Breast Cancer

SAN ANTONIO – Survival is nearly identical in early-stage breast cancer regardless of whether or not bone marrow micrometastases are present, according to the prospective Swiss Multicenter Study Group trial.

Among 410 women with T1 and T2 disease and no palpable axillary lymph nodes, the 5-year overall survival was 92.5% with bone marrow micrometastases (BMM) and 92.7% without (P = .85).

Dr. Igor Langer

The 5-year disease-free survival reached 92.2% in patients with BMM and 93.6% in those without (P = .50), Dr. Igor Langer said during a plenary session at a symposium sponsored by the Society of Surgical Oncology. Micrometastases were detected in 118 patients (29%).

Audience members asked Dr. Langer to explain his findings in light of those from the ACOSOG (American College of Surgeons Oncology Group) Z0010 trial, which also involved T1 and T2 disease. In that trial, BMMs were detected by immunohistochemistry in just 3% of women, and were associated with a significantly lower 5-year survival rate of 90% vs. 95% in patients without BMMs, according to data presented at the 2010 annual meeting of the American Society of Clinical Oncology.

Dr. Langer of the department of surgery at the Lindenhofspital in Bern, Switzerland, replied that most studies looking for BMM can identify them in 15%-40% of patients. "So I don’t know if it is a methodological difference, in terms of preparation of the bone marrow and identification of these cells," he said. "The difference in prognosis is multifactorial."

He pointed out that there is no standardized method to detect BMMs, that different methods were used to identify sentinel lymph nodes (SLNs), that patients received different adjuvant regimens, and that the number of cases who developed BMMs was so low, it could easily change outcomes.

Another attendee asked whether there is a particular cutoff for BMMs, noting that in many cancers the presence of micrometastases has no impact on survival, and that they are prognostic in melanoma only when they are at least 0.2 mm in the lymph nodes. Dr. Langer said that the median number of tumor cells in the analysis was two, but he balked at the possibility of using BMM testing in early breast cancer.

"You shouldn’t do the bone marrow aspiration," he said in an interview. "It might have prognostic impact, but if it doesn’t drive your therapy – if it doesn’t influence what you are doing – you have findings and you don’t know what to do with them. It’s too immature. We first have to standardize the testing."

Dr. Langer reported on 659 women from 13 Swiss centers who underwent intraoperative SLN examination by frozen section and paraffin serial sectioning at a cutting interval of 250 mcm with H&E (hematoxylin and eosin) staining and immunohistochemistry.

As previously reported, SLNs were identified in 98% of patients, including 71% with T1 disease and 29% with T2 disease (Breast Cancer Res. Treat. 2009;113:129-36). Their median age was 59 years, and 80% were postmenopausal. The median tumor size was 17 mm.

Of the 659 patients, 410 also underwent bone marrow aspiration from both iliac crests; these formed the basis of the current analysis. The mononuclear cells of the bone marrow aspirates were isolated by density gradient centrifugation through Ficoll. In all, 2 million bone marrow cells were evaluated, and the presence of one or more tumor cells was regarded as BMM positive, Dr. Langer said.

Cancer cells were stained with monoclonal antibodies A45-B/B3 against cytokeratin 8, 18, and 19 and were counted by an automated, computerized digital microscope. All results were reviewed by one pathologist.

Bone marrow micrometastases were detected in 118 (28.8%) of the 410 women. About 210 women were SLN negative and BMM negative, although considerable discordance was observed, Dr. Langer said. In all, 67 women (16.4%) were BMM positive and SLN negative, whereas 82 women (20%) were BMM negative and SLN positive.

In multivariate logistic regression analysis that included tumor size, tumor grade, tumor receptor status, and menopausal status, the presence of positive SLNs was the only significant independent predictor for the presence of BMM (P = .007; odds ratio, 1.860). T stage was not significant; only N stage was, he said.

In the earlier published analysis, the Swiss researchers identified SLN micrometastases or isolated tumor cells in 47 patients who underwent delayed ALND (axillary lymph node dissection). In 96% of these patients, the second operation was not beneficial because the ALND specimens were free of macrometastases. This finding – coupled with an overall accuracy of frozen section of 90% in the detection of SLN macrometastases – led the group to strongly recommend the routine use of SLN frozen section in early-stage breast cancer.

The recently published ACOSOG Z0011 trial concluded that ALND offers no survival advantage over SLN dissection alone in women with T1-T2 invasive breast cancer with no palpable adenopathy and one or two lymph nodes that contain metastases identified by frozen section, touch preparation, or H&E staining.

Sentinel node micrometastases (defined as H&E tumor deposits no greater than 2 mm in size) were identified in 37.5% of patients in the ALND group vs. 45% of those in the SLND group (JAMA 2011;305:569-75).

The Swiss Group for Clinical Cancer Research and the Cancer League of Basel-Stadt and Basel-Land funded the study. Dr. Langer and his coauthors disclosed no conflicts.

SAN ANTONIO – Survival is nearly identical in early-stage breast cancer regardless of whether or not bone marrow micrometastases are present, according to the prospective Swiss Multicenter Study Group trial.

Among 410 women with T1 and T2 disease and no palpable axillary lymph nodes, the 5-year overall survival was 92.5% with bone marrow micrometastases (BMM) and 92.7% without (P = .85).

Dr. Igor Langer

The 5-year disease-free survival reached 92.2% in patients with BMM and 93.6% in those without (P = .50), Dr. Igor Langer said during a plenary session at a symposium sponsored by the Society of Surgical Oncology. Micrometastases were detected in 118 patients (29%).

Audience members asked Dr. Langer to explain his findings in light of those from the ACOSOG (American College of Surgeons Oncology Group) Z0010 trial, which also involved T1 and T2 disease. In that trial, BMMs were detected by immunohistochemistry in just 3% of women, and were associated with a significantly lower 5-year survival rate of 90% vs. 95% in patients without BMMs, according to data presented at the 2010 annual meeting of the American Society of Clinical Oncology.

Dr. Langer of the department of surgery at the Lindenhofspital in Bern, Switzerland, replied that most studies looking for BMM can identify them in 15%-40% of patients. "So I don’t know if it is a methodological difference, in terms of preparation of the bone marrow and identification of these cells," he said. "The difference in prognosis is multifactorial."

He pointed out that there is no standardized method to detect BMMs, that different methods were used to identify sentinel lymph nodes (SLNs), that patients received different adjuvant regimens, and that the number of cases who developed BMMs was so low, it could easily change outcomes.

Another attendee asked whether there is a particular cutoff for BMMs, noting that in many cancers the presence of micrometastases has no impact on survival, and that they are prognostic in melanoma only when they are at least 0.2 mm in the lymph nodes. Dr. Langer said that the median number of tumor cells in the analysis was two, but he balked at the possibility of using BMM testing in early breast cancer.

"You shouldn’t do the bone marrow aspiration," he said in an interview. "It might have prognostic impact, but if it doesn’t drive your therapy – if it doesn’t influence what you are doing – you have findings and you don’t know what to do with them. It’s too immature. We first have to standardize the testing."

Dr. Langer reported on 659 women from 13 Swiss centers who underwent intraoperative SLN examination by frozen section and paraffin serial sectioning at a cutting interval of 250 mcm with H&E (hematoxylin and eosin) staining and immunohistochemistry.

As previously reported, SLNs were identified in 98% of patients, including 71% with T1 disease and 29% with T2 disease (Breast Cancer Res. Treat. 2009;113:129-36). Their median age was 59 years, and 80% were postmenopausal. The median tumor size was 17 mm.

Of the 659 patients, 410 also underwent bone marrow aspiration from both iliac crests; these formed the basis of the current analysis. The mononuclear cells of the bone marrow aspirates were isolated by density gradient centrifugation through Ficoll. In all, 2 million bone marrow cells were evaluated, and the presence of one or more tumor cells was regarded as BMM positive, Dr. Langer said.

Cancer cells were stained with monoclonal antibodies A45-B/B3 against cytokeratin 8, 18, and 19 and were counted by an automated, computerized digital microscope. All results were reviewed by one pathologist.

Bone marrow micrometastases were detected in 118 (28.8%) of the 410 women. About 210 women were SLN negative and BMM negative, although considerable discordance was observed, Dr. Langer said. In all, 67 women (16.4%) were BMM positive and SLN negative, whereas 82 women (20%) were BMM negative and SLN positive.

In multivariate logistic regression analysis that included tumor size, tumor grade, tumor receptor status, and menopausal status, the presence of positive SLNs was the only significant independent predictor for the presence of BMM (P = .007; odds ratio, 1.860). T stage was not significant; only N stage was, he said.

In the earlier published analysis, the Swiss researchers identified SLN micrometastases or isolated tumor cells in 47 patients who underwent delayed ALND (axillary lymph node dissection). In 96% of these patients, the second operation was not beneficial because the ALND specimens were free of macrometastases. This finding – coupled with an overall accuracy of frozen section of 90% in the detection of SLN macrometastases – led the group to strongly recommend the routine use of SLN frozen section in early-stage breast cancer.

The recently published ACOSOG Z0011 trial concluded that ALND offers no survival advantage over SLN dissection alone in women with T1-T2 invasive breast cancer with no palpable adenopathy and one or two lymph nodes that contain metastases identified by frozen section, touch preparation, or H&E staining.

Sentinel node micrometastases (defined as H&E tumor deposits no greater than 2 mm in size) were identified in 37.5% of patients in the ALND group vs. 45% of those in the SLND group (JAMA 2011;305:569-75).

The Swiss Group for Clinical Cancer Research and the Cancer League of Basel-Stadt and Basel-Land funded the study. Dr. Langer and his coauthors disclosed no conflicts.

SAN ANTONIO – Survival is nearly identical in early-stage breast cancer regardless of whether or not bone marrow micrometastases are present, according to the prospective Swiss Multicenter Study Group trial.

Among 410 women with T1 and T2 disease and no palpable axillary lymph nodes, the 5-year overall survival was 92.5% with bone marrow micrometastases (BMM) and 92.7% without (P = .85).

Dr. Igor Langer

The 5-year disease-free survival reached 92.2% in patients with BMM and 93.6% in those without (P = .50), Dr. Igor Langer said during a plenary session at a symposium sponsored by the Society of Surgical Oncology. Micrometastases were detected in 118 patients (29%).

Audience members asked Dr. Langer to explain his findings in light of those from the ACOSOG (American College of Surgeons Oncology Group) Z0010 trial, which also involved T1 and T2 disease. In that trial, BMMs were detected by immunohistochemistry in just 3% of women, and were associated with a significantly lower 5-year survival rate of 90% vs. 95% in patients without BMMs, according to data presented at the 2010 annual meeting of the American Society of Clinical Oncology.

Dr. Langer of the department of surgery at the Lindenhofspital in Bern, Switzerland, replied that most studies looking for BMM can identify them in 15%-40% of patients. "So I don’t know if it is a methodological difference, in terms of preparation of the bone marrow and identification of these cells," he said. "The difference in prognosis is multifactorial."

He pointed out that there is no standardized method to detect BMMs, that different methods were used to identify sentinel lymph nodes (SLNs), that patients received different adjuvant regimens, and that the number of cases who developed BMMs was so low, it could easily change outcomes.

Another attendee asked whether there is a particular cutoff for BMMs, noting that in many cancers the presence of micrometastases has no impact on survival, and that they are prognostic in melanoma only when they are at least 0.2 mm in the lymph nodes. Dr. Langer said that the median number of tumor cells in the analysis was two, but he balked at the possibility of using BMM testing in early breast cancer.

"You shouldn’t do the bone marrow aspiration," he said in an interview. "It might have prognostic impact, but if it doesn’t drive your therapy – if it doesn’t influence what you are doing – you have findings and you don’t know what to do with them. It’s too immature. We first have to standardize the testing."

Dr. Langer reported on 659 women from 13 Swiss centers who underwent intraoperative SLN examination by frozen section and paraffin serial sectioning at a cutting interval of 250 mcm with H&E (hematoxylin and eosin) staining and immunohistochemistry.

As previously reported, SLNs were identified in 98% of patients, including 71% with T1 disease and 29% with T2 disease (Breast Cancer Res. Treat. 2009;113:129-36). Their median age was 59 years, and 80% were postmenopausal. The median tumor size was 17 mm.

Of the 659 patients, 410 also underwent bone marrow aspiration from both iliac crests; these formed the basis of the current analysis. The mononuclear cells of the bone marrow aspirates were isolated by density gradient centrifugation through Ficoll. In all, 2 million bone marrow cells were evaluated, and the presence of one or more tumor cells was regarded as BMM positive, Dr. Langer said.

Cancer cells were stained with monoclonal antibodies A45-B/B3 against cytokeratin 8, 18, and 19 and were counted by an automated, computerized digital microscope. All results were reviewed by one pathologist.

Bone marrow micrometastases were detected in 118 (28.8%) of the 410 women. About 210 women were SLN negative and BMM negative, although considerable discordance was observed, Dr. Langer said. In all, 67 women (16.4%) were BMM positive and SLN negative, whereas 82 women (20%) were BMM negative and SLN positive.

In multivariate logistic regression analysis that included tumor size, tumor grade, tumor receptor status, and menopausal status, the presence of positive SLNs was the only significant independent predictor for the presence of BMM (P = .007; odds ratio, 1.860). T stage was not significant; only N stage was, he said.

In the earlier published analysis, the Swiss researchers identified SLN micrometastases or isolated tumor cells in 47 patients who underwent delayed ALND (axillary lymph node dissection). In 96% of these patients, the second operation was not beneficial because the ALND specimens were free of macrometastases. This finding – coupled with an overall accuracy of frozen section of 90% in the detection of SLN macrometastases – led the group to strongly recommend the routine use of SLN frozen section in early-stage breast cancer.

The recently published ACOSOG Z0011 trial concluded that ALND offers no survival advantage over SLN dissection alone in women with T1-T2 invasive breast cancer with no palpable adenopathy and one or two lymph nodes that contain metastases identified by frozen section, touch preparation, or H&E staining.

Sentinel node micrometastases (defined as H&E tumor deposits no greater than 2 mm in size) were identified in 37.5% of patients in the ALND group vs. 45% of those in the SLND group (JAMA 2011;305:569-75).

The Swiss Group for Clinical Cancer Research and the Cancer League of Basel-Stadt and Basel-Land funded the study. Dr. Langer and his coauthors disclosed no conflicts.

SAN ANTONIO – The literature is somewhat checkered over who can claim bragging rights for improved breast cancer outcomes, but the overall trend has favored surgical oncologists over general surgeons.

What’s driving the improved outcomes isn’t entirely clear, but a new analysis suggests that a key mechanism is that patients treated by surgical oncologists participate in clinical trials at dramatically higher rates, lead author Dr. William Dooley said during a plenary session at a symposium sponsored by the Society of Surgical Oncology.

Among 1,220 women analyzed for the period of 2001-2008, 56% of 777 patients treated by a surgical oncologist participated in a clinical trial, compared with only 7% of 443 general surgery patients (P value = .000).

Patients in a clinical trial were more likely to stay connected with the system and followed by their treating physician, said Dr. Dooley, the G. Rainey Williams Professor and chair of surgical breast oncology at the University of Oklahoma Breast Institute, Oklahoma City. The average follow-up was 44.6 months for the 468 trial participants vs. 38.5 months for the 752 nonparticipants (P = .000).

Participation in a clinical trial was associated with a significant survival advantage, increasing overall survival from 26% to 31% at 5 years (P = .000).

The benefits of clinical trial involvement cut across the entire health care team, Dr. Dooley said. Radiologists and pathologists receive outside review of and feedback for their work, while outside monitoring tracks the actions of the treatment team, patient progress through the treatment plan, and adherence of all elements of care to the system.

"When we begin to think about clinical trials and groups like ACOSOG [American College of Surgeons Oncology Group], we need to bring forth the spectrum of clinical trials to cover the whole spectrum of breast disease and encourage all surgeons in the country to be involved," he said. "This may be a very dramatic way that we can improve the quality of breast cancer care nationally."

The entire analysis included 2,191 women who received primary breast cancer treatment from 1995 to 2008 at the Breast Institute, with 752 under the care of a surgical oncologist and 1,439 cared for by a general surgeon. The average age of the women was 54 years and 57 years, respectively.

When the researchers compared their outcomes using standardized measures, the case mix included 25% more late-stage disease than the national population. General surgeons performed right at the national average, while additional oncologic training for surgeons provided a 28% improvement in workup and treatment.

But most significantly, the additional training reduced deaths for stage I-III breast cancer from 39% for stage IIIb disease to 57% for stage I disease, Dr. Dooley said.

Another mechanism driving the improved outcomes is that patients treated by a surgical oncologist are far more likely to complete National Comprehensive Cancer Network guideline–compatible therapy in a timely fashion, he said. In all, 77% of stage I-III patients treated by a surgical oncologist completed chemotherapy or hormonal adjuvant therapy, compared with 68.5% of general surgery patients (P less than .02).

Breast conservation rates were significantly higher for surgical oncology patients than for general surgery patients overall (53% vs. 38%, P less than .001), and for stage 0-II disease (66% vs. 54%, P less than .01).

Radiation therapy for breast conservation was completed by 97% of patients treated by a surgical oncologist and 67% of general surgery patients, and by 99% vs. 74% for stage III disease (P less than .001 for each), Dr. Dooley said.

"Good intentions don’t get us very far," he said. "The Commission on Cancer is starting a program to help us monitor initiation of treatment. It’s not the initiation that counts. It’s whether the patients actually finish that treatment completely."

There were no survival differences for women with stage 0 or IV disease, and their data were excluded from the presentation.

During a discussion of the study, an audience member questioned the presence of comorbidities in each group, observing that patients enrolled in clinical trials tend to be healthier. Dr. Dooley responded that details on comorbidities were limited, but that Charlson Index scores were similar in both groups. In addition, he noted that the same beneficial effect of clinical trial participation has been observed even in trials with just tissue banking.

Rates of stage I, IIA, and IIB disease were similar at 20.5%, 30.5%, and 17% in the surgical oncology group and 19.6%, 32%, and 24% in the general surgery group. Chemotherapy, however, was significantly more common among patients treated by a surgical oncologist than among those in the general surgery group (69% vs. 56%).

Another attendee pointed out that the Rapid Reporting System sends out an alert if cancer patients are not completing therapy. Dr. Dooley said the system was not in place for the entire study period.

Dr. Dooley and his coauthors reported no relevant conflicts of interest.

SAN ANTONIO – The literature is somewhat checkered over who can claim bragging rights for improved breast cancer outcomes, but the overall trend has favored surgical oncologists over general surgeons.

What’s driving the improved outcomes isn’t entirely clear, but a new analysis suggests that a key mechanism is that patients treated by surgical oncologists participate in clinical trials at dramatically higher rates, lead author Dr. William Dooley said during a plenary session at a symposium sponsored by the Society of Surgical Oncology.

Among 1,220 women analyzed for the period of 2001-2008, 56% of 777 patients treated by a surgical oncologist participated in a clinical trial, compared with only 7% of 443 general surgery patients (P value = .000).

Patients in a clinical trial were more likely to stay connected with the system and followed by their treating physician, said Dr. Dooley, the G. Rainey Williams Professor and chair of surgical breast oncology at the University of Oklahoma Breast Institute, Oklahoma City. The average follow-up was 44.6 months for the 468 trial participants vs. 38.5 months for the 752 nonparticipants (P = .000).

Participation in a clinical trial was associated with a significant survival advantage, increasing overall survival from 26% to 31% at 5 years (P = .000).

The benefits of clinical trial involvement cut across the entire health care team, Dr. Dooley said. Radiologists and pathologists receive outside review of and feedback for their work, while outside monitoring tracks the actions of the treatment team, patient progress through the treatment plan, and adherence of all elements of care to the system.

"When we begin to think about clinical trials and groups like ACOSOG [American College of Surgeons Oncology Group], we need to bring forth the spectrum of clinical trials to cover the whole spectrum of breast disease and encourage all surgeons in the country to be involved," he said. "This may be a very dramatic way that we can improve the quality of breast cancer care nationally."

The entire analysis included 2,191 women who received primary breast cancer treatment from 1995 to 2008 at the Breast Institute, with 752 under the care of a surgical oncologist and 1,439 cared for by a general surgeon. The average age of the women was 54 years and 57 years, respectively.

When the researchers compared their outcomes using standardized measures, the case mix included 25% more late-stage disease than the national population. General surgeons performed right at the national average, while additional oncologic training for surgeons provided a 28% improvement in workup and treatment.

But most significantly, the additional training reduced deaths for stage I-III breast cancer from 39% for stage IIIb disease to 57% for stage I disease, Dr. Dooley said.

Another mechanism driving the improved outcomes is that patients treated by a surgical oncologist are far more likely to complete National Comprehensive Cancer Network guideline–compatible therapy in a timely fashion, he said. In all, 77% of stage I-III patients treated by a surgical oncologist completed chemotherapy or hormonal adjuvant therapy, compared with 68.5% of general surgery patients (P less than .02).

Breast conservation rates were significantly higher for surgical oncology patients than for general surgery patients overall (53% vs. 38%, P less than .001), and for stage 0-II disease (66% vs. 54%, P less than .01).

Radiation therapy for breast conservation was completed by 97% of patients treated by a surgical oncologist and 67% of general surgery patients, and by 99% vs. 74% for stage III disease (P less than .001 for each), Dr. Dooley said.

"Good intentions don’t get us very far," he said. "The Commission on Cancer is starting a program to help us monitor initiation of treatment. It’s not the initiation that counts. It’s whether the patients actually finish that treatment completely."

There were no survival differences for women with stage 0 or IV disease, and their data were excluded from the presentation.

During a discussion of the study, an audience member questioned the presence of comorbidities in each group, observing that patients enrolled in clinical trials tend to be healthier. Dr. Dooley responded that details on comorbidities were limited, but that Charlson Index scores were similar in both groups. In addition, he noted that the same beneficial effect of clinical trial participation has been observed even in trials with just tissue banking.

Rates of stage I, IIA, and IIB disease were similar at 20.5%, 30.5%, and 17% in the surgical oncology group and 19.6%, 32%, and 24% in the general surgery group. Chemotherapy, however, was significantly more common among patients treated by a surgical oncologist than among those in the general surgery group (69% vs. 56%).

Another attendee pointed out that the Rapid Reporting System sends out an alert if cancer patients are not completing therapy. Dr. Dooley said the system was not in place for the entire study period.

Dr. Dooley and his coauthors reported no relevant conflicts of interest.

SAN ANTONIO – The literature is somewhat checkered over who can claim bragging rights for improved breast cancer outcomes, but the overall trend has favored surgical oncologists over general surgeons.

What’s driving the improved outcomes isn’t entirely clear, but a new analysis suggests that a key mechanism is that patients treated by surgical oncologists participate in clinical trials at dramatically higher rates, lead author Dr. William Dooley said during a plenary session at a symposium sponsored by the Society of Surgical Oncology.

Among 1,220 women analyzed for the period of 2001-2008, 56% of 777 patients treated by a surgical oncologist participated in a clinical trial, compared with only 7% of 443 general surgery patients (P value = .000).

Patients in a clinical trial were more likely to stay connected with the system and followed by their treating physician, said Dr. Dooley, the G. Rainey Williams Professor and chair of surgical breast oncology at the University of Oklahoma Breast Institute, Oklahoma City. The average follow-up was 44.6 months for the 468 trial participants vs. 38.5 months for the 752 nonparticipants (P = .000).

Participation in a clinical trial was associated with a significant survival advantage, increasing overall survival from 26% to 31% at 5 years (P = .000).

The benefits of clinical trial involvement cut across the entire health care team, Dr. Dooley said. Radiologists and pathologists receive outside review of and feedback for their work, while outside monitoring tracks the actions of the treatment team, patient progress through the treatment plan, and adherence of all elements of care to the system.

"When we begin to think about clinical trials and groups like ACOSOG [American College of Surgeons Oncology Group], we need to bring forth the spectrum of clinical trials to cover the whole spectrum of breast disease and encourage all surgeons in the country to be involved," he said. "This may be a very dramatic way that we can improve the quality of breast cancer care nationally."

The entire analysis included 2,191 women who received primary breast cancer treatment from 1995 to 2008 at the Breast Institute, with 752 under the care of a surgical oncologist and 1,439 cared for by a general surgeon. The average age of the women was 54 years and 57 years, respectively.

When the researchers compared their outcomes using standardized measures, the case mix included 25% more late-stage disease than the national population. General surgeons performed right at the national average, while additional oncologic training for surgeons provided a 28% improvement in workup and treatment.

But most significantly, the additional training reduced deaths for stage I-III breast cancer from 39% for stage IIIb disease to 57% for stage I disease, Dr. Dooley said.

Another mechanism driving the improved outcomes is that patients treated by a surgical oncologist are far more likely to complete National Comprehensive Cancer Network guideline–compatible therapy in a timely fashion, he said. In all, 77% of stage I-III patients treated by a surgical oncologist completed chemotherapy or hormonal adjuvant therapy, compared with 68.5% of general surgery patients (P less than .02).

Breast conservation rates were significantly higher for surgical oncology patients than for general surgery patients overall (53% vs. 38%, P less than .001), and for stage 0-II disease (66% vs. 54%, P less than .01).

Radiation therapy for breast conservation was completed by 97% of patients treated by a surgical oncologist and 67% of general surgery patients, and by 99% vs. 74% for stage III disease (P less than .001 for each), Dr. Dooley said.

"Good intentions don’t get us very far," he said. "The Commission on Cancer is starting a program to help us monitor initiation of treatment. It’s not the initiation that counts. It’s whether the patients actually finish that treatment completely."

There were no survival differences for women with stage 0 or IV disease, and their data were excluded from the presentation.

During a discussion of the study, an audience member questioned the presence of comorbidities in each group, observing that patients enrolled in clinical trials tend to be healthier. Dr. Dooley responded that details on comorbidities were limited, but that Charlson Index scores were similar in both groups. In addition, he noted that the same beneficial effect of clinical trial participation has been observed even in trials with just tissue banking.

Rates of stage I, IIA, and IIB disease were similar at 20.5%, 30.5%, and 17% in the surgical oncology group and 19.6%, 32%, and 24% in the general surgery group. Chemotherapy, however, was significantly more common among patients treated by a surgical oncologist than among those in the general surgery group (69% vs. 56%).

Another attendee pointed out that the Rapid Reporting System sends out an alert if cancer patients are not completing therapy. Dr. Dooley said the system was not in place for the entire study period.

Dr. Dooley and his coauthors reported no relevant conflicts of interest.

SAN ANTONIO – Positive margin and reoperation rates were similar for radio-guided seed localization and wire-guided localization of nonpalpable breast tumors in a prospective multicenter trial – in contrast to results from previous studies.

In an intent-to-treat analysis of 305 women with confirmed invasive or ductal carcinoma in situ who were undergoing localization and breast-conserving surgery, positive margin rates were 10.5% for radio-guided seed localization (RSL) and 11.9% for wire-guided localization (P = .990).

Rates of positive plus close margins (defined as disease within less than 1 mm) were 19% for the seed group and 22% for the wire group (P = .609), Dr. Peter Lovrics reported at a symposium sponsored by the Society of Surgical Oncology.

Rates of reoperation – either re-excision of margins or mastectomy – were also similar (19% and 15%, respectively) in the wire and seed groups, said Dr. Lovrics of the department of surgery at McMaster University in Hamilton, Ont.

The feasibility of RSL for identifying occult breast tumors was first reported a little more than a decade ago, and RSL has been rapidly adopted in many European countries. The procedure involves intratumoral injection of a radiotracer to identify the primary tumor and sentinel lymph nodes for intraoperative gamma probe–guided dissection.

In a recent literature review of 12 studies, Dr. Lovrics and his associates found that RSL yields lower positive margins (odds ratio, 0.367) and fewer reoperations (OR, 0.347) than does wire-guided localization, and three of those studies also suggested improved cosmesis (Eur. J. Surg. Oncol. 2011 Feb. 16 [E-pub ahead of print]).

When asked why RSL failed to produce significantly better outcomes, Dr. Lovrics said it may be that with a larger sample size, RSL would be potentially better, yielding results similar to those of other studies. Notably, overall positive margin rates were low for both groups and were much higher for wire-guided localization in most other studies.

"This may be partially attributed to the fact that all patients had a preoperative core biopsy and a confirmed diagnosis of cancer, so all of the procedures were definitive operations," he said in an interview. "In some other studies, not all patients had confirmed cancer and some operations were diagnostic in intent. Otherwise, the study population was typical – similar to other studies in tumor characteristics."

In the current study, there were 152 patients in the seed group and 153 in the wire group, with 6 patients crossing over to the wire group because the seed did not arrive at the hospital on the day of surgery. Mammogram findings included a mass in 47% of the wire group and in 50% of the seed group, and microcalcifications in 11% and 14%, respectively. Three-fourths of patients had a mass present on ultrasonography. Their average age was 60 years.

Secondary outcomes between groups were very similar, except for a significantly shorter operative time of 19 minutes with seed localization vs. 22 minutes in the wire group (P less than .001), Dr. Lovrics said. Excision difficulty was also ranked significantly easier for surgeons with seed localization (P = .008).

Factors such as skin removal and whether the dissection was taken to the chest wall were similar, as were the number of additional cavity margins excised and postoperative complications at 1 month, he said during a breast-focused plenary session.

Pain-reported anxiety during localization was similar in both groups, although patients in the seed group reported significantly less pain during the localization procedure than did those in the wire group (P = 0.38). An analysis of cosmetic results is ongoing.

Dr. Lovrics said that RSL allows exquisite and precise localization of the tumor, and that radiation exposure to patients and health care workers is negligible.

"For the surgeon, it provides very real-time, enhanced guidance for localization and is preferred by surgeons," he concluded. "Radio-seed localization is an acceptable alternative to wire-guided localization."

During a discussion of the study, audience members asked whether a cost analysis had been performed and whether the seeds were placed on the day of the surgery. Dr. Lovrics said the seeds and the wire both cost about $50, and that they currently place the seed on the day of surgery, but they hope to insert it earlier to further reduce OR time.

When asked whether a radiograph is still needed after seed localization, Dr. Lovrics said that a postoperative radiograph is still essential because of the risk of seed migration. Seeds were misplaced in four cases, one seed migrated, one wire migrated, and one wire fell out.

The Canadian Breast Cancer Foundation funded the study. Dr. Lovrics and his coauthors reported no conflicts of interest.

SAN ANTONIO – Positive margin and reoperation rates were similar for radio-guided seed localization and wire-guided localization of nonpalpable breast tumors in a prospective multicenter trial – in contrast to results from previous studies.

In an intent-to-treat analysis of 305 women with confirmed invasive or ductal carcinoma in situ who were undergoing localization and breast-conserving surgery, positive margin rates were 10.5% for radio-guided seed localization (RSL) and 11.9% for wire-guided localization (P = .990).

Rates of positive plus close margins (defined as disease within less than 1 mm) were 19% for the seed group and 22% for the wire group (P = .609), Dr. Peter Lovrics reported at a symposium sponsored by the Society of Surgical Oncology.

Rates of reoperation – either re-excision of margins or mastectomy – were also similar (19% and 15%, respectively) in the wire and seed groups, said Dr. Lovrics of the department of surgery at McMaster University in Hamilton, Ont.

The feasibility of RSL for identifying occult breast tumors was first reported a little more than a decade ago, and RSL has been rapidly adopted in many European countries. The procedure involves intratumoral injection of a radiotracer to identify the primary tumor and sentinel lymph nodes for intraoperative gamma probe–guided dissection.

In a recent literature review of 12 studies, Dr. Lovrics and his associates found that RSL yields lower positive margins (odds ratio, 0.367) and fewer reoperations (OR, 0.347) than does wire-guided localization, and three of those studies also suggested improved cosmesis (Eur. J. Surg. Oncol. 2011 Feb. 16 [E-pub ahead of print]).

When asked why RSL failed to produce significantly better outcomes, Dr. Lovrics said it may be that with a larger sample size, RSL would be potentially better, yielding results similar to those of other studies. Notably, overall positive margin rates were low for both groups and were much higher for wire-guided localization in most other studies.

"This may be partially attributed to the fact that all patients had a preoperative core biopsy and a confirmed diagnosis of cancer, so all of the procedures were definitive operations," he said in an interview. "In some other studies, not all patients had confirmed cancer and some operations were diagnostic in intent. Otherwise, the study population was typical – similar to other studies in tumor characteristics."

In the current study, there were 152 patients in the seed group and 153 in the wire group, with 6 patients crossing over to the wire group because the seed did not arrive at the hospital on the day of surgery. Mammogram findings included a mass in 47% of the wire group and in 50% of the seed group, and microcalcifications in 11% and 14%, respectively. Three-fourths of patients had a mass present on ultrasonography. Their average age was 60 years.

Secondary outcomes between groups were very similar, except for a significantly shorter operative time of 19 minutes with seed localization vs. 22 minutes in the wire group (P less than .001), Dr. Lovrics said. Excision difficulty was also ranked significantly easier for surgeons with seed localization (P = .008).

Factors such as skin removal and whether the dissection was taken to the chest wall were similar, as were the number of additional cavity margins excised and postoperative complications at 1 month, he said during a breast-focused plenary session.

Pain-reported anxiety during localization was similar in both groups, although patients in the seed group reported significantly less pain during the localization procedure than did those in the wire group (P = 0.38). An analysis of cosmetic results is ongoing.

Dr. Lovrics said that RSL allows exquisite and precise localization of the tumor, and that radiation exposure to patients and health care workers is negligible.

"For the surgeon, it provides very real-time, enhanced guidance for localization and is preferred by surgeons," he concluded. "Radio-seed localization is an acceptable alternative to wire-guided localization."

During a discussion of the study, audience members asked whether a cost analysis had been performed and whether the seeds were placed on the day of the surgery. Dr. Lovrics said the seeds and the wire both cost about $50, and that they currently place the seed on the day of surgery, but they hope to insert it earlier to further reduce OR time.

When asked whether a radiograph is still needed after seed localization, Dr. Lovrics said that a postoperative radiograph is still essential because of the risk of seed migration. Seeds were misplaced in four cases, one seed migrated, one wire migrated, and one wire fell out.

The Canadian Breast Cancer Foundation funded the study. Dr. Lovrics and his coauthors reported no conflicts of interest.

SAN ANTONIO – Positive margin and reoperation rates were similar for radio-guided seed localization and wire-guided localization of nonpalpable breast tumors in a prospective multicenter trial – in contrast to results from previous studies.

In an intent-to-treat analysis of 305 women with confirmed invasive or ductal carcinoma in situ who were undergoing localization and breast-conserving surgery, positive margin rates were 10.5% for radio-guided seed localization (RSL) and 11.9% for wire-guided localization (P = .990).

Rates of positive plus close margins (defined as disease within less than 1 mm) were 19% for the seed group and 22% for the wire group (P = .609), Dr. Peter Lovrics reported at a symposium sponsored by the Society of Surgical Oncology.

Rates of reoperation – either re-excision of margins or mastectomy – were also similar (19% and 15%, respectively) in the wire and seed groups, said Dr. Lovrics of the department of surgery at McMaster University in Hamilton, Ont.

The feasibility of RSL for identifying occult breast tumors was first reported a little more than a decade ago, and RSL has been rapidly adopted in many European countries. The procedure involves intratumoral injection of a radiotracer to identify the primary tumor and sentinel lymph nodes for intraoperative gamma probe–guided dissection.

In a recent literature review of 12 studies, Dr. Lovrics and his associates found that RSL yields lower positive margins (odds ratio, 0.367) and fewer reoperations (OR, 0.347) than does wire-guided localization, and three of those studies also suggested improved cosmesis (Eur. J. Surg. Oncol. 2011 Feb. 16 [E-pub ahead of print]).

When asked why RSL failed to produce significantly better outcomes, Dr. Lovrics said it may be that with a larger sample size, RSL would be potentially better, yielding results similar to those of other studies. Notably, overall positive margin rates were low for both groups and were much higher for wire-guided localization in most other studies.

"This may be partially attributed to the fact that all patients had a preoperative core biopsy and a confirmed diagnosis of cancer, so all of the procedures were definitive operations," he said in an interview. "In some other studies, not all patients had confirmed cancer and some operations were diagnostic in intent. Otherwise, the study population was typical – similar to other studies in tumor characteristics."

In the current study, there were 152 patients in the seed group and 153 in the wire group, with 6 patients crossing over to the wire group because the seed did not arrive at the hospital on the day of surgery. Mammogram findings included a mass in 47% of the wire group and in 50% of the seed group, and microcalcifications in 11% and 14%, respectively. Three-fourths of patients had a mass present on ultrasonography. Their average age was 60 years.

Secondary outcomes between groups were very similar, except for a significantly shorter operative time of 19 minutes with seed localization vs. 22 minutes in the wire group (P less than .001), Dr. Lovrics said. Excision difficulty was also ranked significantly easier for surgeons with seed localization (P = .008).

Factors such as skin removal and whether the dissection was taken to the chest wall were similar, as were the number of additional cavity margins excised and postoperative complications at 1 month, he said during a breast-focused plenary session.

Pain-reported anxiety during localization was similar in both groups, although patients in the seed group reported significantly less pain during the localization procedure than did those in the wire group (P = 0.38). An analysis of cosmetic results is ongoing.

Dr. Lovrics said that RSL allows exquisite and precise localization of the tumor, and that radiation exposure to patients and health care workers is negligible.

"For the surgeon, it provides very real-time, enhanced guidance for localization and is preferred by surgeons," he concluded. "Radio-seed localization is an acceptable alternative to wire-guided localization."

During a discussion of the study, audience members asked whether a cost analysis had been performed and whether the seeds were placed on the day of the surgery. Dr. Lovrics said the seeds and the wire both cost about $50, and that they currently place the seed on the day of surgery, but they hope to insert it earlier to further reduce OR time.

When asked whether a radiograph is still needed after seed localization, Dr. Lovrics said that a postoperative radiograph is still essential because of the risk of seed migration. Seeds were misplaced in four cases, one seed migrated, one wire migrated, and one wire fell out.

The Canadian Breast Cancer Foundation funded the study. Dr. Lovrics and his coauthors reported no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

One year of adjuvant trastuzumab following standard chemotherapy is associated with significantly improved long-term, disease-free survival in women with early-stage HER2-positive breast cancer, according to updated findings from the ongoing international, randomized phase III Herceptin Adjuvant trial.

Disease-free survival at a median follow-up of 48.4 months was 78.6% in 1,703 women who were initially randomized to receive 1 year of treatment with trastuzumab (Herceptin) following chemotherapy, compared with 72.2% in 1,698 women randomized to observation following chemotherapy (hazard ratio, 0.76), Dr. Luca Gianni of the Istituto Nazioniale dei Tumori in Milan and colleagues from the HERA Trial Study Team reported online in the Feb. 25 issue of the Lancet Oncology.

Overall survival did not differ significantly between the treatment and observation groups (89.3% and 87.7%, respectively), but the investigators attributed this to the substantial crossover from the observation group to the treatment group after 1-year follow-up results from this study, which were published in 2005.

"This effect was not recorded at 2-year median follow-up, probably because of the short duration of follow-up after crossover at that time" (median, 2.6 moths vs. 29.1 months in this analysis)," they explained.

More than half (52%) of the observation group patients crossed over to receive trastuzumab after the 1-year analysis, beginning treatment at a median of 22.8 months after randomization. Those patients were found in the current study to have fewer disease-free survival events than did those who did not cross over (adjusted hazard ratio, 0.68), the investigators said (Lancet Oncol. 2011 Feb. 25 [doi:10.1016/S1470-2045(11)70033-x]).

Women in the HERA trial had early-stage HER-2-positive breast cancer, an aggressive form of breast cancer that represents about 15%-25% of breast cancers and confers an increased risk of recurrence and mortality. They were enrolled between December 2001 and June 2005, and were randomized to an observation group, a 1-year treatment group, or a 2-year treatment group. Treatment group patients received trastuzumab, a humanized monoclonal antibody that targets the extracellular domain of the HER2 receptor. Treatment was given as an intravenous infusion over 90 minutes every 3 weeks at an initial loading dose of 8 mg/kg and at a dose of 6 mg/kg thereafter.

Trastuzumab was generally well tolerated, although higher incidence of grades 3/4 and fatal adverse events occurred in the 1-year treatment group than in the observation group, they noted, adding that the most common of these – cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhea – each occurred in fewer than 1% of patients.

The interim analysis at 1 year showed that 12 months of treatment with trastuzumab was associated with a 46% reduction in disease recurrence. The 2-year follow-up data that were published in 2007 confirmed the disease-free survival benefit (HR, 0.64) and also demonstrated an overall survival benefit (HR, 0.66), the investigators noted.

"The HERA trial results confirm that treatment with adjuvant trastuzumab for 1 year is associated with persisting benefit in women with HER2-positive early breast cancer," the investigators said, concluding that trastuzumab given sequentially to chemotherapy "remains an appropriate treatment modality" in these patients.

They also noted that the possibility that women might derive further benefits from treatment for longer than 1 year is currently being explored in a comparison of the outcomes in the 1-year and 2-year treatment groups of the HERA trial.

F. Hoffmann-La Roche and the Michelangelo Foundation funded the study, which was conducted by the Breast International Group (BIG). Several authors, including Dr. Gianni, reported receiving funding from Roche, such as for advisory board membership, research support, speakers honoraria, consultancy, and travel. One author, Susanne Muehlbauer, is an employee of Roche and has stock options in the company. 

One year of adjuvant trastuzumab following standard chemotherapy is associated with significantly improved long-term, disease-free survival in women with early-stage HER2-positive breast cancer, according to updated findings from the ongoing international, randomized phase III Herceptin Adjuvant trial.

Disease-free survival at a median follow-up of 48.4 months was 78.6% in 1,703 women who were initially randomized to receive 1 year of treatment with trastuzumab (Herceptin) following chemotherapy, compared with 72.2% in 1,698 women randomized to observation following chemotherapy (hazard ratio, 0.76), Dr. Luca Gianni of the Istituto Nazioniale dei Tumori in Milan and colleagues from the HERA Trial Study Team reported online in the Feb. 25 issue of the Lancet Oncology.

Overall survival did not differ significantly between the treatment and observation groups (89.3% and 87.7%, respectively), but the investigators attributed this to the substantial crossover from the observation group to the treatment group after 1-year follow-up results from this study, which were published in 2005.

"This effect was not recorded at 2-year median follow-up, probably because of the short duration of follow-up after crossover at that time" (median, 2.6 moths vs. 29.1 months in this analysis)," they explained.

More than half (52%) of the observation group patients crossed over to receive trastuzumab after the 1-year analysis, beginning treatment at a median of 22.8 months after randomization. Those patients were found in the current study to have fewer disease-free survival events than did those who did not cross over (adjusted hazard ratio, 0.68), the investigators said (Lancet Oncol. 2011 Feb. 25 [doi:10.1016/S1470-2045(11)70033-x]).

Women in the HERA trial had early-stage HER-2-positive breast cancer, an aggressive form of breast cancer that represents about 15%-25% of breast cancers and confers an increased risk of recurrence and mortality. They were enrolled between December 2001 and June 2005, and were randomized to an observation group, a 1-year treatment group, or a 2-year treatment group. Treatment group patients received trastuzumab, a humanized monoclonal antibody that targets the extracellular domain of the HER2 receptor. Treatment was given as an intravenous infusion over 90 minutes every 3 weeks at an initial loading dose of 8 mg/kg and at a dose of 6 mg/kg thereafter.

Trastuzumab was generally well tolerated, although higher incidence of grades 3/4 and fatal adverse events occurred in the 1-year treatment group than in the observation group, they noted, adding that the most common of these – cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhea – each occurred in fewer than 1% of patients.

The interim analysis at 1 year showed that 12 months of treatment with trastuzumab was associated with a 46% reduction in disease recurrence. The 2-year follow-up data that were published in 2007 confirmed the disease-free survival benefit (HR, 0.64) and also demonstrated an overall survival benefit (HR, 0.66), the investigators noted.

"The HERA trial results confirm that treatment with adjuvant trastuzumab for 1 year is associated with persisting benefit in women with HER2-positive early breast cancer," the investigators said, concluding that trastuzumab given sequentially to chemotherapy "remains an appropriate treatment modality" in these patients.

They also noted that the possibility that women might derive further benefits from treatment for longer than 1 year is currently being explored in a comparison of the outcomes in the 1-year and 2-year treatment groups of the HERA trial.

F. Hoffmann-La Roche and the Michelangelo Foundation funded the study, which was conducted by the Breast International Group (BIG). Several authors, including Dr. Gianni, reported receiving funding from Roche, such as for advisory board membership, research support, speakers honoraria, consultancy, and travel. One author, Susanne Muehlbauer, is an employee of Roche and has stock options in the company. 

One year of adjuvant trastuzumab following standard chemotherapy is associated with significantly improved long-term, disease-free survival in women with early-stage HER2-positive breast cancer, according to updated findings from the ongoing international, randomized phase III Herceptin Adjuvant trial.

Disease-free survival at a median follow-up of 48.4 months was 78.6% in 1,703 women who were initially randomized to receive 1 year of treatment with trastuzumab (Herceptin) following chemotherapy, compared with 72.2% in 1,698 women randomized to observation following chemotherapy (hazard ratio, 0.76), Dr. Luca Gianni of the Istituto Nazioniale dei Tumori in Milan and colleagues from the HERA Trial Study Team reported online in the Feb. 25 issue of the Lancet Oncology.

Overall survival did not differ significantly between the treatment and observation groups (89.3% and 87.7%, respectively), but the investigators attributed this to the substantial crossover from the observation group to the treatment group after 1-year follow-up results from this study, which were published in 2005.

"This effect was not recorded at 2-year median follow-up, probably because of the short duration of follow-up after crossover at that time" (median, 2.6 moths vs. 29.1 months in this analysis)," they explained.

More than half (52%) of the observation group patients crossed over to receive trastuzumab after the 1-year analysis, beginning treatment at a median of 22.8 months after randomization. Those patients were found in the current study to have fewer disease-free survival events than did those who did not cross over (adjusted hazard ratio, 0.68), the investigators said (Lancet Oncol. 2011 Feb. 25 [doi:10.1016/S1470-2045(11)70033-x]).

Women in the HERA trial had early-stage HER-2-positive breast cancer, an aggressive form of breast cancer that represents about 15%-25% of breast cancers and confers an increased risk of recurrence and mortality. They were enrolled between December 2001 and June 2005, and were randomized to an observation group, a 1-year treatment group, or a 2-year treatment group. Treatment group patients received trastuzumab, a humanized monoclonal antibody that targets the extracellular domain of the HER2 receptor. Treatment was given as an intravenous infusion over 90 minutes every 3 weeks at an initial loading dose of 8 mg/kg and at a dose of 6 mg/kg thereafter.

Trastuzumab was generally well tolerated, although higher incidence of grades 3/4 and fatal adverse events occurred in the 1-year treatment group than in the observation group, they noted, adding that the most common of these – cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhea – each occurred in fewer than 1% of patients.

The interim analysis at 1 year showed that 12 months of treatment with trastuzumab was associated with a 46% reduction in disease recurrence. The 2-year follow-up data that were published in 2007 confirmed the disease-free survival benefit (HR, 0.64) and also demonstrated an overall survival benefit (HR, 0.66), the investigators noted.

"The HERA trial results confirm that treatment with adjuvant trastuzumab for 1 year is associated with persisting benefit in women with HER2-positive early breast cancer," the investigators said, concluding that trastuzumab given sequentially to chemotherapy "remains an appropriate treatment modality" in these patients.

They also noted that the possibility that women might derive further benefits from treatment for longer than 1 year is currently being explored in a comparison of the outcomes in the 1-year and 2-year treatment groups of the HERA trial.

F. Hoffmann-La Roche and the Michelangelo Foundation funded the study, which was conducted by the Breast International Group (BIG). Several authors, including Dr. Gianni, reported receiving funding from Roche, such as for advisory board membership, research support, speakers honoraria, consultancy, and travel. One author, Susanne Muehlbauer, is an employee of Roche and has stock options in the company. 

The Food and Drug Administration has granted Genentech a 2-day hearing on the agency’s plan to strip bevacizumab of accelerated approval for the treatment of metastatic breast cancer, the company announced on Feb. 24.

Genentech, a member of the Roche group, has appealed the proposed withdrawal of the indication for bevacizumab (Avastin) in combination with paclitaxel (Taxol) as a first-line treatment of HER2-negative metastatic breast cancer. The decision was based on the failure of a follow-up study to confirm a progression-free survival benefit for the regimen. It followed a near-unanimous recommendation favoring withdrawal by the FDA’s Oncologic Drugs Advisory Committee, which expressed concern about risks associated with treatment.

In 2008, bevacizumab received the accelerated approval for the metastatic breast cancer indication; conversion to full approval was contingent on the confirmation of benefit in follow-up studies. It is approved for other indications, so the drug itself is not being taken off the market.

The hearing is scheduled for June 28-29, 2011. "We appreciate the opportunity to continue our discussion with the FDA during a public hearing about the use of Avastin in metastatic breast cancer," Dr. Hal Barron, chief medical office and head of Global Product Development at Genentech said in the company statement.

The Food and Drug Administration has granted Genentech a 2-day hearing on the agency’s plan to strip bevacizumab of accelerated approval for the treatment of metastatic breast cancer, the company announced on Feb. 24.

Genentech, a member of the Roche group, has appealed the proposed withdrawal of the indication for bevacizumab (Avastin) in combination with paclitaxel (Taxol) as a first-line treatment of HER2-negative metastatic breast cancer. The decision was based on the failure of a follow-up study to confirm a progression-free survival benefit for the regimen. It followed a near-unanimous recommendation favoring withdrawal by the FDA’s Oncologic Drugs Advisory Committee, which expressed concern about risks associated with treatment.

In 2008, bevacizumab received the accelerated approval for the metastatic breast cancer indication; conversion to full approval was contingent on the confirmation of benefit in follow-up studies. It is approved for other indications, so the drug itself is not being taken off the market.

The hearing is scheduled for June 28-29, 2011. "We appreciate the opportunity to continue our discussion with the FDA during a public hearing about the use of Avastin in metastatic breast cancer," Dr. Hal Barron, chief medical office and head of Global Product Development at Genentech said in the company statement.

The Food and Drug Administration has granted Genentech a 2-day hearing on the agency’s plan to strip bevacizumab of accelerated approval for the treatment of metastatic breast cancer, the company announced on Feb. 24.

Genentech, a member of the Roche group, has appealed the proposed withdrawal of the indication for bevacizumab (Avastin) in combination with paclitaxel (Taxol) as a first-line treatment of HER2-negative metastatic breast cancer. The decision was based on the failure of a follow-up study to confirm a progression-free survival benefit for the regimen. It followed a near-unanimous recommendation favoring withdrawal by the FDA’s Oncologic Drugs Advisory Committee, which expressed concern about risks associated with treatment.

In 2008, bevacizumab received the accelerated approval for the metastatic breast cancer indication; conversion to full approval was contingent on the confirmation of benefit in follow-up studies. It is approved for other indications, so the drug itself is not being taken off the market.

The hearing is scheduled for June 28-29, 2011. "We appreciate the opportunity to continue our discussion with the FDA during a public hearing about the use of Avastin in metastatic breast cancer," Dr. Hal Barron, chief medical office and head of Global Product Development at Genentech said in the company statement.

Yevgeniy Balagula^a, Jennifer R. Hensley^b, Pedram Gerami^c and Mario E. Lacouture^a

 

References¹

1 J.L. Harper, L.E. Franklin, J.M. Jenrette and E.G. Aguero, Skin toxicity during breast irradiation: pathophysiology and management, South Med J 97 (10) (2004), pp. 989–993. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (35)

2 A. Trotti, L.A. Bellm, J.B. Epstein, D. Frame, H.J. Fuchs and C.K. Gwede et al., Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review, Radiother Oncol 66 (3) (2003), pp. 253–262. Article |

PDF (255 K)

| View Record in Scopus | Cited By in Scopus (183)

3 E.A. Elliott, J.R. Wright, R.S. Swann, F. Nguyen-Tan, C. Takita and M.K. Bucci et al., Phase III trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Trial 99-13, J Clin Oncol 24 (13) (2006), pp. 2092–2097. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (13)

4 S.R. Hymes, E.A. Strom and C. Fife, Radiation dermatitis: clinical presentation, pathophysiology, and treatment 2006, J Am Acad Dermatol 54 (1) (2006), pp. 28–46. Article |

PDF (661 K)

| View Record in Scopus | Cited By in Scopus (56)

5 S.M. Bluefarb, Comedos following roentgen ray therapy, Arch Dermatol Syph 56 (1947), pp. 537–539.

6 F. Ronchese, Cicatricial comedos and milia, Arch Dermatol Syph 61 (1950), pp. 498–500. View Record in Scopus | Cited By in Scopus (8)

7 B. Adriaans and A. du Vivier, Acne in an irradiated area, Arch Dermatol 125 (7) (1989), p. 1005. View Record in Scopus | Cited By in Scopus (3)

8 J.F. Walter, Cobalt radiation–induced comedones, Arch Dermatol 116 (9) (1980), pp. 1073–1074. View Record in Scopus | Cited By in Scopus (5)

9 F.S. Larsen, G. Heydenreich and J.V. Christiansen, Comedo formation following cobalt irradiation, Dermatologica 158 (4) (1979), pp. 287–292.

10 E.P. Engels, U. Leavell and Y. Maruyama, Radiogenic acne and comedones, Radiol Clin Biol 43 (1) (1974), pp. 48–55. View Record in Scopus | Cited By in Scopus (6)

11 K.M. Stein, J.J. Leyden and H. Goldschmidt, Localized acneiform eruption following cobalt irradiation, Br J Dermatol 87 (3) (1972), pp. 274–279. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (9)

12 N.C. Hepburn, R.P. Crellin, G.W. Beveridge, A. Rodger and M.J. Tidman, Localized acne as a complication of megavoltage radiotherapy, J Dermatol Treat 3 (1992), pp. 137–138. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (7)

13 P.L. Myskowski and B. Safai, Localized comedo formation after cobalt irradiation, Int J Dermatol 20 (8) (1981), pp. 550–551. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (4)

14 A.J. Aversa and R. Nagy, Localized comedones following radiation therapy, Cutis 31 (3) (1983), pp. 296–303.

15 J. Song, S.J. Ha, C.W. Kim and H.O. Kim, A case of localized acne following radiation therapy, Acta Derm Venereol 82 (1) (2002), pp. 69–70. Full Text via CrossRef

16 S. Swift, Localized acne following deep X-ray therapy, AMA Arch Dermatol 74 (1) (1956), pp. 97–98.

17 W.M. Martin and A.F. Bardsley, The comedo skin reaction to radiotherapy, Br J Radiol 75 (893) (2002), pp. 478–481. View Record in Scopus | Cited By in Scopus (7)

18 W.J. Cunliffe, D.B. Holland, S.M. Clark and G.I. Stables, Comedogenesis: some new aetiological, clinical and therapeutic strategies, Br J Dermatol 142 (6) (2000), pp. 1084–1091. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (76)

19 D. Thiboutot, H. Knaggs, K. Gilliland and G. Lin, Activity of 5-alpha-reductase and 17-beta-hydroxysteroid dehydrogenase in the infrainfundibulum of subjects with and without acne vulgaris, Dermatology 196 (1) (1998), pp. 38–42. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (38)

20 C.C. Zouboulis, L. Xia and H. Akamatsu et al., The human sebocyte culture model provides new insights into development and management of seborrhoea and acne, Dermatology 196 (1) (1998), pp. 21–31. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (96)

21 H. Gollnick, Current concepts of the pathogenesis of acne: implications for drug treatment, Drugs 63 (15) (2003), pp. 1579–1596. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (83)

22 R. Guy, M.R. Green and T. Kealey, Modeling acne in vitro, J Invest Dermatol 106 (1) (1996), pp. 176–182. View Record in Scopus | Cited By in Scopus (82)

23 R. Guy and T. Kealey, The effects of inflammatory cytokines on the isolated human sebaceous infundibulum, J Invest Dermatol 110 (4) (1998), pp. 410–415. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (27)

24 E. Ingham, E.A. Eady, C.E. Goodwin, J.H. Cove and W.J. Cunliffe, Pro-inflammatory levels of interleukin-1 alpha-like bioactivity are present in the majority of open comedones in acne vulgaris, J Invest Dermatol 98 (6) (1992), pp. 895–901. View Record in Scopus | Cited By in Scopus (63)

25 G.F. Webster and J.J. Leyden, Characterization of serum-independent polymorphonuclear leukocyte chemotactic factors produced by Propionibacterium acnes, Inflammation 4 (3) (1980), pp. 261–269. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (34)

26 D.G. Scott, W.J. Cunliffe and G. Gowland, Activation of complement—a mechanism for the inflammation in acne, Br J Dermatol 101 (3) (1979), pp. 315–320. View Record in Scopus | Cited By in Scopus (11)

27 H.R. Ashbee, S.R. Muir, W.J. Cunliffe and E. Ingham, IgG subclasses specific to Staphylococcus epidermidis and Propionibacterium acnes in patients with acne vulgaris, Br J Dermatol 136 (5) (1997), pp. 730–733. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (31)

28 J.W. Denham and M. Hauer-Jensen, The radiotherapeutic injury—a complex ”wound.”, Radiother Oncol 63 (2) (2002), pp. 129–145. Article |

PDF (219 K)

| View Record in Scopus | Cited By in Scopus (149)

29 M.E. Lacouture, C. Hwang, M.H. Marymont and J. Patel, Temporal dependence of the effect of radiation on erlotinib-induced skin rash, J Clin Oncol 25 (15) (2007), p. 2140 author reply 2141. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (15)

30 T.N. Trunnell, R.L. Baer and P. Michaelides, Acneform changes in areas of cobalt irradiation, Arch Dermatol 106 (1) (1972), pp. 73–75. View Record in Scopus | Cited By in Scopus (8)

31 O.H. Mills Jr, A.M. Kligman, P. Pochi and H. Comite, Comparing 2.5%, 5%, and 10% benzoyl peroxide on inflammatory acne vulgaris, Int J Dermatol 25 (10) (1986), pp. 664–667. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (39)

32 M. Sagransky, B.A. Yentzer and S.R. Feldman, Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris, Expert Opin Pharmacother 10 (15) (2009), pp. 2555–2562. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (7)

33 A. Thielitz, M.B. Abdel-Naser, J.W. Fluhr, C.C. Zouboulis and H. Gollnick, Topical retinoids in acne—an evidence-based overview, J Dtsch Dermatol Ges 6 (12) (2008), pp. 1023–1031. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (9)

34 F. Ochsendorf, Minocycline in acne vulgaris: benefits and risks, Am J Clin Dermatol 11 (5) (2010), pp. 327–341. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (2)

Yevgeniy Balagula^a, Jennifer R. Hensley^b, Pedram Gerami^c and Mario E. Lacouture^a

 

References¹

1 J.L. Harper, L.E. Franklin, J.M. Jenrette and E.G. Aguero, Skin toxicity during breast irradiation: pathophysiology and management, South Med J 97 (10) (2004), pp. 989–993. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (35)

2 A. Trotti, L.A. Bellm, J.B. Epstein, D. Frame, H.J. Fuchs and C.K. Gwede et al., Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review, Radiother Oncol 66 (3) (2003), pp. 253–262. Article |

PDF (255 K)

| View Record in Scopus | Cited By in Scopus (183)

3 E.A. Elliott, J.R. Wright, R.S. Swann, F. Nguyen-Tan, C. Takita and M.K. Bucci et al., Phase III trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Trial 99-13, J Clin Oncol 24 (13) (2006), pp. 2092–2097. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (13)

4 S.R. Hymes, E.A. Strom and C. Fife, Radiation dermatitis: clinical presentation, pathophysiology, and treatment 2006, J Am Acad Dermatol 54 (1) (2006), pp. 28–46. Article |

PDF (661 K)

| View Record in Scopus | Cited By in Scopus (56)

5 S.M. Bluefarb, Comedos following roentgen ray therapy, Arch Dermatol Syph 56 (1947), pp. 537–539.

6 F. Ronchese, Cicatricial comedos and milia, Arch Dermatol Syph 61 (1950), pp. 498–500. View Record in Scopus | Cited By in Scopus (8)

7 B. Adriaans and A. du Vivier, Acne in an irradiated area, Arch Dermatol 125 (7) (1989), p. 1005. View Record in Scopus | Cited By in Scopus (3)

8 J.F. Walter, Cobalt radiation–induced comedones, Arch Dermatol 116 (9) (1980), pp. 1073–1074. View Record in Scopus | Cited By in Scopus (5)

9 F.S. Larsen, G. Heydenreich and J.V. Christiansen, Comedo formation following cobalt irradiation, Dermatologica 158 (4) (1979), pp. 287–292.

10 E.P. Engels, U. Leavell and Y. Maruyama, Radiogenic acne and comedones, Radiol Clin Biol 43 (1) (1974), pp. 48–55. View Record in Scopus | Cited By in Scopus (6)

11 K.M. Stein, J.J. Leyden and H. Goldschmidt, Localized acneiform eruption following cobalt irradiation, Br J Dermatol 87 (3) (1972), pp. 274–279. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (9)

12 N.C. Hepburn, R.P. Crellin, G.W. Beveridge, A. Rodger and M.J. Tidman, Localized acne as a complication of megavoltage radiotherapy, J Dermatol Treat 3 (1992), pp. 137–138. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (7)

13 P.L. Myskowski and B. Safai, Localized comedo formation after cobalt irradiation, Int J Dermatol 20 (8) (1981), pp. 550–551. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (4)

14 A.J. Aversa and R. Nagy, Localized comedones following radiation therapy, Cutis 31 (3) (1983), pp. 296–303.

15 J. Song, S.J. Ha, C.W. Kim and H.O. Kim, A case of localized acne following radiation therapy, Acta Derm Venereol 82 (1) (2002), pp. 69–70. Full Text via CrossRef

16 S. Swift, Localized acne following deep X-ray therapy, AMA Arch Dermatol 74 (1) (1956), pp. 97–98.

17 W.M. Martin and A.F. Bardsley, The comedo skin reaction to radiotherapy, Br J Radiol 75 (893) (2002), pp. 478–481. View Record in Scopus | Cited By in Scopus (7)

18 W.J. Cunliffe, D.B. Holland, S.M. Clark and G.I. Stables, Comedogenesis: some new aetiological, clinical and therapeutic strategies, Br J Dermatol 142 (6) (2000), pp. 1084–1091. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (76)

19 D. Thiboutot, H. Knaggs, K. Gilliland and G. Lin, Activity of 5-alpha-reductase and 17-beta-hydroxysteroid dehydrogenase in the infrainfundibulum of subjects with and without acne vulgaris, Dermatology 196 (1) (1998), pp. 38–42. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (38)

20 C.C. Zouboulis, L. Xia and H. Akamatsu et al., The human sebocyte culture model provides new insights into development and management of seborrhoea and acne, Dermatology 196 (1) (1998), pp. 21–31. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (96)

21 H. Gollnick, Current concepts of the pathogenesis of acne: implications for drug treatment, Drugs 63 (15) (2003), pp. 1579–1596. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (83)

22 R. Guy, M.R. Green and T. Kealey, Modeling acne in vitro, J Invest Dermatol 106 (1) (1996), pp. 176–182. View Record in Scopus | Cited By in Scopus (82)

23 R. Guy and T. Kealey, The effects of inflammatory cytokines on the isolated human sebaceous infundibulum, J Invest Dermatol 110 (4) (1998), pp. 410–415. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (27)

24 E. Ingham, E.A. Eady, C.E. Goodwin, J.H. Cove and W.J. Cunliffe, Pro-inflammatory levels of interleukin-1 alpha-like bioactivity are present in the majority of open comedones in acne vulgaris, J Invest Dermatol 98 (6) (1992), pp. 895–901. View Record in Scopus | Cited By in Scopus (63)

25 G.F. Webster and J.J. Leyden, Characterization of serum-independent polymorphonuclear leukocyte chemotactic factors produced by Propionibacterium acnes, Inflammation 4 (3) (1980), pp. 261–269. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (34)

26 D.G. Scott, W.J. Cunliffe and G. Gowland, Activation of complement—a mechanism for the inflammation in acne, Br J Dermatol 101 (3) (1979), pp. 315–320. View Record in Scopus | Cited By in Scopus (11)

27 H.R. Ashbee, S.R. Muir, W.J. Cunliffe and E. Ingham, IgG subclasses specific to Staphylococcus epidermidis and Propionibacterium acnes in patients with acne vulgaris, Br J Dermatol 136 (5) (1997), pp. 730–733. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (31)

28 J.W. Denham and M. Hauer-Jensen, The radiotherapeutic injury—a complex ”wound.”, Radiother Oncol 63 (2) (2002), pp. 129–145. Article |

PDF (219 K)

| View Record in Scopus | Cited By in Scopus (149)

29 M.E. Lacouture, C. Hwang, M.H. Marymont and J. Patel, Temporal dependence of the effect of radiation on erlotinib-induced skin rash, J Clin Oncol 25 (15) (2007), p. 2140 author reply 2141. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (15)

30 T.N. Trunnell, R.L. Baer and P. Michaelides, Acneform changes in areas of cobalt irradiation, Arch Dermatol 106 (1) (1972), pp. 73–75. View Record in Scopus | Cited By in Scopus (8)

31 O.H. Mills Jr, A.M. Kligman, P. Pochi and H. Comite, Comparing 2.5%, 5%, and 10% benzoyl peroxide on inflammatory acne vulgaris, Int J Dermatol 25 (10) (1986), pp. 664–667. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (39)

32 M. Sagransky, B.A. Yentzer and S.R. Feldman, Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris, Expert Opin Pharmacother 10 (15) (2009), pp. 2555–2562. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (7)

33 A. Thielitz, M.B. Abdel-Naser, J.W. Fluhr, C.C. Zouboulis and H. Gollnick, Topical retinoids in acne—an evidence-based overview, J Dtsch Dermatol Ges 6 (12) (2008), pp. 1023–1031. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (9)

34 F. Ochsendorf, Minocycline in acne vulgaris: benefits and risks, Am J Clin Dermatol 11 (5) (2010), pp. 327–341. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (2)

Yevgeniy Balagula^a, Jennifer R. Hensley^b, Pedram Gerami^c and Mario E. Lacouture^a

 

References¹

1 J.L. Harper, L.E. Franklin, J.M. Jenrette and E.G. Aguero, Skin toxicity during breast irradiation: pathophysiology and management, South Med J 97 (10) (2004), pp. 989–993. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (35)

2 A. Trotti, L.A. Bellm, J.B. Epstein, D. Frame, H.J. Fuchs and C.K. Gwede et al., Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review, Radiother Oncol 66 (3) (2003), pp. 253–262. Article |

PDF (255 K)

| View Record in Scopus | Cited By in Scopus (183)

3 E.A. Elliott, J.R. Wright, R.S. Swann, F. Nguyen-Tan, C. Takita and M.K. Bucci et al., Phase III trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Trial 99-13, J Clin Oncol 24 (13) (2006), pp. 2092–2097. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (13)

4 S.R. Hymes, E.A. Strom and C. Fife, Radiation dermatitis: clinical presentation, pathophysiology, and treatment 2006, J Am Acad Dermatol 54 (1) (2006), pp. 28–46. Article |

PDF (661 K)

| View Record in Scopus | Cited By in Scopus (56)

5 S.M. Bluefarb, Comedos following roentgen ray therapy, Arch Dermatol Syph 56 (1947), pp. 537–539.

6 F. Ronchese, Cicatricial comedos and milia, Arch Dermatol Syph 61 (1950), pp. 498–500. View Record in Scopus | Cited By in Scopus (8)

7 B. Adriaans and A. du Vivier, Acne in an irradiated area, Arch Dermatol 125 (7) (1989), p. 1005. View Record in Scopus | Cited By in Scopus (3)

8 J.F. Walter, Cobalt radiation–induced comedones, Arch Dermatol 116 (9) (1980), pp. 1073–1074. View Record in Scopus | Cited By in Scopus (5)

9 F.S. Larsen, G. Heydenreich and J.V. Christiansen, Comedo formation following cobalt irradiation, Dermatologica 158 (4) (1979), pp. 287–292.

10 E.P. Engels, U. Leavell and Y. Maruyama, Radiogenic acne and comedones, Radiol Clin Biol 43 (1) (1974), pp. 48–55. View Record in Scopus | Cited By in Scopus (6)

11 K.M. Stein, J.J. Leyden and H. Goldschmidt, Localized acneiform eruption following cobalt irradiation, Br J Dermatol 87 (3) (1972), pp. 274–279. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (9)

12 N.C. Hepburn, R.P. Crellin, G.W. Beveridge, A. Rodger and M.J. Tidman, Localized acne as a complication of megavoltage radiotherapy, J Dermatol Treat 3 (1992), pp. 137–138. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (7)

13 P.L. Myskowski and B. Safai, Localized comedo formation after cobalt irradiation, Int J Dermatol 20 (8) (1981), pp. 550–551. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (4)

14 A.J. Aversa and R. Nagy, Localized comedones following radiation therapy, Cutis 31 (3) (1983), pp. 296–303.

15 J. Song, S.J. Ha, C.W. Kim and H.O. Kim, A case of localized acne following radiation therapy, Acta Derm Venereol 82 (1) (2002), pp. 69–70. Full Text via CrossRef

16 S. Swift, Localized acne following deep X-ray therapy, AMA Arch Dermatol 74 (1) (1956), pp. 97–98.

17 W.M. Martin and A.F. Bardsley, The comedo skin reaction to radiotherapy, Br J Radiol 75 (893) (2002), pp. 478–481. View Record in Scopus | Cited By in Scopus (7)

18 W.J. Cunliffe, D.B. Holland, S.M. Clark and G.I. Stables, Comedogenesis: some new aetiological, clinical and therapeutic strategies, Br J Dermatol 142 (6) (2000), pp. 1084–1091. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (76)

19 D. Thiboutot, H. Knaggs, K. Gilliland and G. Lin, Activity of 5-alpha-reductase and 17-beta-hydroxysteroid dehydrogenase in the infrainfundibulum of subjects with and without acne vulgaris, Dermatology 196 (1) (1998), pp. 38–42. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (38)

20 C.C. Zouboulis, L. Xia and H. Akamatsu et al., The human sebocyte culture model provides new insights into development and management of seborrhoea and acne, Dermatology 196 (1) (1998), pp. 21–31. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (96)

21 H. Gollnick, Current concepts of the pathogenesis of acne: implications for drug treatment, Drugs 63 (15) (2003), pp. 1579–1596. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (83)

22 R. Guy, M.R. Green and T. Kealey, Modeling acne in vitro, J Invest Dermatol 106 (1) (1996), pp. 176–182. View Record in Scopus | Cited By in Scopus (82)

23 R. Guy and T. Kealey, The effects of inflammatory cytokines on the isolated human sebaceous infundibulum, J Invest Dermatol 110 (4) (1998), pp. 410–415. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (27)

24 E. Ingham, E.A. Eady, C.E. Goodwin, J.H. Cove and W.J. Cunliffe, Pro-inflammatory levels of interleukin-1 alpha-like bioactivity are present in the majority of open comedones in acne vulgaris, J Invest Dermatol 98 (6) (1992), pp. 895–901. View Record in Scopus | Cited By in Scopus (63)

25 G.F. Webster and J.J. Leyden, Characterization of serum-independent polymorphonuclear leukocyte chemotactic factors produced by Propionibacterium acnes, Inflammation 4 (3) (1980), pp. 261–269. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (34)

26 D.G. Scott, W.J. Cunliffe and G. Gowland, Activation of complement—a mechanism for the inflammation in acne, Br J Dermatol 101 (3) (1979), pp. 315–320. View Record in Scopus | Cited By in Scopus (11)

27 H.R. Ashbee, S.R. Muir, W.J. Cunliffe and E. Ingham, IgG subclasses specific to Staphylococcus epidermidis and Propionibacterium acnes in patients with acne vulgaris, Br J Dermatol 136 (5) (1997), pp. 730–733. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (31)

28 J.W. Denham and M. Hauer-Jensen, The radiotherapeutic injury—a complex ”wound.”, Radiother Oncol 63 (2) (2002), pp. 129–145. Article |

PDF (219 K)

| View Record in Scopus | Cited By in Scopus (149)

29 M.E. Lacouture, C. Hwang, M.H. Marymont and J. Patel, Temporal dependence of the effect of radiation on erlotinib-induced skin rash, J Clin Oncol 25 (15) (2007), p. 2140 author reply 2141. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (15)

30 T.N. Trunnell, R.L. Baer and P. Michaelides, Acneform changes in areas of cobalt irradiation, Arch Dermatol 106 (1) (1972), pp. 73–75. View Record in Scopus | Cited By in Scopus (8)

31 O.H. Mills Jr, A.M. Kligman, P. Pochi and H. Comite, Comparing 2.5%, 5%, and 10% benzoyl peroxide on inflammatory acne vulgaris, Int J Dermatol 25 (10) (1986), pp. 664–667. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (39)

32 M. Sagransky, B.A. Yentzer and S.R. Feldman, Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris, Expert Opin Pharmacother 10 (15) (2009), pp. 2555–2562. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (7)

33 A. Thielitz, M.B. Abdel-Naser, J.W. Fluhr, C.C. Zouboulis and H. Gollnick, Topical retinoids in acne—an evidence-based overview, J Dtsch Dermatol Ges 6 (12) (2008), pp. 1023–1031. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (9)

34 F. Ochsendorf, Minocycline in acne vulgaris: benefits and risks, Am J Clin Dermatol 11 (5) (2010), pp. 327–341. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (2)

Original research

Elenir B.C. Avritscher MD, PhD, MBA/MHA

^{, a,}

, Ya-Chen T. Shih PhD^a, Charlotte C. Sun DrPH^a, Richard J. Gralla MD^a, Steven M. Grunberg MD^a, Ying Xu MD, MS^a and Linda S. Elting DrPH^a

References¹

1 S.M. Grunberg, D. Osoba and P.J. Hesketh et al., Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity—an update, Support Care Cancer 13 (2005), pp. 80–84 [15599601]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (68)

2 C.M. Booth, M. Clemons and G. Dranitsaris et al., Chemotherapy-induced nausea and vomiting in breast cancer patients: a prospective observational study, J Support Oncol 5 (2007), pp. 374–380 [17944146]. View Record in Scopus | Cited By in Scopus (10)

3 M. de Boer-Dennert, R. de Wit and P.I. Schmitz et al., Patient perceptions of the side-effects of chemotherapy: the influence of 5HT3 antagonists, Br J Cancer 76 (1997), pp. 1055–1061 [9376266]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (128)

4 P. Eisenberg, J. Figueroa-Vadillo, R. Zamora et al. and 99-04 Palonosetron Study Group, Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron, Cancer 98 (2003), pp. 2473–2482 [14635083]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (171)

5 R. Gralla, M. Lichinitser and S. Van Der Vegt et al., Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron, Ann Oncol 14 (2003), pp. 1570–1577 [14504060]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (177)

6 M. Saito, K. Aogi and I. Sekine et al., Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial, Lancet Oncol 10 (2009), pp. 115–124 [19135415]. Article |

PDF (140 K)

| View Record in Scopus | Cited By in Scopus (43)

7 D.G. Warr, P.J. Hesketh and R.J. Gralla et al., Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy, J Clin Oncol 23 (2005), pp. 2822–2830 [15837996]. View Record in Scopus | Cited By in Scopus (139)

8 American Society of Clinical Oncology, M.G. Kris, P.J. Hesketh and M.R. Somerfield et al., American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006, J Clin Oncol 24 (2006), pp. 2932–2947 [16717289]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (311)

9 D.S. Ettinger, D.K. Armstrong and S. Barbour et al., National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology—Antiemesis, version 2.2010 http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf Accessed September 20, 2010.

10 R.W. Carlson and B. McCormick, Update: NCCN breast cancer clinical practice guidelines, J Natl Compr Cancer Netw 3 (suppl 1) (2005), pp. S7–S11 [16280118].

11 The Italian Group for Antiemetic Research, Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer, N Engl J Med 332 (1995), pp. 1–5 [7990859].

12 The Italian Group for Antiemetic Research, Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy, N Engl J Med 342 (2000), pp. 1554–1559 [10824073].

13 S.M. Grunberg, M. Dugan and H. Muss et al., Effectiveness of a single-day three-drug regimen of dexamethasone, palonosetron, and aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy, Support Care Cancer 17 (2009), pp. 589–594 [19037667]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (14)

14 J. Herrstedt, H.B. Muss and D.G. Warr et al., Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy, Cancer 104 (2005), pp. 1548–1555 [16104039]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (43)

15 Centers for Medicare and Medicaid Services, Medicare Part B Drug Average Sales Price: 2008 ASP Drug Pricing Files http://www.cms.hhs.gov/apps/ama/license.asp?file=/McrPartBDrugAvgSalesPrice/downloads/July2008ASPPricingFilebyHCPCS.zip Accessed July 18, 2008.

16 Thomson. Medstat, 1997–2002 MarketScan Health and Productivity Management Database User Guide and Data Dictionary, Thomson Medstat, Ann Arbor, MI (2003).

17 Centers for Medicare and Medicaid Services, National Physician Fee Schedule and Relative Value: 2008 Physician Fee Schedule National Payment Amount File http://www.cms.hhs.gov/PFSlookup/02_PFSSearch.asp Accessed July 18, 2008.

18 National Inpatient Sample (NIS), NIS description of data elements, Healthcare Cost and Utilization Project (HCUP) databases, Agency for Healthcare Research and Quality, Rockville, MD (2004) http://www.hcup-us.ahrq.gov/nisoverview.jsp#Data Accessed May 16, 2010.

19 S. Haislip, J. Gilmore, W.H. Lenz, T. Gondesen and B. Feinberg, Theory in practice: improving patient outcomes and practice efficiency with a simple change in 5-HT3 receptor antagonist for preventing chemotherapy-induced nausea and vomiting (CINV) In: Third Annual Meeting of the Hematology/Oncology Pharmacy Association; Abstract #PR6. June 14–16, 2007; Denver, Colorado http://www.hoparx.org/documents/2007programbook.pdf Accessed November 2, 2010.

20 C.C. Sun, D.C. Bodurka and C.B. Weaver et al., Rankings and symptom assessments of side effects from chemotherapy: insights from experienced patients with ovarian cancer, Support Care Cancer 13 (2005), pp. 219–227 [15538640]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (53)

21 M.F. Drummond, M.J. Sculpher, G.W. Torrance, B.J. O'Brien and G.L. Stoddart, Methods for the Economic Evaluation of Health Care Programmes (3rd ed.), Oxford University Press, New York (2005).

22 J. Hayman, J. Weeks and P. Mauch, Economic analyses in health care: an introduction to the methodology with an emphasis on radiation therapy, Int J Radiat Oncol Biol Phys 35 (1996), pp. 827–841 [8690653]. Article |

PDF (1827 K)

| View Record in Scopus | Cited By in Scopus (33)

23 B.E. Hillner, J.C. Weeks, C.E. Desch and T.J. Smith, Pamidronate in prevention of bone complications in metastatic breast cancer: a cost–effectiveness analysis, J Clin Oncol 18 (2000), pp. 72–79 [10623695]. View Record in Scopus | Cited By in Scopus (90)

24 S.D. Ramsey, Z. Liu and R. Boer et al., Cost–effectiveness of primary versus secondary prophylaxis with pegfilgrastim in women with early-stage breast cancer receiving chemotherapy, Value Health 11 (2008), pp. 172–179 [18673353].

25 B.E. Hillner, J.N. Ingle, R.T. Chlebowski et al. and American Society of Clinical Oncology, American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer, J Clin Oncol 21 (2003), pp. 4042–4057 [12963702]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (533)

26 T.J. Smith, J. Khatcheressian and G.H. Lyman et al., 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline, J Clin Oncol 24 (2006), pp. 3187–3205 [16682719]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (485)

27 National Cancer Institute, Surveillance Epidemiology and End Results: SEER Stat Fact Sheets: Breast http://seer.cancer.gov/statfacts/html/breast.html Accessed May 16, 2010.

28 J.W. Tumeh, S.G. Moore, R. Shapiro and C.R. Flowers, Practical approach for using Medicare data to estimate costs for cost–effectiveness analysis, Expert Rev Pharmacoecon Outcomes Res 5 (2005), pp. 153–162 [19807571]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (5)

29 P.A. Ubel, R.A. Hirth, M.E. Chernew and A.M. Fendrick, What is the price of life and why doesn't it increase at the rate of inflation?, Arch Intern Med 163 (2003), pp. 1637–1641 [12885677]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (225)

30 J.C. Hornberger, D.A. Redelmeier and J. Petersen, Variability among methods to assess patients' well-being and consequent effect on a cost–effectiveness analysis, J Clin Epidemiol 45 (1992), pp. 505–512 [1588356]. Article |

PDF (857 K)

| View Record in Scopus | Cited By in Scopus (138)

31 R.A. Hirth, M.E. Chernew, E. Miller, A.M. Fendrick and W.G. Weissert, Willingness to pay for a quality-adjusted life year: in search of a standard, Med Decis Making 20 (2000), pp. 332–342 [10929856]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (291)

32 Y.C. Shih and M.T. Halpern, Economic evaluations of medical care interventions for cancer patients: how, why, and what does it mean?, CA Cancer J Clin 58 (2008), pp. 231–244 [18596196]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (18)

33 E. Nadler, B. Eckert and P.J. Neumann, Do oncologists believe new cancer drugs offer good value?, Oncologist 11 (2006), pp. 90–95 [16476830]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (50)

34 R.S. Braithwaite, D.O. Meltzer, J.T. King Jr, D. Leslie and M.S. Roberts, What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule?, Med Care 46 (2008), pp. 349–356 [18362813]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (64)

35 National Institutes of Health Consensus Development Panel, 1997 Consensus Statement: Breast Cancer Screening for Women Ages 40–49 http://consensus.nih.gov/1997/1997BreastCancerScreening103html.htm Accessed October 13, 2007.

36 P. Salzmann, K. Kerlikowske and K. Phillips, Cost–effectiveness of extending screening mammography guidelines to include women 40 to 49 years of age, Ann Intern Med 127 (1997), pp. 955–965 [9412300]. View Record in Scopus | Cited By in Scopus (169)

37 Y.C. Shih, S. Han and S.B. Cantor, Impact of generic drug entry on cost–effectiveness analysis, Med Decis Making 25 (2005), pp. 71–80 [15673583]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (6)

38 F. Roila, P.J. Hesketh, J. Herrstedt and Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer, Prevention of chemotherapy- and radiotherapy-induced emesis: results of the 2004 Perugia International Antiemetic Consensus Conference, Ann Oncol 17 (2006), pp. 20–28 [16314401]. View Record in Scopus | Cited By in Scopus (90)

39 S.M. Grunberg and A. Ireland, Epidemiology of chemotherapy-induced nausea and vomiting, Adv Studies Nurs 3 (1) (2005), pp. 9–15 http://www.jhasin.com/files/articlefiles/pdf/XASIN_3_1_p9_15.pdf Accessed September 16, 2010.

40 T. Grote, J. Hajdenberg, A. Cartmell, S. Ferguson, A. Ginkel and V. Charu, Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant, J Support Oncol 4 (2006), pp. 403–408 [17004515]. View Record in Scopus | Cited By in Scopus (38)

41 S.M. Grunberg, M. Dugan, H.B. Muss, M. Wood, S. Burdette-Radoux and T. Weisberg, Efficacy of a 1-day 3-drug antiemetic regimen for prevention of acute and delayed nausea and vomiting induced by moderately emetogenic chemotherapy, J Clin Oncol 25 (18S) (2007), p. 9111.

42 U. S. Department of Labor. Bureau of Labor Statistics. Consumer Price Index http://www.bls.gov/cpi/home.htm Accessed May 16, 2010.

43 Department of Health and Human Services. Centers for Medicare & Medicaid Services, Medicare Program; Proposed Changes to the Hospital Inpatient Prospective Payment Systems and Fiscal Year 2008 Rates CMS-1533-P, pp 1070–1073 http://www.cms.hhs.gov/AcuteInpatientPPS/downloads/CMS-1533-P.pdf Accessed May 16, 2010.

This study was supported in part by a grant from MGI Pharma, Inc. MGI Pharma, Inc., had no role in the study design, data analysis, interpretation of results, content of the final article, or the decision to submit it for publication.

Conflicts of interest: Dr. Sun discloses that her husband was an employee of MGI Pharma, Inc., at the time this article was being written. Dr. Gralla discloses that he is a consultant for MGI Pharma, Inc., GlaxoSmithKline, Sanofi-aventis, and Merck; he also receives honoraria from MGI Pharma, Inc., and Merck and research support from Sanofi-aventis. Dr. Grunberg discloses that he is a consultant for MGI Pharma, Inc.

Correspondence to: Elenir B. C. Avritscher, MD, PhD, MBA/MHA, Section of Health Services Research, Department of Biostatistics and Applied Mathematics, The University of Texas M. D. Anderson Cancer Center, 1400 Pressler Street, Unit 1411, Houston, TX 77230; telephone: (713) 563-8920; fax: (713) 563-4243

Original research

Elenir B.C. Avritscher MD, PhD, MBA/MHA

^{, a,}

, Ya-Chen T. Shih PhD^a, Charlotte C. Sun DrPH^a, Richard J. Gralla MD^a, Steven M. Grunberg MD^a, Ying Xu MD, MS^a and Linda S. Elting DrPH^a

References¹

1 S.M. Grunberg, D. Osoba and P.J. Hesketh et al., Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity—an update, Support Care Cancer 13 (2005), pp. 80–84 [15599601]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (68)

2 C.M. Booth, M. Clemons and G. Dranitsaris et al., Chemotherapy-induced nausea and vomiting in breast cancer patients: a prospective observational study, J Support Oncol 5 (2007), pp. 374–380 [17944146]. View Record in Scopus | Cited By in Scopus (10)

3 M. de Boer-Dennert, R. de Wit and P.I. Schmitz et al., Patient perceptions of the side-effects of chemotherapy: the influence of 5HT3 antagonists, Br J Cancer 76 (1997), pp. 1055–1061 [9376266]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (128)

4 P. Eisenberg, J. Figueroa-Vadillo, R. Zamora et al. and 99-04 Palonosetron Study Group, Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron, Cancer 98 (2003), pp. 2473–2482 [14635083]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (171)

5 R. Gralla, M. Lichinitser and S. Van Der Vegt et al., Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron, Ann Oncol 14 (2003), pp. 1570–1577 [14504060]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (177)

6 M. Saito, K. Aogi and I. Sekine et al., Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial, Lancet Oncol 10 (2009), pp. 115–124 [19135415]. Article |

PDF (140 K)

| View Record in Scopus | Cited By in Scopus (43)

7 D.G. Warr, P.J. Hesketh and R.J. Gralla et al., Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy, J Clin Oncol 23 (2005), pp. 2822–2830 [15837996]. View Record in Scopus | Cited By in Scopus (139)

8 American Society of Clinical Oncology, M.G. Kris, P.J. Hesketh and M.R. Somerfield et al., American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006, J Clin Oncol 24 (2006), pp. 2932–2947 [16717289]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (311)

9 D.S. Ettinger, D.K. Armstrong and S. Barbour et al., National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology—Antiemesis, version 2.2010 http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf Accessed September 20, 2010.

10 R.W. Carlson and B. McCormick, Update: NCCN breast cancer clinical practice guidelines, J Natl Compr Cancer Netw 3 (suppl 1) (2005), pp. S7–S11 [16280118].

11 The Italian Group for Antiemetic Research, Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer, N Engl J Med 332 (1995), pp. 1–5 [7990859].

12 The Italian Group for Antiemetic Research, Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy, N Engl J Med 342 (2000), pp. 1554–1559 [10824073].

13 S.M. Grunberg, M. Dugan and H. Muss et al., Effectiveness of a single-day three-drug regimen of dexamethasone, palonosetron, and aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy, Support Care Cancer 17 (2009), pp. 589–594 [19037667]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (14)

14 J. Herrstedt, H.B. Muss and D.G. Warr et al., Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy, Cancer 104 (2005), pp. 1548–1555 [16104039]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (43)

15 Centers for Medicare and Medicaid Services, Medicare Part B Drug Average Sales Price: 2008 ASP Drug Pricing Files http://www.cms.hhs.gov/apps/ama/license.asp?file=/McrPartBDrugAvgSalesPrice/downloads/July2008ASPPricingFilebyHCPCS.zip Accessed July 18, 2008.

16 Thomson. Medstat, 1997–2002 MarketScan Health and Productivity Management Database User Guide and Data Dictionary, Thomson Medstat, Ann Arbor, MI (2003).

17 Centers for Medicare and Medicaid Services, National Physician Fee Schedule and Relative Value: 2008 Physician Fee Schedule National Payment Amount File http://www.cms.hhs.gov/PFSlookup/02_PFSSearch.asp Accessed July 18, 2008.

18 National Inpatient Sample (NIS), NIS description of data elements, Healthcare Cost and Utilization Project (HCUP) databases, Agency for Healthcare Research and Quality, Rockville, MD (2004) http://www.hcup-us.ahrq.gov/nisoverview.jsp#Data Accessed May 16, 2010.

19 S. Haislip, J. Gilmore, W.H. Lenz, T. Gondesen and B. Feinberg, Theory in practice: improving patient outcomes and practice efficiency with a simple change in 5-HT3 receptor antagonist for preventing chemotherapy-induced nausea and vomiting (CINV) In: Third Annual Meeting of the Hematology/Oncology Pharmacy Association; Abstract #PR6. June 14–16, 2007; Denver, Colorado http://www.hoparx.org/documents/2007programbook.pdf Accessed November 2, 2010.

20 C.C. Sun, D.C. Bodurka and C.B. Weaver et al., Rankings and symptom assessments of side effects from chemotherapy: insights from experienced patients with ovarian cancer, Support Care Cancer 13 (2005), pp. 219–227 [15538640]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (53)

21 M.F. Drummond, M.J. Sculpher, G.W. Torrance, B.J. O'Brien and G.L. Stoddart, Methods for the Economic Evaluation of Health Care Programmes (3rd ed.), Oxford University Press, New York (2005).

22 J. Hayman, J. Weeks and P. Mauch, Economic analyses in health care: an introduction to the methodology with an emphasis on radiation therapy, Int J Radiat Oncol Biol Phys 35 (1996), pp. 827–841 [8690653]. Article |

PDF (1827 K)

| View Record in Scopus | Cited By in Scopus (33)

23 B.E. Hillner, J.C. Weeks, C.E. Desch and T.J. Smith, Pamidronate in prevention of bone complications in metastatic breast cancer: a cost–effectiveness analysis, J Clin Oncol 18 (2000), pp. 72–79 [10623695]. View Record in Scopus | Cited By in Scopus (90)

24 S.D. Ramsey, Z. Liu and R. Boer et al., Cost–effectiveness of primary versus secondary prophylaxis with pegfilgrastim in women with early-stage breast cancer receiving chemotherapy, Value Health 11 (2008), pp. 172–179 [18673353].

25 B.E. Hillner, J.N. Ingle, R.T. Chlebowski et al. and American Society of Clinical Oncology, American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer, J Clin Oncol 21 (2003), pp. 4042–4057 [12963702]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (533)

26 T.J. Smith, J. Khatcheressian and G.H. Lyman et al., 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline, J Clin Oncol 24 (2006), pp. 3187–3205 [16682719]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (485)

27 National Cancer Institute, Surveillance Epidemiology and End Results: SEER Stat Fact Sheets: Breast http://seer.cancer.gov/statfacts/html/breast.html Accessed May 16, 2010.

28 J.W. Tumeh, S.G. Moore, R. Shapiro and C.R. Flowers, Practical approach for using Medicare data to estimate costs for cost–effectiveness analysis, Expert Rev Pharmacoecon Outcomes Res 5 (2005), pp. 153–162 [19807571]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (5)

29 P.A. Ubel, R.A. Hirth, M.E. Chernew and A.M. Fendrick, What is the price of life and why doesn't it increase at the rate of inflation?, Arch Intern Med 163 (2003), pp. 1637–1641 [12885677]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (225)

30 J.C. Hornberger, D.A. Redelmeier and J. Petersen, Variability among methods to assess patients' well-being and consequent effect on a cost–effectiveness analysis, J Clin Epidemiol 45 (1992), pp. 505–512 [1588356]. Article |

PDF (857 K)

| View Record in Scopus | Cited By in Scopus (138)

31 R.A. Hirth, M.E. Chernew, E. Miller, A.M. Fendrick and W.G. Weissert, Willingness to pay for a quality-adjusted life year: in search of a standard, Med Decis Making 20 (2000), pp. 332–342 [10929856]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (291)

32 Y.C. Shih and M.T. Halpern, Economic evaluations of medical care interventions for cancer patients: how, why, and what does it mean?, CA Cancer J Clin 58 (2008), pp. 231–244 [18596196]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (18)

33 E. Nadler, B. Eckert and P.J. Neumann, Do oncologists believe new cancer drugs offer good value?, Oncologist 11 (2006), pp. 90–95 [16476830]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (50)

34 R.S. Braithwaite, D.O. Meltzer, J.T. King Jr, D. Leslie and M.S. Roberts, What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule?, Med Care 46 (2008), pp. 349–356 [18362813]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (64)

35 National Institutes of Health Consensus Development Panel, 1997 Consensus Statement: Breast Cancer Screening for Women Ages 40–49 http://consensus.nih.gov/1997/1997BreastCancerScreening103html.htm Accessed October 13, 2007.

36 P. Salzmann, K. Kerlikowske and K. Phillips, Cost–effectiveness of extending screening mammography guidelines to include women 40 to 49 years of age, Ann Intern Med 127 (1997), pp. 955–965 [9412300]. View Record in Scopus | Cited By in Scopus (169)

37 Y.C. Shih, S. Han and S.B. Cantor, Impact of generic drug entry on cost–effectiveness analysis, Med Decis Making 25 (2005), pp. 71–80 [15673583]. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (6)

38 F. Roila, P.J. Hesketh, J. Herrstedt and Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer, Prevention of chemotherapy- and radiotherapy-induced emesis: results of the 2004 Perugia International Antiemetic Consensus Conference, Ann Oncol 17 (2006), pp. 20–28 [16314401]. View Record in Scopus | Cited By in Scopus (90)

39 S.M. Grunberg and A. Ireland, Epidemiology of chemotherapy-induced nausea and vomiting, Adv Studies Nurs 3 (1) (2005), pp. 9–15 http://www.jhasin.com/files/articlefiles/pdf/XASIN_3_1_p9_15.pdf Accessed September 16, 2010.

40 T. Grote, J. Hajdenberg, A. Cartmell, S. Ferguson, A. Ginkel and V. Charu, Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant, J Support Oncol 4 (2006), pp. 403–408 [17004515]. View Record in Scopus | Cited By in Scopus (38)

41 S.M. Grunberg, M. Dugan, H.B. Muss, M. Wood, S. Burdette-Radoux and T. Weisberg, Efficacy of a 1-day 3-drug antiemetic regimen for prevention of acute and delayed nausea and vomiting induced by moderately emetogenic chemotherapy, J Clin Oncol 25 (18S) (2007), p. 9111.

42 U. S. Department of Labor. Bureau of Labor Statistics. Consumer Price Index http://www.bls.gov/cpi/home.htm Accessed May 16, 2010.

43 Department of Health and Human Services. Centers for Medicare & Medicaid Services, Medicare Program; Proposed Changes to the Hospital Inpatient Prospective Payment Systems and Fiscal Year 2008 Rates CMS-1533-P, pp 1070–1073 http://www.cms.hhs.gov/AcuteInpatientPPS/downloads/CMS-1533-P.pdf Accessed May 16, 2010.