Michael Schooff, MD

BACKGROUND: Medical professionals routinely teach women breast self-examination (BSE) as a screen for detecting breast cancer, yet there are conflicting recommendations regarding BSE from different professional organizations. One study has shown that only 7.6% of women with breast tumors who were practicing regular BSE actually detected the tumor by means of self-examination. Different studies have estimated the sensitivity of BSE as between 26% and 89% and the specificity between 66% and 81%. The US Preventive Services Task Force found insufficient evidence to recommend for or against teaching BSE. The purpose of this review was to evaluate the evidence relating to the effectiveness of BSE in preventing death of breast cancer to make recommendations for the Canadian Task Force on Preventive Health Care.

POPULATION STUDIED: The studies’ populations included women between ages 31 and 64 years in one study and from 40 to 69 years in the other studies. These women were from multiple areas of the world, including Shanghai, Russia, the United Kingdom, Canada, the United States, and Finland.

STUDY DESIGN AND VALIDITY: his is a systematic review of articles found using an electronic database search of abstracts and reports published from 1966 to October 2000. The author identified 2 randomized controlled trials, one quasi-randomized controlled trial, 2 large cohort studies, and several case-control studies that evaluated the effects of BSE on breast cancer outcomes. The 2 randomized-controlled trials and the quasi-randomized controlled trial were large studies enrolling more than 625,000 women with at least 5 years of follow-up and confirmation that women in the BSE group actually learned how to perform the maneuver. One of the cohort studies appeared to have a significant selection bias, rendering its results difficult to interpret. Since different designs were used in the review, the studies could not be combined using meta-analysis.

OUTCOMES MEASURED: The prevention of death resulting from breast cancer was viewed as the most important outcome. Other outcomes examined included the rate of benign biopsy results, the number of patient visits for breast complaints, the stage of cancer detected, and psychological benefits and harms.

RESULTS: Of the 8 studies included in this review, 7 studies, including the 2 randomized controlled trials and the quasi-randomized controlled trial, found no difference between groups taught BSE and the control groups with regard to rates of breast cancer diagnosis, breast cancer death, or in tumor stage or size. In the 2 randomized controlled trials and the quasi-randomized controlled trial, there were higher rates of benign biopsy results in the BSE groups, approximately 1 additional biopsy for every 200 women performing BSE. Women in the BSE groups also presented to the physician’s office more frequently for breast complaints.

BACKGROUND: Medical professionals routinely teach women breast self-examination (BSE) as a screen for detecting breast cancer, yet there are conflicting recommendations regarding BSE from different professional organizations. One study has shown that only 7.6% of women with breast tumors who were practicing regular BSE actually detected the tumor by means of self-examination. Different studies have estimated the sensitivity of BSE as between 26% and 89% and the specificity between 66% and 81%. The US Preventive Services Task Force found insufficient evidence to recommend for or against teaching BSE. The purpose of this review was to evaluate the evidence relating to the effectiveness of BSE in preventing death of breast cancer to make recommendations for the Canadian Task Force on Preventive Health Care.

POPULATION STUDIED: The studies’ populations included women between ages 31 and 64 years in one study and from 40 to 69 years in the other studies. These women were from multiple areas of the world, including Shanghai, Russia, the United Kingdom, Canada, the United States, and Finland.

STUDY DESIGN AND VALIDITY: his is a systematic review of articles found using an electronic database search of abstracts and reports published from 1966 to October 2000. The author identified 2 randomized controlled trials, one quasi-randomized controlled trial, 2 large cohort studies, and several case-control studies that evaluated the effects of BSE on breast cancer outcomes. The 2 randomized-controlled trials and the quasi-randomized controlled trial were large studies enrolling more than 625,000 women with at least 5 years of follow-up and confirmation that women in the BSE group actually learned how to perform the maneuver. One of the cohort studies appeared to have a significant selection bias, rendering its results difficult to interpret. Since different designs were used in the review, the studies could not be combined using meta-analysis.

OUTCOMES MEASURED: The prevention of death resulting from breast cancer was viewed as the most important outcome. Other outcomes examined included the rate of benign biopsy results, the number of patient visits for breast complaints, the stage of cancer detected, and psychological benefits and harms.

RESULTS: Of the 8 studies included in this review, 7 studies, including the 2 randomized controlled trials and the quasi-randomized controlled trial, found no difference between groups taught BSE and the control groups with regard to rates of breast cancer diagnosis, breast cancer death, or in tumor stage or size. In the 2 randomized controlled trials and the quasi-randomized controlled trial, there were higher rates of benign biopsy results in the BSE groups, approximately 1 additional biopsy for every 200 women performing BSE. Women in the BSE groups also presented to the physician’s office more frequently for breast complaints.

BACKGROUND: Medical professionals routinely teach women breast self-examination (BSE) as a screen for detecting breast cancer, yet there are conflicting recommendations regarding BSE from different professional organizations. One study has shown that only 7.6% of women with breast tumors who were practicing regular BSE actually detected the tumor by means of self-examination. Different studies have estimated the sensitivity of BSE as between 26% and 89% and the specificity between 66% and 81%. The US Preventive Services Task Force found insufficient evidence to recommend for or against teaching BSE. The purpose of this review was to evaluate the evidence relating to the effectiveness of BSE in preventing death of breast cancer to make recommendations for the Canadian Task Force on Preventive Health Care.

POPULATION STUDIED: The studies’ populations included women between ages 31 and 64 years in one study and from 40 to 69 years in the other studies. These women were from multiple areas of the world, including Shanghai, Russia, the United Kingdom, Canada, the United States, and Finland.

STUDY DESIGN AND VALIDITY: his is a systematic review of articles found using an electronic database search of abstracts and reports published from 1966 to October 2000. The author identified 2 randomized controlled trials, one quasi-randomized controlled trial, 2 large cohort studies, and several case-control studies that evaluated the effects of BSE on breast cancer outcomes. The 2 randomized-controlled trials and the quasi-randomized controlled trial were large studies enrolling more than 625,000 women with at least 5 years of follow-up and confirmation that women in the BSE group actually learned how to perform the maneuver. One of the cohort studies appeared to have a significant selection bias, rendering its results difficult to interpret. Since different designs were used in the review, the studies could not be combined using meta-analysis.

OUTCOMES MEASURED: The prevention of death resulting from breast cancer was viewed as the most important outcome. Other outcomes examined included the rate of benign biopsy results, the number of patient visits for breast complaints, the stage of cancer detected, and psychological benefits and harms.

RESULTS: Of the 8 studies included in this review, 7 studies, including the 2 randomized controlled trials and the quasi-randomized controlled trial, found no difference between groups taught BSE and the control groups with regard to rates of breast cancer diagnosis, breast cancer death, or in tumor stage or size. In the 2 randomized controlled trials and the quasi-randomized controlled trial, there were higher rates of benign biopsy results in the BSE groups, approximately 1 additional biopsy for every 200 women performing BSE. Women in the BSE groups also presented to the physician’s office more frequently for breast complaints.

BACKGROUND: With the high morbidity and mortality associated with AF, it is important to define safe effective treatments to convert AF to sinus rhythm. Although patients with underlying cardiac disease are at higher risk for developing serious arrhythmias and hypotension from Class III antiarrhythmics, comparable risks have not been shown in a low-risk population with new-onset AF. The authors of this study evaluated the risks and benefits of using the Class III antiarrhythmics sotalol and amiodarone versus digoxin in conversion of new-onset AF to sinus rhythm at 48 hours.

POPULATION STUDIED: The authors of this study enrolled 115 patients with new-onset (<24 hours) AF. Patients with significant left ventricular dysfunction (ejection fraction <30% or requiring >40 mg of furosemide daily) or wide complex tachycardia were excluded. Patients who had used any of the study drugs within a defined period of time or who were prescribed a b-blocker were also excluded.

STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Concealed allocation did not occur for the majority of patients enrolled in the study. Patients were randomized to receive amiodarone, sotalol, or digoxin; all 3 groups had similar baseline characteristics. The trial medication was discontinued before 48 hours of treatment in 5 patients because of stroke, hypotension, or bradyarrhythmia, but these patients were still included in the analysis. At 24 hours those patients still in AF were started on heparin. Cardioversion was attempted in 20 of 29 patients who remained in AF after 48 hours of the study drug. The 9 patients excluded from cardioversion had significant left ventricular dysfunction, stroke, inadequate anticoagulation, or hypotension. Adverse events from all medications were recorded and analyzed. This study lacked long-term follow-up for monitoring of subsequent spontaneous reversion to AF, which may be a major factor in the drug to choose for sinus rhythm conversion. In addition, this study excluded those patients who had left ventricular dysfunction, a group that is at particular risk for developing complications from new-onset AF.

OUTCOMES MEASURED: The primary outcome measured was successful conversion to sinus rhythm within 48 hours of antiarrhythmic treatment or cardioversion. Secondary outcomes considered were time to conversion; ventricular rate if in AF at 4, 24, and 48 hours; and adverse events.

RESULTS: The number of patients in sinus rhythm after 48 hours of medication was greater in both the amiodarone (77%) and sotalol (88%; number needed to treat=3) groups compared with the digoxin group (58%) This was statistically significant (P <.01) for the sotalol group and the combined sotalol and aminodarone groups. There was also a nonsignificant trend toward more successful cardioversion in those receiving either study drug. The average time to reversion was greater for digoxin-treated patients (27 hours) than amiodarone-treated (18 hours; P <.05) or sotalol-treated (13 hours; P <.01) patients. Major adverse events included left ventricular failure, bradyarrhythmia, hypotension, and stroke. Digoxin treatment was associated with a significantly higher risk of major complications compared with either other drug (22% vs 7.7% and 5%).

BACKGROUND: With the high morbidity and mortality associated with AF, it is important to define safe effective treatments to convert AF to sinus rhythm. Although patients with underlying cardiac disease are at higher risk for developing serious arrhythmias and hypotension from Class III antiarrhythmics, comparable risks have not been shown in a low-risk population with new-onset AF. The authors of this study evaluated the risks and benefits of using the Class III antiarrhythmics sotalol and amiodarone versus digoxin in conversion of new-onset AF to sinus rhythm at 48 hours.

POPULATION STUDIED: The authors of this study enrolled 115 patients with new-onset (<24 hours) AF. Patients with significant left ventricular dysfunction (ejection fraction <30% or requiring >40 mg of furosemide daily) or wide complex tachycardia were excluded. Patients who had used any of the study drugs within a defined period of time or who were prescribed a b-blocker were also excluded.

STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Concealed allocation did not occur for the majority of patients enrolled in the study. Patients were randomized to receive amiodarone, sotalol, or digoxin; all 3 groups had similar baseline characteristics. The trial medication was discontinued before 48 hours of treatment in 5 patients because of stroke, hypotension, or bradyarrhythmia, but these patients were still included in the analysis. At 24 hours those patients still in AF were started on heparin. Cardioversion was attempted in 20 of 29 patients who remained in AF after 48 hours of the study drug. The 9 patients excluded from cardioversion had significant left ventricular dysfunction, stroke, inadequate anticoagulation, or hypotension. Adverse events from all medications were recorded and analyzed. This study lacked long-term follow-up for monitoring of subsequent spontaneous reversion to AF, which may be a major factor in the drug to choose for sinus rhythm conversion. In addition, this study excluded those patients who had left ventricular dysfunction, a group that is at particular risk for developing complications from new-onset AF.

OUTCOMES MEASURED: The primary outcome measured was successful conversion to sinus rhythm within 48 hours of antiarrhythmic treatment or cardioversion. Secondary outcomes considered were time to conversion; ventricular rate if in AF at 4, 24, and 48 hours; and adverse events.

RESULTS: The number of patients in sinus rhythm after 48 hours of medication was greater in both the amiodarone (77%) and sotalol (88%; number needed to treat=3) groups compared with the digoxin group (58%) This was statistically significant (P <.01) for the sotalol group and the combined sotalol and aminodarone groups. There was also a nonsignificant trend toward more successful cardioversion in those receiving either study drug. The average time to reversion was greater for digoxin-treated patients (27 hours) than amiodarone-treated (18 hours; P <.05) or sotalol-treated (13 hours; P <.01) patients. Major adverse events included left ventricular failure, bradyarrhythmia, hypotension, and stroke. Digoxin treatment was associated with a significantly higher risk of major complications compared with either other drug (22% vs 7.7% and 5%).

BACKGROUND: With the high morbidity and mortality associated with AF, it is important to define safe effective treatments to convert AF to sinus rhythm. Although patients with underlying cardiac disease are at higher risk for developing serious arrhythmias and hypotension from Class III antiarrhythmics, comparable risks have not been shown in a low-risk population with new-onset AF. The authors of this study evaluated the risks and benefits of using the Class III antiarrhythmics sotalol and amiodarone versus digoxin in conversion of new-onset AF to sinus rhythm at 48 hours.

POPULATION STUDIED: The authors of this study enrolled 115 patients with new-onset (<24 hours) AF. Patients with significant left ventricular dysfunction (ejection fraction <30% or requiring >40 mg of furosemide daily) or wide complex tachycardia were excluded. Patients who had used any of the study drugs within a defined period of time or who were prescribed a b-blocker were also excluded.

STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Concealed allocation did not occur for the majority of patients enrolled in the study. Patients were randomized to receive amiodarone, sotalol, or digoxin; all 3 groups had similar baseline characteristics. The trial medication was discontinued before 48 hours of treatment in 5 patients because of stroke, hypotension, or bradyarrhythmia, but these patients were still included in the analysis. At 24 hours those patients still in AF were started on heparin. Cardioversion was attempted in 20 of 29 patients who remained in AF after 48 hours of the study drug. The 9 patients excluded from cardioversion had significant left ventricular dysfunction, stroke, inadequate anticoagulation, or hypotension. Adverse events from all medications were recorded and analyzed. This study lacked long-term follow-up for monitoring of subsequent spontaneous reversion to AF, which may be a major factor in the drug to choose for sinus rhythm conversion. In addition, this study excluded those patients who had left ventricular dysfunction, a group that is at particular risk for developing complications from new-onset AF.

OUTCOMES MEASURED: The primary outcome measured was successful conversion to sinus rhythm within 48 hours of antiarrhythmic treatment or cardioversion. Secondary outcomes considered were time to conversion; ventricular rate if in AF at 4, 24, and 48 hours; and adverse events.

RESULTS: The number of patients in sinus rhythm after 48 hours of medication was greater in both the amiodarone (77%) and sotalol (88%; number needed to treat=3) groups compared with the digoxin group (58%) This was statistically significant (P <.01) for the sotalol group and the combined sotalol and aminodarone groups. There was also a nonsignificant trend toward more successful cardioversion in those receiving either study drug. The average time to reversion was greater for digoxin-treated patients (27 hours) than amiodarone-treated (18 hours; P <.05) or sotalol-treated (13 hours; P <.01) patients. Major adverse events included left ventricular failure, bradyarrhythmia, hypotension, and stroke. Digoxin treatment was associated with a significantly higher risk of major complications compared with either other drug (22% vs 7.7% and 5%).

CLINICAL QUESTION: Does screening mammography reduce breast cancer mortality?

BACKGROUND: Randomized controlled trials have found that mammography screening for breast cancer reduces mortality. Overall, though, this effect is very small and could have been influenced by very small changes. The 8 randomized studies have evaluated more than 450,000 women, with less than 1% of them dying of breast cancer. In this large group, the difference in mortality in the the screened versus the unscreened groups was only 65 women (837 breast cancer deaths in the screened groups, 902 in the unscreened groups).

Since this difference between the 2 groups is so small, it is crucial that screened and unscreened groups have identical characteristics, so that the initial risk of breast cancer is the same. This study reviewed the methodologic quality of past trials to determine whether methodologic issues could have affected the RESULTS: of these studies.

POPULATION STUDIED: The authors identified 8 randomized controlled clinical trials of screening mammography. To evaluate the studies for the meta-analysis, they carefully scrutinized the methodology of these studies. The reviewers focused primarily on how the researchers concealed the assignment to the groups so that no one knew in advance whether the next woman to be entered in the study would be randomized. If this concealment occurred properly, the randomized groups should have similar characteristics.

OUTCOME MEASURED: The primary focus of this analysis was whether the methodology of the studies, rather than a beneficial effect of mammography screening, could have accounted for the difference in mortality. The analysis compared risk of mortality—both due to any cause and due to breast cancer—in trials with and without appropriate randomization methods.

RESULTS: he authors concluded that 6 of the 8 trials used a process of randomization that failed to produce similar groups. One trial enrolled women in pairs but somehow ended up with unequal numbers of women in the 2 groups. In another trial, approximately twice as many women in the screened group were in the highest socioeconomic stratum, an imbalance that should not have occurred if the enrollment was truly random. One trial enrolled significantly fewer women in the screened group who had a preexisting breast lump. All of these imbalances suggest that the 2 groups being compared were not truly comparable. In one trial, women who were not screened were an average of 6 months older than those who received screening, a statistically significant and important difference when the outcome being considered is mortality rate.

In addition, 4 of the 6 trials failed to account consistently for the patients enrolled in their study. Patients initially enrolled in the study were not included in the final analysis, presumably because of administrative problems with managing the patient database.

These 6 flawed studies are the ones that support the usefulness of mammography screening. Breast cancer-related deaths were significantly lower in the screened group (relative risk [RR]=0.75; 95% confidence interval [CI], 0.67-0.83).

Two trials used adequate randomization and accounted for all of the enrolled women. Those 2 trials also used masked assessment of the cause of death, eliminating another source of potential bias. The combined data from those 2 trials showed no effect of screening on breast cancer mortality (RR=1.04; 95% CI, 0.84-1.27) or on total mortality (RR=0.99; 95% CI, 0.94-1.05).

Three trials evaluated the effect of mammography on overall mortality rates. All-cause mortality was not significantly affected by mammography screening. Two trials evaluated morbidity, finding surgery and radiotherapy to be performed more frequently in the screened patients. Also, benign findings in biopsy samples were reported 2 to 4 times more frequently in the screened patients.

CLINICAL QUESTION: Does screening mammography reduce breast cancer mortality?

BACKGROUND: Randomized controlled trials have found that mammography screening for breast cancer reduces mortality. Overall, though, this effect is very small and could have been influenced by very small changes. The 8 randomized studies have evaluated more than 450,000 women, with less than 1% of them dying of breast cancer. In this large group, the difference in mortality in the the screened versus the unscreened groups was only 65 women (837 breast cancer deaths in the screened groups, 902 in the unscreened groups).

Since this difference between the 2 groups is so small, it is crucial that screened and unscreened groups have identical characteristics, so that the initial risk of breast cancer is the same. This study reviewed the methodologic quality of past trials to determine whether methodologic issues could have affected the RESULTS: of these studies.

POPULATION STUDIED: The authors identified 8 randomized controlled clinical trials of screening mammography. To evaluate the studies for the meta-analysis, they carefully scrutinized the methodology of these studies. The reviewers focused primarily on how the researchers concealed the assignment to the groups so that no one knew in advance whether the next woman to be entered in the study would be randomized. If this concealment occurred properly, the randomized groups should have similar characteristics.

OUTCOME MEASURED: The primary focus of this analysis was whether the methodology of the studies, rather than a beneficial effect of mammography screening, could have accounted for the difference in mortality. The analysis compared risk of mortality—both due to any cause and due to breast cancer—in trials with and without appropriate randomization methods.

RESULTS: he authors concluded that 6 of the 8 trials used a process of randomization that failed to produce similar groups. One trial enrolled women in pairs but somehow ended up with unequal numbers of women in the 2 groups. In another trial, approximately twice as many women in the screened group were in the highest socioeconomic stratum, an imbalance that should not have occurred if the enrollment was truly random. One trial enrolled significantly fewer women in the screened group who had a preexisting breast lump. All of these imbalances suggest that the 2 groups being compared were not truly comparable. In one trial, women who were not screened were an average of 6 months older than those who received screening, a statistically significant and important difference when the outcome being considered is mortality rate.

In addition, 4 of the 6 trials failed to account consistently for the patients enrolled in their study. Patients initially enrolled in the study were not included in the final analysis, presumably because of administrative problems with managing the patient database.

These 6 flawed studies are the ones that support the usefulness of mammography screening. Breast cancer-related deaths were significantly lower in the screened group (relative risk [RR]=0.75; 95% confidence interval [CI], 0.67-0.83).

Two trials used adequate randomization and accounted for all of the enrolled women. Those 2 trials also used masked assessment of the cause of death, eliminating another source of potential bias. The combined data from those 2 trials showed no effect of screening on breast cancer mortality (RR=1.04; 95% CI, 0.84-1.27) or on total mortality (RR=0.99; 95% CI, 0.94-1.05).

Three trials evaluated the effect of mammography on overall mortality rates. All-cause mortality was not significantly affected by mammography screening. Two trials evaluated morbidity, finding surgery and radiotherapy to be performed more frequently in the screened patients. Also, benign findings in biopsy samples were reported 2 to 4 times more frequently in the screened patients.

CLINICAL QUESTION: Does screening mammography reduce breast cancer mortality?

BACKGROUND: Randomized controlled trials have found that mammography screening for breast cancer reduces mortality. Overall, though, this effect is very small and could have been influenced by very small changes. The 8 randomized studies have evaluated more than 450,000 women, with less than 1% of them dying of breast cancer. In this large group, the difference in mortality in the the screened versus the unscreened groups was only 65 women (837 breast cancer deaths in the screened groups, 902 in the unscreened groups).

Since this difference between the 2 groups is so small, it is crucial that screened and unscreened groups have identical characteristics, so that the initial risk of breast cancer is the same. This study reviewed the methodologic quality of past trials to determine whether methodologic issues could have affected the RESULTS: of these studies.

POPULATION STUDIED: The authors identified 8 randomized controlled clinical trials of screening mammography. To evaluate the studies for the meta-analysis, they carefully scrutinized the methodology of these studies. The reviewers focused primarily on how the researchers concealed the assignment to the groups so that no one knew in advance whether the next woman to be entered in the study would be randomized. If this concealment occurred properly, the randomized groups should have similar characteristics.

OUTCOME MEASURED: The primary focus of this analysis was whether the methodology of the studies, rather than a beneficial effect of mammography screening, could have accounted for the difference in mortality. The analysis compared risk of mortality—both due to any cause and due to breast cancer—in trials with and without appropriate randomization methods.

RESULTS: he authors concluded that 6 of the 8 trials used a process of randomization that failed to produce similar groups. One trial enrolled women in pairs but somehow ended up with unequal numbers of women in the 2 groups. In another trial, approximately twice as many women in the screened group were in the highest socioeconomic stratum, an imbalance that should not have occurred if the enrollment was truly random. One trial enrolled significantly fewer women in the screened group who had a preexisting breast lump. All of these imbalances suggest that the 2 groups being compared were not truly comparable. In one trial, women who were not screened were an average of 6 months older than those who received screening, a statistically significant and important difference when the outcome being considered is mortality rate.

In addition, 4 of the 6 trials failed to account consistently for the patients enrolled in their study. Patients initially enrolled in the study were not included in the final analysis, presumably because of administrative problems with managing the patient database.

These 6 flawed studies are the ones that support the usefulness of mammography screening. Breast cancer-related deaths were significantly lower in the screened group (relative risk [RR]=0.75; 95% confidence interval [CI], 0.67-0.83).

Two trials used adequate randomization and accounted for all of the enrolled women. Those 2 trials also used masked assessment of the cause of death, eliminating another source of potential bias. The combined data from those 2 trials showed no effect of screening on breast cancer mortality (RR=1.04; 95% CI, 0.84-1.27) or on total mortality (RR=0.99; 95% CI, 0.94-1.05).

Three trials evaluated the effect of mammography on overall mortality rates. All-cause mortality was not significantly affected by mammography screening. Two trials evaluated morbidity, finding surgery and radiotherapy to be performed more frequently in the screened patients. Also, benign findings in biopsy samples were reported 2 to 4 times more frequently in the screened patients.