Breast Cancer

More rigorous and/or more frequent exercise was associated with a significantly reduced risk of cardiovascular events in women with nonmetastatic breast cancer, regardless of age and type of anticancer therapy received, investigators reported.

“CVD [Cardiovascular disease] is now the leading cause of death among women with nonmetastatic breast cancer, especially for those older than 65 years of age and with preexisting CVD risk factors (eg., hypertension, obesity, history of cardiovascular disease) at diagnosis. Moreover, patients with nonmetastatic breast cancer may be at increased risk of CVD, compared with age-matched women without a history of breast cancer because of the direct toxic effects of anticancer therapy,” wrote Dr. Lee Jones of the Memorial Sloan Kettering Cancer Center, New York, and associates (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2015.65.6603).

Kristan Hutchison (Property of National Science Foundation)/ (Antarctic Photo Library (Image link)) [Attribution], via Wikimedia Commons

To see whether exercise reduces risk, investigators gave the Arizona Activity Frequency Questionnaire to 2,973 women diagnosed with nonmetastatic breast cancer who were participating in two cohort studies. Frequency, duration, and type of exercise were standardized into metabolic equivalent tasks (MET), which were quartiled into the following categories: less than or equal to 2 h/wk, 2.1-10.3 h/wk, 10.4-24.5 h/wk, and greater than 24.6 h/wk. Cardiovascular events, defined as coronary artery disease, nonfatal myocardial infarction, heart failure, valve abnormality, arrhythmia, stroke or cardiovascular disease–related death, were monitored via electronic medical records.

Median follow-up time was 8.6 years. In age-adjusted analysis, the risk of cardiovascular events declined across increasing quartiles of total MET h/wk (1.00, 0.83, 0.72, 0.57, respectively, P less than .001).

Adherence to national exercise guidelines for adult patients (MET score equal to or greater than 9) was associated with a significant 23% reduction in cardiovascular events. Patients who met the national exercise guidelines had a significant reduction in cardiovascular events regardless of age, menopausal status, type of anticancer therapy, or cardiovascular risk factors at cancer diagnosis when compared with patients who not did meet the national exercise guidelines.

“Irrespective of therapy-induced risk, CVD will remain a leading cause of mortality in early-stage breast cancer given continual improvements in cancer-specific mortality together with the rapidly aging population. Thus, our finding that the cardioprotective effects of exercise are comparable in middle-aged women irrespective of exposure to anticancer therapies is novel and important. … Nevertheless, at present, at least in the United States, exercise treatment is not considered an aspect of first-line therapy for the adverse CV consequences of breast cancer adjuvant therapy, similar to that for the primary or secondary prevention of CVD. As such, confirmatory data from randomized trials are urgently required,” the investigators wrote.

This study was supported by a National Institute of Health Award and research grants from the National Cancer Institute and the Memorial Sloan Kettering Cancer Center. One investigator reported having stock or ownership interests in Exercise by Science. Two investigators reported serving in advisory roles or receiving financial compensation from various companies. The other investigators reported having no disclosures.

[email protected]

On Twitter @JessCraig_OP

More rigorous and/or more frequent exercise was associated with a significantly reduced risk of cardiovascular events in women with nonmetastatic breast cancer, regardless of age and type of anticancer therapy received, investigators reported.

“CVD [Cardiovascular disease] is now the leading cause of death among women with nonmetastatic breast cancer, especially for those older than 65 years of age and with preexisting CVD risk factors (eg., hypertension, obesity, history of cardiovascular disease) at diagnosis. Moreover, patients with nonmetastatic breast cancer may be at increased risk of CVD, compared with age-matched women without a history of breast cancer because of the direct toxic effects of anticancer therapy,” wrote Dr. Lee Jones of the Memorial Sloan Kettering Cancer Center, New York, and associates (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2015.65.6603).

Kristan Hutchison (Property of National Science Foundation)/ (Antarctic Photo Library (Image link)) [Attribution], via Wikimedia Commons

To see whether exercise reduces risk, investigators gave the Arizona Activity Frequency Questionnaire to 2,973 women diagnosed with nonmetastatic breast cancer who were participating in two cohort studies. Frequency, duration, and type of exercise were standardized into metabolic equivalent tasks (MET), which were quartiled into the following categories: less than or equal to 2 h/wk, 2.1-10.3 h/wk, 10.4-24.5 h/wk, and greater than 24.6 h/wk. Cardiovascular events, defined as coronary artery disease, nonfatal myocardial infarction, heart failure, valve abnormality, arrhythmia, stroke or cardiovascular disease–related death, were monitored via electronic medical records.

Median follow-up time was 8.6 years. In age-adjusted analysis, the risk of cardiovascular events declined across increasing quartiles of total MET h/wk (1.00, 0.83, 0.72, 0.57, respectively, P less than .001).

Adherence to national exercise guidelines for adult patients (MET score equal to or greater than 9) was associated with a significant 23% reduction in cardiovascular events. Patients who met the national exercise guidelines had a significant reduction in cardiovascular events regardless of age, menopausal status, type of anticancer therapy, or cardiovascular risk factors at cancer diagnosis when compared with patients who not did meet the national exercise guidelines.

“Irrespective of therapy-induced risk, CVD will remain a leading cause of mortality in early-stage breast cancer given continual improvements in cancer-specific mortality together with the rapidly aging population. Thus, our finding that the cardioprotective effects of exercise are comparable in middle-aged women irrespective of exposure to anticancer therapies is novel and important. … Nevertheless, at present, at least in the United States, exercise treatment is not considered an aspect of first-line therapy for the adverse CV consequences of breast cancer adjuvant therapy, similar to that for the primary or secondary prevention of CVD. As such, confirmatory data from randomized trials are urgently required,” the investigators wrote.

This study was supported by a National Institute of Health Award and research grants from the National Cancer Institute and the Memorial Sloan Kettering Cancer Center. One investigator reported having stock or ownership interests in Exercise by Science. Two investigators reported serving in advisory roles or receiving financial compensation from various companies. The other investigators reported having no disclosures.

[email protected]

On Twitter @JessCraig_OP

More rigorous and/or more frequent exercise was associated with a significantly reduced risk of cardiovascular events in women with nonmetastatic breast cancer, regardless of age and type of anticancer therapy received, investigators reported.

“CVD [Cardiovascular disease] is now the leading cause of death among women with nonmetastatic breast cancer, especially for those older than 65 years of age and with preexisting CVD risk factors (eg., hypertension, obesity, history of cardiovascular disease) at diagnosis. Moreover, patients with nonmetastatic breast cancer may be at increased risk of CVD, compared with age-matched women without a history of breast cancer because of the direct toxic effects of anticancer therapy,” wrote Dr. Lee Jones of the Memorial Sloan Kettering Cancer Center, New York, and associates (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2015.65.6603).

Kristan Hutchison (Property of National Science Foundation)/ (Antarctic Photo Library (Image link)) [Attribution], via Wikimedia Commons

To see whether exercise reduces risk, investigators gave the Arizona Activity Frequency Questionnaire to 2,973 women diagnosed with nonmetastatic breast cancer who were participating in two cohort studies. Frequency, duration, and type of exercise were standardized into metabolic equivalent tasks (MET), which were quartiled into the following categories: less than or equal to 2 h/wk, 2.1-10.3 h/wk, 10.4-24.5 h/wk, and greater than 24.6 h/wk. Cardiovascular events, defined as coronary artery disease, nonfatal myocardial infarction, heart failure, valve abnormality, arrhythmia, stroke or cardiovascular disease–related death, were monitored via electronic medical records.

Median follow-up time was 8.6 years. In age-adjusted analysis, the risk of cardiovascular events declined across increasing quartiles of total MET h/wk (1.00, 0.83, 0.72, 0.57, respectively, P less than .001).

Adherence to national exercise guidelines for adult patients (MET score equal to or greater than 9) was associated with a significant 23% reduction in cardiovascular events. Patients who met the national exercise guidelines had a significant reduction in cardiovascular events regardless of age, menopausal status, type of anticancer therapy, or cardiovascular risk factors at cancer diagnosis when compared with patients who not did meet the national exercise guidelines.

“Irrespective of therapy-induced risk, CVD will remain a leading cause of mortality in early-stage breast cancer given continual improvements in cancer-specific mortality together with the rapidly aging population. Thus, our finding that the cardioprotective effects of exercise are comparable in middle-aged women irrespective of exposure to anticancer therapies is novel and important. … Nevertheless, at present, at least in the United States, exercise treatment is not considered an aspect of first-line therapy for the adverse CV consequences of breast cancer adjuvant therapy, similar to that for the primary or secondary prevention of CVD. As such, confirmatory data from randomized trials are urgently required,” the investigators wrote.

This study was supported by a National Institute of Health Award and research grants from the National Cancer Institute and the Memorial Sloan Kettering Cancer Center. One investigator reported having stock or ownership interests in Exercise by Science. Two investigators reported serving in advisory roles or receiving financial compensation from various companies. The other investigators reported having no disclosures.

[email protected]

On Twitter @JessCraig_OP

The American Society of Clinical Oncology has issued new guidelines for endocrine therapy for women with hormone receptor–positive metastatic breast cancer.

The consensus recommendations note that hormonal therapy should be offered to patients whose tumors express any level of estrogen and/or progesterone receptors, and that endocrine therapy should be recommended as initial treatment for all patients with hormone receptor–positive (HR+) metastatic breast cancer (MBC), with treatment continued until unequivocal evidence of disease progression, except for those patients who have immediately life-threatening disease or who develop rapid recurrence of the disease in the viscera during adjuvant endocrine therapy.

©Thomas Northcut/Thinkstock

The use of combined endocrine therapy and chemotherapy is not recommended.

The guidelines also state that first-line therapy for postmenopausal women should include aromatase inhibitors (AIs), and that, for patients with metastatic breast cancer with no prior exposure to adjuvant endocrine therapy, combination hormone therapy with a nonsteroidal AI and fulvestrant 500 mg with a loading schedule may be offered.

“Premenopausal women with HR-positive MBC should be offered ovarian suppression or ablation and hormone therapy, because contemporary hormonal agents have only been studied among postmenopausal women,” Dr. Hope S. Rugo of the University of California, San Francisco, and other members of the expert panel caution (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2016.67.1487).

For second-line therapy, the guidelines recommend sequential hormone therapy for patients with endocrine responsive disease, except in women for whom there is rapid progression with organ dysfunction.

Fulvestrant, when administered, should be given with the 500-mg dose and with a loading schedule at treatment start, days 15 and 28, and then once monthly.

The guidelines, developed after the ASCO expert panel conducted a systematic review of evidence from 2008 through 2015, also mention targeted therapy combinations for specific circumstances:

• A nonsteroidal AI and palbociclib (Ibrance) for postmenopausal women with treatment-naive HR-positive MBC, because of an advantage in progression-free survival (PFS) but not overall survival, compared with letrozole (Femara) alone.

• Exemestane (Aromasin) and everolimus (Afinitor) for postmenopausal women with HR-positive MBC who experienced progression during prior treatment with nonsteroidal AIs with or without one line of prior chemotherapy, either before or after treatment with fulvestrant. This combination showed a PFS but not an overall survival advantage, compared with exemestane alone.

• Fulvestrant and palbociclib for patients who experienced progression during prior treatment with AIs with or without one line of prior chemotherapy (PFS improved, compared with fulvestrant alone). The guidelines caution that treatment should be limited to those without prior exposure to cyclin-dependent kinase 4/6 inhibitors.

• Human epidermal growth factor receptor–targeted therapy should be added to a first-line AI in patients with HR- and HER2-positive metastatic disease for whom chemotherapy is not immediately indicated.

“Genomic or expression profiling should not be used at this time to select treatment for HR-positive MBC,” the authors state.

The guidelines also emphasize that it is “mandatory for all patients to have ER and HER2 status determined in their cancers. Often a biopsy is recommended to determine or confirm whether a suspicious lesion represents MBC; in this case, markers should be obtained.”

The American Society of Clinical Oncology has issued new guidelines for endocrine therapy for women with hormone receptor–positive metastatic breast cancer.

The consensus recommendations note that hormonal therapy should be offered to patients whose tumors express any level of estrogen and/or progesterone receptors, and that endocrine therapy should be recommended as initial treatment for all patients with hormone receptor–positive (HR+) metastatic breast cancer (MBC), with treatment continued until unequivocal evidence of disease progression, except for those patients who have immediately life-threatening disease or who develop rapid recurrence of the disease in the viscera during adjuvant endocrine therapy.

©Thomas Northcut/Thinkstock

The use of combined endocrine therapy and chemotherapy is not recommended.

The guidelines also state that first-line therapy for postmenopausal women should include aromatase inhibitors (AIs), and that, for patients with metastatic breast cancer with no prior exposure to adjuvant endocrine therapy, combination hormone therapy with a nonsteroidal AI and fulvestrant 500 mg with a loading schedule may be offered.

“Premenopausal women with HR-positive MBC should be offered ovarian suppression or ablation and hormone therapy, because contemporary hormonal agents have only been studied among postmenopausal women,” Dr. Hope S. Rugo of the University of California, San Francisco, and other members of the expert panel caution (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2016.67.1487).

For second-line therapy, the guidelines recommend sequential hormone therapy for patients with endocrine responsive disease, except in women for whom there is rapid progression with organ dysfunction.

Fulvestrant, when administered, should be given with the 500-mg dose and with a loading schedule at treatment start, days 15 and 28, and then once monthly.

The guidelines, developed after the ASCO expert panel conducted a systematic review of evidence from 2008 through 2015, also mention targeted therapy combinations for specific circumstances:

• A nonsteroidal AI and palbociclib (Ibrance) for postmenopausal women with treatment-naive HR-positive MBC, because of an advantage in progression-free survival (PFS) but not overall survival, compared with letrozole (Femara) alone.

• Exemestane (Aromasin) and everolimus (Afinitor) for postmenopausal women with HR-positive MBC who experienced progression during prior treatment with nonsteroidal AIs with or without one line of prior chemotherapy, either before or after treatment with fulvestrant. This combination showed a PFS but not an overall survival advantage, compared with exemestane alone.

• Fulvestrant and palbociclib for patients who experienced progression during prior treatment with AIs with or without one line of prior chemotherapy (PFS improved, compared with fulvestrant alone). The guidelines caution that treatment should be limited to those without prior exposure to cyclin-dependent kinase 4/6 inhibitors.

• Human epidermal growth factor receptor–targeted therapy should be added to a first-line AI in patients with HR- and HER2-positive metastatic disease for whom chemotherapy is not immediately indicated.

“Genomic or expression profiling should not be used at this time to select treatment for HR-positive MBC,” the authors state.

The guidelines also emphasize that it is “mandatory for all patients to have ER and HER2 status determined in their cancers. Often a biopsy is recommended to determine or confirm whether a suspicious lesion represents MBC; in this case, markers should be obtained.”

The American Society of Clinical Oncology has issued new guidelines for endocrine therapy for women with hormone receptor–positive metastatic breast cancer.

The consensus recommendations note that hormonal therapy should be offered to patients whose tumors express any level of estrogen and/or progesterone receptors, and that endocrine therapy should be recommended as initial treatment for all patients with hormone receptor–positive (HR+) metastatic breast cancer (MBC), with treatment continued until unequivocal evidence of disease progression, except for those patients who have immediately life-threatening disease or who develop rapid recurrence of the disease in the viscera during adjuvant endocrine therapy.

©Thomas Northcut/Thinkstock

The use of combined endocrine therapy and chemotherapy is not recommended.

The guidelines also state that first-line therapy for postmenopausal women should include aromatase inhibitors (AIs), and that, for patients with metastatic breast cancer with no prior exposure to adjuvant endocrine therapy, combination hormone therapy with a nonsteroidal AI and fulvestrant 500 mg with a loading schedule may be offered.

“Premenopausal women with HR-positive MBC should be offered ovarian suppression or ablation and hormone therapy, because contemporary hormonal agents have only been studied among postmenopausal women,” Dr. Hope S. Rugo of the University of California, San Francisco, and other members of the expert panel caution (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2016.67.1487).

For second-line therapy, the guidelines recommend sequential hormone therapy for patients with endocrine responsive disease, except in women for whom there is rapid progression with organ dysfunction.

Fulvestrant, when administered, should be given with the 500-mg dose and with a loading schedule at treatment start, days 15 and 28, and then once monthly.

The guidelines, developed after the ASCO expert panel conducted a systematic review of evidence from 2008 through 2015, also mention targeted therapy combinations for specific circumstances:

• A nonsteroidal AI and palbociclib (Ibrance) for postmenopausal women with treatment-naive HR-positive MBC, because of an advantage in progression-free survival (PFS) but not overall survival, compared with letrozole (Femara) alone.

• Exemestane (Aromasin) and everolimus (Afinitor) for postmenopausal women with HR-positive MBC who experienced progression during prior treatment with nonsteroidal AIs with or without one line of prior chemotherapy, either before or after treatment with fulvestrant. This combination showed a PFS but not an overall survival advantage, compared with exemestane alone.

• Fulvestrant and palbociclib for patients who experienced progression during prior treatment with AIs with or without one line of prior chemotherapy (PFS improved, compared with fulvestrant alone). The guidelines caution that treatment should be limited to those without prior exposure to cyclin-dependent kinase 4/6 inhibitors.

• Human epidermal growth factor receptor–targeted therapy should be added to a first-line AI in patients with HR- and HER2-positive metastatic disease for whom chemotherapy is not immediately indicated.

“Genomic or expression profiling should not be used at this time to select treatment for HR-positive MBC,” the authors state.

The guidelines also emphasize that it is “mandatory for all patients to have ER and HER2 status determined in their cancers. Often a biopsy is recommended to determine or confirm whether a suspicious lesion represents MBC; in this case, markers should be obtained.”

The combination of a 21-gene recurrence score and quantitative estrogen receptor expression may help clinicians identify patients with estrogen receptor–positive breast cancer who are most likely to benefit from hormonal therapy extended beyond the customary 5 years, according to researchers.

Long-term follow-up of patients with recurrence score information from two National Surgical Adjuvant Breast and Bowel Project (NSABP) studies showed that recurrence score is strongly prognostic for late distant recurrences among patients with higher quantitative estrogen receptor expression (ESR1) levels, reported Dr. Norman Wolmark and colleagues from the NSABP Operations Centers and other institutions.

“These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high [recurrence score] with higher ESR1 expression at initial diagnosis,” they wrote (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2015.62.6630).

HconQ/ThinkStock

The authors looked at data on patients with recurrence score information who were enrolled in the tamoxifen-only arm of the NSABP B-14 trial and in the B-28 trial, which compared four cycles of doxorubicin plus cyclophosphamide (AC) with four cycles of AC followed by four cycles of paclitaxel plus 5 years of tamoxifen for hormone receptor–positive patients. The recurrence score cohorts for the studies included 668 and 1,065 patients, respectively.

After a median follow-up of 11.2 years in B-28, recurrence score was associated with both early (0 to 5 years) and distant recurrence (P less than .001 and P = .02, respectively), regardless of ESR1 expression.

The investigators then used B-28 to establish a quantitative ESR1 cut-point to identify patients for whom recurrence scores predicted late distant recurrences. They determined it to be 9.1 normalized expression cycle threshold units (CT), and then validated this cutoff in B-14.

In the B-14 cohort, a recurrence score of less than 18 CT was associated with a distant recurrence rate in years 5 through 15 of 6.8%, a score from 18 to 30 was associated with a 11.2% rate, and a score of 31 or greater was associated with a 16.4% rate (P less than .01).

The results “confirm studies of other molecular assays in postmenopausal patients and extend these findings to premenopausal women: at-risk patients have varying rates of [late distant recurrence], and a low-risk group with less than a 5% risk of recurrence in the second [5 years] can be identified,” the researchers wrote.

The data also confirm and extend results of foundational gene expression studies showing that highly proliferative, high-ER-gene–expressing tumors are at the greatest risk of late relapse, they said.

However, additional studies are needed before clinicians can rely on genomic factors to predict which patients require only 5 years of hormonal therapy, they cautioned.

The study was supported by National Cancer Institute grants, Susan G. Komen for the Cure grants, Bristol-Myers Squibb, Pharmaceutical Research Institute, AstraZeneca, and Genomic Health. Several authors disclosed relationships with various pharmaceutical companies, and five are employed by Genomic Health.

The combination of a 21-gene recurrence score and quantitative estrogen receptor expression may help clinicians identify patients with estrogen receptor–positive breast cancer who are most likely to benefit from hormonal therapy extended beyond the customary 5 years, according to researchers.

Long-term follow-up of patients with recurrence score information from two National Surgical Adjuvant Breast and Bowel Project (NSABP) studies showed that recurrence score is strongly prognostic for late distant recurrences among patients with higher quantitative estrogen receptor expression (ESR1) levels, reported Dr. Norman Wolmark and colleagues from the NSABP Operations Centers and other institutions.

“These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high [recurrence score] with higher ESR1 expression at initial diagnosis,” they wrote (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2015.62.6630).

HconQ/ThinkStock

The authors looked at data on patients with recurrence score information who were enrolled in the tamoxifen-only arm of the NSABP B-14 trial and in the B-28 trial, which compared four cycles of doxorubicin plus cyclophosphamide (AC) with four cycles of AC followed by four cycles of paclitaxel plus 5 years of tamoxifen for hormone receptor–positive patients. The recurrence score cohorts for the studies included 668 and 1,065 patients, respectively.

After a median follow-up of 11.2 years in B-28, recurrence score was associated with both early (0 to 5 years) and distant recurrence (P less than .001 and P = .02, respectively), regardless of ESR1 expression.

The investigators then used B-28 to establish a quantitative ESR1 cut-point to identify patients for whom recurrence scores predicted late distant recurrences. They determined it to be 9.1 normalized expression cycle threshold units (CT), and then validated this cutoff in B-14.

In the B-14 cohort, a recurrence score of less than 18 CT was associated with a distant recurrence rate in years 5 through 15 of 6.8%, a score from 18 to 30 was associated with a 11.2% rate, and a score of 31 or greater was associated with a 16.4% rate (P less than .01).

The results “confirm studies of other molecular assays in postmenopausal patients and extend these findings to premenopausal women: at-risk patients have varying rates of [late distant recurrence], and a low-risk group with less than a 5% risk of recurrence in the second [5 years] can be identified,” the researchers wrote.

The data also confirm and extend results of foundational gene expression studies showing that highly proliferative, high-ER-gene–expressing tumors are at the greatest risk of late relapse, they said.

However, additional studies are needed before clinicians can rely on genomic factors to predict which patients require only 5 years of hormonal therapy, they cautioned.

The study was supported by National Cancer Institute grants, Susan G. Komen for the Cure grants, Bristol-Myers Squibb, Pharmaceutical Research Institute, AstraZeneca, and Genomic Health. Several authors disclosed relationships with various pharmaceutical companies, and five are employed by Genomic Health.

The combination of a 21-gene recurrence score and quantitative estrogen receptor expression may help clinicians identify patients with estrogen receptor–positive breast cancer who are most likely to benefit from hormonal therapy extended beyond the customary 5 years, according to researchers.

Long-term follow-up of patients with recurrence score information from two National Surgical Adjuvant Breast and Bowel Project (NSABP) studies showed that recurrence score is strongly prognostic for late distant recurrences among patients with higher quantitative estrogen receptor expression (ESR1) levels, reported Dr. Norman Wolmark and colleagues from the NSABP Operations Centers and other institutions.

“These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high [recurrence score] with higher ESR1 expression at initial diagnosis,” they wrote (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2015.62.6630).

HconQ/ThinkStock

The authors looked at data on patients with recurrence score information who were enrolled in the tamoxifen-only arm of the NSABP B-14 trial and in the B-28 trial, which compared four cycles of doxorubicin plus cyclophosphamide (AC) with four cycles of AC followed by four cycles of paclitaxel plus 5 years of tamoxifen for hormone receptor–positive patients. The recurrence score cohorts for the studies included 668 and 1,065 patients, respectively.

After a median follow-up of 11.2 years in B-28, recurrence score was associated with both early (0 to 5 years) and distant recurrence (P less than .001 and P = .02, respectively), regardless of ESR1 expression.

The investigators then used B-28 to establish a quantitative ESR1 cut-point to identify patients for whom recurrence scores predicted late distant recurrences. They determined it to be 9.1 normalized expression cycle threshold units (CT), and then validated this cutoff in B-14.

In the B-14 cohort, a recurrence score of less than 18 CT was associated with a distant recurrence rate in years 5 through 15 of 6.8%, a score from 18 to 30 was associated with a 11.2% rate, and a score of 31 or greater was associated with a 16.4% rate (P less than .01).

The results “confirm studies of other molecular assays in postmenopausal patients and extend these findings to premenopausal women: at-risk patients have varying rates of [late distant recurrence], and a low-risk group with less than a 5% risk of recurrence in the second [5 years] can be identified,” the researchers wrote.

The data also confirm and extend results of foundational gene expression studies showing that highly proliferative, high-ER-gene–expressing tumors are at the greatest risk of late relapse, they said.

However, additional studies are needed before clinicians can rely on genomic factors to predict which patients require only 5 years of hormonal therapy, they cautioned.

The study was supported by National Cancer Institute grants, Susan G. Komen for the Cure grants, Bristol-Myers Squibb, Pharmaceutical Research Institute, AstraZeneca, and Genomic Health. Several authors disclosed relationships with various pharmaceutical companies, and five are employed by Genomic Health.

It’s common sense that adherence to a therapy with proven efficacy can result in better outcomes, and now there’s good scientific evidence to back it up.

A retrospective study of patients enrolled in a seminal clinical trial shows that postmenopausal women with early hormone receptor–positive breast cancer who stopped taking the aromatase inhibitor letrozole (Femara) before 5 years were up had an approximately 50% reduction in disease-free survival (DFS) compared with women who took the drug as prescribed, reported Dr. Jacquie H. Chirgwin of the Maroondah Breast Clinic in Ringwood East, Victoria, Australia, and colleagues (J Clin Oncol. 2016 May 23 doi: 10.1200/JCO.2015.63.8619).

“These results reinforce the importance of optimizing adherence by educating and supporting patients about the prognostic importance of adherence, the possible [adverse events] associated with switching treatment, and effective toxicity management,” they said.

The authors looked at data on 6,144 women who took part in the Breast International Group 1-98 (BIG 1-98) trial, which showed that 5 years of letrozole was associated with better overall survival (OS) than 5 years of tamoxifen, that sequential tamoxifen and letrozole were adequate for intermediate-risk patients, and that 5 years of either drug or a sequence were equally effective for low-risk patients.

To see whether shorter duration of therapy or less-than-ideal adherence to dosing had an adverse effect on outcomes, the investigators conducted regression analyses examining the relationship between DFS and both persistence (duration) of therapy, and compliance (adherence to dose and regularity of dosing).

They found that early cessation of letrozole was associated with a multivariable model hazard ratio (HR) for DFS of 1.45 (P = .01) and that a compliance score of less than 90% was associated with an HR of 1.61 (P = .02).

About 20% of women who took sequential therapy were nonpersistent, compared with 16.9% of women who took tamoxifen, and 17.6% of those who took letrozole.

In the large majority of cases (82.7%) adverse events were the primary reason for early discontinuation of therapy.

Patients who were older, smoked, had node-negative disease or had a prior thromboembolic event were less likely to be adherent, the investigators found.

It’s common sense that adherence to a therapy with proven efficacy can result in better outcomes, and now there’s good scientific evidence to back it up.

A retrospective study of patients enrolled in a seminal clinical trial shows that postmenopausal women with early hormone receptor–positive breast cancer who stopped taking the aromatase inhibitor letrozole (Femara) before 5 years were up had an approximately 50% reduction in disease-free survival (DFS) compared with women who took the drug as prescribed, reported Dr. Jacquie H. Chirgwin of the Maroondah Breast Clinic in Ringwood East, Victoria, Australia, and colleagues (J Clin Oncol. 2016 May 23 doi: 10.1200/JCO.2015.63.8619).

“These results reinforce the importance of optimizing adherence by educating and supporting patients about the prognostic importance of adherence, the possible [adverse events] associated with switching treatment, and effective toxicity management,” they said.

The authors looked at data on 6,144 women who took part in the Breast International Group 1-98 (BIG 1-98) trial, which showed that 5 years of letrozole was associated with better overall survival (OS) than 5 years of tamoxifen, that sequential tamoxifen and letrozole were adequate for intermediate-risk patients, and that 5 years of either drug or a sequence were equally effective for low-risk patients.

To see whether shorter duration of therapy or less-than-ideal adherence to dosing had an adverse effect on outcomes, the investigators conducted regression analyses examining the relationship between DFS and both persistence (duration) of therapy, and compliance (adherence to dose and regularity of dosing).

They found that early cessation of letrozole was associated with a multivariable model hazard ratio (HR) for DFS of 1.45 (P = .01) and that a compliance score of less than 90% was associated with an HR of 1.61 (P = .02).

About 20% of women who took sequential therapy were nonpersistent, compared with 16.9% of women who took tamoxifen, and 17.6% of those who took letrozole.

In the large majority of cases (82.7%) adverse events were the primary reason for early discontinuation of therapy.

Patients who were older, smoked, had node-negative disease or had a prior thromboembolic event were less likely to be adherent, the investigators found.

It’s common sense that adherence to a therapy with proven efficacy can result in better outcomes, and now there’s good scientific evidence to back it up.

A retrospective study of patients enrolled in a seminal clinical trial shows that postmenopausal women with early hormone receptor–positive breast cancer who stopped taking the aromatase inhibitor letrozole (Femara) before 5 years were up had an approximately 50% reduction in disease-free survival (DFS) compared with women who took the drug as prescribed, reported Dr. Jacquie H. Chirgwin of the Maroondah Breast Clinic in Ringwood East, Victoria, Australia, and colleagues (J Clin Oncol. 2016 May 23 doi: 10.1200/JCO.2015.63.8619).

“These results reinforce the importance of optimizing adherence by educating and supporting patients about the prognostic importance of adherence, the possible [adverse events] associated with switching treatment, and effective toxicity management,” they said.

The authors looked at data on 6,144 women who took part in the Breast International Group 1-98 (BIG 1-98) trial, which showed that 5 years of letrozole was associated with better overall survival (OS) than 5 years of tamoxifen, that sequential tamoxifen and letrozole were adequate for intermediate-risk patients, and that 5 years of either drug or a sequence were equally effective for low-risk patients.

To see whether shorter duration of therapy or less-than-ideal adherence to dosing had an adverse effect on outcomes, the investigators conducted regression analyses examining the relationship between DFS and both persistence (duration) of therapy, and compliance (adherence to dose and regularity of dosing).

They found that early cessation of letrozole was associated with a multivariable model hazard ratio (HR) for DFS of 1.45 (P = .01) and that a compliance score of less than 90% was associated with an HR of 1.61 (P = .02).

About 20% of women who took sequential therapy were nonpersistent, compared with 16.9% of women who took tamoxifen, and 17.6% of those who took letrozole.

In the large majority of cases (82.7%) adverse events were the primary reason for early discontinuation of therapy.

Patients who were older, smoked, had node-negative disease or had a prior thromboembolic event were less likely to be adherent, the investigators found.

Extreme users of disease-monitoring tests do not have significantly improved overall survival, investigators reported.

A review of Surveillance, Epidemiology, and End Results (SEER) Medicare data on 2,460 women older than 65 years of age with advanced breast cancer revealed that 924 patients (37.6%) were extreme users of disease-monitoring tests, defined as having had more than 12 serum-tumor marker (STM) tests and/or more than four radiographic imaging tests in a 1-year time period.

©Thinkstock

“The objectives of this study were to identify patterns and predictors of use and extreme use of disease-monitoring tests among women with [metastatic breast cancer],” reported Dr. Melissa Accordino of Columbia University, New York, and her colleagues (JCO. 2016 May 9. [doi: 10.1200/JCO.2016.66.6313]).

The investigators reviewed SEER Medicare data on women with pathologically confirmed metastatic breast cancer diagnosed from 2002 to 2011. Costs of care were calculated from Medicare reimbursement claims from physician, hospital, outpatient, durable medical equipment, and hospice filings from the date of diagnosis through the date of death or the end of the study period. Per-patient-per-year serum tumor marker testing rate and per-patient-per-year radiographic imaging rates were calculated.

Of the 2,460-person cohort, 37.6% were classified as extreme users (9% were extreme users of STM and 32.8% were extreme users of radiographic imaging tests), Dr. Accordino and her associates reported.

There was no difference in overall survival between extreme users and the rest of the cohort (HR, 0.93; 95% CI, 0.86-1.02).

A multivariate model showed that women who were older than 80 years (OR, 0.58; 95% CI, 0.45-0.75) and patients who were single (OR, 0.77; 95% CI, 0.63-0.93) were less likely to be extreme users while patients who had more frequent oncology-related doctor’s visits were more likely to be extreme users (OR, 3.14; 95% CI, 2.49-3.96).

A linear regression model revealed that costs of care were significantly higher for patients categorized as extreme users whose mean annual cost of care was 50.6% (95% CI, 40.7-61.1) higher than the mean cost of care for those who weren’t extreme users (P less than .001).

“In addition to cost, frequent disease monitoring can be associated with emotional harm. The prevalence of anxiety and depression among patients with advanced cancers is estimated to be 25%-65%. Previous work has shown that depression and anxiety can increase over time in patients with metastatic solid tumors and has been attributed to multiple factors, including fear of death and fear of disease progression. … In a study that assessed distress in women during the surveillance period, women with more frequent testing had higher levels of anxiety without survival benefit,” the investigators wrote.

The investigators also discussed the potential conflict of interest for physicians who benefit financially from disease-monitoring tests. “A successful strategy may be to change policy for reimbursement,” they wrote.

“In addition, better evidence is needed with regard to the benefits and harms of frequent disease-monitoring testing to inform guidelines,” the investigators wrote. “Future research should determine the most cost-effective strategy to monitor patients with [metastatic breast cancer].”

This study was supported by fellowships and grants from the National Cancer Institute, the ASCO/Breast Cancer Research Foundation, and the Conquer Cancer Foundation. Dr. Accordino reported having no disclosures. One investigator reported having a consulting/advisory role with Pfizer, TEVA Pharmaceutical Industries, Otsuka, United Biosource, and EHE International.

[email protected]

On Twitter@JessCraig_OP

Extreme users of disease-monitoring tests do not have significantly improved overall survival, investigators reported.

A review of Surveillance, Epidemiology, and End Results (SEER) Medicare data on 2,460 women older than 65 years of age with advanced breast cancer revealed that 924 patients (37.6%) were extreme users of disease-monitoring tests, defined as having had more than 12 serum-tumor marker (STM) tests and/or more than four radiographic imaging tests in a 1-year time period.

©Thinkstock

“The objectives of this study were to identify patterns and predictors of use and extreme use of disease-monitoring tests among women with [metastatic breast cancer],” reported Dr. Melissa Accordino of Columbia University, New York, and her colleagues (JCO. 2016 May 9. [doi: 10.1200/JCO.2016.66.6313]).

The investigators reviewed SEER Medicare data on women with pathologically confirmed metastatic breast cancer diagnosed from 2002 to 2011. Costs of care were calculated from Medicare reimbursement claims from physician, hospital, outpatient, durable medical equipment, and hospice filings from the date of diagnosis through the date of death or the end of the study period. Per-patient-per-year serum tumor marker testing rate and per-patient-per-year radiographic imaging rates were calculated.

Of the 2,460-person cohort, 37.6% were classified as extreme users (9% were extreme users of STM and 32.8% were extreme users of radiographic imaging tests), Dr. Accordino and her associates reported.

There was no difference in overall survival between extreme users and the rest of the cohort (HR, 0.93; 95% CI, 0.86-1.02).

A multivariate model showed that women who were older than 80 years (OR, 0.58; 95% CI, 0.45-0.75) and patients who were single (OR, 0.77; 95% CI, 0.63-0.93) were less likely to be extreme users while patients who had more frequent oncology-related doctor’s visits were more likely to be extreme users (OR, 3.14; 95% CI, 2.49-3.96).

A linear regression model revealed that costs of care were significantly higher for patients categorized as extreme users whose mean annual cost of care was 50.6% (95% CI, 40.7-61.1) higher than the mean cost of care for those who weren’t extreme users (P less than .001).

“In addition to cost, frequent disease monitoring can be associated with emotional harm. The prevalence of anxiety and depression among patients with advanced cancers is estimated to be 25%-65%. Previous work has shown that depression and anxiety can increase over time in patients with metastatic solid tumors and has been attributed to multiple factors, including fear of death and fear of disease progression. … In a study that assessed distress in women during the surveillance period, women with more frequent testing had higher levels of anxiety without survival benefit,” the investigators wrote.

The investigators also discussed the potential conflict of interest for physicians who benefit financially from disease-monitoring tests. “A successful strategy may be to change policy for reimbursement,” they wrote.

“In addition, better evidence is needed with regard to the benefits and harms of frequent disease-monitoring testing to inform guidelines,” the investigators wrote. “Future research should determine the most cost-effective strategy to monitor patients with [metastatic breast cancer].”

This study was supported by fellowships and grants from the National Cancer Institute, the ASCO/Breast Cancer Research Foundation, and the Conquer Cancer Foundation. Dr. Accordino reported having no disclosures. One investigator reported having a consulting/advisory role with Pfizer, TEVA Pharmaceutical Industries, Otsuka, United Biosource, and EHE International.

[email protected]

On Twitter@JessCraig_OP

Extreme users of disease-monitoring tests do not have significantly improved overall survival, investigators reported.

A review of Surveillance, Epidemiology, and End Results (SEER) Medicare data on 2,460 women older than 65 years of age with advanced breast cancer revealed that 924 patients (37.6%) were extreme users of disease-monitoring tests, defined as having had more than 12 serum-tumor marker (STM) tests and/or more than four radiographic imaging tests in a 1-year time period.

©Thinkstock

“The objectives of this study were to identify patterns and predictors of use and extreme use of disease-monitoring tests among women with [metastatic breast cancer],” reported Dr. Melissa Accordino of Columbia University, New York, and her colleagues (JCO. 2016 May 9. [doi: 10.1200/JCO.2016.66.6313]).

The investigators reviewed SEER Medicare data on women with pathologically confirmed metastatic breast cancer diagnosed from 2002 to 2011. Costs of care were calculated from Medicare reimbursement claims from physician, hospital, outpatient, durable medical equipment, and hospice filings from the date of diagnosis through the date of death or the end of the study period. Per-patient-per-year serum tumor marker testing rate and per-patient-per-year radiographic imaging rates were calculated.

Of the 2,460-person cohort, 37.6% were classified as extreme users (9% were extreme users of STM and 32.8% were extreme users of radiographic imaging tests), Dr. Accordino and her associates reported.

There was no difference in overall survival between extreme users and the rest of the cohort (HR, 0.93; 95% CI, 0.86-1.02).

A multivariate model showed that women who were older than 80 years (OR, 0.58; 95% CI, 0.45-0.75) and patients who were single (OR, 0.77; 95% CI, 0.63-0.93) were less likely to be extreme users while patients who had more frequent oncology-related doctor’s visits were more likely to be extreme users (OR, 3.14; 95% CI, 2.49-3.96).

A linear regression model revealed that costs of care were significantly higher for patients categorized as extreme users whose mean annual cost of care was 50.6% (95% CI, 40.7-61.1) higher than the mean cost of care for those who weren’t extreme users (P less than .001).

“In addition to cost, frequent disease monitoring can be associated with emotional harm. The prevalence of anxiety and depression among patients with advanced cancers is estimated to be 25%-65%. Previous work has shown that depression and anxiety can increase over time in patients with metastatic solid tumors and has been attributed to multiple factors, including fear of death and fear of disease progression. … In a study that assessed distress in women during the surveillance period, women with more frequent testing had higher levels of anxiety without survival benefit,” the investigators wrote.

The investigators also discussed the potential conflict of interest for physicians who benefit financially from disease-monitoring tests. “A successful strategy may be to change policy for reimbursement,” they wrote.

“In addition, better evidence is needed with regard to the benefits and harms of frequent disease-monitoring testing to inform guidelines,” the investigators wrote. “Future research should determine the most cost-effective strategy to monitor patients with [metastatic breast cancer].”

This study was supported by fellowships and grants from the National Cancer Institute, the ASCO/Breast Cancer Research Foundation, and the Conquer Cancer Foundation. Dr. Accordino reported having no disclosures. One investigator reported having a consulting/advisory role with Pfizer, TEVA Pharmaceutical Industries, Otsuka, United Biosource, and EHE International.

[email protected]

On Twitter@JessCraig_OP

In premenopausal women with estrogen receptor–positive primary breast cancer, 2 years of adjuvant tamoxifen resulted in the long-term reduction of breast cancer–related mortality, compared with patients who received no systemic treatment, a phase III randomized trial showed.

Tamoxifen is the endocrine therapy of choice for most premenopausal patients with ER-positive disease, wrote Dr. Maria Ekholm and her colleagues. “The long-term effect reported in this study is particularly important for young patients with a potentially long life expectancy who are at risk for late relapse, as is commonly seen in [estrogen receptor]-positive breast cancer.”

In the phase III trial, the investigators randomized 564 (362 ER-positive) premenopausal women with stage II breast cancer: 276 received tamoxifen and 288 received no adjuvant treatment, reported Dr. Ekholm, an oncologist at Lund (Sweden) University and her colleagues (J Clin Oncol. 2016 May 9. doi: 10.1200/JCO.2015.65.6272).

Among the group with ER-positive tumors, patients younger than 40 years had the greatest mortality reduction (less than 40 years: hazard ratio, 0.37; 95% confidence interval, 0.17-0.82; greater than 40 years: HR, 0.87; 95% CI, 0.61-1.22; interaction P = .044). Of the 314 deaths, 262 were breast cancer related. Also, tamoxifen had a greater effect in the patient subgroup with grade 3 tumors, compared with subgroups with grade 1 or 2 tumors, Dr. Ekholm and her colleagues found.

ER-positive patients had a high fatality rate during the first few years of follow-up, and tamoxifen had no effect during this time. Tamoxifen’s beneficial effect on cumulative mortality and cumulative breast cancer–related mortality was highest during years 5-15 of follow-up, with relative mortality reductions of nearly 50%, compared with the control group.

“The positive effect of tamoxifen was weaker for the last follow-up period (greater than 15 years), including fewer events and hence lower power, but the [hazard ratios] and estimates of [cumulative mortality] and [cumulative breast cancer–related mortality] indicate a possible carryover effect beyond 15 years,” the investigators wrote.

Dr. Ekholm reported financial ties to Amgen. Two coauthors also reported ties to industry sources.

In premenopausal women with estrogen receptor–positive primary breast cancer, 2 years of adjuvant tamoxifen resulted in the long-term reduction of breast cancer–related mortality, compared with patients who received no systemic treatment, a phase III randomized trial showed.

Tamoxifen is the endocrine therapy of choice for most premenopausal patients with ER-positive disease, wrote Dr. Maria Ekholm and her colleagues. “The long-term effect reported in this study is particularly important for young patients with a potentially long life expectancy who are at risk for late relapse, as is commonly seen in [estrogen receptor]-positive breast cancer.”

In the phase III trial, the investigators randomized 564 (362 ER-positive) premenopausal women with stage II breast cancer: 276 received tamoxifen and 288 received no adjuvant treatment, reported Dr. Ekholm, an oncologist at Lund (Sweden) University and her colleagues (J Clin Oncol. 2016 May 9. doi: 10.1200/JCO.2015.65.6272).

Among the group with ER-positive tumors, patients younger than 40 years had the greatest mortality reduction (less than 40 years: hazard ratio, 0.37; 95% confidence interval, 0.17-0.82; greater than 40 years: HR, 0.87; 95% CI, 0.61-1.22; interaction P = .044). Of the 314 deaths, 262 were breast cancer related. Also, tamoxifen had a greater effect in the patient subgroup with grade 3 tumors, compared with subgroups with grade 1 or 2 tumors, Dr. Ekholm and her colleagues found.

ER-positive patients had a high fatality rate during the first few years of follow-up, and tamoxifen had no effect during this time. Tamoxifen’s beneficial effect on cumulative mortality and cumulative breast cancer–related mortality was highest during years 5-15 of follow-up, with relative mortality reductions of nearly 50%, compared with the control group.

“The positive effect of tamoxifen was weaker for the last follow-up period (greater than 15 years), including fewer events and hence lower power, but the [hazard ratios] and estimates of [cumulative mortality] and [cumulative breast cancer–related mortality] indicate a possible carryover effect beyond 15 years,” the investigators wrote.

Dr. Ekholm reported financial ties to Amgen. Two coauthors also reported ties to industry sources.

In premenopausal women with estrogen receptor–positive primary breast cancer, 2 years of adjuvant tamoxifen resulted in the long-term reduction of breast cancer–related mortality, compared with patients who received no systemic treatment, a phase III randomized trial showed.

Tamoxifen is the endocrine therapy of choice for most premenopausal patients with ER-positive disease, wrote Dr. Maria Ekholm and her colleagues. “The long-term effect reported in this study is particularly important for young patients with a potentially long life expectancy who are at risk for late relapse, as is commonly seen in [estrogen receptor]-positive breast cancer.”

In the phase III trial, the investigators randomized 564 (362 ER-positive) premenopausal women with stage II breast cancer: 276 received tamoxifen and 288 received no adjuvant treatment, reported Dr. Ekholm, an oncologist at Lund (Sweden) University and her colleagues (J Clin Oncol. 2016 May 9. doi: 10.1200/JCO.2015.65.6272).

Among the group with ER-positive tumors, patients younger than 40 years had the greatest mortality reduction (less than 40 years: hazard ratio, 0.37; 95% confidence interval, 0.17-0.82; greater than 40 years: HR, 0.87; 95% CI, 0.61-1.22; interaction P = .044). Of the 314 deaths, 262 were breast cancer related. Also, tamoxifen had a greater effect in the patient subgroup with grade 3 tumors, compared with subgroups with grade 1 or 2 tumors, Dr. Ekholm and her colleagues found.

ER-positive patients had a high fatality rate during the first few years of follow-up, and tamoxifen had no effect during this time. Tamoxifen’s beneficial effect on cumulative mortality and cumulative breast cancer–related mortality was highest during years 5-15 of follow-up, with relative mortality reductions of nearly 50%, compared with the control group.

“The positive effect of tamoxifen was weaker for the last follow-up period (greater than 15 years), including fewer events and hence lower power, but the [hazard ratios] and estimates of [cumulative mortality] and [cumulative breast cancer–related mortality] indicate a possible carryover effect beyond 15 years,” the investigators wrote.

Dr. Ekholm reported financial ties to Amgen. Two coauthors also reported ties to industry sources.