Susan London

Most women do not have an accurate understanding of their breast cancer risk—a finding that has important implications for prevention and early detection, as well as psychological well-being, according to a survey of nearly 10,000 women undergoing mammography screening.

When asked to estimate their lifetime personal breast cancer risk, just 9.4% of the women gave a value that was within 10% of their actual calculated risk, according to data reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology, where the study will be presented in full.

"Despite all the ongoing media attention, awareness campaigns, pink ribbons, breast cancer walks, and breast cancer month, most women lack accurate knowledge of their own breast cancer risk," maintained first author Dr. Jonathan D. Herman, an ob.gyn. at Hofstra University, New Hyde Park, N.Y. This tells us that "our education messaging is far off and we should change the way breast cancer awareness is presented."

"We began to think: What happens to women when they underestimate their risk of breast cancer? Well, they probably don’t get the necessary or most accurate treatment," he said. In particular, this group could benefit from a tailored plan of chemoprevention and early detection. On the other hand, "we think that women who overestimate their risk are worrying about getting breast cancer more than they really have to."

In the study, the investigators surveyed 9,873 women aged 35-70 years who were about to undergo screening at 21 Long Island mammography centers. The anonymous questionnaire included many questions adapted from the National Cancer Institute’s Breast Cancer Risk Assessment Tool, which is available online and typically used by physicians.

The women’s subjective estimate of risk was compared with their risk as calculated with the tool. Their estimate was considered inaccurate if it differed from their calculated risk by more than 10%.

Most of the women were at average calculated risk, with 35% having a 5%-10% lifetime risk and 40% having a 10%-15% lifetime risk.

Just 9.4% of the women, however, accurately estimated their risk, while 46% overestimated their risk and 45% underestimated their risk.

The predominant direction of estimation error varied by race/ethnicity. Of the white women, 10% accurately estimated their risk, 39% underestimated, and 51% overestimated their risk. Women of other ethnicities were more likely to underestimate their breast cancer risks. Just 9% of African American women were in line with their risk, with 58% underestimating and 34% overestimating. Asian women had similar assessments. Hispanic women’s inaccurate assessments were more balanced, with 50% underestimating and 41% overestimating risk. Although these differences were statistically significant, it is more important to note that the overall level of understanding was very low, Dr. Herman said.

Ideally, patients should learn of their breast cancer risk from their physician, he said, but the study data told another story. "All of these women were about to have mammography, so they obviously had some interest in their breast health," but when asked when they last spoke to their doctor about their personal breast cancer risk, "we were shocked to find that 40% of women said they never ever had a conversation with a health care provider," he reported.

The findings suggest a need to improve communication about risk by primary care providers, especially as the U.S. Preventive Services Task Force is now putting greater emphasis on informed decision making, Dr. Herman acknowledged.

But patients could be spurred to action as well, by moving beyond the pink ribbons and asking their physician, "What are my breast cancer numbers? I need to know that," he proposed.

Dr. Steven O’Day, director of clinical research at the Beverly Hills (Calif.) Cancer Institute and moderator of the press briefing, noted that the study has important implications for making use of guidelines for women at elevated risk. "To make decisions about chemoprevention, an accurate understanding of prognosis and risk both from the patient’s perspective and the physician’s is going to be essential to making good decisions in terms of surveillance and chemoprevention," he said.

A follow-up study planned by Dr. Herman will be important for informing efforts to improve risk communication, according to Dr. O’Day. "It’s a huge hurdle, yet how we are going to implement this [in primary care], as well as the tertiary-care oncology setting?" he commented. "If we don’t, the implications are huge; interventions by increased surveillance or chemoprevention are not trivial in terms of cost as well as potential side effects and morbidity. And these are difficult decisions even with accurate information. And without the information, you really can’t make any decision, in my mind."

Dr. Herman disclosed no relevant conflicts of interest. Dr. O’Day disclosed no relevant conflicts of interest.

Most women do not have an accurate understanding of their breast cancer risk—a finding that has important implications for prevention and early detection, as well as psychological well-being, according to a survey of nearly 10,000 women undergoing mammography screening.

When asked to estimate their lifetime personal breast cancer risk, just 9.4% of the women gave a value that was within 10% of their actual calculated risk, according to data reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology, where the study will be presented in full.

"Despite all the ongoing media attention, awareness campaigns, pink ribbons, breast cancer walks, and breast cancer month, most women lack accurate knowledge of their own breast cancer risk," maintained first author Dr. Jonathan D. Herman, an ob.gyn. at Hofstra University, New Hyde Park, N.Y. This tells us that "our education messaging is far off and we should change the way breast cancer awareness is presented."

"We began to think: What happens to women when they underestimate their risk of breast cancer? Well, they probably don’t get the necessary or most accurate treatment," he said. In particular, this group could benefit from a tailored plan of chemoprevention and early detection. On the other hand, "we think that women who overestimate their risk are worrying about getting breast cancer more than they really have to."

In the study, the investigators surveyed 9,873 women aged 35-70 years who were about to undergo screening at 21 Long Island mammography centers. The anonymous questionnaire included many questions adapted from the National Cancer Institute’s Breast Cancer Risk Assessment Tool, which is available online and typically used by physicians.

The women’s subjective estimate of risk was compared with their risk as calculated with the tool. Their estimate was considered inaccurate if it differed from their calculated risk by more than 10%.

Most of the women were at average calculated risk, with 35% having a 5%-10% lifetime risk and 40% having a 10%-15% lifetime risk.

Just 9.4% of the women, however, accurately estimated their risk, while 46% overestimated their risk and 45% underestimated their risk.

The predominant direction of estimation error varied by race/ethnicity. Of the white women, 10% accurately estimated their risk, 39% underestimated, and 51% overestimated their risk. Women of other ethnicities were more likely to underestimate their breast cancer risks. Just 9% of African American women were in line with their risk, with 58% underestimating and 34% overestimating. Asian women had similar assessments. Hispanic women’s inaccurate assessments were more balanced, with 50% underestimating and 41% overestimating risk. Although these differences were statistically significant, it is more important to note that the overall level of understanding was very low, Dr. Herman said.

Ideally, patients should learn of their breast cancer risk from their physician, he said, but the study data told another story. "All of these women were about to have mammography, so they obviously had some interest in their breast health," but when asked when they last spoke to their doctor about their personal breast cancer risk, "we were shocked to find that 40% of women said they never ever had a conversation with a health care provider," he reported.

The findings suggest a need to improve communication about risk by primary care providers, especially as the U.S. Preventive Services Task Force is now putting greater emphasis on informed decision making, Dr. Herman acknowledged.

But patients could be spurred to action as well, by moving beyond the pink ribbons and asking their physician, "What are my breast cancer numbers? I need to know that," he proposed.

Dr. Steven O’Day, director of clinical research at the Beverly Hills (Calif.) Cancer Institute and moderator of the press briefing, noted that the study has important implications for making use of guidelines for women at elevated risk. "To make decisions about chemoprevention, an accurate understanding of prognosis and risk both from the patient’s perspective and the physician’s is going to be essential to making good decisions in terms of surveillance and chemoprevention," he said.

A follow-up study planned by Dr. Herman will be important for informing efforts to improve risk communication, according to Dr. O’Day. "It’s a huge hurdle, yet how we are going to implement this [in primary care], as well as the tertiary-care oncology setting?" he commented. "If we don’t, the implications are huge; interventions by increased surveillance or chemoprevention are not trivial in terms of cost as well as potential side effects and morbidity. And these are difficult decisions even with accurate information. And without the information, you really can’t make any decision, in my mind."

Dr. Herman disclosed no relevant conflicts of interest. Dr. O’Day disclosed no relevant conflicts of interest.

Most women do not have an accurate understanding of their breast cancer risk—a finding that has important implications for prevention and early detection, as well as psychological well-being, according to a survey of nearly 10,000 women undergoing mammography screening.

When asked to estimate their lifetime personal breast cancer risk, just 9.4% of the women gave a value that was within 10% of their actual calculated risk, according to data reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology, where the study will be presented in full.

"Despite all the ongoing media attention, awareness campaigns, pink ribbons, breast cancer walks, and breast cancer month, most women lack accurate knowledge of their own breast cancer risk," maintained first author Dr. Jonathan D. Herman, an ob.gyn. at Hofstra University, New Hyde Park, N.Y. This tells us that "our education messaging is far off and we should change the way breast cancer awareness is presented."

"We began to think: What happens to women when they underestimate their risk of breast cancer? Well, they probably don’t get the necessary or most accurate treatment," he said. In particular, this group could benefit from a tailored plan of chemoprevention and early detection. On the other hand, "we think that women who overestimate their risk are worrying about getting breast cancer more than they really have to."

In the study, the investigators surveyed 9,873 women aged 35-70 years who were about to undergo screening at 21 Long Island mammography centers. The anonymous questionnaire included many questions adapted from the National Cancer Institute’s Breast Cancer Risk Assessment Tool, which is available online and typically used by physicians.

The women’s subjective estimate of risk was compared with their risk as calculated with the tool. Their estimate was considered inaccurate if it differed from their calculated risk by more than 10%.

Most of the women were at average calculated risk, with 35% having a 5%-10% lifetime risk and 40% having a 10%-15% lifetime risk.

Just 9.4% of the women, however, accurately estimated their risk, while 46% overestimated their risk and 45% underestimated their risk.

The predominant direction of estimation error varied by race/ethnicity. Of the white women, 10% accurately estimated their risk, 39% underestimated, and 51% overestimated their risk. Women of other ethnicities were more likely to underestimate their breast cancer risks. Just 9% of African American women were in line with their risk, with 58% underestimating and 34% overestimating. Asian women had similar assessments. Hispanic women’s inaccurate assessments were more balanced, with 50% underestimating and 41% overestimating risk. Although these differences were statistically significant, it is more important to note that the overall level of understanding was very low, Dr. Herman said.

Ideally, patients should learn of their breast cancer risk from their physician, he said, but the study data told another story. "All of these women were about to have mammography, so they obviously had some interest in their breast health," but when asked when they last spoke to their doctor about their personal breast cancer risk, "we were shocked to find that 40% of women said they never ever had a conversation with a health care provider," he reported.

The findings suggest a need to improve communication about risk by primary care providers, especially as the U.S. Preventive Services Task Force is now putting greater emphasis on informed decision making, Dr. Herman acknowledged.

But patients could be spurred to action as well, by moving beyond the pink ribbons and asking their physician, "What are my breast cancer numbers? I need to know that," he proposed.

Dr. Steven O’Day, director of clinical research at the Beverly Hills (Calif.) Cancer Institute and moderator of the press briefing, noted that the study has important implications for making use of guidelines for women at elevated risk. "To make decisions about chemoprevention, an accurate understanding of prognosis and risk both from the patient’s perspective and the physician’s is going to be essential to making good decisions in terms of surveillance and chemoprevention," he said.

A follow-up study planned by Dr. Herman will be important for informing efforts to improve risk communication, according to Dr. O’Day. "It’s a huge hurdle, yet how we are going to implement this [in primary care], as well as the tertiary-care oncology setting?" he commented. "If we don’t, the implications are huge; interventions by increased surveillance or chemoprevention are not trivial in terms of cost as well as potential side effects and morbidity. And these are difficult decisions even with accurate information. And without the information, you really can’t make any decision, in my mind."

Dr. Herman disclosed no relevant conflicts of interest. Dr. O’Day disclosed no relevant conflicts of interest.

Most women do not have an accurate understanding of their breast cancer risk – a finding that has important implications for prevention and early detection, as well as psychological well-being, according to a survey of nearly 10,000 women undergoing mammography screening.

When asked to estimate their lifetime personal breast cancer risk, just 9.4% of the women gave a value that was within 10% of their actual calculated risk, according to data reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology, where the study will be presented in full.

"Despite all the ongoing media attention, awareness campaigns, pink ribbons, breast cancer walks, and breast cancer month, most women lack accurate knowledge of their own breast cancer risk," maintained first author Dr. Jonathan D. Herman, an ob.gyn. at Hofstra University, New Hyde Park, N.Y. This tells us that "our education messaging is far off and we should change the way breast cancer awareness is presented."

"We began to think: What happens to women when they underestimate their risk of breast cancer? Well, they probably don’t get the necessary or most accurate treatment," he said. In particular, this group could benefit from a tailored plan of chemoprevention and early detection. On the other hand, "we think that women who overestimate their risk are worrying about getting breast cancer more than they really have to."

In the study, the investigators surveyed 9,873 women aged 35-70 years who were about to undergo screening at 21 Long Island mammography centers. The anonymous questionnaire included many questions adapted from the National Cancer Institute’s Breast Cancer Risk Assessment Tool, which is available online and typically used by physicians.

The women’s subjective estimate of risk was compared with their risk as calculated with the tool. Their estimate was considered inaccurate if it differed from their calculated risk by more than 10%.

Most of the women were at average calculated risk, with 35% having a 5%-10% lifetime risk and 40% having a 10%-15% lifetime risk.

Just 9.4% of the women, however, accurately estimated their risk, while 46% overestimated their risk and 45% underestimated their risk.

The predominant direction of estimation error varied by race/ethnicity. Of the white women, 10% accurately estimated their risk, 39% underestimated, and 51% overestimated their risk. Women of other ethnicities were more likely to underestimate their breast cancer risks. Just 9% of African American women were in line with their risk, with 58% underestimating and 34% overestimating. Asian women had similar assessments. Hispanic women’s inaccurate assessments were more balanced, with 50% underestimating and 41% overestimating risk. Although these differences were statistically significant, it is more important to note that the overall level of understanding was very low, Dr. Herman said.

Ideally, patients should learn of their breast cancer risk from their physician, he said, but the study data told another story. "All of these women were about to have mammography, so they obviously had some interest in their breast health," but when asked when they last spoke to their doctor about their personal breast cancer risk, "we were shocked to find that 40% of women said they never ever had a conversation with a health care provider," he reported.

The findings suggest a need to improve communication about risk by primary care providers, especially as the U.S. Preventive Services Task Force is now putting greater emphasis on informed decision making, Dr. Herman acknowledged.

But patients could be spurred to action as well, by moving beyond the pink ribbons and asking their physician, "What are my breast cancer numbers? I need to know that," he proposed.

Dr. Steven O’Day, director of clinical research at the Beverly Hills (Calif.) Cancer Institute and moderator of the press briefing, noted that the study has important implications for making use of guidelines for women at elevated risk. "To make decisions about chemoprevention, an accurate understanding of prognosis and risk both from the patient’s perspective and the physician’s is going to be essential to making good decisions in terms of surveillance and chemoprevention," he said.

A follow-up study planned by Dr. Herman will be important for informing efforts to improve risk communication, according to Dr. O’Day. "It’s a huge hurdle, yet how we are going to implement this [in primary care], as well as the tertiary-care oncology setting?" he commented. "If we don’t, the implications are huge; interventions by increased surveillance or chemoprevention are not trivial in terms of cost as well as potential side effects and morbidity. And these are difficult decisions even with accurate information. And without the information, you really can’t make any decision, in my mind."

Dr. Herman disclosed no relevant conflicts of interest. Dr. O’Day disclosed no relevant conflicts of interest.

Most women do not have an accurate understanding of their breast cancer risk – a finding that has important implications for prevention and early detection, as well as psychological well-being, according to a survey of nearly 10,000 women undergoing mammography screening.

When asked to estimate their lifetime personal breast cancer risk, just 9.4% of the women gave a value that was within 10% of their actual calculated risk, according to data reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology, where the study will be presented in full.

"Despite all the ongoing media attention, awareness campaigns, pink ribbons, breast cancer walks, and breast cancer month, most women lack accurate knowledge of their own breast cancer risk," maintained first author Dr. Jonathan D. Herman, an ob.gyn. at Hofstra University, New Hyde Park, N.Y. This tells us that "our education messaging is far off and we should change the way breast cancer awareness is presented."

"We began to think: What happens to women when they underestimate their risk of breast cancer? Well, they probably don’t get the necessary or most accurate treatment," he said. In particular, this group could benefit from a tailored plan of chemoprevention and early detection. On the other hand, "we think that women who overestimate their risk are worrying about getting breast cancer more than they really have to."

In the study, the investigators surveyed 9,873 women aged 35-70 years who were about to undergo screening at 21 Long Island mammography centers. The anonymous questionnaire included many questions adapted from the National Cancer Institute’s Breast Cancer Risk Assessment Tool, which is available online and typically used by physicians.

The women’s subjective estimate of risk was compared with their risk as calculated with the tool. Their estimate was considered inaccurate if it differed from their calculated risk by more than 10%.

Most of the women were at average calculated risk, with 35% having a 5%-10% lifetime risk and 40% having a 10%-15% lifetime risk.

Just 9.4% of the women, however, accurately estimated their risk, while 46% overestimated their risk and 45% underestimated their risk.

The predominant direction of estimation error varied by race/ethnicity. Of the white women, 10% accurately estimated their risk, 39% underestimated, and 51% overestimated their risk. Women of other ethnicities were more likely to underestimate their breast cancer risks. Just 9% of African American women were in line with their risk, with 58% underestimating and 34% overestimating. Asian women had similar assessments. Hispanic women’s inaccurate assessments were more balanced, with 50% underestimating and 41% overestimating risk. Although these differences were statistically significant, it is more important to note that the overall level of understanding was very low, Dr. Herman said.

Ideally, patients should learn of their breast cancer risk from their physician, he said, but the study data told another story. "All of these women were about to have mammography, so they obviously had some interest in their breast health," but when asked when they last spoke to their doctor about their personal breast cancer risk, "we were shocked to find that 40% of women said they never ever had a conversation with a health care provider," he reported.

The findings suggest a need to improve communication about risk by primary care providers, especially as the U.S. Preventive Services Task Force is now putting greater emphasis on informed decision making, Dr. Herman acknowledged.

But patients could be spurred to action as well, by moving beyond the pink ribbons and asking their physician, "What are my breast cancer numbers? I need to know that," he proposed.

Dr. Steven O’Day, director of clinical research at the Beverly Hills (Calif.) Cancer Institute and moderator of the press briefing, noted that the study has important implications for making use of guidelines for women at elevated risk. "To make decisions about chemoprevention, an accurate understanding of prognosis and risk both from the patient’s perspective and the physician’s is going to be essential to making good decisions in terms of surveillance and chemoprevention," he said.

A follow-up study planned by Dr. Herman will be important for informing efforts to improve risk communication, according to Dr. O’Day. "It’s a huge hurdle, yet how we are going to implement this [in primary care], as well as the tertiary-care oncology setting?" he commented. "If we don’t, the implications are huge; interventions by increased surveillance or chemoprevention are not trivial in terms of cost as well as potential side effects and morbidity. And these are difficult decisions even with accurate information. And without the information, you really can’t make any decision, in my mind."

Dr. Herman disclosed no relevant conflicts of interest. Dr. O’Day disclosed no relevant conflicts of interest.

Most women do not have an accurate understanding of their breast cancer risk – a finding that has important implications for prevention and early detection, as well as psychological well-being, according to a survey of nearly 10,000 women undergoing mammography screening.

When asked to estimate their lifetime personal breast cancer risk, just 9.4% of the women gave a value that was within 10% of their actual calculated risk, according to data reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology, where the study will be presented in full.

"Despite all the ongoing media attention, awareness campaigns, pink ribbons, breast cancer walks, and breast cancer month, most women lack accurate knowledge of their own breast cancer risk," maintained first author Dr. Jonathan D. Herman, an ob.gyn. at Hofstra University, New Hyde Park, N.Y. This tells us that "our education messaging is far off and we should change the way breast cancer awareness is presented."

"We began to think: What happens to women when they underestimate their risk of breast cancer? Well, they probably don’t get the necessary or most accurate treatment," he said. In particular, this group could benefit from a tailored plan of chemoprevention and early detection. On the other hand, "we think that women who overestimate their risk are worrying about getting breast cancer more than they really have to."

In the study, the investigators surveyed 9,873 women aged 35-70 years who were about to undergo screening at 21 Long Island mammography centers. The anonymous questionnaire included many questions adapted from the National Cancer Institute’s Breast Cancer Risk Assessment Tool, which is available online and typically used by physicians.

The women’s subjective estimate of risk was compared with their risk as calculated with the tool. Their estimate was considered inaccurate if it differed from their calculated risk by more than 10%.

Most of the women were at average calculated risk, with 35% having a 5%-10% lifetime risk and 40% having a 10%-15% lifetime risk.

Just 9.4% of the women, however, accurately estimated their risk, while 46% overestimated their risk and 45% underestimated their risk.

The predominant direction of estimation error varied by race/ethnicity. Of the white women, 10% accurately estimated their risk, 39% underestimated, and 51% overestimated their risk. Women of other ethnicities were more likely to underestimate their breast cancer risks. Just 9% of African American women were in line with their risk, with 58% underestimating and 34% overestimating. Asian women had similar assessments. Hispanic women’s inaccurate assessments were more balanced, with 50% underestimating and 41% overestimating risk. Although these differences were statistically significant, it is more important to note that the overall level of understanding was very low, Dr. Herman said.

Ideally, patients should learn of their breast cancer risk from their physician, he said, but the study data told another story. "All of these women were about to have mammography, so they obviously had some interest in their breast health," but when asked when they last spoke to their doctor about their personal breast cancer risk, "we were shocked to find that 40% of women said they never ever had a conversation with a health care provider," he reported.

The findings suggest a need to improve communication about risk by primary care providers, especially as the U.S. Preventive Services Task Force is now putting greater emphasis on informed decision making, Dr. Herman acknowledged.

But patients could be spurred to action as well, by moving beyond the pink ribbons and asking their physician, "What are my breast cancer numbers? I need to know that," he proposed.

Dr. Steven O’Day, director of clinical research at the Beverly Hills (Calif.) Cancer Institute and moderator of the press briefing, noted that the study has important implications for making use of guidelines for women at elevated risk. "To make decisions about chemoprevention, an accurate understanding of prognosis and risk both from the patient’s perspective and the physician’s is going to be essential to making good decisions in terms of surveillance and chemoprevention," he said.

A follow-up study planned by Dr. Herman will be important for informing efforts to improve risk communication, according to Dr. O’Day. "It’s a huge hurdle, yet how we are going to implement this [in primary care], as well as the tertiary-care oncology setting?" he commented. "If we don’t, the implications are huge; interventions by increased surveillance or chemoprevention are not trivial in terms of cost as well as potential side effects and morbidity. And these are difficult decisions even with accurate information. And without the information, you really can’t make any decision, in my mind."

Dr. Herman disclosed no relevant conflicts of interest. Dr. O’Day disclosed no relevant conflicts of interest.

Women who receive radiation therapy as part of their treatment for very early breast cancer do not have an elevated risk of developing or dying from cardiovascular disease later in life, new data suggest.

In a population-based cohort study, researchers assessed cardiovascular outcomes among 10,468 women in the Netherlands given a diagnosis of ductal carcinoma in situ (DCIS) before the age of 75 years during 1989-2004.

Overall, 28% of the cohort received radiation therapy after their surgery (lumpectomy or mastectomy), lead investigator Naomi B. Boekel reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology, where the findings will be presented in full.

During a median follow-up of 10 years, about 9% of the patients received a diagnosis of cardiovascular disease.

There was no significant difference in the rate between patients who did vs. did not receive radiation, or between patients who received left-sided radiation (in which the heart gets a low direct dose) vs. right-sided radiation (in which the heart gets only a scatter dose).

Specifically, the rate of cardiovascular disease diagnosis was 9% in patients who received surgery alone, compared with 8% in patients who received surgery plus radiation, a nonsignificant difference. The CVD rate was 7% in patients who received left-sided radiation therapy vs. 8% in their counterparts who received right-sided radiation therapy, another nonsignificant difference.

Furthermore, DCIS survivors as a whole had a 23% lower risk of dying from cardiovascular disease, compared with peers in the general Dutch population.

"This lower risk might be due to lifestyle adaption after DCIS diagnosis," proposed Ms. Boekel, a doctoral student at the Netherlands Cancer Institute in Amsterdam. "It could be due to conflicting risk factors between DCIS and cardiovascular disease, such as age at menopause. Or it could also be due to differences in health consciousness in that DCIS patients are probably more health conscious than the general population."

The risk of all-cause mortality was essentially the same between the DCIS cohort and the general population.

"We also looked at this for specific cardiovascular diseases and there were similar results, so there is no risk difference between these treatment groups," Ms. Boekel reported.

"Although these results are reassuring, longer follow-up is necessary before definitive conclusions can be drawn," she commented.

There is no established upper limit for such follow-up, she said. "But other studies have shown that the increased risk of cardiovascular disease starts after 5 to 10 years. ... We do have half of the cohort at more than 10 years, but [estimates] are less precise. So we need another 5 to 10 years before we are sure."

Strengths of the study, according to Dr. Steven O’Day, director of clinical research at the Beverly Hills (Calif.) Cancer Institute and moderator of the press briefing, included its occurrence in a time period in which more modern radiation therapy techniques were used. Also, the follow-up was fairly lengthy, although he agreed that more is needed.

"This is an important study that allows us to feel comfortable continuing our aggressive treatment of DCIS, with screening and trying to reduce overall mortality from breast cancer," Dr. O’Day maintained.

Ms. Boekel disclosed no relevant conflicts of interest. Dr. O’Day disclosed no relevant conflicts of interest.

Women who receive radiation therapy as part of their treatment for very early breast cancer do not have an elevated risk of developing or dying from cardiovascular disease later in life, new data suggest.

In a population-based cohort study, researchers assessed cardiovascular outcomes among 10,468 women in the Netherlands given a diagnosis of ductal carcinoma in situ (DCIS) before the age of 75 years during 1989-2004.

Overall, 28% of the cohort received radiation therapy after their surgery (lumpectomy or mastectomy), lead investigator Naomi B. Boekel reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology, where the findings will be presented in full.

During a median follow-up of 10 years, about 9% of the patients received a diagnosis of cardiovascular disease.

There was no significant difference in the rate between patients who did vs. did not receive radiation, or between patients who received left-sided radiation (in which the heart gets a low direct dose) vs. right-sided radiation (in which the heart gets only a scatter dose).

Specifically, the rate of cardiovascular disease diagnosis was 9% in patients who received surgery alone, compared with 8% in patients who received surgery plus radiation, a nonsignificant difference. The CVD rate was 7% in patients who received left-sided radiation therapy vs. 8% in their counterparts who received right-sided radiation therapy, another nonsignificant difference.

Furthermore, DCIS survivors as a whole had a 23% lower risk of dying from cardiovascular disease, compared with peers in the general Dutch population.

"This lower risk might be due to lifestyle adaption after DCIS diagnosis," proposed Ms. Boekel, a doctoral student at the Netherlands Cancer Institute in Amsterdam. "It could be due to conflicting risk factors between DCIS and cardiovascular disease, such as age at menopause. Or it could also be due to differences in health consciousness in that DCIS patients are probably more health conscious than the general population."

The risk of all-cause mortality was essentially the same between the DCIS cohort and the general population.

"We also looked at this for specific cardiovascular diseases and there were similar results, so there is no risk difference between these treatment groups," Ms. Boekel reported.

"Although these results are reassuring, longer follow-up is necessary before definitive conclusions can be drawn," she commented.

There is no established upper limit for such follow-up, she said. "But other studies have shown that the increased risk of cardiovascular disease starts after 5 to 10 years. ... We do have half of the cohort at more than 10 years, but [estimates] are less precise. So we need another 5 to 10 years before we are sure."

Strengths of the study, according to Dr. Steven O’Day, director of clinical research at the Beverly Hills (Calif.) Cancer Institute and moderator of the press briefing, included its occurrence in a time period in which more modern radiation therapy techniques were used. Also, the follow-up was fairly lengthy, although he agreed that more is needed.

"This is an important study that allows us to feel comfortable continuing our aggressive treatment of DCIS, with screening and trying to reduce overall mortality from breast cancer," Dr. O’Day maintained.

Ms. Boekel disclosed no relevant conflicts of interest. Dr. O’Day disclosed no relevant conflicts of interest.

Women who receive radiation therapy as part of their treatment for very early breast cancer do not have an elevated risk of developing or dying from cardiovascular disease later in life, new data suggest.

In a population-based cohort study, researchers assessed cardiovascular outcomes among 10,468 women in the Netherlands given a diagnosis of ductal carcinoma in situ (DCIS) before the age of 75 years during 1989-2004.

Overall, 28% of the cohort received radiation therapy after their surgery (lumpectomy or mastectomy), lead investigator Naomi B. Boekel reported in a press briefing held in advance of the breast cancer symposium sponsored by the American Society of Clinical Oncology, where the findings will be presented in full.

During a median follow-up of 10 years, about 9% of the patients received a diagnosis of cardiovascular disease.

There was no significant difference in the rate between patients who did vs. did not receive radiation, or between patients who received left-sided radiation (in which the heart gets a low direct dose) vs. right-sided radiation (in which the heart gets only a scatter dose).

Specifically, the rate of cardiovascular disease diagnosis was 9% in patients who received surgery alone, compared with 8% in patients who received surgery plus radiation, a nonsignificant difference. The CVD rate was 7% in patients who received left-sided radiation therapy vs. 8% in their counterparts who received right-sided radiation therapy, another nonsignificant difference.

Furthermore, DCIS survivors as a whole had a 23% lower risk of dying from cardiovascular disease, compared with peers in the general Dutch population.

"This lower risk might be due to lifestyle adaption after DCIS diagnosis," proposed Ms. Boekel, a doctoral student at the Netherlands Cancer Institute in Amsterdam. "It could be due to conflicting risk factors between DCIS and cardiovascular disease, such as age at menopause. Or it could also be due to differences in health consciousness in that DCIS patients are probably more health conscious than the general population."

The risk of all-cause mortality was essentially the same between the DCIS cohort and the general population.

"We also looked at this for specific cardiovascular diseases and there were similar results, so there is no risk difference between these treatment groups," Ms. Boekel reported.

"Although these results are reassuring, longer follow-up is necessary before definitive conclusions can be drawn," she commented.

There is no established upper limit for such follow-up, she said. "But other studies have shown that the increased risk of cardiovascular disease starts after 5 to 10 years. ... We do have half of the cohort at more than 10 years, but [estimates] are less precise. So we need another 5 to 10 years before we are sure."

Strengths of the study, according to Dr. Steven O’Day, director of clinical research at the Beverly Hills (Calif.) Cancer Institute and moderator of the press briefing, included its occurrence in a time period in which more modern radiation therapy techniques were used. Also, the follow-up was fairly lengthy, although he agreed that more is needed.

"This is an important study that allows us to feel comfortable continuing our aggressive treatment of DCIS, with screening and trying to reduce overall mortality from breast cancer," Dr. O’Day maintained.

Ms. Boekel disclosed no relevant conflicts of interest. Dr. O’Day disclosed no relevant conflicts of interest.

The following reports are based on presentations at the annual meeting of the American Society of Clinical Oncology held May 31-June 4 in Chicago. Many of the presentations heralded a new era of precision medicine, that is, treatment based on patient and tumor genetics, rather than tumor location alone, according to outgoing ASCO president Sandra Swain, MD. Immunotherapies, specifically the PD-L1 antibodies featured prominently.

*Click on the link to the left for a PDF of the full article.

The following reports are based on presentations at the annual meeting of the American Society of Clinical Oncology held May 31-June 4 in Chicago. Many of the presentations heralded a new era of precision medicine, that is, treatment based on patient and tumor genetics, rather than tumor location alone, according to outgoing ASCO president Sandra Swain, MD. Immunotherapies, specifically the PD-L1 antibodies featured prominently.

*Click on the link to the left for a PDF of the full article.

The following reports are based on presentations at the annual meeting of the American Society of Clinical Oncology held May 31-June 4 in Chicago. Many of the presentations heralded a new era of precision medicine, that is, treatment based on patient and tumor genetics, rather than tumor location alone, according to outgoing ASCO president Sandra Swain, MD. Immunotherapies, specifically the PD-L1 antibodies featured prominently.

*Click on the link to the left for a PDF of the full article.

Tumor-induced genetic changes in the immune cells of lymph nodes predict outcomes in patients with follicular lymphoma, according to a study published in the Journal of Clinical Oncology.

Investigators performed gene expression profiling of tumor-infiltrating T cells (TILs) from lymph node biopsies at diagnosis in 172 treatment-naive patients with follicular lymphoma and of T cells from reactive tonsils and peripheral blood of 12 healthy donors.

Compared with the T cells from healthy donors, the TILs had marked upregulation of several genes and downregulation of others, as well as impaired motility. Moreover, similar changes could be induced in healthy T cells by exposing them to lymphoma cells, said Dr. Shahryar Kiaii of the Institute of Cancer and Barts and the London School of Medicine and Dentistry and his associates.

The numbers and locations within the lymph nodes of the TILs showing altered gene expression predicted both overall survival and the time to transformation to B-cell lymphoma – sometimes dramatically. Certain combinations were associated with 70%-80% reductions in the risks of these outcomes.

"These results contribute to our understanding of the complex interactions of lymphoma cells, TILs, and macrophages in their microenvironment and help us generate hypotheses. But until we have a better understanding of these interactions, it does not yet seem feasible to incorporate [immunohistochemistry] analysis of TILs in [follicular lymphoma] for prognosis," the investigators wrote.

"However, because nonmalignant infiltrating immune cells play a crucial role in outcomes in [follicular lymphoma], understanding the nature and impact of the abnormalities induced in TILs in these patients is vital before any immunotherapeutic strategies can be implemented to alter the immune microenvironment in [follicular lymphoma]," they added.

In the study, the investigators constructed tissue microarrays and used mRNA expression profiles, real-time polymerase chain reaction assays, and immunohistochemistry to assess gene expression in highly purified CD4 and CD8 T cells.

Results showed that the TILs had an abnormal gene expression profile when compared with the healthy T cells, Dr. Kiaii and his associates said (J. Clin. Oncol. 2013;31:2654-61).

The genes showing the greatest upregulation were those for pro-melanin–concentrating hormone (PMCH); ETS translocation variant 1 (ETV1); and tumor necrosis factor receptor superfamily, member 9 (TNFRSF9).

One of the genes showing greatest downregulation was the gene that encodes the cytoskeletal protein actinin (ACTN1), and the TILs indeed showed reduced motility when compared with the healthy T cells (P less than .025).

When cultured alone, healthy T cells did not express PMCH and had normal motility, but when cultured with follicular lymphoma cells, the T cells expressed this protein highly and had reduced motility (P = .0002).

The number of TILs expressing PMCH, ETV1, and NAMPT (nicotinamide phosphoribosyltransferase) and their locations in lymph nodes – in the malignant follicle (intrafollicular area), in the area between follicles (interfollicular area), and overall – as determined immunohistochemically, were significantly associated with both overall survival and time to transformation, the investigators said.

In multivariate analyses, the combination of the interfollicular-to-intrafollicular ratio of PMCH-expressing cells plus a high level of expression of NAMPT and a low level of expression of ETV1 in the intrafollicular area was the strongest predictor of longer time to transformation (hazard ratio, 0.19; P = .003).

Similarly, the combination of the number of PMCH- and NAMPT-expressing cells in the interfollicular area plus the interfollicular-to-intrafollicular ratio of ETV1 cells was the strongest predictor of better overall survival (hazard ratio, 0.32; P = .007).

The study was supported by grants from Cancer Research UK and the National Cancer Institute. One of the investigators disclosed receiving honoraria from Roche/Genentech and Celgene.

Tumor-induced genetic changes in the immune cells of lymph nodes predict outcomes in patients with follicular lymphoma, according to a study published in the Journal of Clinical Oncology.

Investigators performed gene expression profiling of tumor-infiltrating T cells (TILs) from lymph node biopsies at diagnosis in 172 treatment-naive patients with follicular lymphoma and of T cells from reactive tonsils and peripheral blood of 12 healthy donors.

Compared with the T cells from healthy donors, the TILs had marked upregulation of several genes and downregulation of others, as well as impaired motility. Moreover, similar changes could be induced in healthy T cells by exposing them to lymphoma cells, said Dr. Shahryar Kiaii of the Institute of Cancer and Barts and the London School of Medicine and Dentistry and his associates.

The numbers and locations within the lymph nodes of the TILs showing altered gene expression predicted both overall survival and the time to transformation to B-cell lymphoma – sometimes dramatically. Certain combinations were associated with 70%-80% reductions in the risks of these outcomes.

"These results contribute to our understanding of the complex interactions of lymphoma cells, TILs, and macrophages in their microenvironment and help us generate hypotheses. But until we have a better understanding of these interactions, it does not yet seem feasible to incorporate [immunohistochemistry] analysis of TILs in [follicular lymphoma] for prognosis," the investigators wrote.

"However, because nonmalignant infiltrating immune cells play a crucial role in outcomes in [follicular lymphoma], understanding the nature and impact of the abnormalities induced in TILs in these patients is vital before any immunotherapeutic strategies can be implemented to alter the immune microenvironment in [follicular lymphoma]," they added.

In the study, the investigators constructed tissue microarrays and used mRNA expression profiles, real-time polymerase chain reaction assays, and immunohistochemistry to assess gene expression in highly purified CD4 and CD8 T cells.

Results showed that the TILs had an abnormal gene expression profile when compared with the healthy T cells, Dr. Kiaii and his associates said (J. Clin. Oncol. 2013;31:2654-61).

The genes showing the greatest upregulation were those for pro-melanin–concentrating hormone (PMCH); ETS translocation variant 1 (ETV1); and tumor necrosis factor receptor superfamily, member 9 (TNFRSF9).

One of the genes showing greatest downregulation was the gene that encodes the cytoskeletal protein actinin (ACTN1), and the TILs indeed showed reduced motility when compared with the healthy T cells (P less than .025).

When cultured alone, healthy T cells did not express PMCH and had normal motility, but when cultured with follicular lymphoma cells, the T cells expressed this protein highly and had reduced motility (P = .0002).

The number of TILs expressing PMCH, ETV1, and NAMPT (nicotinamide phosphoribosyltransferase) and their locations in lymph nodes – in the malignant follicle (intrafollicular area), in the area between follicles (interfollicular area), and overall – as determined immunohistochemically, were significantly associated with both overall survival and time to transformation, the investigators said.

In multivariate analyses, the combination of the interfollicular-to-intrafollicular ratio of PMCH-expressing cells plus a high level of expression of NAMPT and a low level of expression of ETV1 in the intrafollicular area was the strongest predictor of longer time to transformation (hazard ratio, 0.19; P = .003).

Similarly, the combination of the number of PMCH- and NAMPT-expressing cells in the interfollicular area plus the interfollicular-to-intrafollicular ratio of ETV1 cells was the strongest predictor of better overall survival (hazard ratio, 0.32; P = .007).

The study was supported by grants from Cancer Research UK and the National Cancer Institute. One of the investigators disclosed receiving honoraria from Roche/Genentech and Celgene.

Tumor-induced genetic changes in the immune cells of lymph nodes predict outcomes in patients with follicular lymphoma, according to a study published in the Journal of Clinical Oncology.

Investigators performed gene expression profiling of tumor-infiltrating T cells (TILs) from lymph node biopsies at diagnosis in 172 treatment-naive patients with follicular lymphoma and of T cells from reactive tonsils and peripheral blood of 12 healthy donors.

Compared with the T cells from healthy donors, the TILs had marked upregulation of several genes and downregulation of others, as well as impaired motility. Moreover, similar changes could be induced in healthy T cells by exposing them to lymphoma cells, said Dr. Shahryar Kiaii of the Institute of Cancer and Barts and the London School of Medicine and Dentistry and his associates.

The numbers and locations within the lymph nodes of the TILs showing altered gene expression predicted both overall survival and the time to transformation to B-cell lymphoma – sometimes dramatically. Certain combinations were associated with 70%-80% reductions in the risks of these outcomes.

"These results contribute to our understanding of the complex interactions of lymphoma cells, TILs, and macrophages in their microenvironment and help us generate hypotheses. But until we have a better understanding of these interactions, it does not yet seem feasible to incorporate [immunohistochemistry] analysis of TILs in [follicular lymphoma] for prognosis," the investigators wrote.

"However, because nonmalignant infiltrating immune cells play a crucial role in outcomes in [follicular lymphoma], understanding the nature and impact of the abnormalities induced in TILs in these patients is vital before any immunotherapeutic strategies can be implemented to alter the immune microenvironment in [follicular lymphoma]," they added.

In the study, the investigators constructed tissue microarrays and used mRNA expression profiles, real-time polymerase chain reaction assays, and immunohistochemistry to assess gene expression in highly purified CD4 and CD8 T cells.

Results showed that the TILs had an abnormal gene expression profile when compared with the healthy T cells, Dr. Kiaii and his associates said (J. Clin. Oncol. 2013;31:2654-61).

The genes showing the greatest upregulation were those for pro-melanin–concentrating hormone (PMCH); ETS translocation variant 1 (ETV1); and tumor necrosis factor receptor superfamily, member 9 (TNFRSF9).

One of the genes showing greatest downregulation was the gene that encodes the cytoskeletal protein actinin (ACTN1), and the TILs indeed showed reduced motility when compared with the healthy T cells (P less than .025).

When cultured alone, healthy T cells did not express PMCH and had normal motility, but when cultured with follicular lymphoma cells, the T cells expressed this protein highly and had reduced motility (P = .0002).

The number of TILs expressing PMCH, ETV1, and NAMPT (nicotinamide phosphoribosyltransferase) and their locations in lymph nodes – in the malignant follicle (intrafollicular area), in the area between follicles (interfollicular area), and overall – as determined immunohistochemically, were significantly associated with both overall survival and time to transformation, the investigators said.

In multivariate analyses, the combination of the interfollicular-to-intrafollicular ratio of PMCH-expressing cells plus a high level of expression of NAMPT and a low level of expression of ETV1 in the intrafollicular area was the strongest predictor of longer time to transformation (hazard ratio, 0.19; P = .003).

Similarly, the combination of the number of PMCH- and NAMPT-expressing cells in the interfollicular area plus the interfollicular-to-intrafollicular ratio of ETV1 cells was the strongest predictor of better overall survival (hazard ratio, 0.32; P = .007).

The study was supported by grants from Cancer Research UK and the National Cancer Institute. One of the investigators disclosed receiving honoraria from Roche/Genentech and Celgene.

The Revised International Prognostic Scoring System is superior to other commonly used systems when it comes to predicting leukemic evolution and survival in patients with myelodysplastic syndromes and may therefore help guide treatment decisions, new data suggest.

Dr. Maria Teresa Voso and her colleagues validated the new system and tested its predictive ability against two other commonly used systems – the classic International Prognostic Scoring System (IPSS) and the World Health Organization’s Prognostic Scoring System (WPSS) – in a retrospective cohort study of 380 patients treated between 2001 and 2011.

Compared with these others systems, which rely mainly on disease-related factors, the Revised IPSS (IPSS-R) additionally incorporates detailed cytogenetic groupings, the severity of bone marrow infiltration, and the depth of cytopenias.

Study results appearing in the Journal of Clinical Oncology confirmed that the IPSS-R significantly predicted both leukemia-free survival and overall survival in this cohort with myelodysplastic syndromes (MDS), and that it outperformed both of the other systems.

Moreover, the IPSS-R was an independent predictor of leukemia-free survival and overall survival in a multivariate model that included both of these other systems as well as a host of demographic, clinical, and treatment factors, the investigators noted.

For example, compared with counterparts having scores that put them into the IPSS-R intermediate-risk group, patients having scores that put them into the high-risk group had a 1.72-fold higher risk of leukemia or death and a 1.67-fold higher risk of death.

"Our data show that the IPSS-R is an excellent predictor of MDS prognosis in the era of disease-modifying treatments," said Dr. Voso of Università Cattolica del Sacro Cuore, Rome, and her associates (J. Clin. Oncol. 2013;31:2671-7).

"In the future, the integration of comorbidity scores and time-dependent scores, which consider the evolutive nature of MDS, may further address the decision-making process for a correct treatment approach. The early recognition of patients at high risk of progression to aggressive disease may also optimize treatment timing, before worsening of comorbidities," they added.

The patients studied were 182 women and 198 men having a median age of 71 years from the Italian Gruppo Romano Mielodisplasie (GROM) registry, which captures data in unselected patients with MDS starting at the time of initial diagnosis.

The majority of the patients received supportive treatments such as vitamins (24%), erythropoiesis-stimulating agents (49%), and transfusions (58%). A minority received active treatment with lenalidomide (6%), azacitidine (18%), or cytotoxic drugs (2%).

In terms of IPSS-R scores, 38% of the patients fell into the very-low-risk group, 33% into the low-risk group, 18% into the intermediate-risk group, 7% into the high-risk group, and 4% into the very-high-risk group, Dr. Voso and her colleagues said.

With a median follow-up of 2.8 years, the IPSS-R predicted leukemia-free survival (P less than .001) and overall survival (P less than .001), and it was superior to both the classic IPSS and the WPSS in its predictive ability (P less than .001), they wrote.

In a multivariate model that considered all three scoring systems plus a variety of potential confounders (age, lactate dehydrogenase concentration, ferritin concentration, performance status, transfusion dependency, and type of therapy), the IPSS-R score was an independent predictor.

When peers in the intermediate-risk group were used as the comparator, patients had better leukemia-free survival if they fell in the very-low-risk group (hazard ratio [HR], 0.26; P less than .001) or low-risk group (HR, 0.58; P = .02), and patients had poorer leukemia-free survival if they fell in the high-risk group (HR, 1.72; P = .08) or very-high-risk group (HR, 3.26; P = .004).

Similarly, patients had better overall survival if they were in the very-low-risk group (HR, 0.29; P less than .001) or low-risk group (HR, 0.59; P = .04), and patients had poorer overall survival if they were in the high-risk group (HR, 1.67; P = .10) or very-high-risk group (HR, 5.13; P less than .001).

Dr. Voso disclosed receiving honoraria from Celgene.

The Revised International Prognostic Scoring System is superior to other commonly used systems when it comes to predicting leukemic evolution and survival in patients with myelodysplastic syndromes and may therefore help guide treatment decisions, new data suggest.

Dr. Maria Teresa Voso and her colleagues validated the new system and tested its predictive ability against two other commonly used systems – the classic International Prognostic Scoring System (IPSS) and the World Health Organization’s Prognostic Scoring System (WPSS) – in a retrospective cohort study of 380 patients treated between 2001 and 2011.

Compared with these others systems, which rely mainly on disease-related factors, the Revised IPSS (IPSS-R) additionally incorporates detailed cytogenetic groupings, the severity of bone marrow infiltration, and the depth of cytopenias.

Study results appearing in the Journal of Clinical Oncology confirmed that the IPSS-R significantly predicted both leukemia-free survival and overall survival in this cohort with myelodysplastic syndromes (MDS), and that it outperformed both of the other systems.

Moreover, the IPSS-R was an independent predictor of leukemia-free survival and overall survival in a multivariate model that included both of these other systems as well as a host of demographic, clinical, and treatment factors, the investigators noted.

For example, compared with counterparts having scores that put them into the IPSS-R intermediate-risk group, patients having scores that put them into the high-risk group had a 1.72-fold higher risk of leukemia or death and a 1.67-fold higher risk of death.

"Our data show that the IPSS-R is an excellent predictor of MDS prognosis in the era of disease-modifying treatments," said Dr. Voso of Università Cattolica del Sacro Cuore, Rome, and her associates (J. Clin. Oncol. 2013;31:2671-7).

"In the future, the integration of comorbidity scores and time-dependent scores, which consider the evolutive nature of MDS, may further address the decision-making process for a correct treatment approach. The early recognition of patients at high risk of progression to aggressive disease may also optimize treatment timing, before worsening of comorbidities," they added.

The patients studied were 182 women and 198 men having a median age of 71 years from the Italian Gruppo Romano Mielodisplasie (GROM) registry, which captures data in unselected patients with MDS starting at the time of initial diagnosis.

The majority of the patients received supportive treatments such as vitamins (24%), erythropoiesis-stimulating agents (49%), and transfusions (58%). A minority received active treatment with lenalidomide (6%), azacitidine (18%), or cytotoxic drugs (2%).

In terms of IPSS-R scores, 38% of the patients fell into the very-low-risk group, 33% into the low-risk group, 18% into the intermediate-risk group, 7% into the high-risk group, and 4% into the very-high-risk group, Dr. Voso and her colleagues said.

With a median follow-up of 2.8 years, the IPSS-R predicted leukemia-free survival (P less than .001) and overall survival (P less than .001), and it was superior to both the classic IPSS and the WPSS in its predictive ability (P less than .001), they wrote.

In a multivariate model that considered all three scoring systems plus a variety of potential confounders (age, lactate dehydrogenase concentration, ferritin concentration, performance status, transfusion dependency, and type of therapy), the IPSS-R score was an independent predictor.

When peers in the intermediate-risk group were used as the comparator, patients had better leukemia-free survival if they fell in the very-low-risk group (hazard ratio [HR], 0.26; P less than .001) or low-risk group (HR, 0.58; P = .02), and patients had poorer leukemia-free survival if they fell in the high-risk group (HR, 1.72; P = .08) or very-high-risk group (HR, 3.26; P = .004).

Similarly, patients had better overall survival if they were in the very-low-risk group (HR, 0.29; P less than .001) or low-risk group (HR, 0.59; P = .04), and patients had poorer overall survival if they were in the high-risk group (HR, 1.67; P = .10) or very-high-risk group (HR, 5.13; P less than .001).

Dr. Voso disclosed receiving honoraria from Celgene.

The Revised International Prognostic Scoring System is superior to other commonly used systems when it comes to predicting leukemic evolution and survival in patients with myelodysplastic syndromes and may therefore help guide treatment decisions, new data suggest.

Dr. Maria Teresa Voso and her colleagues validated the new system and tested its predictive ability against two other commonly used systems – the classic International Prognostic Scoring System (IPSS) and the World Health Organization’s Prognostic Scoring System (WPSS) – in a retrospective cohort study of 380 patients treated between 2001 and 2011.

Compared with these others systems, which rely mainly on disease-related factors, the Revised IPSS (IPSS-R) additionally incorporates detailed cytogenetic groupings, the severity of bone marrow infiltration, and the depth of cytopenias.

Study results appearing in the Journal of Clinical Oncology confirmed that the IPSS-R significantly predicted both leukemia-free survival and overall survival in this cohort with myelodysplastic syndromes (MDS), and that it outperformed both of the other systems.

Moreover, the IPSS-R was an independent predictor of leukemia-free survival and overall survival in a multivariate model that included both of these other systems as well as a host of demographic, clinical, and treatment factors, the investigators noted.

For example, compared with counterparts having scores that put them into the IPSS-R intermediate-risk group, patients having scores that put them into the high-risk group had a 1.72-fold higher risk of leukemia or death and a 1.67-fold higher risk of death.

"Our data show that the IPSS-R is an excellent predictor of MDS prognosis in the era of disease-modifying treatments," said Dr. Voso of Università Cattolica del Sacro Cuore, Rome, and her associates (J. Clin. Oncol. 2013;31:2671-7).

"In the future, the integration of comorbidity scores and time-dependent scores, which consider the evolutive nature of MDS, may further address the decision-making process for a correct treatment approach. The early recognition of patients at high risk of progression to aggressive disease may also optimize treatment timing, before worsening of comorbidities," they added.

The patients studied were 182 women and 198 men having a median age of 71 years from the Italian Gruppo Romano Mielodisplasie (GROM) registry, which captures data in unselected patients with MDS starting at the time of initial diagnosis.

The majority of the patients received supportive treatments such as vitamins (24%), erythropoiesis-stimulating agents (49%), and transfusions (58%). A minority received active treatment with lenalidomide (6%), azacitidine (18%), or cytotoxic drugs (2%).

In terms of IPSS-R scores, 38% of the patients fell into the very-low-risk group, 33% into the low-risk group, 18% into the intermediate-risk group, 7% into the high-risk group, and 4% into the very-high-risk group, Dr. Voso and her colleagues said.

With a median follow-up of 2.8 years, the IPSS-R predicted leukemia-free survival (P less than .001) and overall survival (P less than .001), and it was superior to both the classic IPSS and the WPSS in its predictive ability (P less than .001), they wrote.

In a multivariate model that considered all three scoring systems plus a variety of potential confounders (age, lactate dehydrogenase concentration, ferritin concentration, performance status, transfusion dependency, and type of therapy), the IPSS-R score was an independent predictor.

When peers in the intermediate-risk group were used as the comparator, patients had better leukemia-free survival if they fell in the very-low-risk group (hazard ratio [HR], 0.26; P less than .001) or low-risk group (HR, 0.58; P = .02), and patients had poorer leukemia-free survival if they fell in the high-risk group (HR, 1.72; P = .08) or very-high-risk group (HR, 3.26; P = .004).

Similarly, patients had better overall survival if they were in the very-low-risk group (HR, 0.29; P less than .001) or low-risk group (HR, 0.59; P = .04), and patients had poorer overall survival if they were in the high-risk group (HR, 1.67; P = .10) or very-high-risk group (HR, 5.13; P less than .001).

Dr. Voso disclosed receiving honoraria from Celgene.

African American men with very-low-risk prostate cancer undergoing prostatectomy still have a higher likelihood of poor oncologic outcomes that should be discussed during counseling, according to results from a retrospective cohort study appearing in the Journal of Clinical Oncology.

Investigators at Johns Hopkins University, Baltimore, studied 1,801 men – 14% African American, 82% white, and 4% other races/ethnicities – treated in the prostate-specific antigen era who met criteria for very-low-risk disease but opted for an immediate radical prostatectomy instead.

Study results showed that relative to white peers, African American men were significantly more likely to have tumors with adverse pathologic features, upgrading at prostatectomy, positive surgical margins, and scores predicting a higher risk of recurrence, Dr. Debasish Sundi and his colleagues reported.

In a multivariate analysis restricted to the 359 men treated with modern practices (extended biopsy sampling and contemporary Gleason grading), African American men had a more than tripling of the odds of adverse tumor features and a more than doubling of the odds of pathologic upgrading relative to men of other races/ethnicities.

The investigators wrote that the study "shows a disparity in outcomes for African American men after radical prostatectomy by multiple metrics, even within a highly selected and contemporary cohort of very-low–risk patients. This underscores the need to develop and use race-based risk classifiers when counseling patients about different management strategies."

"African American men with very low risk of prostate cancer should be counseled about increased oncologic risk when deciding among their disease management options," they recommended.

However, "the results of our study do not support the universal rejection of active surveillance in African American men but rather should promote future studies to address whether alternate race-specific surveillance entry criteria should be used for African American men to ensure oncologic parity with their white counterparts."

The investigators retrospectively studied men undergoing radical prostatectomy at Johns Hopkins since 1992, excluding any who received neoadjuvant hormonal therapy and restricting analyses to those who met National Comprehensive Cancer Network criteria for very-low-risk disease.

Relative to their white peers, African American men were more likely to have upgrading at prostatectomy (27.3% vs. 14.4%), positive surgical margins (9.8% vs. 5.9%), adverse pathologic features (14.1% vs. 7.7%), and a CAPRA-S (Cancer of the Prostate Risk Assessment Post-Surgical scoring system) score of 3 or higher, indicating a higher risk of biochemical recurrence (14.8% vs. 6.9%), the investigators reported (J. Clin. Oncol. 2013 June 17 [doi: 10.1200/JCO.2012.47.0302]).

With a median follow-up of 3 years, African Americans also had a higher rate of biochemical recurrence (4% vs. 1.4%), but the two groups were statistically indistinguishable with respect to metastasis-free, cancer-specific, or overall survival.

In the subset of men treated with modern clinical practices, compared with white men, African American men again had higher rates of upgrading (32.7% vs. 12.6%), positive margins (19% vs. 6.3%), adverse pathology (19.8% vs. 7.2%), and higher CAPRA-S scores (21% vs. 5.7%).

A multivariate analysis in this subset showed that compared with white men and other men combined, African American men still had higher odds of upgrading at prostatectomy (odds ratio, 2.26; P = .03), adverse pathology (OR, 3.23; P = .03), and higher CAPRA-S scores (OR, 6.57; P = .001).

The authors disclosed no potential conflicts of interest.

African American men with very-low-risk prostate cancer undergoing prostatectomy still have a higher likelihood of poor oncologic outcomes that should be discussed during counseling, according to results from a retrospective cohort study appearing in the Journal of Clinical Oncology.

Investigators at Johns Hopkins University, Baltimore, studied 1,801 men – 14% African American, 82% white, and 4% other races/ethnicities – treated in the prostate-specific antigen era who met criteria for very-low-risk disease but opted for an immediate radical prostatectomy instead.

Study results showed that relative to white peers, African American men were significantly more likely to have tumors with adverse pathologic features, upgrading at prostatectomy, positive surgical margins, and scores predicting a higher risk of recurrence, Dr. Debasish Sundi and his colleagues reported.

In a multivariate analysis restricted to the 359 men treated with modern practices (extended biopsy sampling and contemporary Gleason grading), African American men had a more than tripling of the odds of adverse tumor features and a more than doubling of the odds of pathologic upgrading relative to men of other races/ethnicities.

The investigators wrote that the study "shows a disparity in outcomes for African American men after radical prostatectomy by multiple metrics, even within a highly selected and contemporary cohort of very-low–risk patients. This underscores the need to develop and use race-based risk classifiers when counseling patients about different management strategies."

"African American men with very low risk of prostate cancer should be counseled about increased oncologic risk when deciding among their disease management options," they recommended.

However, "the results of our study do not support the universal rejection of active surveillance in African American men but rather should promote future studies to address whether alternate race-specific surveillance entry criteria should be used for African American men to ensure oncologic parity with their white counterparts."

The investigators retrospectively studied men undergoing radical prostatectomy at Johns Hopkins since 1992, excluding any who received neoadjuvant hormonal therapy and restricting analyses to those who met National Comprehensive Cancer Network criteria for very-low-risk disease.

Relative to their white peers, African American men were more likely to have upgrading at prostatectomy (27.3% vs. 14.4%), positive surgical margins (9.8% vs. 5.9%), adverse pathologic features (14.1% vs. 7.7%), and a CAPRA-S (Cancer of the Prostate Risk Assessment Post-Surgical scoring system) score of 3 or higher, indicating a higher risk of biochemical recurrence (14.8% vs. 6.9%), the investigators reported (J. Clin. Oncol. 2013 June 17 [doi: 10.1200/JCO.2012.47.0302]).

With a median follow-up of 3 years, African Americans also had a higher rate of biochemical recurrence (4% vs. 1.4%), but the two groups were statistically indistinguishable with respect to metastasis-free, cancer-specific, or overall survival.

In the subset of men treated with modern clinical practices, compared with white men, African American men again had higher rates of upgrading (32.7% vs. 12.6%), positive margins (19% vs. 6.3%), adverse pathology (19.8% vs. 7.2%), and higher CAPRA-S scores (21% vs. 5.7%).

A multivariate analysis in this subset showed that compared with white men and other men combined, African American men still had higher odds of upgrading at prostatectomy (odds ratio, 2.26; P = .03), adverse pathology (OR, 3.23; P = .03), and higher CAPRA-S scores (OR, 6.57; P = .001).

The authors disclosed no potential conflicts of interest.

African American men with very-low-risk prostate cancer undergoing prostatectomy still have a higher likelihood of poor oncologic outcomes that should be discussed during counseling, according to results from a retrospective cohort study appearing in the Journal of Clinical Oncology.

Investigators at Johns Hopkins University, Baltimore, studied 1,801 men – 14% African American, 82% white, and 4% other races/ethnicities – treated in the prostate-specific antigen era who met criteria for very-low-risk disease but opted for an immediate radical prostatectomy instead.

Study results showed that relative to white peers, African American men were significantly more likely to have tumors with adverse pathologic features, upgrading at prostatectomy, positive surgical margins, and scores predicting a higher risk of recurrence, Dr. Debasish Sundi and his colleagues reported.

In a multivariate analysis restricted to the 359 men treated with modern practices (extended biopsy sampling and contemporary Gleason grading), African American men had a more than tripling of the odds of adverse tumor features and a more than doubling of the odds of pathologic upgrading relative to men of other races/ethnicities.

The investigators wrote that the study "shows a disparity in outcomes for African American men after radical prostatectomy by multiple metrics, even within a highly selected and contemporary cohort of very-low–risk patients. This underscores the need to develop and use race-based risk classifiers when counseling patients about different management strategies."

"African American men with very low risk of prostate cancer should be counseled about increased oncologic risk when deciding among their disease management options," they recommended.

However, "the results of our study do not support the universal rejection of active surveillance in African American men but rather should promote future studies to address whether alternate race-specific surveillance entry criteria should be used for African American men to ensure oncologic parity with their white counterparts."

The investigators retrospectively studied men undergoing radical prostatectomy at Johns Hopkins since 1992, excluding any who received neoadjuvant hormonal therapy and restricting analyses to those who met National Comprehensive Cancer Network criteria for very-low-risk disease.

Relative to their white peers, African American men were more likely to have upgrading at prostatectomy (27.3% vs. 14.4%), positive surgical margins (9.8% vs. 5.9%), adverse pathologic features (14.1% vs. 7.7%), and a CAPRA-S (Cancer of the Prostate Risk Assessment Post-Surgical scoring system) score of 3 or higher, indicating a higher risk of biochemical recurrence (14.8% vs. 6.9%), the investigators reported (J. Clin. Oncol. 2013 June 17 [doi: 10.1200/JCO.2012.47.0302]).

With a median follow-up of 3 years, African Americans also had a higher rate of biochemical recurrence (4% vs. 1.4%), but the two groups were statistically indistinguishable with respect to metastasis-free, cancer-specific, or overall survival.

In the subset of men treated with modern clinical practices, compared with white men, African American men again had higher rates of upgrading (32.7% vs. 12.6%), positive margins (19% vs. 6.3%), adverse pathology (19.8% vs. 7.2%), and higher CAPRA-S scores (21% vs. 5.7%).

A multivariate analysis in this subset showed that compared with white men and other men combined, African American men still had higher odds of upgrading at prostatectomy (odds ratio, 2.26; P = .03), adverse pathology (OR, 3.23; P = .03), and higher CAPRA-S scores (OR, 6.57; P = .001).

The authors disclosed no potential conflicts of interest.

PHOENIX – Applying continuous negative pressure to the incisional wound sharply reduces the incidence of surgical site infection after open colorectal surgery, according to results from a retrospective study.

A team led by Dr. Allison M. Bonds, a general surgery resident at the University of Texas Southwestern Medical Center at Dallas, studied 254 patients who underwent open colorectal surgery, whether planned or converted from a laparoscopic procedure.

In 13% of the patients, surgeons used incisional negative-pressure wound therapy, which entails standard wound closure followed by placement of a wound vacuum device over the completed stapled skin closure.

Study results, reported at the annual meeting of the American Society of Colon and Rectal Surgeons, showed that relative to the group receiving usual wound care, patients receiving incisional negative-pressure wound therapy were two-thirds less likely to develop a surgical site infection.

"Our study, although a retrospective chart review, does seem to show that the use of incisional negative-pressure wound therapy is associated with a decreased risk of surgical site infection," Dr. Bonds asserted. "This finding is significant enough that we feel it further needs a randomized controlled trial to see if there is actually a significant effect in the colorectal population."

Several attendees wondered about the cost of the negative-pressure wound therapy and how that was covered in the study population.

"We didn’t do an official cost analysis," Dr. Bonds replied. "Normally, the device that we used is associated with about $200 extra initially and then ... another $500 a day to use. So it is a fairly expensive addition to the care of the patients." She said she did not have data on how this cost was covered.

Dr. Jason Hall of the Lahey Clinic in Burlington, Mass., asked, "What was the indication to use the vac in those 32 patients?" and further wondered whether the patients receiving this therapy differed in ways that may have confounded the results.

"Placement of the vacuum wound device was left to the discretion of the surgeons," Dr. Bonds replied. "It’s hard to know exactly which patients would have been chosen for the study. There is some chance that the surgeons would have chosen the patients that they didn’t think would have a high rate of infection risk. But from our talking with the surgeons who use this, we believe that most of the vacuum devices were placed on patients who they had a high suspicion were going to get surgical site infections."

She agreed that there might have been selection bias at play, despite the study’s use of multivariate analysis. "That’s exactly why we believe that a randomized controlled trial is really the only way to show whether this is going to be a good technique to use or not," she said.

Cost of the therapy and its coverage will be major issues going forward, according to session comoderator Dr. Mark Welton of Stanford (Calif.) University. "Any time you are talking about downstream benefit to the insurer, they really need to see robust data before they are going to start to pay for that. So, especially in today’s health care environment, it’s going to come back to the patient paying for it. If you could talk about driving the cost associated with the wound infection down significantly, then the insurance companies would pay for it."

"Interestingly, there are companies coming out producing less expensive and less cumbersome devices. So I think it’s actually a very exciting idea, it’s intriguing. But we have a long way to go, and we do get to this cost-benefit question, and who’s going to pay for it," he said in an interview.

Dr. Kim Rhoads, the other session comoderator, also of Stanford University, said that "it’s an interesting concept," but she would like to see a standardized protocol detailing, for example, whether the vacuum and dressing are changed at some point and how long it has to be used for benefit; additionally, the indication for use should be worked out.

Also, "what we didn’t hear is how much fluid actually comes out ... because if nothing is coming out, you have to ask, what’s happening here and would that patient not have otherwise been wound infection free," she said. "We don’t know."

Incisional negative-pressure wound therapy has been used in orthopedic surgery for several years, according to Dr. Bonds. "At UT Southwestern, we began using this in 2010 [in colorectal surgery], and anecdotally saw that it seemed to be decreasing the rate of infections in our patients, so we thought that this warranted further study," she explained.

With this therapy, surgeons close the incision with standard staples, apply a strip of bridge dressing (GranuFoam, made by KCI), and cover the area with clear occlusion tape. The vacuum device (V.A.C. Therapy, made by KCI) is then applied at 75 mm Hg of continuous suction; in patients having a stoma, the stoma is returned after the device is in place.

In the study, the vacuum device was left on until postoperative day 5 or 7, and was removed before patients were discharged, according to Dr. Bonds.

Overall, 27.2% of the patients developed a surgical site infection. The rate was 12.5% in the group given incisional negative-pressure wound therapy, compared with 29.3% in the group given standard care.

In a multivariate analysis, patients in the negative-pressure wound therapy group were 68% less likely to develop a surgical site infection (odds ratio, 0.32; P = .04).

The only other independent predictor of this outcome was diabetes mellitus, which was associated with roughly a doubling of risk (OR, 1.98; P = .03).

"There are several proposed mechanisms for why this therapy would work," Dr. Bonds noted. The device prevents the incision from coming into contact with the surrounding environment, and decreases patient mobility and shear forces on the wound.

"In addition, the continuous suction seems to remove infectious material and the interstitial fluid, thereby decreasing the wound edema. Studies have also shown that the wound vacuum device increases vascularity to the wound, which would seem to help it heal as well," she said.

Dr. Bonds disclosed no relevant conflicts of interest. One coinvestigator has an affiliation with KCI.

PHOENIX – Applying continuous negative pressure to the incisional wound sharply reduces the incidence of surgical site infection after open colorectal surgery, according to results from a retrospective study.

A team led by Dr. Allison M. Bonds, a general surgery resident at the University of Texas Southwestern Medical Center at Dallas, studied 254 patients who underwent open colorectal surgery, whether planned or converted from a laparoscopic procedure.

In 13% of the patients, surgeons used incisional negative-pressure wound therapy, which entails standard wound closure followed by placement of a wound vacuum device over the completed stapled skin closure.

Study results, reported at the annual meeting of the American Society of Colon and Rectal Surgeons, showed that relative to the group receiving usual wound care, patients receiving incisional negative-pressure wound therapy were two-thirds less likely to develop a surgical site infection.

"Our study, although a retrospective chart review, does seem to show that the use of incisional negative-pressure wound therapy is associated with a decreased risk of surgical site infection," Dr. Bonds asserted. "This finding is significant enough that we feel it further needs a randomized controlled trial to see if there is actually a significant effect in the colorectal population."

Several attendees wondered about the cost of the negative-pressure wound therapy and how that was covered in the study population.

"We didn’t do an official cost analysis," Dr. Bonds replied. "Normally, the device that we used is associated with about $200 extra initially and then ... another $500 a day to use. So it is a fairly expensive addition to the care of the patients." She said she did not have data on how this cost was covered.

Dr. Jason Hall of the Lahey Clinic in Burlington, Mass., asked, "What was the indication to use the vac in those 32 patients?" and further wondered whether the patients receiving this therapy differed in ways that may have confounded the results.

"Placement of the vacuum wound device was left to the discretion of the surgeons," Dr. Bonds replied. "It’s hard to know exactly which patients would have been chosen for the study. There is some chance that the surgeons would have chosen the patients that they didn’t think would have a high rate of infection risk. But from our talking with the surgeons who use this, we believe that most of the vacuum devices were placed on patients who they had a high suspicion were going to get surgical site infections."

She agreed that there might have been selection bias at play, despite the study’s use of multivariate analysis. "That’s exactly why we believe that a randomized controlled trial is really the only way to show whether this is going to be a good technique to use or not," she said.

Cost of the therapy and its coverage will be major issues going forward, according to session comoderator Dr. Mark Welton of Stanford (Calif.) University. "Any time you are talking about downstream benefit to the insurer, they really need to see robust data before they are going to start to pay for that. So, especially in today’s health care environment, it’s going to come back to the patient paying for it. If you could talk about driving the cost associated with the wound infection down significantly, then the insurance companies would pay for it."

"Interestingly, there are companies coming out producing less expensive and less cumbersome devices. So I think it’s actually a very exciting idea, it’s intriguing. But we have a long way to go, and we do get to this cost-benefit question, and who’s going to pay for it," he said in an interview.

Dr. Kim Rhoads, the other session comoderator, also of Stanford University, said that "it’s an interesting concept," but she would like to see a standardized protocol detailing, for example, whether the vacuum and dressing are changed at some point and how long it has to be used for benefit; additionally, the indication for use should be worked out.

Also, "what we didn’t hear is how much fluid actually comes out ... because if nothing is coming out, you have to ask, what’s happening here and would that patient not have otherwise been wound infection free," she said. "We don’t know."

Incisional negative-pressure wound therapy has been used in orthopedic surgery for several years, according to Dr. Bonds. "At UT Southwestern, we began using this in 2010 [in colorectal surgery], and anecdotally saw that it seemed to be decreasing the rate of infections in our patients, so we thought that this warranted further study," she explained.

With this therapy, surgeons close the incision with standard staples, apply a strip of bridge dressing (GranuFoam, made by KCI), and cover the area with clear occlusion tape. The vacuum device (V.A.C. Therapy, made by KCI) is then applied at 75 mm Hg of continuous suction; in patients having a stoma, the stoma is returned after the device is in place.

In the study, the vacuum device was left on until postoperative day 5 or 7, and was removed before patients were discharged, according to Dr. Bonds.

Overall, 27.2% of the patients developed a surgical site infection. The rate was 12.5% in the group given incisional negative-pressure wound therapy, compared with 29.3% in the group given standard care.

In a multivariate analysis, patients in the negative-pressure wound therapy group were 68% less likely to develop a surgical site infection (odds ratio, 0.32; P = .04).

The only other independent predictor of this outcome was diabetes mellitus, which was associated with roughly a doubling of risk (OR, 1.98; P = .03).

"There are several proposed mechanisms for why this therapy would work," Dr. Bonds noted. The device prevents the incision from coming into contact with the surrounding environment, and decreases patient mobility and shear forces on the wound.

"In addition, the continuous suction seems to remove infectious material and the interstitial fluid, thereby decreasing the wound edema. Studies have also shown that the wound vacuum device increases vascularity to the wound, which would seem to help it heal as well," she said.

Dr. Bonds disclosed no relevant conflicts of interest. One coinvestigator has an affiliation with KCI.

PHOENIX – Applying continuous negative pressure to the incisional wound sharply reduces the incidence of surgical site infection after open colorectal surgery, according to results from a retrospective study.

A team led by Dr. Allison M. Bonds, a general surgery resident at the University of Texas Southwestern Medical Center at Dallas, studied 254 patients who underwent open colorectal surgery, whether planned or converted from a laparoscopic procedure.

In 13% of the patients, surgeons used incisional negative-pressure wound therapy, which entails standard wound closure followed by placement of a wound vacuum device over the completed stapled skin closure.

Study results, reported at the annual meeting of the American Society of Colon and Rectal Surgeons, showed that relative to the group receiving usual wound care, patients receiving incisional negative-pressure wound therapy were two-thirds less likely to develop a surgical site infection.

"Our study, although a retrospective chart review, does seem to show that the use of incisional negative-pressure wound therapy is associated with a decreased risk of surgical site infection," Dr. Bonds asserted. "This finding is significant enough that we feel it further needs a randomized controlled trial to see if there is actually a significant effect in the colorectal population."

Several attendees wondered about the cost of the negative-pressure wound therapy and how that was covered in the study population.

"We didn’t do an official cost analysis," Dr. Bonds replied. "Normally, the device that we used is associated with about $200 extra initially and then ... another $500 a day to use. So it is a fairly expensive addition to the care of the patients." She said she did not have data on how this cost was covered.

Dr. Jason Hall of the Lahey Clinic in Burlington, Mass., asked, "What was the indication to use the vac in those 32 patients?" and further wondered whether the patients receiving this therapy differed in ways that may have confounded the results.

"Placement of the vacuum wound device was left to the discretion of the surgeons," Dr. Bonds replied. "It’s hard to know exactly which patients would have been chosen for the study. There is some chance that the surgeons would have chosen the patients that they didn’t think would have a high rate of infection risk. But from our talking with the surgeons who use this, we believe that most of the vacuum devices were placed on patients who they had a high suspicion were going to get surgical site infections."

She agreed that there might have been selection bias at play, despite the study’s use of multivariate analysis. "That’s exactly why we believe that a randomized controlled trial is really the only way to show whether this is going to be a good technique to use or not," she said.

Cost of the therapy and its coverage will be major issues going forward, according to session comoderator Dr. Mark Welton of Stanford (Calif.) University. "Any time you are talking about downstream benefit to the insurer, they really need to see robust data before they are going to start to pay for that. So, especially in today’s health care environment, it’s going to come back to the patient paying for it. If you could talk about driving the cost associated with the wound infection down significantly, then the insurance companies would pay for it."

"Interestingly, there are companies coming out producing less expensive and less cumbersome devices. So I think it’s actually a very exciting idea, it’s intriguing. But we have a long way to go, and we do get to this cost-benefit question, and who’s going to pay for it," he said in an interview.

Dr. Kim Rhoads, the other session comoderator, also of Stanford University, said that "it’s an interesting concept," but she would like to see a standardized protocol detailing, for example, whether the vacuum and dressing are changed at some point and how long it has to be used for benefit; additionally, the indication for use should be worked out.

Also, "what we didn’t hear is how much fluid actually comes out ... because if nothing is coming out, you have to ask, what’s happening here and would that patient not have otherwise been wound infection free," she said. "We don’t know."

Incisional negative-pressure wound therapy has been used in orthopedic surgery for several years, according to Dr. Bonds. "At UT Southwestern, we began using this in 2010 [in colorectal surgery], and anecdotally saw that it seemed to be decreasing the rate of infections in our patients, so we thought that this warranted further study," she explained.

With this therapy, surgeons close the incision with standard staples, apply a strip of bridge dressing (GranuFoam, made by KCI), and cover the area with clear occlusion tape. The vacuum device (V.A.C. Therapy, made by KCI) is then applied at 75 mm Hg of continuous suction; in patients having a stoma, the stoma is returned after the device is in place.

In the study, the vacuum device was left on until postoperative day 5 or 7, and was removed before patients were discharged, according to Dr. Bonds.

Overall, 27.2% of the patients developed a surgical site infection. The rate was 12.5% in the group given incisional negative-pressure wound therapy, compared with 29.3% in the group given standard care.

In a multivariate analysis, patients in the negative-pressure wound therapy group were 68% less likely to develop a surgical site infection (odds ratio, 0.32; P = .04).

The only other independent predictor of this outcome was diabetes mellitus, which was associated with roughly a doubling of risk (OR, 1.98; P = .03).

"There are several proposed mechanisms for why this therapy would work," Dr. Bonds noted. The device prevents the incision from coming into contact with the surrounding environment, and decreases patient mobility and shear forces on the wound.

"In addition, the continuous suction seems to remove infectious material and the interstitial fluid, thereby decreasing the wound edema. Studies have also shown that the wound vacuum device increases vascularity to the wound, which would seem to help it heal as well," she said.

Dr. Bonds disclosed no relevant conflicts of interest. One coinvestigator has an affiliation with KCI.

CHICAGO – The benefit of everolimus in hormone receptor–positive, HER2-negative advanced breast cancer appears to be greater for women who have little or no genetic alteration in this cancer’s most commonly altered molecular signaling pathways, based on data presented at the annual meeting of the American Society of Clinical Oncology.

A team led by Dr. Gabriel N. Hortobagyi performed next-generation sequencing on archival tumor tissue from patients enrolled in the randomized BOLERO-2 trial, which tested the addition to exemestane of everolimus, an inhibitor of the mammalian target of rapamycin (mTOR).

Among all 227 patients whose tumors were tested, adding everolimus reduced the risk of progression or death by 60% as compared with adding placebo.

Patients having alterations in any of the four genes that were most commonly altered in the tumors or that were part of their respective signaling pathways derived similar benefit from everolimus as patients who had wild-type (normal) genes.

Thus, "no predictive marker of everolimus efficacy was identified in individual analysis of the four pathways," commented Dr. Hortobagyi, who chairs the department of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

However, there was differential benefit when patients were broadly grouped according to the extent of alterations – either minimal or multiple.

Three-fourths had minimal (none or one) alteration of these genes or another gene lying on the same pathway: the PIK3CA gene or the PTEN gene (PI3 kinase pathway), the CCND1 gene (cell cycle pathway), or the FGFR1 gene (FGFR1/2 pathway).

This group had a 73% reduction in the risk of progression or death if given everolimus as compared with placebo. In contrast, the group having multiple (two or more) alterations of these genes had a much smaller 22% reduction in risk.

"Further delineation of the interaction of these genetic events might help us to understand how the oncogenic signal cascades work and find better options to attenuate disease progression," Dr. Hortobagyi proposed. "These results are hypothesis generating only and should be validated in independent patient cohorts. But if confirmed, they could lead to new hypotheses for development of novel and more effective combination targeted therapies in hormone receptor–positive, HER2-negative breast cancer."

Session attendee Dr. Larry Norton of the Memorial Sloan-Kettering Cancer Center in New York, asked, "How many of these biopsies came from metastatic lesions and how many came from the primary? And if you just looked at the ones from the metastatic sites, do you see any differences there, because as we know, there is clonal evolution in the metastatic sites."

"About 20% came from metastatic disease, and about 80% from the primary. There are a number of individual differences between the two groups, but unfortunately, the numbers in the metastatic group are so small that you can’t really derive patterns," Dr. Hortobagyi replied. "Now all of the samples, both the primary and the metastatic ones, were from before the study, so it would not really directly reflect on the study itself. But that’s a very important question that we eventually have to address."

Attendee Dr. Ian Krop of the Dana-Farber Cancer Institute in Boston, commented, "It was interesting that those tumors that had multiple alterations in one of those four genes had what appeared to be decreased benefit from everolimus. Could that represent just genomic instability? In other words, if you look at random alterations in your data set, did that also correlate with lack of benefit?"

"We looked at that, and the genetic background for the two groups is very similar," Dr. Hortobagyi replied. "So my a priori thinking was exactly as you mentioned, that those would be associated with instability and therefore multiple driver pathways. But we did not see that."

Women in the BOLERO-2 trial were postmenopausal and had locally advanced or metastatic breast cancer that was refractory to a nonsteroidal aromatase inhibitor. They were assigned 2:1 to exemestane (brand name Aromasin) plus either everolimus (Afinitor) or placebo.

Everolimus is currently approved by the Food and Drug Administration for use in combination with exemestane to treat advanced hormone receptor–positive breast cancer in postmenopausal women. It is also approved for selected indications in other cancers.

In the new retrospective exploratory analysis, Dr. Hortobagyi’s team collected formalin-fixed, paraffin-embedded archival tumor tissue in a subset of patients and performed sequencing for 3,230 exons in 182 oncogenes and tumor suppressor genes.

Results showed that the four most commonly altered genes were PIK3CA (altered in 48% of patients), CCND1 (31%), TP53 (23%), and FGFR1 (18%).

In the patient subset as a whole, addition of everolimus was associated with a significant reduction in the risk of progression or death (hazard ratio, 0.40) similar to that previously reported in the entire trial population (HR, 0.45).

Neither alteration of any one of these four genes nor alteration of any one gene in their respective pathways predicted everolimus benefit. "Basically, the treatment effect was independent of the genetic status of these genes and pathways," Dr. Hortobagyi commented.

But when the pathways were considered simultaneously, patients having minimal genetic alteration derived a progression-free survival benefit from everolimus that exceeded that in the whole subset (HR, 0.27), whereas their counterparts having multiple alterations derived a benefit much less than that in the whole subset (HR, 0.78).

Dr. Hortobagyi disclosed that he is a consultant to Allergan, AstraZeneca, Galena Biopharma, Genentech, Myriad Genetics, Novartis, and Sanofi; receives research funding from Novartis; and has other affiliations with Genentech, Novartis, and Sanofi. The BOLERO-2 trial was sponsored by Novartis.

CHICAGO – The benefit of everolimus in hormone receptor–positive, HER2-negative advanced breast cancer appears to be greater for women who have little or no genetic alteration in this cancer’s most commonly altered molecular signaling pathways, based on data presented at the annual meeting of the American Society of Clinical Oncology.

A team led by Dr. Gabriel N. Hortobagyi performed next-generation sequencing on archival tumor tissue from patients enrolled in the randomized BOLERO-2 trial, which tested the addition to exemestane of everolimus, an inhibitor of the mammalian target of rapamycin (mTOR).

Among all 227 patients whose tumors were tested, adding everolimus reduced the risk of progression or death by 60% as compared with adding placebo.

Patients having alterations in any of the four genes that were most commonly altered in the tumors or that were part of their respective signaling pathways derived similar benefit from everolimus as patients who had wild-type (normal) genes.

Thus, "no predictive marker of everolimus efficacy was identified in individual analysis of the four pathways," commented Dr. Hortobagyi, who chairs the department of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

However, there was differential benefit when patients were broadly grouped according to the extent of alterations – either minimal or multiple.

Three-fourths had minimal (none or one) alteration of these genes or another gene lying on the same pathway: the PIK3CA gene or the PTEN gene (PI3 kinase pathway), the CCND1 gene (cell cycle pathway), or the FGFR1 gene (FGFR1/2 pathway).

This group had a 73% reduction in the risk of progression or death if given everolimus as compared with placebo. In contrast, the group having multiple (two or more) alterations of these genes had a much smaller 22% reduction in risk.

"Further delineation of the interaction of these genetic events might help us to understand how the oncogenic signal cascades work and find better options to attenuate disease progression," Dr. Hortobagyi proposed. "These results are hypothesis generating only and should be validated in independent patient cohorts. But if confirmed, they could lead to new hypotheses for development of novel and more effective combination targeted therapies in hormone receptor–positive, HER2-negative breast cancer."

Session attendee Dr. Larry Norton of the Memorial Sloan-Kettering Cancer Center in New York, asked, "How many of these biopsies came from metastatic lesions and how many came from the primary? And if you just looked at the ones from the metastatic sites, do you see any differences there, because as we know, there is clonal evolution in the metastatic sites."

"About 20% came from metastatic disease, and about 80% from the primary. There are a number of individual differences between the two groups, but unfortunately, the numbers in the metastatic group are so small that you can’t really derive patterns," Dr. Hortobagyi replied. "Now all of the samples, both the primary and the metastatic ones, were from before the study, so it would not really directly reflect on the study itself. But that’s a very important question that we eventually have to address."

Attendee Dr. Ian Krop of the Dana-Farber Cancer Institute in Boston, commented, "It was interesting that those tumors that had multiple alterations in one of those four genes had what appeared to be decreased benefit from everolimus. Could that represent just genomic instability? In other words, if you look at random alterations in your data set, did that also correlate with lack of benefit?"

"We looked at that, and the genetic background for the two groups is very similar," Dr. Hortobagyi replied. "So my a priori thinking was exactly as you mentioned, that those would be associated with instability and therefore multiple driver pathways. But we did not see that."

Women in the BOLERO-2 trial were postmenopausal and had locally advanced or metastatic breast cancer that was refractory to a nonsteroidal aromatase inhibitor. They were assigned 2:1 to exemestane (brand name Aromasin) plus either everolimus (Afinitor) or placebo.

Everolimus is currently approved by the Food and Drug Administration for use in combination with exemestane to treat advanced hormone receptor–positive breast cancer in postmenopausal women. It is also approved for selected indications in other cancers.

In the new retrospective exploratory analysis, Dr. Hortobagyi’s team collected formalin-fixed, paraffin-embedded archival tumor tissue in a subset of patients and performed sequencing for 3,230 exons in 182 oncogenes and tumor suppressor genes.

Results showed that the four most commonly altered genes were PIK3CA (altered in 48% of patients), CCND1 (31%), TP53 (23%), and FGFR1 (18%).

In the patient subset as a whole, addition of everolimus was associated with a significant reduction in the risk of progression or death (hazard ratio, 0.40) similar to that previously reported in the entire trial population (HR, 0.45).

Neither alteration of any one of these four genes nor alteration of any one gene in their respective pathways predicted everolimus benefit. "Basically, the treatment effect was independent of the genetic status of these genes and pathways," Dr. Hortobagyi commented.

But when the pathways were considered simultaneously, patients having minimal genetic alteration derived a progression-free survival benefit from everolimus that exceeded that in the whole subset (HR, 0.27), whereas their counterparts having multiple alterations derived a benefit much less than that in the whole subset (HR, 0.78).

Dr. Hortobagyi disclosed that he is a consultant to Allergan, AstraZeneca, Galena Biopharma, Genentech, Myriad Genetics, Novartis, and Sanofi; receives research funding from Novartis; and has other affiliations with Genentech, Novartis, and Sanofi. The BOLERO-2 trial was sponsored by Novartis.

CHICAGO – The benefit of everolimus in hormone receptor–positive, HER2-negative advanced breast cancer appears to be greater for women who have little or no genetic alteration in this cancer’s most commonly altered molecular signaling pathways, based on data presented at the annual meeting of the American Society of Clinical Oncology.

A team led by Dr. Gabriel N. Hortobagyi performed next-generation sequencing on archival tumor tissue from patients enrolled in the randomized BOLERO-2 trial, which tested the addition to exemestane of everolimus, an inhibitor of the mammalian target of rapamycin (mTOR).

Among all 227 patients whose tumors were tested, adding everolimus reduced the risk of progression or death by 60% as compared with adding placebo.

Patients having alterations in any of the four genes that were most commonly altered in the tumors or that were part of their respective signaling pathways derived similar benefit from everolimus as patients who had wild-type (normal) genes.

Thus, "no predictive marker of everolimus efficacy was identified in individual analysis of the four pathways," commented Dr. Hortobagyi, who chairs the department of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

However, there was differential benefit when patients were broadly grouped according to the extent of alterations – either minimal or multiple.

Three-fourths had minimal (none or one) alteration of these genes or another gene lying on the same pathway: the PIK3CA gene or the PTEN gene (PI3 kinase pathway), the CCND1 gene (cell cycle pathway), or the FGFR1 gene (FGFR1/2 pathway).

This group had a 73% reduction in the risk of progression or death if given everolimus as compared with placebo. In contrast, the group having multiple (two or more) alterations of these genes had a much smaller 22% reduction in risk.

"Further delineation of the interaction of these genetic events might help us to understand how the oncogenic signal cascades work and find better options to attenuate disease progression," Dr. Hortobagyi proposed. "These results are hypothesis generating only and should be validated in independent patient cohorts. But if confirmed, they could lead to new hypotheses for development of novel and more effective combination targeted therapies in hormone receptor–positive, HER2-negative breast cancer."

Session attendee Dr. Larry Norton of the Memorial Sloan-Kettering Cancer Center in New York, asked, "How many of these biopsies came from metastatic lesions and how many came from the primary? And if you just looked at the ones from the metastatic sites, do you see any differences there, because as we know, there is clonal evolution in the metastatic sites."

"About 20% came from metastatic disease, and about 80% from the primary. There are a number of individual differences between the two groups, but unfortunately, the numbers in the metastatic group are so small that you can’t really derive patterns," Dr. Hortobagyi replied. "Now all of the samples, both the primary and the metastatic ones, were from before the study, so it would not really directly reflect on the study itself. But that’s a very important question that we eventually have to address."

Attendee Dr. Ian Krop of the Dana-Farber Cancer Institute in Boston, commented, "It was interesting that those tumors that had multiple alterations in one of those four genes had what appeared to be decreased benefit from everolimus. Could that represent just genomic instability? In other words, if you look at random alterations in your data set, did that also correlate with lack of benefit?"

"We looked at that, and the genetic background for the two groups is very similar," Dr. Hortobagyi replied. "So my a priori thinking was exactly as you mentioned, that those would be associated with instability and therefore multiple driver pathways. But we did not see that."

Women in the BOLERO-2 trial were postmenopausal and had locally advanced or metastatic breast cancer that was refractory to a nonsteroidal aromatase inhibitor. They were assigned 2:1 to exemestane (brand name Aromasin) plus either everolimus (Afinitor) or placebo.

Everolimus is currently approved by the Food and Drug Administration for use in combination with exemestane to treat advanced hormone receptor–positive breast cancer in postmenopausal women. It is also approved for selected indications in other cancers.

In the new retrospective exploratory analysis, Dr. Hortobagyi’s team collected formalin-fixed, paraffin-embedded archival tumor tissue in a subset of patients and performed sequencing for 3,230 exons in 182 oncogenes and tumor suppressor genes.

Results showed that the four most commonly altered genes were PIK3CA (altered in 48% of patients), CCND1 (31%), TP53 (23%), and FGFR1 (18%).

In the patient subset as a whole, addition of everolimus was associated with a significant reduction in the risk of progression or death (hazard ratio, 0.40) similar to that previously reported in the entire trial population (HR, 0.45).

Neither alteration of any one of these four genes nor alteration of any one gene in their respective pathways predicted everolimus benefit. "Basically, the treatment effect was independent of the genetic status of these genes and pathways," Dr. Hortobagyi commented.

But when the pathways were considered simultaneously, patients having minimal genetic alteration derived a progression-free survival benefit from everolimus that exceeded that in the whole subset (HR, 0.27), whereas their counterparts having multiple alterations derived a benefit much less than that in the whole subset (HR, 0.78).

Dr. Hortobagyi disclosed that he is a consultant to Allergan, AstraZeneca, Galena Biopharma, Genentech, Myriad Genetics, Novartis, and Sanofi; receives research funding from Novartis; and has other affiliations with Genentech, Novartis, and Sanofi. The BOLERO-2 trial was sponsored by Novartis.

CHICAGO – Upamostat, an investigational oral inhibitor of urokinase-type plasminogen activator, did not add to the efficacy of capecitabine monotherapy when given as first-line therapy to unselected patients with HER2-negative metastatic breast cancer, based on the results of a phase II trial.

The 132 women studied were assigned evenly to capecitabine monotherapy or to capecitabine plus upamostat. Median progression-free survival, the trial’s primary endpoint, was statistically indistinguishable at about 8 months in each group.

Courtesy Fox Chase Cancer Center

However, upamostat was associated with a 4-month gain in this outcome in the subset of patients who had previously received chemotherapy in the adjuvant or neoadjuvant setting, an unplanned exploratory analysis found.

"Treatment with prior chemotherapy potentially defines a more homogeneous subpopulation in this study. Also, prior chemotherapy could possibly identify a population with more aggressive disease due to higher expression of uPA [urokinase-type plasminogen activator]," said lead author Dr. Lori J. Goldstein of the Fox Chase Cancer Center in Philadelphia. "This would be in line with the treatment effects seen in the group who progressed early after initial diagnosis."

"Future studies with upamostat should target a more homogeneous patient population and incorporate biomarker-specific strategies for patient characterization and selection," Dr. Goldstein recommended.

Adding upamostat to chemotherapy, for nearly 3 years in some cases, was generally safe and well tolerated. The only increase in adverse events was in the incidence of hand-foot syndrome.

"Upamostat can safely be given over extended periods of time. [The study] is also the first proof of activity of an anti-uPA inhibitor in breast cancer therapy," Dr. Goldstein said at the annual meeting of the American Society of Clinical Oncology.

Part of the plasminogen activation system, uPA promotes tumor cell invasion, migration, and proliferation, Dr. Goldstein explained, giving some background to the research.

"As the uPA system is quantitatively more expressed in tumor cells and tumor-associated stromal cells, it is an interesting target for cancer therapy. uPA and PAI-1 [plasminogen activator inhibitor-1] are both ASCO-recommended prognostic and predictive biomarkers for early-stage breast cancer," she said.

Among all the patients enrolled in the trial, median progression-free survival was 8.3 months with the upamostat-capecitabine combination and 7.5 months with capecitabine alone, a nonsignificant difference. The estimated 6-month rates of progression-free survival were 56% and 50%.

Archival tumor specimens were not available for uPA and PAI-1 testing, according to Dr. Goldstein. And testing of serial plasma samples for a variety of biomarkers – uPA, PAI-1, CAIX (a marker associated with poorer prognostic features), and the fibrin degradation product D-dimer – failed to show any differences between groups.

In unplanned exploratory analyses, median progression-free survival among patients who had received prior adjuvant or neoadjuvant chemotherapy was 8.3 months with upamostat-capecitabine combination therapy and 4.3 months with capecitabine monotherapy.

The combination therapy also seemed to have an edge among patients who had experienced their recurrence within 3 years from initial diagnosis (5.6 vs. 2.7 months), Dr. Goldstein reported.

The upamostat-capecitabine group had a higher rate of any-grade hand-foot syndrome (77% vs. 46%), possibly related to a longer duration of treatment, whereas rates of other toxicities were similar.

"The pharmacokinetic analyses demonstrated no drug-drug interactions between upamostat and capecitabine," she noted.

Dr. Goldstein disclosed that she receives research funding from the U.S. Department of Defense and Wilex. The trial was sponsored by Wilex, the maker of upamostat.

CHICAGO – Upamostat, an investigational oral inhibitor of urokinase-type plasminogen activator, did not add to the efficacy of capecitabine monotherapy when given as first-line therapy to unselected patients with HER2-negative metastatic breast cancer, based on the results of a phase II trial.

The 132 women studied were assigned evenly to capecitabine monotherapy or to capecitabine plus upamostat. Median progression-free survival, the trial’s primary endpoint, was statistically indistinguishable at about 8 months in each group.

Courtesy Fox Chase Cancer Center

However, upamostat was associated with a 4-month gain in this outcome in the subset of patients who had previously received chemotherapy in the adjuvant or neoadjuvant setting, an unplanned exploratory analysis found.

"Treatment with prior chemotherapy potentially defines a more homogeneous subpopulation in this study. Also, prior chemotherapy could possibly identify a population with more aggressive disease due to higher expression of uPA [urokinase-type plasminogen activator]," said lead author Dr. Lori J. Goldstein of the Fox Chase Cancer Center in Philadelphia. "This would be in line with the treatment effects seen in the group who progressed early after initial diagnosis."

"Future studies with upamostat should target a more homogeneous patient population and incorporate biomarker-specific strategies for patient characterization and selection," Dr. Goldstein recommended.

Adding upamostat to chemotherapy, for nearly 3 years in some cases, was generally safe and well tolerated. The only increase in adverse events was in the incidence of hand-foot syndrome.

"Upamostat can safely be given over extended periods of time. [The study] is also the first proof of activity of an anti-uPA inhibitor in breast cancer therapy," Dr. Goldstein said at the annual meeting of the American Society of Clinical Oncology.

Part of the plasminogen activation system, uPA promotes tumor cell invasion, migration, and proliferation, Dr. Goldstein explained, giving some background to the research.

"As the uPA system is quantitatively more expressed in tumor cells and tumor-associated stromal cells, it is an interesting target for cancer therapy. uPA and PAI-1 [plasminogen activator inhibitor-1] are both ASCO-recommended prognostic and predictive biomarkers for early-stage breast cancer," she said.

Among all the patients enrolled in the trial, median progression-free survival was 8.3 months with the upamostat-capecitabine combination and 7.5 months with capecitabine alone, a nonsignificant difference. The estimated 6-month rates of progression-free survival were 56% and 50%.

Archival tumor specimens were not available for uPA and PAI-1 testing, according to Dr. Goldstein. And testing of serial plasma samples for a variety of biomarkers – uPA, PAI-1, CAIX (a marker associated with poorer prognostic features), and the fibrin degradation product D-dimer – failed to show any differences between groups.

In unplanned exploratory analyses, median progression-free survival among patients who had received prior adjuvant or neoadjuvant chemotherapy was 8.3 months with upamostat-capecitabine combination therapy and 4.3 months with capecitabine monotherapy.

The combination therapy also seemed to have an edge among patients who had experienced their recurrence within 3 years from initial diagnosis (5.6 vs. 2.7 months), Dr. Goldstein reported.

The upamostat-capecitabine group had a higher rate of any-grade hand-foot syndrome (77% vs. 46%), possibly related to a longer duration of treatment, whereas rates of other toxicities were similar.

"The pharmacokinetic analyses demonstrated no drug-drug interactions between upamostat and capecitabine," she noted.

Dr. Goldstein disclosed that she receives research funding from the U.S. Department of Defense and Wilex. The trial was sponsored by Wilex, the maker of upamostat.

CHICAGO – Upamostat, an investigational oral inhibitor of urokinase-type plasminogen activator, did not add to the efficacy of capecitabine monotherapy when given as first-line therapy to unselected patients with HER2-negative metastatic breast cancer, based on the results of a phase II trial.

The 132 women studied were assigned evenly to capecitabine monotherapy or to capecitabine plus upamostat. Median progression-free survival, the trial’s primary endpoint, was statistically indistinguishable at about 8 months in each group.

Courtesy Fox Chase Cancer Center

However, upamostat was associated with a 4-month gain in this outcome in the subset of patients who had previously received chemotherapy in the adjuvant or neoadjuvant setting, an unplanned exploratory analysis found.

"Treatment with prior chemotherapy potentially defines a more homogeneous subpopulation in this study. Also, prior chemotherapy could possibly identify a population with more aggressive disease due to higher expression of uPA [urokinase-type plasminogen activator]," said lead author Dr. Lori J. Goldstein of the Fox Chase Cancer Center in Philadelphia. "This would be in line with the treatment effects seen in the group who progressed early after initial diagnosis."

"Future studies with upamostat should target a more homogeneous patient population and incorporate biomarker-specific strategies for patient characterization and selection," Dr. Goldstein recommended.

Adding upamostat to chemotherapy, for nearly 3 years in some cases, was generally safe and well tolerated. The only increase in adverse events was in the incidence of hand-foot syndrome.

"Upamostat can safely be given over extended periods of time. [The study] is also the first proof of activity of an anti-uPA inhibitor in breast cancer therapy," Dr. Goldstein said at the annual meeting of the American Society of Clinical Oncology.

Part of the plasminogen activation system, uPA promotes tumor cell invasion, migration, and proliferation, Dr. Goldstein explained, giving some background to the research.

"As the uPA system is quantitatively more expressed in tumor cells and tumor-associated stromal cells, it is an interesting target for cancer therapy. uPA and PAI-1 [plasminogen activator inhibitor-1] are both ASCO-recommended prognostic and predictive biomarkers for early-stage breast cancer," she said.

Among all the patients enrolled in the trial, median progression-free survival was 8.3 months with the upamostat-capecitabine combination and 7.5 months with capecitabine alone, a nonsignificant difference. The estimated 6-month rates of progression-free survival were 56% and 50%.

Archival tumor specimens were not available for uPA and PAI-1 testing, according to Dr. Goldstein. And testing of serial plasma samples for a variety of biomarkers – uPA, PAI-1, CAIX (a marker associated with poorer prognostic features), and the fibrin degradation product D-dimer – failed to show any differences between groups.

In unplanned exploratory analyses, median progression-free survival among patients who had received prior adjuvant or neoadjuvant chemotherapy was 8.3 months with upamostat-capecitabine combination therapy and 4.3 months with capecitabine monotherapy.

The combination therapy also seemed to have an edge among patients who had experienced their recurrence within 3 years from initial diagnosis (5.6 vs. 2.7 months), Dr. Goldstein reported.

The upamostat-capecitabine group had a higher rate of any-grade hand-foot syndrome (77% vs. 46%), possibly related to a longer duration of treatment, whereas rates of other toxicities were similar.

"The pharmacokinetic analyses demonstrated no drug-drug interactions between upamostat and capecitabine," she noted.

Dr. Goldstein disclosed that she receives research funding from the U.S. Department of Defense and Wilex. The trial was sponsored by Wilex, the maker of upamostat.