival, but patient accrual was terminated early (at 338 of the 2,150 planned participants), because of a loss of funding from sponsor Novartis Pharmaceuticals, leaving that question unanswered.
Patients were eligible to participate in the study if they had been diagnosed in the last 36 months, had a body mass index of 24 kg/m2 or higher, and were receiving letrozole for hormone receptor–positive breast cancer. Study participants were randomly assigned to receive general health information by mail, or to a lifestyle intervention where they received weight loss advice by telephone in addition to the health information by mail.
The telephone-based lifestyle intervention included a dietary goal (500-1,000 kcal per day deficit) and a physical activity goal (150-200 minutes of moderate-intensity physical activity per week) to achieve weight loss.
"Our results support the use of telephone-based delivery of weight-loss interventions in patients with breast cancer, and they suggest that our approach will be generally effective in postmenopausal patients receiving an aromatase inhibitor," the investigators concluded.
The results, combined with the recognition that obesity is associated with poor breast cancer outcomes, provide support for a randomized trial using a telephone-based weight-loss intervention that is adequately powered to detect clinically important effects on breast cancer outcomes, they said.
While the findings add to a growing body of evidence supporting the benefits of weight-loss interventions in overweight breast cancer survivors, questions remain regarding the effect of weight loss on breast cancer recurrence and mortality, said Melinda L. Irwin, Ph.D., M.P.H., in an accompanying editorial (J. Clin. Oncol. 2014 June 16 [doi: 10.1200/JCO.2014.56.4583]).
"How can important lifestyle trials with definitive mortality end points best be funded?" asked Dr. Irwin of Yale University, New Haven, Conn. She suggested that pharmaceutical companies be required to include a lifestyle intervention arm in drug trials.
"Given that pharmaceutical companies primarily fund therapeutic trials, with little incentive to fund lifestyle interventions, and given the scarcity of funding from government agencies for large-scale long-term trials of lifestyle interventions with disease-free survival endpoints, another option may be to require pharmaceutical companies to include lifestyle interventions as an active comparison arm to drug trials, especially in cases when drug options provide modest benefit, or uptake or adherence to particular medications [is] low," she said.
The study was funded by Novartis Pharmaceuticals. Dr. Goodwin and Dr. Irwin reported no disclosures. Two coauthors disclosed honoraria or research funding from Novartis and other companies.
A telephone-based lifestyle intervention can have a significant effect on weight loss in overweight breast cancer survivors, according to a study that also highlights the dilemmas of funding large lifestyle trials with definitive mortality endpoints.
Mean weight loss at 6 months was greater in women who received telephone-based coaching and were mailed health information vs. women who received mailed information only (5.3% vs. 0.7%; P less than .001), investigators reported online June 16 in the Journal of Clinical Oncology. The study was part of the multicenter LISA(Lifestyle Intervention Study in Adjuvant Treatment of Early Breast Cancer) trial.
At 24 months the weight loss still compared favorably in the intervention group (3.6% loss vs. 0.4% in the mail-only group; P less than .001), reported Dr. Pamela J. Goodwin of the Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, and her associates (J. Clin. Oncol. 2014 June 16 [doi: 10.1200/JCO.2013.53.1517].
But will losing weight improve breast cancer outcomes?
The original aim of LISA was to examine the effect of weight loss on disease-free survival, but patient accrual was terminated early (at 338 of the 2,150 planned participants), because of a loss of funding from sponsor Novartis Pharmaceuticals, leaving that question unanswered.
Patients were eligible to participate in the study if they had been diagnosed in the last 36 months, had a body mass index of 24 kg/m2 or higher, and were receiving letrozole for hormone receptor–positive breast cancer. Study participants were randomly assigned to receive general health information by mail, or to a lifestyle intervention where they received weight loss advice by telephone in addition to the health information by mail.
The telephone-based lifestyle intervention included a dietary goal (500-1,000 kcal per day deficit) and a physical activity goal (150-200 minutes of moderate-intensity physical activity per week) to achieve weight loss.
"Our results support the use of telephone-based delivery of weight-loss interventions in patients with breast cancer, and they suggest that our approach will be generally effective in postmenopausal patients receiving an aromatase inhibitor," the investigators concluded.
The results, combined with the recognition that obesity is associated with poor breast cancer outcomes, provide support for a randomized trial using a telephone-based weight-loss intervention that is adequately powered to detect clinically important effects on breast cancer outcomes, they said.
While the findings add to a growing body of evidence supporting the benefits of weight-loss interventions in overweight breast cancer survivors, questions remain regarding the effect of weight loss on breast cancer recurrence and mortality, said Melinda L. Irwin, Ph.D., M.P.H., in an accompanying editorial (J. Clin. Oncol. 2014 June 16 [doi: 10.1200/JCO.2014.56.4583]).
"How can important lifestyle trials with definitive mortality end points best be funded?" asked Dr. Irwin of Yale University, New Haven, Conn. She suggested that pharmaceutical companies be required to include a lifestyle intervention arm in drug trials.
"Given that pharmaceutical companies primarily fund therapeutic trials, with little incentive to fund lifestyle interventions, and given the scarcity of funding from government agencies for large-scale long-term trials of lifestyle interventions with disease-free survival endpoints, another option may be to require pharmaceutical companies to include lifestyle interventions as an active comparison arm to drug trials, especially in cases when drug options provide modest benefit, or uptake or adherence to particular medications [is] low," she said.
The study was funded by Novartis Pharmaceuticals. Dr. Goodwin and Dr. Irwin reported no disclosures. Two coauthors disclosed honoraria or research funding from Novartis and other companies.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: A telephone-based lifestyle intervention was effective in helping overweight breast cancer patients who were receiving an aromatase inhibitor, achieve weight loss. But the original question of the intervention’s effect on breast cancer mortality was left unanswered because of withdrawal of funding.
Major finding: Women receiving a telephone-based lifestyle intervention in addition to mailed health information lost significantly more weight at 6 months than women who received the mailed information only (5.3% vs. 0.7%; P less than .001).
Data source: A multicenter, randomized trail of overweight patients with early breast cancer who were receiving adjuvant letrozole; patient accrual was terminated early (at 338 of the 2,150 planned participants) because of withdrawal of funding.
Disclosures: The study was funded by Novartis Pharmaceuticals. Dr. Goodwin reported no disclosures. Two coauthors disclosed honoraria or research funding from Novartis and other companies.
Frail women less likely to initiate hormonal therapy for breast cancer
Older women with breast cancer are less likely to initiate adjuvant hormonal therapy if they are frail, according to researchers.
In a prospective cohort study of women aged 65 and older diagnosed with invasive, nonmetastatic estrogen receptor–positive breast cancers (n = 1,062), about a quarter of the women were frail or prefrail (4.9% and 18.7%, respectively) based on a validated frailty score determined at baseline, reported Vanessa Sheppard, Ph.D., of Georgetown University Medical Center, Washington (J. Clin. Oncol. 2014 June 16 [doi:10.1200/JCO.2013.51.7367]).
Overall, 14% of the women in the study did not initiate hormonal therapy. Women considered prefrail or frail were significantly less likely to initiate therapy than were those considered "robust" or nonfrail (odds ratio, 1.63; 95% CI, 1.11-2.40; P =.013). Nonwhite race was also significantly associated with noninitiation of therapy (OR, 1.71; CI, 1.04-2.80; P = 0.33).
Baseline frailty was not predictive of discontinuation of therapy after a median follow-up of 3 years, Dr. Sheppard and colleagues reported.
The findings suggest "women and/or their providers are making informed judgments about the risks and benefits," the researchers wrote. "An alternative explanation is that women with greater frailty may have been concerned about adverse effects based on interactions of hormonal therapy and specific comorbidities, such as cardio- and/or cerebrovascular disease and risk of thromboembolic events," they added.
Limitations of the study include a potential for bias associated with self-reporting (discontinuation of therapy was measured only through self-report) and measurement of frailty only at baseline, the investigators said.
The National Institutes of Health, Amgen, and the Cancer and Leukemia Group B (CALGB) Foundation funded the study. Four of Dr. Sheppard’s coauthors, Dr. Gretchen Kimmick, Dr. Eric Winer, Dr. Arti Hurria, and Dr. Claudine Isaacs reported ties with pharmaceutical manufacturers.
Older women with breast cancer are less likely to initiate adjuvant hormonal therapy if they are frail, according to researchers.
In a prospective cohort study of women aged 65 and older diagnosed with invasive, nonmetastatic estrogen receptor–positive breast cancers (n = 1,062), about a quarter of the women were frail or prefrail (4.9% and 18.7%, respectively) based on a validated frailty score determined at baseline, reported Vanessa Sheppard, Ph.D., of Georgetown University Medical Center, Washington (J. Clin. Oncol. 2014 June 16 [doi:10.1200/JCO.2013.51.7367]).
Overall, 14% of the women in the study did not initiate hormonal therapy. Women considered prefrail or frail were significantly less likely to initiate therapy than were those considered "robust" or nonfrail (odds ratio, 1.63; 95% CI, 1.11-2.40; P =.013). Nonwhite race was also significantly associated with noninitiation of therapy (OR, 1.71; CI, 1.04-2.80; P = 0.33).
Baseline frailty was not predictive of discontinuation of therapy after a median follow-up of 3 years, Dr. Sheppard and colleagues reported.
The findings suggest "women and/or their providers are making informed judgments about the risks and benefits," the researchers wrote. "An alternative explanation is that women with greater frailty may have been concerned about adverse effects based on interactions of hormonal therapy and specific comorbidities, such as cardio- and/or cerebrovascular disease and risk of thromboembolic events," they added.
Limitations of the study include a potential for bias associated with self-reporting (discontinuation of therapy was measured only through self-report) and measurement of frailty only at baseline, the investigators said.
The National Institutes of Health, Amgen, and the Cancer and Leukemia Group B (CALGB) Foundation funded the study. Four of Dr. Sheppard’s coauthors, Dr. Gretchen Kimmick, Dr. Eric Winer, Dr. Arti Hurria, and Dr. Claudine Isaacs reported ties with pharmaceutical manufacturers.
Older women with breast cancer are less likely to initiate adjuvant hormonal therapy if they are frail, according to researchers.
In a prospective cohort study of women aged 65 and older diagnosed with invasive, nonmetastatic estrogen receptor–positive breast cancers (n = 1,062), about a quarter of the women were frail or prefrail (4.9% and 18.7%, respectively) based on a validated frailty score determined at baseline, reported Vanessa Sheppard, Ph.D., of Georgetown University Medical Center, Washington (J. Clin. Oncol. 2014 June 16 [doi:10.1200/JCO.2013.51.7367]).
Overall, 14% of the women in the study did not initiate hormonal therapy. Women considered prefrail or frail were significantly less likely to initiate therapy than were those considered "robust" or nonfrail (odds ratio, 1.63; 95% CI, 1.11-2.40; P =.013). Nonwhite race was also significantly associated with noninitiation of therapy (OR, 1.71; CI, 1.04-2.80; P = 0.33).
Baseline frailty was not predictive of discontinuation of therapy after a median follow-up of 3 years, Dr. Sheppard and colleagues reported.
The findings suggest "women and/or their providers are making informed judgments about the risks and benefits," the researchers wrote. "An alternative explanation is that women with greater frailty may have been concerned about adverse effects based on interactions of hormonal therapy and specific comorbidities, such as cardio- and/or cerebrovascular disease and risk of thromboembolic events," they added.
Limitations of the study include a potential for bias associated with self-reporting (discontinuation of therapy was measured only through self-report) and measurement of frailty only at baseline, the investigators said.
The National Institutes of Health, Amgen, and the Cancer and Leukemia Group B (CALGB) Foundation funded the study. Four of Dr. Sheppard’s coauthors, Dr. Gretchen Kimmick, Dr. Eric Winer, Dr. Arti Hurria, and Dr. Claudine Isaacs reported ties with pharmaceutical manufacturers.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Older women with breast cancer are less likely to initiate adjuvant hormonal therapy if they are frail.
Major finding: Odds ratio for noninitiation of hormonal therapy was 1.63 for frail women compared with nonfrail women (95% CI, 1.11 to 2.40; P = .013) after covariate adjustment.
Data source: A prospective cohort of 1,288 older women diagnosed with invasive, nonmetastatic breast cancer recruited from 78 sites from 2004 to 2011, of which 1,062 had estrogen receptor–positive tumors.
Disclosures: The National Institutes of Health, Amgen, and the Cancer and Leukemia Group B (CALGB) Foundation funded the study. Four of Dr. Sheppard’s coauthors, Dr. Gretchen Kimmick, Dr. Eric Winer, Dr. Arti Hurria, and Dr. Claudine Isaacs reported ties with pharmaceutical manufacturers.
ASCO endorses "no ink on tumor" guidelines for breast cancer surgery
An expert review panel from the American Society for Clinical Oncology largely endorsed new guidelines for "no ink on tumor" margins in early breast conservation surgery, while emphasizing the role of post-lumpectomy imaging in patients with microcalcifications and adding several other "minor qualifications."
Published earlier this year, the guidelines from the Society of Surgical Oncology (SSO) and the American Society of Radiation Oncology (ASTRO) focus on stage I and II breast cancer patients who are undergoing lumpectomy with whole-breast radiation. In these patients, a "no ink on tumor" margin "is associated with low rates of [ipsilateral breast tumor recurrence] and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs," the guideline’s authors wrote (Ann. Surg. Oncol. 2014;21:704-16). The guidelines mark a step toward consensus on a historically controversial topic. "Widespread adoption of this guideline, which defines a margin as being adequate as long as there is no cancer at the inked lumpectomy surface by microscopic pathology evaluation, will result in fewer re-excision lumpectomies and enhanced cosmesis with breast conserving surgery," said Dr. Lisa Newman.
The recommended margin reflects the current era of treatment, in which better systemic therapies and earlier diagnosis of breast cancer mean that patients may no longer derive extra benefit from thicker or "widely negative" lumpectomy margins, Dr. Newman added in an interview.
Two staff members at ASCO reviewed the guidelines for developmental rigor. The guidelines "scored high (77%) in terms of methodologic quality, with only minor deviations from the ideal," members of the separate ad hoc panel of ASCO experts wrote (J. Clin. Onc. 2014 [doi:10.1200/JCO.2014.55.1572]). But panel members also called for flexibility in applying the guideline, citing the "inherent weaknesses" and "selection bias" of the retrospective, observational studies on which the recommendations were based.
The guidelines provide a framework, but clinical judgment remains important in managing breast-conserving surgery patients, emphasized Dr. Newman, who served as cochair on the ASCO panel that reviewed the guideline and who is a surgical oncologist, professor of surgery, and director of the Breast Care Center for the University of Michigan, Ann Arbor. She said clinicians should carefully evaluate lumpectomy margins, which "can provide important clues regarding the burden of disease in the breast, and the likelihood of successful treatment with lumpectomy and breast radiation."
ASCO panel members also stressed the importance of postsurgical imaging in cases involving microcalcifications. Imaging is important to minimize the risk of leaving pockets of disease in the breast despite achieving microscopically negative margins, Dr. Newman said. Surgeons can work with their colleagues in breast imaging to review microcalcifications and correlate them with pathology findings, she added.
In particular, a lumpectomy specimen that has several close margins and evidence of diffuse disease "may well represent a different category of risk regarding local recurrence, compared to a well defined, unifocal cancer that has a single microscopic focus of cancer abutting one margin," Dr. Newman added. Ideally, surgeons and radiation oncologists should discuss these aspects of cases, and should consider them when counseling patients about outcomes from lumpectomy surgery, she said.
Both ASCO and SSO/ASTRO recommended monitoring outcomes as institutions implement the new margin guidelines. Authors of the ASCO opinion reported having no conflicts of interest.
An expert review panel from the American Society for Clinical Oncology largely endorsed new guidelines for "no ink on tumor" margins in early breast conservation surgery, while emphasizing the role of post-lumpectomy imaging in patients with microcalcifications and adding several other "minor qualifications."
Published earlier this year, the guidelines from the Society of Surgical Oncology (SSO) and the American Society of Radiation Oncology (ASTRO) focus on stage I and II breast cancer patients who are undergoing lumpectomy with whole-breast radiation. In these patients, a "no ink on tumor" margin "is associated with low rates of [ipsilateral breast tumor recurrence] and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs," the guideline’s authors wrote (Ann. Surg. Oncol. 2014;21:704-16). The guidelines mark a step toward consensus on a historically controversial topic. "Widespread adoption of this guideline, which defines a margin as being adequate as long as there is no cancer at the inked lumpectomy surface by microscopic pathology evaluation, will result in fewer re-excision lumpectomies and enhanced cosmesis with breast conserving surgery," said Dr. Lisa Newman.
The recommended margin reflects the current era of treatment, in which better systemic therapies and earlier diagnosis of breast cancer mean that patients may no longer derive extra benefit from thicker or "widely negative" lumpectomy margins, Dr. Newman added in an interview.
Two staff members at ASCO reviewed the guidelines for developmental rigor. The guidelines "scored high (77%) in terms of methodologic quality, with only minor deviations from the ideal," members of the separate ad hoc panel of ASCO experts wrote (J. Clin. Onc. 2014 [doi:10.1200/JCO.2014.55.1572]). But panel members also called for flexibility in applying the guideline, citing the "inherent weaknesses" and "selection bias" of the retrospective, observational studies on which the recommendations were based.
The guidelines provide a framework, but clinical judgment remains important in managing breast-conserving surgery patients, emphasized Dr. Newman, who served as cochair on the ASCO panel that reviewed the guideline and who is a surgical oncologist, professor of surgery, and director of the Breast Care Center for the University of Michigan, Ann Arbor. She said clinicians should carefully evaluate lumpectomy margins, which "can provide important clues regarding the burden of disease in the breast, and the likelihood of successful treatment with lumpectomy and breast radiation."
ASCO panel members also stressed the importance of postsurgical imaging in cases involving microcalcifications. Imaging is important to minimize the risk of leaving pockets of disease in the breast despite achieving microscopically negative margins, Dr. Newman said. Surgeons can work with their colleagues in breast imaging to review microcalcifications and correlate them with pathology findings, she added.
In particular, a lumpectomy specimen that has several close margins and evidence of diffuse disease "may well represent a different category of risk regarding local recurrence, compared to a well defined, unifocal cancer that has a single microscopic focus of cancer abutting one margin," Dr. Newman added. Ideally, surgeons and radiation oncologists should discuss these aspects of cases, and should consider them when counseling patients about outcomes from lumpectomy surgery, she said.
Both ASCO and SSO/ASTRO recommended monitoring outcomes as institutions implement the new margin guidelines. Authors of the ASCO opinion reported having no conflicts of interest.
An expert review panel from the American Society for Clinical Oncology largely endorsed new guidelines for "no ink on tumor" margins in early breast conservation surgery, while emphasizing the role of post-lumpectomy imaging in patients with microcalcifications and adding several other "minor qualifications."
Published earlier this year, the guidelines from the Society of Surgical Oncology (SSO) and the American Society of Radiation Oncology (ASTRO) focus on stage I and II breast cancer patients who are undergoing lumpectomy with whole-breast radiation. In these patients, a "no ink on tumor" margin "is associated with low rates of [ipsilateral breast tumor recurrence] and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs," the guideline’s authors wrote (Ann. Surg. Oncol. 2014;21:704-16). The guidelines mark a step toward consensus on a historically controversial topic. "Widespread adoption of this guideline, which defines a margin as being adequate as long as there is no cancer at the inked lumpectomy surface by microscopic pathology evaluation, will result in fewer re-excision lumpectomies and enhanced cosmesis with breast conserving surgery," said Dr. Lisa Newman.
The recommended margin reflects the current era of treatment, in which better systemic therapies and earlier diagnosis of breast cancer mean that patients may no longer derive extra benefit from thicker or "widely negative" lumpectomy margins, Dr. Newman added in an interview.
Two staff members at ASCO reviewed the guidelines for developmental rigor. The guidelines "scored high (77%) in terms of methodologic quality, with only minor deviations from the ideal," members of the separate ad hoc panel of ASCO experts wrote (J. Clin. Onc. 2014 [doi:10.1200/JCO.2014.55.1572]). But panel members also called for flexibility in applying the guideline, citing the "inherent weaknesses" and "selection bias" of the retrospective, observational studies on which the recommendations were based.
The guidelines provide a framework, but clinical judgment remains important in managing breast-conserving surgery patients, emphasized Dr. Newman, who served as cochair on the ASCO panel that reviewed the guideline and who is a surgical oncologist, professor of surgery, and director of the Breast Care Center for the University of Michigan, Ann Arbor. She said clinicians should carefully evaluate lumpectomy margins, which "can provide important clues regarding the burden of disease in the breast, and the likelihood of successful treatment with lumpectomy and breast radiation."
ASCO panel members also stressed the importance of postsurgical imaging in cases involving microcalcifications. Imaging is important to minimize the risk of leaving pockets of disease in the breast despite achieving microscopically negative margins, Dr. Newman said. Surgeons can work with their colleagues in breast imaging to review microcalcifications and correlate them with pathology findings, she added.
In particular, a lumpectomy specimen that has several close margins and evidence of diffuse disease "may well represent a different category of risk regarding local recurrence, compared to a well defined, unifocal cancer that has a single microscopic focus of cancer abutting one margin," Dr. Newman added. Ideally, surgeons and radiation oncologists should discuss these aspects of cases, and should consider them when counseling patients about outcomes from lumpectomy surgery, she said.
Both ASCO and SSO/ASTRO recommended monitoring outcomes as institutions implement the new margin guidelines. Authors of the ASCO opinion reported having no conflicts of interest.