Breast Cancer

WASHINGTON – Higher levels of stress may partially account for aggressive tumor growth in African American and Hispanic women with breast cancer, according to Garth H. Rauscher, Ph.D., of the University of Illinois at Chicago.

This is one of the first studies to look closely at the potential role of psychosocial stress on tumor progression in breast cancer, said Dr. Rauscher, an associate professor of epidemiology at the university’s School of Public Health. However, he acknowledged that the study is "flawed" because it is cross-sectional and has other limitations. "This is definitely an exploratory study," Dr. Rauscher said at the American Association for Cancer Research Science of Cancer Health Disparities meeting.

It was already known, especially in Chicago, that there was a wide disparity in mortality rates between black women and white women, said Dr. Rauscher. The data are not as well defined for Hispanic women, he said. Tumor aggressiveness likely contributes to higher mortality rates in the minorities. Both African Americans and Hispanics generally have higher-grade tumors and hormone receptor–negative tumors, said Dr. Rauscher. The researchers wanted to investigate why these women have the more aggressive tumor types.

They chose to examine psychosocial factors.

Dr. Rauscher and his colleagues examined associations between patient-reported stress and aggressive breast cancer in a cross-sectional study of 397 non-Hispanic whites, 411 non-Hispanic blacks, and 181 Hispanics. Data were collected through patient interviews and medical record extraction. Stress was assessed using the four-item Cohen Perceived Stress Subscale, the UCLA Loneliness Scale, and the Cockburn psychological consequences scale. The three scales were combined into a single, standardized stress score.

Patients were interviewed just after their diagnosis of breast cancer. Dr. Rauscher explained that the researchers assumed that if patients were experiencing high stress post diagnosis, they were likely to have been under stress before diagnosis as well. But he acknowledged that this assumption is a major limitation of the study.

Of 989 patients, the researchers were able to get tumor grades for 772: 149 had low-grade tumors; 308 were intermediate, and 315 were high-grade tumors. A total of 21% (66 of 315) of patients with high-grade tumors reported elevated stress, 19% (58 of 308) of patients with intermediate-grade tumors reported elevated stress, and 11% (16 of 149) of patients with low-grade tumors reported elevated stress.

The differences were statistically significant, until Dr. Rauscher and his colleagues adjusted for age, treatment, income, and other factors.

A total of 28% of women with hormone receptor–negative tumors reported stress, compared with 14% of those with receptor-positive growths. Patients with hormone receptor–negative disease reported one-third of a standard deviation higher than did patients with receptor-positive disease (P = .0003). The difference held up after adjustment, Dr. Rauscher said.

Overall, psychosocial stress scores were higher for black and Hispanic women than for whites.

There’s still no way to know, however, what accounts for those differences, said Dr. Rauscher. "If you have a more aggressive diagnosis, does that make you worry more? You could certainly put that out there as a possibility," he said. Patients with more aggressive disease might also undergo more aggressive treatment, which could also lead to greater stress, he said. "There could be causal arrows going in both directions here, but we can’t tease that out." Even so, he said, "our results are consistent with a role for stress in the etiology of aggressive breast cancer."

Dr. Rauscher suggested that other researchers could help confirm his work by delving further into existing cohort studies that measured stress and had banked tumor samples. By comparing tumor type to patients reporting stress, they might be able to tease out an association, he said.

Dr. Rauscher reported no conflicts.

WASHINGTON – Higher levels of stress may partially account for aggressive tumor growth in African American and Hispanic women with breast cancer, according to Garth H. Rauscher, Ph.D., of the University of Illinois at Chicago.

This is one of the first studies to look closely at the potential role of psychosocial stress on tumor progression in breast cancer, said Dr. Rauscher, an associate professor of epidemiology at the university’s School of Public Health. However, he acknowledged that the study is "flawed" because it is cross-sectional and has other limitations. "This is definitely an exploratory study," Dr. Rauscher said at the American Association for Cancer Research Science of Cancer Health Disparities meeting.

It was already known, especially in Chicago, that there was a wide disparity in mortality rates between black women and white women, said Dr. Rauscher. The data are not as well defined for Hispanic women, he said. Tumor aggressiveness likely contributes to higher mortality rates in the minorities. Both African Americans and Hispanics generally have higher-grade tumors and hormone receptor–negative tumors, said Dr. Rauscher. The researchers wanted to investigate why these women have the more aggressive tumor types.

They chose to examine psychosocial factors.

Dr. Rauscher and his colleagues examined associations between patient-reported stress and aggressive breast cancer in a cross-sectional study of 397 non-Hispanic whites, 411 non-Hispanic blacks, and 181 Hispanics. Data were collected through patient interviews and medical record extraction. Stress was assessed using the four-item Cohen Perceived Stress Subscale, the UCLA Loneliness Scale, and the Cockburn psychological consequences scale. The three scales were combined into a single, standardized stress score.

Patients were interviewed just after their diagnosis of breast cancer. Dr. Rauscher explained that the researchers assumed that if patients were experiencing high stress post diagnosis, they were likely to have been under stress before diagnosis as well. But he acknowledged that this assumption is a major limitation of the study.

Of 989 patients, the researchers were able to get tumor grades for 772: 149 had low-grade tumors; 308 were intermediate, and 315 were high-grade tumors. A total of 21% (66 of 315) of patients with high-grade tumors reported elevated stress, 19% (58 of 308) of patients with intermediate-grade tumors reported elevated stress, and 11% (16 of 149) of patients with low-grade tumors reported elevated stress.

The differences were statistically significant, until Dr. Rauscher and his colleagues adjusted for age, treatment, income, and other factors.

A total of 28% of women with hormone receptor–negative tumors reported stress, compared with 14% of those with receptor-positive growths. Patients with hormone receptor–negative disease reported one-third of a standard deviation higher than did patients with receptor-positive disease (P = .0003). The difference held up after adjustment, Dr. Rauscher said.

Overall, psychosocial stress scores were higher for black and Hispanic women than for whites.

There’s still no way to know, however, what accounts for those differences, said Dr. Rauscher. "If you have a more aggressive diagnosis, does that make you worry more? You could certainly put that out there as a possibility," he said. Patients with more aggressive disease might also undergo more aggressive treatment, which could also lead to greater stress, he said. "There could be causal arrows going in both directions here, but we can’t tease that out." Even so, he said, "our results are consistent with a role for stress in the etiology of aggressive breast cancer."

Dr. Rauscher suggested that other researchers could help confirm his work by delving further into existing cohort studies that measured stress and had banked tumor samples. By comparing tumor type to patients reporting stress, they might be able to tease out an association, he said.

Dr. Rauscher reported no conflicts.

WASHINGTON – Higher levels of stress may partially account for aggressive tumor growth in African American and Hispanic women with breast cancer, according to Garth H. Rauscher, Ph.D., of the University of Illinois at Chicago.

This is one of the first studies to look closely at the potential role of psychosocial stress on tumor progression in breast cancer, said Dr. Rauscher, an associate professor of epidemiology at the university’s School of Public Health. However, he acknowledged that the study is "flawed" because it is cross-sectional and has other limitations. "This is definitely an exploratory study," Dr. Rauscher said at the American Association for Cancer Research Science of Cancer Health Disparities meeting.

It was already known, especially in Chicago, that there was a wide disparity in mortality rates between black women and white women, said Dr. Rauscher. The data are not as well defined for Hispanic women, he said. Tumor aggressiveness likely contributes to higher mortality rates in the minorities. Both African Americans and Hispanics generally have higher-grade tumors and hormone receptor–negative tumors, said Dr. Rauscher. The researchers wanted to investigate why these women have the more aggressive tumor types.

They chose to examine psychosocial factors.

Dr. Rauscher and his colleagues examined associations between patient-reported stress and aggressive breast cancer in a cross-sectional study of 397 non-Hispanic whites, 411 non-Hispanic blacks, and 181 Hispanics. Data were collected through patient interviews and medical record extraction. Stress was assessed using the four-item Cohen Perceived Stress Subscale, the UCLA Loneliness Scale, and the Cockburn psychological consequences scale. The three scales were combined into a single, standardized stress score.

Patients were interviewed just after their diagnosis of breast cancer. Dr. Rauscher explained that the researchers assumed that if patients were experiencing high stress post diagnosis, they were likely to have been under stress before diagnosis as well. But he acknowledged that this assumption is a major limitation of the study.

Of 989 patients, the researchers were able to get tumor grades for 772: 149 had low-grade tumors; 308 were intermediate, and 315 were high-grade tumors. A total of 21% (66 of 315) of patients with high-grade tumors reported elevated stress, 19% (58 of 308) of patients with intermediate-grade tumors reported elevated stress, and 11% (16 of 149) of patients with low-grade tumors reported elevated stress.

The differences were statistically significant, until Dr. Rauscher and his colleagues adjusted for age, treatment, income, and other factors.

A total of 28% of women with hormone receptor–negative tumors reported stress, compared with 14% of those with receptor-positive growths. Patients with hormone receptor–negative disease reported one-third of a standard deviation higher than did patients with receptor-positive disease (P = .0003). The difference held up after adjustment, Dr. Rauscher said.

Overall, psychosocial stress scores were higher for black and Hispanic women than for whites.

There’s still no way to know, however, what accounts for those differences, said Dr. Rauscher. "If you have a more aggressive diagnosis, does that make you worry more? You could certainly put that out there as a possibility," he said. Patients with more aggressive disease might also undergo more aggressive treatment, which could also lead to greater stress, he said. "There could be causal arrows going in both directions here, but we can’t tease that out." Even so, he said, "our results are consistent with a role for stress in the etiology of aggressive breast cancer."

Dr. Rauscher suggested that other researchers could help confirm his work by delving further into existing cohort studies that measured stress and had banked tumor samples. By comparing tumor type to patients reporting stress, they might be able to tease out an association, he said.

Dr. Rauscher reported no conflicts.

SAN FRANCISCO – The development of taxane-induced peripheral neuropathy does not appear to be a marker for better outcomes in women with early breast cancer, new data show.

In a secondary analysis of the Eastern Cooperative Oncology Group E1199 trial involving 4,554 women, 13%-22% developed peripheral neuropathy, depending on which of four taxane regimens they received.

The women who developed peripheral neuropathy did not have better recurrence-free, disease-free, or overall survival than did their counterparts who escaped this toxicity, lead investigator Dr. Bryan P. Schneider reported on behalf of several North American breast cancer groups. Results were the same regardless of tumor type (estrogen receptor positive, HER2 positive, or triple negative) and the taxane regimen received.

He noted that the findings are important, given recent identification of six single-nucleotide polymorphisms (SNPs) predicting the likelihood of peripheral neuropathy in women receiving paclitaxel-containing chemotherapy (ASCO 2011, abstract 1000).

"Neuropathy did not correlate with outcome in E1199. The relevance is that SNPs or biomarkers that predict a subgroup protected from neuropathy are thus unlikely to enrich for inferior outcome," he explained.

Discussant Dr. William J. Gradishar, director of the center for women’s cancer care at Northwestern University in Chicago, said that "at the end of the day, at least with the present data we have, it doesn’t appear that the presence of neuropathy has any bearing on overall clinical outcome from those end points."

Trials thus far have failed to identify effective agents for preventing peripheral neuropathy in this setting, but there are some new agents on the horizon, he noted.

"The hope will be, because these [chemotherapy drugs] are such a mainstay of our therapies in both the adjuvant and metastatic disease setting, that one or a few of [the new agents] may ultimately prove to be fruitful for our patients," concluded Dr. Gradishar.

Women participating in the E1199 trial all received four cycles of doxorubicin and cyclophosphamide. They then received one of four taxane regimens: paclitaxel (Taxol) every 3 weeks for 4 cycles (control), paclitaxel weekly for 12 cycles, docetaxel (Taxotere) every 3 weeks for 4 cycles, or docetaxel weekly for 12 cycles. Median follow-up was 95.5 months.

Peripheral neuropathy (grade 2-4, either sensory or motor) was the most common nonhematologic toxicity seen in the trial, according to Dr. Schneider of Indiana University in Indianapolis. It occurred in 22.0% of women treated with weekly paclitaxel, in 17.5% of women treated with paclitaxel every 3 weeks, in 14.7% of women treated with docetaxel every 3 weeks, and in 13.4% of women treated with weekly docetaxel.

In a multivariate model, women were significantly more likely to develop peripheral neuropathy if they had treatment-associated hyperglycemia (hazard ratio, 1.47), and were marginally more likely if they were black, obese, or postmenopausal.

Risk also varied by taxane regimen. It was higher for women who received weekly paclitaxel vs. paclitaxel every 3 week (HR, 1.52), paclitaxel every 3 weeks vs. weekly docetaxel (HR, 3.00), or paclitaxel every 3 weeks vs. docetaxel every 3 weeks (HR, 1.91).

In several types of analyses including multivariate models, the development of peripheral neuropathy was not significantly associated with recurrence-free, disease-free, or overall survival.

The findings contrast with those of an earlier study in which women receiving paclitaxel-containing chemotherapy without trastuzumab did have better outcomes if they developed peripheral neuropathy (SABCS 2009, abstract A-2100).

"Every-3-week docetaxel and weekly paclitaxel are viable therapeutic options for breast cancer," commented Dr. Schneider. The former is associated with more grade 3/4 toxicity in general, whereas the latter is associated with more peripheral neuropathy.

"Our goal is to study SNPs that have previously been shown to predict neuropathy in E1199," he concluded. "We hope to validate those top SNPs and ultimately identify which therapy has the optimal risk-benefit ratio for a given subgroup based on genotype."

Dr. Schneider reported that he had no relevant conflicts of interest. Dr. Gradishar had relationships with several companies that make taxanes.

SAN FRANCISCO – The development of taxane-induced peripheral neuropathy does not appear to be a marker for better outcomes in women with early breast cancer, new data show.

In a secondary analysis of the Eastern Cooperative Oncology Group E1199 trial involving 4,554 women, 13%-22% developed peripheral neuropathy, depending on which of four taxane regimens they received.

The women who developed peripheral neuropathy did not have better recurrence-free, disease-free, or overall survival than did their counterparts who escaped this toxicity, lead investigator Dr. Bryan P. Schneider reported on behalf of several North American breast cancer groups. Results were the same regardless of tumor type (estrogen receptor positive, HER2 positive, or triple negative) and the taxane regimen received.

He noted that the findings are important, given recent identification of six single-nucleotide polymorphisms (SNPs) predicting the likelihood of peripheral neuropathy in women receiving paclitaxel-containing chemotherapy (ASCO 2011, abstract 1000).

"Neuropathy did not correlate with outcome in E1199. The relevance is that SNPs or biomarkers that predict a subgroup protected from neuropathy are thus unlikely to enrich for inferior outcome," he explained.

Discussant Dr. William J. Gradishar, director of the center for women’s cancer care at Northwestern University in Chicago, said that "at the end of the day, at least with the present data we have, it doesn’t appear that the presence of neuropathy has any bearing on overall clinical outcome from those end points."

Trials thus far have failed to identify effective agents for preventing peripheral neuropathy in this setting, but there are some new agents on the horizon, he noted.

"The hope will be, because these [chemotherapy drugs] are such a mainstay of our therapies in both the adjuvant and metastatic disease setting, that one or a few of [the new agents] may ultimately prove to be fruitful for our patients," concluded Dr. Gradishar.

Women participating in the E1199 trial all received four cycles of doxorubicin and cyclophosphamide. They then received one of four taxane regimens: paclitaxel (Taxol) every 3 weeks for 4 cycles (control), paclitaxel weekly for 12 cycles, docetaxel (Taxotere) every 3 weeks for 4 cycles, or docetaxel weekly for 12 cycles. Median follow-up was 95.5 months.

Peripheral neuropathy (grade 2-4, either sensory or motor) was the most common nonhematologic toxicity seen in the trial, according to Dr. Schneider of Indiana University in Indianapolis. It occurred in 22.0% of women treated with weekly paclitaxel, in 17.5% of women treated with paclitaxel every 3 weeks, in 14.7% of women treated with docetaxel every 3 weeks, and in 13.4% of women treated with weekly docetaxel.

In a multivariate model, women were significantly more likely to develop peripheral neuropathy if they had treatment-associated hyperglycemia (hazard ratio, 1.47), and were marginally more likely if they were black, obese, or postmenopausal.

Risk also varied by taxane regimen. It was higher for women who received weekly paclitaxel vs. paclitaxel every 3 week (HR, 1.52), paclitaxel every 3 weeks vs. weekly docetaxel (HR, 3.00), or paclitaxel every 3 weeks vs. docetaxel every 3 weeks (HR, 1.91).

In several types of analyses including multivariate models, the development of peripheral neuropathy was not significantly associated with recurrence-free, disease-free, or overall survival.

The findings contrast with those of an earlier study in which women receiving paclitaxel-containing chemotherapy without trastuzumab did have better outcomes if they developed peripheral neuropathy (SABCS 2009, abstract A-2100).

"Every-3-week docetaxel and weekly paclitaxel are viable therapeutic options for breast cancer," commented Dr. Schneider. The former is associated with more grade 3/4 toxicity in general, whereas the latter is associated with more peripheral neuropathy.

"Our goal is to study SNPs that have previously been shown to predict neuropathy in E1199," he concluded. "We hope to validate those top SNPs and ultimately identify which therapy has the optimal risk-benefit ratio for a given subgroup based on genotype."

Dr. Schneider reported that he had no relevant conflicts of interest. Dr. Gradishar had relationships with several companies that make taxanes.

SAN FRANCISCO – The development of taxane-induced peripheral neuropathy does not appear to be a marker for better outcomes in women with early breast cancer, new data show.

In a secondary analysis of the Eastern Cooperative Oncology Group E1199 trial involving 4,554 women, 13%-22% developed peripheral neuropathy, depending on which of four taxane regimens they received.

The women who developed peripheral neuropathy did not have better recurrence-free, disease-free, or overall survival than did their counterparts who escaped this toxicity, lead investigator Dr. Bryan P. Schneider reported on behalf of several North American breast cancer groups. Results were the same regardless of tumor type (estrogen receptor positive, HER2 positive, or triple negative) and the taxane regimen received.

He noted that the findings are important, given recent identification of six single-nucleotide polymorphisms (SNPs) predicting the likelihood of peripheral neuropathy in women receiving paclitaxel-containing chemotherapy (ASCO 2011, abstract 1000).

"Neuropathy did not correlate with outcome in E1199. The relevance is that SNPs or biomarkers that predict a subgroup protected from neuropathy are thus unlikely to enrich for inferior outcome," he explained.

Discussant Dr. William J. Gradishar, director of the center for women’s cancer care at Northwestern University in Chicago, said that "at the end of the day, at least with the present data we have, it doesn’t appear that the presence of neuropathy has any bearing on overall clinical outcome from those end points."

Trials thus far have failed to identify effective agents for preventing peripheral neuropathy in this setting, but there are some new agents on the horizon, he noted.

"The hope will be, because these [chemotherapy drugs] are such a mainstay of our therapies in both the adjuvant and metastatic disease setting, that one or a few of [the new agents] may ultimately prove to be fruitful for our patients," concluded Dr. Gradishar.

Women participating in the E1199 trial all received four cycles of doxorubicin and cyclophosphamide. They then received one of four taxane regimens: paclitaxel (Taxol) every 3 weeks for 4 cycles (control), paclitaxel weekly for 12 cycles, docetaxel (Taxotere) every 3 weeks for 4 cycles, or docetaxel weekly for 12 cycles. Median follow-up was 95.5 months.

Peripheral neuropathy (grade 2-4, either sensory or motor) was the most common nonhematologic toxicity seen in the trial, according to Dr. Schneider of Indiana University in Indianapolis. It occurred in 22.0% of women treated with weekly paclitaxel, in 17.5% of women treated with paclitaxel every 3 weeks, in 14.7% of women treated with docetaxel every 3 weeks, and in 13.4% of women treated with weekly docetaxel.

In a multivariate model, women were significantly more likely to develop peripheral neuropathy if they had treatment-associated hyperglycemia (hazard ratio, 1.47), and were marginally more likely if they were black, obese, or postmenopausal.

Risk also varied by taxane regimen. It was higher for women who received weekly paclitaxel vs. paclitaxel every 3 week (HR, 1.52), paclitaxel every 3 weeks vs. weekly docetaxel (HR, 3.00), or paclitaxel every 3 weeks vs. docetaxel every 3 weeks (HR, 1.91).

In several types of analyses including multivariate models, the development of peripheral neuropathy was not significantly associated with recurrence-free, disease-free, or overall survival.

The findings contrast with those of an earlier study in which women receiving paclitaxel-containing chemotherapy without trastuzumab did have better outcomes if they developed peripheral neuropathy (SABCS 2009, abstract A-2100).

"Every-3-week docetaxel and weekly paclitaxel are viable therapeutic options for breast cancer," commented Dr. Schneider. The former is associated with more grade 3/4 toxicity in general, whereas the latter is associated with more peripheral neuropathy.

"Our goal is to study SNPs that have previously been shown to predict neuropathy in E1199," he concluded. "We hope to validate those top SNPs and ultimately identify which therapy has the optimal risk-benefit ratio for a given subgroup based on genotype."

Dr. Schneider reported that he had no relevant conflicts of interest. Dr. Gradishar had relationships with several companies that make taxanes.

Depression emerged as a significant barrier to secondary cancer screening in Latina survivors of breast cancer in a thought-provoking study released Sept. 19 at the American Association of Cancer Research Conference on the Science of Cancer Health Disparities in Washington.

The cross-sectional study explored adherence to recommended screening guidelines for ovarian and colorectal cancer among 117 Latina breast cancer survivors. Not surprisingly, but disturbingly, adherence was low among this very-high-risk group. Nearly 60% (69 of 117) failed to receive standard screening for either disease.

One would hope that these high-risk women knew, based on their prior treatment, how to negotiate financial and logistical barriers to care. It would seem likely that they formed relationships with health care professionals. Certainly, it would be expected that they learned that early detection saves lives; perhaps, it had already saved theirs.

So what happened? How did the prevention message fail to reach women who had already directly faced the reality of a cancer diagnosis, and survived?

One sobering possibility lies in the fact that nearly a third of Latinas in the study met the criteria for depression, according to scores for the simple but comprehensive CES-D (Center for Epidemiologic Studies) screening tool.

The self-administered questionnaire assesses mood "("I felt that I could not shake off the blues, even with help from family or friends"; "I [did not] feel hopeful about the future"), somatic symptoms ("I did not feel like eating; my appetite was poor"), behavior ("I talked less than usual"), and self-concept ("I thought my life had been a failure").

Depression was associated with poor rates of ovarian screening, along with language barriers, unemployment, worries about the cost of screening, and the lack of a family history of cancer.

Poor rates of colorectal cancer screening were associated with being unmarried.

In online video interview from a 2010 AACR breast cancer meeting, the current study’s primary investigator, Amelie G. Ramirez, Dr. P.H., spoke of challenging issues surrounding Latina access to cancer prevention and care, driven by cultural as well as socioeconomic issues.

Sheer terror of cancer, she explained, wields a powerful influence over portions of the Latina community.

"When they hear the word cancer, it’s very fearful for them. It almost shuts down all ... communication," said Dr. Ramirez, director of the Institute for Health Promotion Research and professor of epidemiology and biostatistics at the University of Texas, San Antonio.

Depression, too, casts a dark, silent cloud over the Latino community.

In a 2009 study, University of California, Los Angeles, researchers identified a strong link between self-perceived stigma and secrecy surrounding depressive symptoms, less likelihood of taking antidepressants, and – importantly with regard to the current screening study – more missed medical appointments among Latinos.

Taken together, these studies and observations begin to paint a picture of the type of woman whose life might be reflected in the numbers in Dr. Ramirez’s study. She is poor and unemployed; she struggles with English. She survived a disease that is unspeakably terrifying in her community and perhaps in her family as well. She may be unmarried.

And now, with bills and scars still reminding her of the trauma, a new, equally unmentionable burden shadows her days. She sleeps restlessly and cannot eat; she is quiet and withdrawn; she cannot shake off the blues. She feels that her life has been a failure.

Assuming the best possible scenario, a card arrives in the mail, reminding her that she is due for cancer screening: an annual pelvic exam, perhaps, or a colonoscopy.

Is it any wonder she fails to comply?

Dr. Freed is a clinical psychologist in Santa Barbara, Calif., and a medical journalist. She has no relevant financial disclosures.

Depression emerged as a significant barrier to secondary cancer screening in Latina survivors of breast cancer in a thought-provoking study released Sept. 19 at the American Association of Cancer Research Conference on the Science of Cancer Health Disparities in Washington.

The cross-sectional study explored adherence to recommended screening guidelines for ovarian and colorectal cancer among 117 Latina breast cancer survivors. Not surprisingly, but disturbingly, adherence was low among this very-high-risk group. Nearly 60% (69 of 117) failed to receive standard screening for either disease.

One would hope that these high-risk women knew, based on their prior treatment, how to negotiate financial and logistical barriers to care. It would seem likely that they formed relationships with health care professionals. Certainly, it would be expected that they learned that early detection saves lives; perhaps, it had already saved theirs.

So what happened? How did the prevention message fail to reach women who had already directly faced the reality of a cancer diagnosis, and survived?

One sobering possibility lies in the fact that nearly a third of Latinas in the study met the criteria for depression, according to scores for the simple but comprehensive CES-D (Center for Epidemiologic Studies) screening tool.

The self-administered questionnaire assesses mood "("I felt that I could not shake off the blues, even with help from family or friends"; "I [did not] feel hopeful about the future"), somatic symptoms ("I did not feel like eating; my appetite was poor"), behavior ("I talked less than usual"), and self-concept ("I thought my life had been a failure").

Depression was associated with poor rates of ovarian screening, along with language barriers, unemployment, worries about the cost of screening, and the lack of a family history of cancer.

Poor rates of colorectal cancer screening were associated with being unmarried.

In online video interview from a 2010 AACR breast cancer meeting, the current study’s primary investigator, Amelie G. Ramirez, Dr. P.H., spoke of challenging issues surrounding Latina access to cancer prevention and care, driven by cultural as well as socioeconomic issues.

Sheer terror of cancer, she explained, wields a powerful influence over portions of the Latina community.

"When they hear the word cancer, it’s very fearful for them. It almost shuts down all ... communication," said Dr. Ramirez, director of the Institute for Health Promotion Research and professor of epidemiology and biostatistics at the University of Texas, San Antonio.

Depression, too, casts a dark, silent cloud over the Latino community.

In a 2009 study, University of California, Los Angeles, researchers identified a strong link between self-perceived stigma and secrecy surrounding depressive symptoms, less likelihood of taking antidepressants, and – importantly with regard to the current screening study – more missed medical appointments among Latinos.

Taken together, these studies and observations begin to paint a picture of the type of woman whose life might be reflected in the numbers in Dr. Ramirez’s study. She is poor and unemployed; she struggles with English. She survived a disease that is unspeakably terrifying in her community and perhaps in her family as well. She may be unmarried.

And now, with bills and scars still reminding her of the trauma, a new, equally unmentionable burden shadows her days. She sleeps restlessly and cannot eat; she is quiet and withdrawn; she cannot shake off the blues. She feels that her life has been a failure.

Assuming the best possible scenario, a card arrives in the mail, reminding her that she is due for cancer screening: an annual pelvic exam, perhaps, or a colonoscopy.

Is it any wonder she fails to comply?

Dr. Freed is a clinical psychologist in Santa Barbara, Calif., and a medical journalist. She has no relevant financial disclosures.

Depression emerged as a significant barrier to secondary cancer screening in Latina survivors of breast cancer in a thought-provoking study released Sept. 19 at the American Association of Cancer Research Conference on the Science of Cancer Health Disparities in Washington.

The cross-sectional study explored adherence to recommended screening guidelines for ovarian and colorectal cancer among 117 Latina breast cancer survivors. Not surprisingly, but disturbingly, adherence was low among this very-high-risk group. Nearly 60% (69 of 117) failed to receive standard screening for either disease.

One would hope that these high-risk women knew, based on their prior treatment, how to negotiate financial and logistical barriers to care. It would seem likely that they formed relationships with health care professionals. Certainly, it would be expected that they learned that early detection saves lives; perhaps, it had already saved theirs.

So what happened? How did the prevention message fail to reach women who had already directly faced the reality of a cancer diagnosis, and survived?

One sobering possibility lies in the fact that nearly a third of Latinas in the study met the criteria for depression, according to scores for the simple but comprehensive CES-D (Center for Epidemiologic Studies) screening tool.

The self-administered questionnaire assesses mood "("I felt that I could not shake off the blues, even with help from family or friends"; "I [did not] feel hopeful about the future"), somatic symptoms ("I did not feel like eating; my appetite was poor"), behavior ("I talked less than usual"), and self-concept ("I thought my life had been a failure").

Depression was associated with poor rates of ovarian screening, along with language barriers, unemployment, worries about the cost of screening, and the lack of a family history of cancer.

Poor rates of colorectal cancer screening were associated with being unmarried.

In online video interview from a 2010 AACR breast cancer meeting, the current study’s primary investigator, Amelie G. Ramirez, Dr. P.H., spoke of challenging issues surrounding Latina access to cancer prevention and care, driven by cultural as well as socioeconomic issues.

Sheer terror of cancer, she explained, wields a powerful influence over portions of the Latina community.

"When they hear the word cancer, it’s very fearful for them. It almost shuts down all ... communication," said Dr. Ramirez, director of the Institute for Health Promotion Research and professor of epidemiology and biostatistics at the University of Texas, San Antonio.

Depression, too, casts a dark, silent cloud over the Latino community.

In a 2009 study, University of California, Los Angeles, researchers identified a strong link between self-perceived stigma and secrecy surrounding depressive symptoms, less likelihood of taking antidepressants, and – importantly with regard to the current screening study – more missed medical appointments among Latinos.

Taken together, these studies and observations begin to paint a picture of the type of woman whose life might be reflected in the numbers in Dr. Ramirez’s study. She is poor and unemployed; she struggles with English. She survived a disease that is unspeakably terrifying in her community and perhaps in her family as well. She may be unmarried.

And now, with bills and scars still reminding her of the trauma, a new, equally unmentionable burden shadows her days. She sleeps restlessly and cannot eat; she is quiet and withdrawn; she cannot shake off the blues. She feels that her life has been a failure.

Assuming the best possible scenario, a card arrives in the mail, reminding her that she is due for cancer screening: an annual pelvic exam, perhaps, or a colonoscopy.

Is it any wonder she fails to comply?

Dr. Freed is a clinical psychologist in Santa Barbara, Calif., and a medical journalist. She has no relevant financial disclosures.

The Prolia brand of denosumab has been approved as a treatment for bone loss in people receiving hormone ablation therapy for prostate or breast cancer, according to a statement from Amgen, the manufacturer.

The approved indications are for increasing bone mass in women at high risk for fracture on adjuvant aromatase inhibitor therapy for breast cancer and in men at high risk for fracture on androgen deprivation therapy (ADT) for nonmetastatic prostate cancer, the company's statement said.

Denosumab, a RANK ligand inhibitor, was first approved in June 2010 for treating postmenopausal women with osteoporosis at high risk of fracture and is marketed as Prolia for this indication. Prolia is administered in a subcutaneous injection once every 6 months, at a dose of 60 mg.

In November 2010, denosumab was also approved for preventing skeletal-related events in patients with bone metastases from solid tumors. It is marketed as Xgeva and administered more frequently at a higher dose for this indication.

Approval of the new indications for Prolia was based on phase III studies of these two groups of patients, according to Amgen. In an international study of almost 1,500 men with nonmetastatic prostate cancer who were being treated with ADT, bone mineral density at the lumbar spine after 2 years of treatment was significantly higher among men who had received denosumab compared with those who received placebo. After 3 years of treatment, the incidence of new vertebral fractures was 1.5% among those treated with denosumab, compared with 3.9% for those on placebo, a risk reduction of 62%, the company said.

And in a study of 252 postmenopausal women with breast cancer under treatment with an aromatase inhibitor, bone mineral density at the lumbar spine was significantly higher among those treated with denosumab compared with those on placebo after 12 months of treatment, according to the statement.

Arthralgia and back pain were the most common adverse events associated with treatment in these two groups of patients. Hypocalcemia was also reported; denosumab is contraindicated in people with hypocalcemia. Treatment was associated with cataract events in men in the prostate cancer trial.

In the European Union, denosumab is approved for the osteoporosis indication as well as the prostate cancer indication just approved in the United States, according to Amgen.

The Prolia brand of denosumab has been approved as a treatment for bone loss in people receiving hormone ablation therapy for prostate or breast cancer, according to a statement from Amgen, the manufacturer.

The approved indications are for increasing bone mass in women at high risk for fracture on adjuvant aromatase inhibitor therapy for breast cancer and in men at high risk for fracture on androgen deprivation therapy (ADT) for nonmetastatic prostate cancer, the company's statement said.

Denosumab, a RANK ligand inhibitor, was first approved in June 2010 for treating postmenopausal women with osteoporosis at high risk of fracture and is marketed as Prolia for this indication. Prolia is administered in a subcutaneous injection once every 6 months, at a dose of 60 mg.

In November 2010, denosumab was also approved for preventing skeletal-related events in patients with bone metastases from solid tumors. It is marketed as Xgeva and administered more frequently at a higher dose for this indication.

Approval of the new indications for Prolia was based on phase III studies of these two groups of patients, according to Amgen. In an international study of almost 1,500 men with nonmetastatic prostate cancer who were being treated with ADT, bone mineral density at the lumbar spine after 2 years of treatment was significantly higher among men who had received denosumab compared with those who received placebo. After 3 years of treatment, the incidence of new vertebral fractures was 1.5% among those treated with denosumab, compared with 3.9% for those on placebo, a risk reduction of 62%, the company said.

And in a study of 252 postmenopausal women with breast cancer under treatment with an aromatase inhibitor, bone mineral density at the lumbar spine was significantly higher among those treated with denosumab compared with those on placebo after 12 months of treatment, according to the statement.

Arthralgia and back pain were the most common adverse events associated with treatment in these two groups of patients. Hypocalcemia was also reported; denosumab is contraindicated in people with hypocalcemia. Treatment was associated with cataract events in men in the prostate cancer trial.

In the European Union, denosumab is approved for the osteoporosis indication as well as the prostate cancer indication just approved in the United States, according to Amgen.

The Prolia brand of denosumab has been approved as a treatment for bone loss in people receiving hormone ablation therapy for prostate or breast cancer, according to a statement from Amgen, the manufacturer.

The approved indications are for increasing bone mass in women at high risk for fracture on adjuvant aromatase inhibitor therapy for breast cancer and in men at high risk for fracture on androgen deprivation therapy (ADT) for nonmetastatic prostate cancer, the company's statement said.

Denosumab, a RANK ligand inhibitor, was first approved in June 2010 for treating postmenopausal women with osteoporosis at high risk of fracture and is marketed as Prolia for this indication. Prolia is administered in a subcutaneous injection once every 6 months, at a dose of 60 mg.

In November 2010, denosumab was also approved for preventing skeletal-related events in patients with bone metastases from solid tumors. It is marketed as Xgeva and administered more frequently at a higher dose for this indication.

Approval of the new indications for Prolia was based on phase III studies of these two groups of patients, according to Amgen. In an international study of almost 1,500 men with nonmetastatic prostate cancer who were being treated with ADT, bone mineral density at the lumbar spine after 2 years of treatment was significantly higher among men who had received denosumab compared with those who received placebo. After 3 years of treatment, the incidence of new vertebral fractures was 1.5% among those treated with denosumab, compared with 3.9% for those on placebo, a risk reduction of 62%, the company said.

And in a study of 252 postmenopausal women with breast cancer under treatment with an aromatase inhibitor, bone mineral density at the lumbar spine was significantly higher among those treated with denosumab compared with those on placebo after 12 months of treatment, according to the statement.

Arthralgia and back pain were the most common adverse events associated with treatment in these two groups of patients. Hypocalcemia was also reported; denosumab is contraindicated in people with hypocalcemia. Treatment was associated with cataract events in men in the prostate cancer trial.

In the European Union, denosumab is approved for the osteoporosis indication as well as the prostate cancer indication just approved in the United States, according to Amgen.

SAN FRANCISCO – Entinostat, a novel oral histone deacetylase inhibitor taken once weekly, may overcome resistance to hormonal therapy in breast cancer, the results of a randomized phase-II trial suggest.

Investigators studied 130 women with estrogen receptor–positive advanced breast cancer progressing on aromatase inhibitor (AI) therapy. Results showed that, compared with exemestane (Aromasin) plus placebo, exemestane plus entinostat reduced the risk of progression-free survival events by 27% and the risk of death by 44%. It also was well tolerated.

"The combination ... is delaying the time to disease progression, allowing patients to maintain hormonal therapy longer, and delaying the need for change of therapy and subsequent considerations of chemotherapy," principal investigator Dr. Denise A. Yardley reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

"These results support our plans for a global, pivotal phase-III study due to begin enrollment in 2012," added Dr. Yardley, an oncologist with the Sarah Cannon Research Institute and Tennessee Oncology PLLC, both in Nashville.

In an additional finding, median progression-free survival was greatest, 8.5 months, in patients treated with the combination who had hyperacetylation of proteins in blood cells during the first cycle of treatment, suggesting that this could be a biomarker for efficacy. These data reveal "for the first time in a matched controlled trial, evidence of hyperacetylation from an HDAC [histone deacetylase] inhibitor correlating with improved outcomes," she noted.

Session chair Dr. Joyce O’Shaughnessy, an oncologist with the Baylor Sammons Cancer Center in Dallas, Texas Oncology, and US Oncology, characterized the trial’s findings as "very, very promising," saying, "I agree that it’s time for a phase III" trial. To her knowledge, this is the first randomized trial of an HDAC inhibitor in breast cancer.

A particularly impressive finding was the long progression-free survival seen in hyperacetylators, according to Dr. O’Shaughnessy. It will be important to determine whether this correlates with toxicity, as lack of toxicity might then identify patients who could benefit from dose-escalation of entinostat. "They need to really carefully look at that because you really want to optimize it for all the people in the phase-III trial," she commented.

Giving some mechanistic background to the trial, Dr. Yardley noted that HDAC inhibitors interfere with the condensation of chromatin and the silencing of genes, such as tumor suppressor genes.

Resistance to AIs occurs from upregulation and activation of growth factor signaling pathways that are not estrogen dependent. "Entinostat targets these growth factor signaling pathways, ultimately inhibiting tumor cell growth," she explained. Preclinical data also suggest that the drug resensitizes tumors to AIs.

The randomized phase-II trial, called ENCORE 301 (Entinostat Combinations Overcoming Resistance), was conducted among women in North America, the European Union, and Russia who were postmenopausal and had locally advanced or metastatic estrogen receptor–positive breast cancer that was progressing on a nonsteroidal AI (anastrozole or letrozole). Those with metastatic disease could have received up to one prior chemotherapy for metastases.

The patients were randomized in balanced fashion to double-blind treatment with exemestane plus placebo or exemestane plus entinostat. By study design, P values less than .1 were considered statistically significant.

Demographically, the patients were 62 years old on average. Eighty-five percent had experienced progression on an AI in the metastatic setting.

With a median follow-up of 18 months, entinostat was associated with longer median progression-free survival (4.28 vs. 2.27 months; hazard ratio, 0.73; P = .06), with similar findings in subgroups stratified by locally advanced vs. metastatic disease, age, and site of metastasis, Dr. Yardley reported.

In 49 patients, blood samples collected before and during the first cycle of therapy were analyzed to determine the percent change of lysines in peripheral blood mononuclear cell proteins that were acetylated. Results showed that progression-free survival was greatest, at 8.54 months, among entinostat-treated patients who had hyperacetylation, defined as an above-median percent change in lysines that were acetylated during the first cycle of treatment.

These findings "suggest that entinostat-induced hyperacetylation appeared to track with improved outcomes in these patients and suggest quite provocatively within the very first cycle of treatment that this may be a potential marker to assess the benefit from this treatment," said Dr. Yardley.

Furthermore, the association raises the "question, if you can identify early on a group that is not acetylating, whether increasing the dose may get them to be hyperacetylators and derive more benefit from the HDAC inhibitor," she said. Additionally, ongoing analyses are looking at whether hyperacetylation correlated with toxicity and could then be used as a surrogate for efficacy.

"We are going to have more correlative work planned as a part of the phase-III trial that is coming up," Dr. Yardley added.

In an analysis that was exploratory because follow-up is still short, entinostat was also associated with better overall survival (26.9 vs. 20.3 months; HR, 0.56; P = .027). Additional data with longer follow-up will be reported at the San Antonio Breast Cancer Symposium later this year.

The combination of entinostat and exemestane was well tolerated, with no unexpected safety signals. The most common grade 3/4 adverse events in the entinostat group were fatigue (13%), neutropenia (13%), nausea (5%), and vomiting (5%). The rate of discontinuation because of adverse events was 1% in the placebo group and 11% in the entinostat group.

Dr. Yardley reported that she had no relevant conflicts of interest. Syndax Pharmaceuticals, developer of entinostat, was not among Dr. O’Shaughnessy’s disclosures.

SAN FRANCISCO – Entinostat, a novel oral histone deacetylase inhibitor taken once weekly, may overcome resistance to hormonal therapy in breast cancer, the results of a randomized phase-II trial suggest.

Investigators studied 130 women with estrogen receptor–positive advanced breast cancer progressing on aromatase inhibitor (AI) therapy. Results showed that, compared with exemestane (Aromasin) plus placebo, exemestane plus entinostat reduced the risk of progression-free survival events by 27% and the risk of death by 44%. It also was well tolerated.

"The combination ... is delaying the time to disease progression, allowing patients to maintain hormonal therapy longer, and delaying the need for change of therapy and subsequent considerations of chemotherapy," principal investigator Dr. Denise A. Yardley reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

"These results support our plans for a global, pivotal phase-III study due to begin enrollment in 2012," added Dr. Yardley, an oncologist with the Sarah Cannon Research Institute and Tennessee Oncology PLLC, both in Nashville.

In an additional finding, median progression-free survival was greatest, 8.5 months, in patients treated with the combination who had hyperacetylation of proteins in blood cells during the first cycle of treatment, suggesting that this could be a biomarker for efficacy. These data reveal "for the first time in a matched controlled trial, evidence of hyperacetylation from an HDAC [histone deacetylase] inhibitor correlating with improved outcomes," she noted.

Session chair Dr. Joyce O’Shaughnessy, an oncologist with the Baylor Sammons Cancer Center in Dallas, Texas Oncology, and US Oncology, characterized the trial’s findings as "very, very promising," saying, "I agree that it’s time for a phase III" trial. To her knowledge, this is the first randomized trial of an HDAC inhibitor in breast cancer.

A particularly impressive finding was the long progression-free survival seen in hyperacetylators, according to Dr. O’Shaughnessy. It will be important to determine whether this correlates with toxicity, as lack of toxicity might then identify patients who could benefit from dose-escalation of entinostat. "They need to really carefully look at that because you really want to optimize it for all the people in the phase-III trial," she commented.

Giving some mechanistic background to the trial, Dr. Yardley noted that HDAC inhibitors interfere with the condensation of chromatin and the silencing of genes, such as tumor suppressor genes.

Resistance to AIs occurs from upregulation and activation of growth factor signaling pathways that are not estrogen dependent. "Entinostat targets these growth factor signaling pathways, ultimately inhibiting tumor cell growth," she explained. Preclinical data also suggest that the drug resensitizes tumors to AIs.

The randomized phase-II trial, called ENCORE 301 (Entinostat Combinations Overcoming Resistance), was conducted among women in North America, the European Union, and Russia who were postmenopausal and had locally advanced or metastatic estrogen receptor–positive breast cancer that was progressing on a nonsteroidal AI (anastrozole or letrozole). Those with metastatic disease could have received up to one prior chemotherapy for metastases.

The patients were randomized in balanced fashion to double-blind treatment with exemestane plus placebo or exemestane plus entinostat. By study design, P values less than .1 were considered statistically significant.

Demographically, the patients were 62 years old on average. Eighty-five percent had experienced progression on an AI in the metastatic setting.

With a median follow-up of 18 months, entinostat was associated with longer median progression-free survival (4.28 vs. 2.27 months; hazard ratio, 0.73; P = .06), with similar findings in subgroups stratified by locally advanced vs. metastatic disease, age, and site of metastasis, Dr. Yardley reported.

In 49 patients, blood samples collected before and during the first cycle of therapy were analyzed to determine the percent change of lysines in peripheral blood mononuclear cell proteins that were acetylated. Results showed that progression-free survival was greatest, at 8.54 months, among entinostat-treated patients who had hyperacetylation, defined as an above-median percent change in lysines that were acetylated during the first cycle of treatment.

These findings "suggest that entinostat-induced hyperacetylation appeared to track with improved outcomes in these patients and suggest quite provocatively within the very first cycle of treatment that this may be a potential marker to assess the benefit from this treatment," said Dr. Yardley.

Furthermore, the association raises the "question, if you can identify early on a group that is not acetylating, whether increasing the dose may get them to be hyperacetylators and derive more benefit from the HDAC inhibitor," she said. Additionally, ongoing analyses are looking at whether hyperacetylation correlated with toxicity and could then be used as a surrogate for efficacy.

"We are going to have more correlative work planned as a part of the phase-III trial that is coming up," Dr. Yardley added.

In an analysis that was exploratory because follow-up is still short, entinostat was also associated with better overall survival (26.9 vs. 20.3 months; HR, 0.56; P = .027). Additional data with longer follow-up will be reported at the San Antonio Breast Cancer Symposium later this year.

The combination of entinostat and exemestane was well tolerated, with no unexpected safety signals. The most common grade 3/4 adverse events in the entinostat group were fatigue (13%), neutropenia (13%), nausea (5%), and vomiting (5%). The rate of discontinuation because of adverse events was 1% in the placebo group and 11% in the entinostat group.

Dr. Yardley reported that she had no relevant conflicts of interest. Syndax Pharmaceuticals, developer of entinostat, was not among Dr. O’Shaughnessy’s disclosures.

SAN FRANCISCO – Entinostat, a novel oral histone deacetylase inhibitor taken once weekly, may overcome resistance to hormonal therapy in breast cancer, the results of a randomized phase-II trial suggest.

Investigators studied 130 women with estrogen receptor–positive advanced breast cancer progressing on aromatase inhibitor (AI) therapy. Results showed that, compared with exemestane (Aromasin) plus placebo, exemestane plus entinostat reduced the risk of progression-free survival events by 27% and the risk of death by 44%. It also was well tolerated.

"The combination ... is delaying the time to disease progression, allowing patients to maintain hormonal therapy longer, and delaying the need for change of therapy and subsequent considerations of chemotherapy," principal investigator Dr. Denise A. Yardley reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

"These results support our plans for a global, pivotal phase-III study due to begin enrollment in 2012," added Dr. Yardley, an oncologist with the Sarah Cannon Research Institute and Tennessee Oncology PLLC, both in Nashville.

In an additional finding, median progression-free survival was greatest, 8.5 months, in patients treated with the combination who had hyperacetylation of proteins in blood cells during the first cycle of treatment, suggesting that this could be a biomarker for efficacy. These data reveal "for the first time in a matched controlled trial, evidence of hyperacetylation from an HDAC [histone deacetylase] inhibitor correlating with improved outcomes," she noted.

Session chair Dr. Joyce O’Shaughnessy, an oncologist with the Baylor Sammons Cancer Center in Dallas, Texas Oncology, and US Oncology, characterized the trial’s findings as "very, very promising," saying, "I agree that it’s time for a phase III" trial. To her knowledge, this is the first randomized trial of an HDAC inhibitor in breast cancer.

A particularly impressive finding was the long progression-free survival seen in hyperacetylators, according to Dr. O’Shaughnessy. It will be important to determine whether this correlates with toxicity, as lack of toxicity might then identify patients who could benefit from dose-escalation of entinostat. "They need to really carefully look at that because you really want to optimize it for all the people in the phase-III trial," she commented.

Giving some mechanistic background to the trial, Dr. Yardley noted that HDAC inhibitors interfere with the condensation of chromatin and the silencing of genes, such as tumor suppressor genes.

Resistance to AIs occurs from upregulation and activation of growth factor signaling pathways that are not estrogen dependent. "Entinostat targets these growth factor signaling pathways, ultimately inhibiting tumor cell growth," she explained. Preclinical data also suggest that the drug resensitizes tumors to AIs.

The randomized phase-II trial, called ENCORE 301 (Entinostat Combinations Overcoming Resistance), was conducted among women in North America, the European Union, and Russia who were postmenopausal and had locally advanced or metastatic estrogen receptor–positive breast cancer that was progressing on a nonsteroidal AI (anastrozole or letrozole). Those with metastatic disease could have received up to one prior chemotherapy for metastases.

The patients were randomized in balanced fashion to double-blind treatment with exemestane plus placebo or exemestane plus entinostat. By study design, P values less than .1 were considered statistically significant.

Demographically, the patients were 62 years old on average. Eighty-five percent had experienced progression on an AI in the metastatic setting.

With a median follow-up of 18 months, entinostat was associated with longer median progression-free survival (4.28 vs. 2.27 months; hazard ratio, 0.73; P = .06), with similar findings in subgroups stratified by locally advanced vs. metastatic disease, age, and site of metastasis, Dr. Yardley reported.

In 49 patients, blood samples collected before and during the first cycle of therapy were analyzed to determine the percent change of lysines in peripheral blood mononuclear cell proteins that were acetylated. Results showed that progression-free survival was greatest, at 8.54 months, among entinostat-treated patients who had hyperacetylation, defined as an above-median percent change in lysines that were acetylated during the first cycle of treatment.

These findings "suggest that entinostat-induced hyperacetylation appeared to track with improved outcomes in these patients and suggest quite provocatively within the very first cycle of treatment that this may be a potential marker to assess the benefit from this treatment," said Dr. Yardley.

Furthermore, the association raises the "question, if you can identify early on a group that is not acetylating, whether increasing the dose may get them to be hyperacetylators and derive more benefit from the HDAC inhibitor," she said. Additionally, ongoing analyses are looking at whether hyperacetylation correlated with toxicity and could then be used as a surrogate for efficacy.

"We are going to have more correlative work planned as a part of the phase-III trial that is coming up," Dr. Yardley added.

In an analysis that was exploratory because follow-up is still short, entinostat was also associated with better overall survival (26.9 vs. 20.3 months; HR, 0.56; P = .027). Additional data with longer follow-up will be reported at the San Antonio Breast Cancer Symposium later this year.

The combination of entinostat and exemestane was well tolerated, with no unexpected safety signals. The most common grade 3/4 adverse events in the entinostat group were fatigue (13%), neutropenia (13%), nausea (5%), and vomiting (5%). The rate of discontinuation because of adverse events was 1% in the placebo group and 11% in the entinostat group.

Dr. Yardley reported that she had no relevant conflicts of interest. Syndax Pharmaceuticals, developer of entinostat, was not among Dr. O’Shaughnessy’s disclosures.

Venlafaxine and clonidine both outperformed placebo in controlling hot flashes among women with breast cancer in a study published online Sept. 12 in the Journal of Clinical Oncology.

Effective treatments for hot flashes may improve these patients’ ability to continue their anticancer therapies, said Dr. Annelies H. Boekhout of The Netherlands Cancer Institute, Amsterdam, and her associates.

The SSNRI venlafaxine (Effexor) and the antihypertensive clonidine "both are often prescribed treatments and are recommended in clinical guidelines in the management of hot flashes. However, a three-arm trial comparing clonidine, venlafaxine, and placebo in patients with breast cancer has not been conducted" until now, they noted.

In their double-blind study at three Dutch hospitals, 102 women with breast cancer who experienced at least two hot flashes per day were stratified by age, duration of symptoms, concurrent endocrine therapy, and previous chemotherapy, and randomly assigned to receive 75 mg venlafaxine (41 patients), 0.1 mg clonidine (41 patients), or matching placebo (20 patients) daily for 12 weeks.

The women completed daily diaries recording the frequency and severity of hot flashes. They also reported every week on adverse events such as reduced appetite, nausea, sleepiness, dizziness, fatigue, dry mouth, and constipation. They recorded their sleep quality, anxiety, depression, and sexual function at 4 weeks and at the conclusion of treatment.

A total of 22 subjects (22%) either dropped out of the study or were lost to follow-up. Two patients (5%) in the venlafaxine group and six (15%) in the clonidine group cited adverse effects such as somnolence, dizziness, and dry mouth as their reason for discontinuing. Another 9% of patients discontinued because of noncompliance, which "had some effect on the observed differences between treatments in this study."

Among the 35 women assigned to venlafaxine who completed the trial, there was a 42% decline in hot flashes during weeks 1-4, compared with the placebo group. Over the entire study period, the reduction in hot flashes was 41% with venlafaxine, compared with placebo.

Among the 28 women assigned to clonidine who completed the trial, hot flashes declined by only 26% during weeks 1-4 but then declined another 22% during the remainder of the study, for an overall reduction of approximately 45%.

Thus, both active agents decreased the frequency and severity of hot flashes compared with placebo, with no discernible difference between the two by week 12. "A more rapid reduction of hot flashes suggests that venlafaxine is to be preferred over clonidine," Dr. Boekhout and her colleagues said (J. Clin. Oncol. 2011 Sept. 12 [doi:10.1200/JCO.2010.33.1298]).

They added that it is "advisable to treat patients to manage hot flashes with venlafaxine 37.5 mg daily in the first week and increase the venlafaxine dose to 75 mg if greater efficacy is desired."

A total of 14 patients (34%) in the clonidine group, 23 (56%) in the venlafaxine group, and 4 (20%) in the placebo group said they wished to continue the study treatment at the end of the trial.

Women taking clonidine reported more symptoms of anxiety and women taking venlafaxine reported more symptoms of depression. Sexual function and sleep quality did not differ between the two groups. However, the duration of this study may have been too short to adequately assess these adverse effects, the researchers noted.

No conflicts of interest were reported.

Venlafaxine and clonidine both outperformed placebo in controlling hot flashes among women with breast cancer in a study published online Sept. 12 in the Journal of Clinical Oncology.

Effective treatments for hot flashes may improve these patients’ ability to continue their anticancer therapies, said Dr. Annelies H. Boekhout of The Netherlands Cancer Institute, Amsterdam, and her associates.

The SSNRI venlafaxine (Effexor) and the antihypertensive clonidine "both are often prescribed treatments and are recommended in clinical guidelines in the management of hot flashes. However, a three-arm trial comparing clonidine, venlafaxine, and placebo in patients with breast cancer has not been conducted" until now, they noted.

In their double-blind study at three Dutch hospitals, 102 women with breast cancer who experienced at least two hot flashes per day were stratified by age, duration of symptoms, concurrent endocrine therapy, and previous chemotherapy, and randomly assigned to receive 75 mg venlafaxine (41 patients), 0.1 mg clonidine (41 patients), or matching placebo (20 patients) daily for 12 weeks.

The women completed daily diaries recording the frequency and severity of hot flashes. They also reported every week on adverse events such as reduced appetite, nausea, sleepiness, dizziness, fatigue, dry mouth, and constipation. They recorded their sleep quality, anxiety, depression, and sexual function at 4 weeks and at the conclusion of treatment.

A total of 22 subjects (22%) either dropped out of the study or were lost to follow-up. Two patients (5%) in the venlafaxine group and six (15%) in the clonidine group cited adverse effects such as somnolence, dizziness, and dry mouth as their reason for discontinuing. Another 9% of patients discontinued because of noncompliance, which "had some effect on the observed differences between treatments in this study."

Among the 35 women assigned to venlafaxine who completed the trial, there was a 42% decline in hot flashes during weeks 1-4, compared with the placebo group. Over the entire study period, the reduction in hot flashes was 41% with venlafaxine, compared with placebo.

Among the 28 women assigned to clonidine who completed the trial, hot flashes declined by only 26% during weeks 1-4 but then declined another 22% during the remainder of the study, for an overall reduction of approximately 45%.

Thus, both active agents decreased the frequency and severity of hot flashes compared with placebo, with no discernible difference between the two by week 12. "A more rapid reduction of hot flashes suggests that venlafaxine is to be preferred over clonidine," Dr. Boekhout and her colleagues said (J. Clin. Oncol. 2011 Sept. 12 [doi:10.1200/JCO.2010.33.1298]).

They added that it is "advisable to treat patients to manage hot flashes with venlafaxine 37.5 mg daily in the first week and increase the venlafaxine dose to 75 mg if greater efficacy is desired."

A total of 14 patients (34%) in the clonidine group, 23 (56%) in the venlafaxine group, and 4 (20%) in the placebo group said they wished to continue the study treatment at the end of the trial.

Women taking clonidine reported more symptoms of anxiety and women taking venlafaxine reported more symptoms of depression. Sexual function and sleep quality did not differ between the two groups. However, the duration of this study may have been too short to adequately assess these adverse effects, the researchers noted.

No conflicts of interest were reported.

Venlafaxine and clonidine both outperformed placebo in controlling hot flashes among women with breast cancer in a study published online Sept. 12 in the Journal of Clinical Oncology.

Effective treatments for hot flashes may improve these patients’ ability to continue their anticancer therapies, said Dr. Annelies H. Boekhout of The Netherlands Cancer Institute, Amsterdam, and her associates.

The SSNRI venlafaxine (Effexor) and the antihypertensive clonidine "both are often prescribed treatments and are recommended in clinical guidelines in the management of hot flashes. However, a three-arm trial comparing clonidine, venlafaxine, and placebo in patients with breast cancer has not been conducted" until now, they noted.

In their double-blind study at three Dutch hospitals, 102 women with breast cancer who experienced at least two hot flashes per day were stratified by age, duration of symptoms, concurrent endocrine therapy, and previous chemotherapy, and randomly assigned to receive 75 mg venlafaxine (41 patients), 0.1 mg clonidine (41 patients), or matching placebo (20 patients) daily for 12 weeks.

The women completed daily diaries recording the frequency and severity of hot flashes. They also reported every week on adverse events such as reduced appetite, nausea, sleepiness, dizziness, fatigue, dry mouth, and constipation. They recorded their sleep quality, anxiety, depression, and sexual function at 4 weeks and at the conclusion of treatment.

A total of 22 subjects (22%) either dropped out of the study or were lost to follow-up. Two patients (5%) in the venlafaxine group and six (15%) in the clonidine group cited adverse effects such as somnolence, dizziness, and dry mouth as their reason for discontinuing. Another 9% of patients discontinued because of noncompliance, which "had some effect on the observed differences between treatments in this study."

Among the 35 women assigned to venlafaxine who completed the trial, there was a 42% decline in hot flashes during weeks 1-4, compared with the placebo group. Over the entire study period, the reduction in hot flashes was 41% with venlafaxine, compared with placebo.

Among the 28 women assigned to clonidine who completed the trial, hot flashes declined by only 26% during weeks 1-4 but then declined another 22% during the remainder of the study, for an overall reduction of approximately 45%.

Thus, both active agents decreased the frequency and severity of hot flashes compared with placebo, with no discernible difference between the two by week 12. "A more rapid reduction of hot flashes suggests that venlafaxine is to be preferred over clonidine," Dr. Boekhout and her colleagues said (J. Clin. Oncol. 2011 Sept. 12 [doi:10.1200/JCO.2010.33.1298]).

They added that it is "advisable to treat patients to manage hot flashes with venlafaxine 37.5 mg daily in the first week and increase the venlafaxine dose to 75 mg if greater efficacy is desired."

A total of 14 patients (34%) in the clonidine group, 23 (56%) in the venlafaxine group, and 4 (20%) in the placebo group said they wished to continue the study treatment at the end of the trial.

Women taking clonidine reported more symptoms of anxiety and women taking venlafaxine reported more symptoms of depression. Sexual function and sleep quality did not differ between the two groups. However, the duration of this study may have been too short to adequately assess these adverse effects, the researchers noted.

No conflicts of interest were reported.

ADELPHI, MD. – Data on the safety and effectiveness of bisphosphonate drugs for the long-term treatment of osteoporosis is lacking and direly needed, according to a joint Food and Drug Administration advisory committee meeting.

Specifically, the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 17-6 on Sept. 9 that labeling for these drugs should be changed to clarify the duration of use for this drug class.

The agency convened the joint meeting to evaluate particular concerns about the long-term use bisphosphonate drugs, given reports of atypical subtrochanteric and femoral fractures, jaw osteonecrosis, and esophageal cancer associated with bisphosphonate use.

The labels of bisphosphonate drugs – alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast) – already include "important limitation of use" information. This labeling states that the optimal duration of treatment (for an individual drug) has not been determined and that all patients on bisphosphonate therapy should be periodically reassessed for the necessity of continued therapy.

While the panel voted to clarify the label language, they were emphatic that much more data are needed to establish the long-term efficacy and safety of bisphosphonates in general and with special regard to atypical fractures, jaw osteonecrosis, and esophageal cancer.

The two committees also were asked to assess the strength of data on the long-term use of bisphosphonates; the overall risks and benefits of continuous long-term use (3-5 years or more); whether restricting the duration of use or implementing a drug holiday would be beneficial; which outcomes require further evidence; and how should this data be obtained.

The expert consensus is that existing data – some of which go out to roughly 10 years for one drug – do not address the efficacy of the long-term use of bisphosphonates. They recommended that (in no particular order) additional data are needed with regard to the occurrence of atypical fractures, osteonecrosis of the jaw, esophageal cancer, osteoporotic fracture reduction efficacy with long-term (at least 3-5 years) continuous bisphosphonate use, and the effect of a "drug holiday" on drug safety and effectiveness.

Osteoporosis currently affects approximately 10 million Americans, according to the American Society for Bone and Mineral Research. An additional 34 million have low bone mass, which may progress to osteoporosis.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver, but none were given at this meeting.

ADELPHI, MD. – Data on the safety and effectiveness of bisphosphonate drugs for the long-term treatment of osteoporosis is lacking and direly needed, according to a joint Food and Drug Administration advisory committee meeting.

Specifically, the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 17-6 on Sept. 9 that labeling for these drugs should be changed to clarify the duration of use for this drug class.

The agency convened the joint meeting to evaluate particular concerns about the long-term use bisphosphonate drugs, given reports of atypical subtrochanteric and femoral fractures, jaw osteonecrosis, and esophageal cancer associated with bisphosphonate use.

The labels of bisphosphonate drugs – alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast) – already include "important limitation of use" information. This labeling states that the optimal duration of treatment (for an individual drug) has not been determined and that all patients on bisphosphonate therapy should be periodically reassessed for the necessity of continued therapy.

While the panel voted to clarify the label language, they were emphatic that much more data are needed to establish the long-term efficacy and safety of bisphosphonates in general and with special regard to atypical fractures, jaw osteonecrosis, and esophageal cancer.

The two committees also were asked to assess the strength of data on the long-term use of bisphosphonates; the overall risks and benefits of continuous long-term use (3-5 years or more); whether restricting the duration of use or implementing a drug holiday would be beneficial; which outcomes require further evidence; and how should this data be obtained.

The expert consensus is that existing data – some of which go out to roughly 10 years for one drug – do not address the efficacy of the long-term use of bisphosphonates. They recommended that (in no particular order) additional data are needed with regard to the occurrence of atypical fractures, osteonecrosis of the jaw, esophageal cancer, osteoporotic fracture reduction efficacy with long-term (at least 3-5 years) continuous bisphosphonate use, and the effect of a "drug holiday" on drug safety and effectiveness.

Osteoporosis currently affects approximately 10 million Americans, according to the American Society for Bone and Mineral Research. An additional 34 million have low bone mass, which may progress to osteoporosis.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver, but none were given at this meeting.

ADELPHI, MD. – Data on the safety and effectiveness of bisphosphonate drugs for the long-term treatment of osteoporosis is lacking and direly needed, according to a joint Food and Drug Administration advisory committee meeting.

Specifically, the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 17-6 on Sept. 9 that labeling for these drugs should be changed to clarify the duration of use for this drug class.

The agency convened the joint meeting to evaluate particular concerns about the long-term use bisphosphonate drugs, given reports of atypical subtrochanteric and femoral fractures, jaw osteonecrosis, and esophageal cancer associated with bisphosphonate use.

The labels of bisphosphonate drugs – alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast) – already include "important limitation of use" information. This labeling states that the optimal duration of treatment (for an individual drug) has not been determined and that all patients on bisphosphonate therapy should be periodically reassessed for the necessity of continued therapy.

While the panel voted to clarify the label language, they were emphatic that much more data are needed to establish the long-term efficacy and safety of bisphosphonates in general and with special regard to atypical fractures, jaw osteonecrosis, and esophageal cancer.

The two committees also were asked to assess the strength of data on the long-term use of bisphosphonates; the overall risks and benefits of continuous long-term use (3-5 years or more); whether restricting the duration of use or implementing a drug holiday would be beneficial; which outcomes require further evidence; and how should this data be obtained.

The expert consensus is that existing data – some of which go out to roughly 10 years for one drug – do not address the efficacy of the long-term use of bisphosphonates. They recommended that (in no particular order) additional data are needed with regard to the occurrence of atypical fractures, osteonecrosis of the jaw, esophageal cancer, osteoporotic fracture reduction efficacy with long-term (at least 3-5 years) continuous bisphosphonate use, and the effect of a "drug holiday" on drug safety and effectiveness.

Osteoporosis currently affects approximately 10 million Americans, according to the American Society for Bone and Mineral Research. An additional 34 million have low bone mass, which may progress to osteoporosis.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver, but none were given at this meeting.

SAN FRANCISCO – The more metabolically active a woman’s bone metastases of breast cancer are on imaging, the greater her risk of death, researchers reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In a retrospective cohort study of 269 women with newly diagnosed metastatic breast cancer, those whose bone metastases were "hotter" on a PET/CT – as assessed from maximum standardized uptake value (SUV-max) – had poorer overall survival.

Compared with their counterparts with values in the bottom tertile of SUV-max values, women with values in the middle and top tertiles were roughly two to three times more likely to die after other prognostic factors were taken into account.

"To our understanding, this is the first large retrospective series to correlate SUV-max at metastatic breast cancer diagnosis with overall survival," said lead author Dr. Komal Jhaveri of Memorial Sloan-Kettering Cancer Center, New York.

The risk of death also rose with increasing tertile of SUV-max in liver, lung, and lymph node metastases, but those associations were not significant. Their nonsignificance may have been due to the smaller numbers of patients having metastases in those sites, she said.

Session chair Dr. Robert R. Kuske, a radiation oncologist with Arizona Breast Cancer Specialists in Scottsdale, noted that SUV-max is a surrogate for how rapidly the tumor cells are proliferating and, hence, the tumor’s aggressiveness. "So there should be a strong correlation between this SUV on the PET and the Ki-67 [histologic proliferation index]," he said.

"This gives us another tool in our tool chest to evaluate how patients are going to do," he commented. "Now [oncologists] can look at a metastasis on PET, measure the SUV, and get a handle on what the future of that patient is going to be – is it going to be a rapid slide to death, or is it going to be a very slow, indolent progression maybe over 10 or 15 years. And they can tailor the therapy based on the aggressiveness of the disease."

The PET/CT is usually done to determine whether the patient has metastases, so this additional prognostic information "is a little something extra you get from the test."

Will these new findings be practice changing? "I’ll start looking at SUV values in my patients with newly diagnosed metastasis," said Dr. Kuske. "Yes, it will change my practice."

In the study, Dr. Jhaveri and her coinvestigators reviewed records for women with metastatic breast cancer diagnosed between 2001 and 2008 who had a PET/CT scan performed within 60 days of the detection of metastases; had at least one avid metastasis in bone, liver, lung, or lymph node; and had not received chemotherapy in the month before the scan. Prior or current hormonal therapy was permitted.

The investigators determined the SUV-max for individual metastatic sites. They compared values only within a given site because of known variation across sites such as liver and lung, Dr. Jhaveri explained.

The women had a median age of 58 years. The median time elapsed between primary breast cancer diagnosis and PET/CT was 2.3 years. A fifth each had triple-negative disease and HER2-positive disease.

The median duration of follow-up was 40 months. In a multivariate analysis that included other prognostic factors (grade, tumor phenotype, and visceral metastases), overall survival differed across tertiles of SUV-max for bone metastases (P = .006). Women with values in the middle and top tertiles were 1.87 and 2.67 times more likely to die, respectively, than their counterparts with values in the bottom tertile.

"Given the variation in SUV and the differential impact on survival by site, it is possible that SUV-max may not be the most optimal PET variable," Dr. Jhaveri commented. She proposed that an alternate variable, called total lesion glycolysis (TLG), which incorporates tumor lesion size, might perform better and be more informative.

"Ultimately, prospective studies are required to further delineate the role of PET/CT as a prognostic tool in metastatic breast cancer," she concluded.

Dr. Jhaveri and Dr. Kuske reported having no relevant conflicts of interest.

SAN FRANCISCO – The more metabolically active a woman’s bone metastases of breast cancer are on imaging, the greater her risk of death, researchers reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In a retrospective cohort study of 269 women with newly diagnosed metastatic breast cancer, those whose bone metastases were "hotter" on a PET/CT – as assessed from maximum standardized uptake value (SUV-max) – had poorer overall survival.

Compared with their counterparts with values in the bottom tertile of SUV-max values, women with values in the middle and top tertiles were roughly two to three times more likely to die after other prognostic factors were taken into account.

"To our understanding, this is the first large retrospective series to correlate SUV-max at metastatic breast cancer diagnosis with overall survival," said lead author Dr. Komal Jhaveri of Memorial Sloan-Kettering Cancer Center, New York.

The risk of death also rose with increasing tertile of SUV-max in liver, lung, and lymph node metastases, but those associations were not significant. Their nonsignificance may have been due to the smaller numbers of patients having metastases in those sites, she said.

Session chair Dr. Robert R. Kuske, a radiation oncologist with Arizona Breast Cancer Specialists in Scottsdale, noted that SUV-max is a surrogate for how rapidly the tumor cells are proliferating and, hence, the tumor’s aggressiveness. "So there should be a strong correlation between this SUV on the PET and the Ki-67 [histologic proliferation index]," he said.

"This gives us another tool in our tool chest to evaluate how patients are going to do," he commented. "Now [oncologists] can look at a metastasis on PET, measure the SUV, and get a handle on what the future of that patient is going to be – is it going to be a rapid slide to death, or is it going to be a very slow, indolent progression maybe over 10 or 15 years. And they can tailor the therapy based on the aggressiveness of the disease."

The PET/CT is usually done to determine whether the patient has metastases, so this additional prognostic information "is a little something extra you get from the test."

Will these new findings be practice changing? "I’ll start looking at SUV values in my patients with newly diagnosed metastasis," said Dr. Kuske. "Yes, it will change my practice."

In the study, Dr. Jhaveri and her coinvestigators reviewed records for women with metastatic breast cancer diagnosed between 2001 and 2008 who had a PET/CT scan performed within 60 days of the detection of metastases; had at least one avid metastasis in bone, liver, lung, or lymph node; and had not received chemotherapy in the month before the scan. Prior or current hormonal therapy was permitted.

The investigators determined the SUV-max for individual metastatic sites. They compared values only within a given site because of known variation across sites such as liver and lung, Dr. Jhaveri explained.

The women had a median age of 58 years. The median time elapsed between primary breast cancer diagnosis and PET/CT was 2.3 years. A fifth each had triple-negative disease and HER2-positive disease.

The median duration of follow-up was 40 months. In a multivariate analysis that included other prognostic factors (grade, tumor phenotype, and visceral metastases), overall survival differed across tertiles of SUV-max for bone metastases (P = .006). Women with values in the middle and top tertiles were 1.87 and 2.67 times more likely to die, respectively, than their counterparts with values in the bottom tertile.

"Given the variation in SUV and the differential impact on survival by site, it is possible that SUV-max may not be the most optimal PET variable," Dr. Jhaveri commented. She proposed that an alternate variable, called total lesion glycolysis (TLG), which incorporates tumor lesion size, might perform better and be more informative.

"Ultimately, prospective studies are required to further delineate the role of PET/CT as a prognostic tool in metastatic breast cancer," she concluded.

Dr. Jhaveri and Dr. Kuske reported having no relevant conflicts of interest.

SAN FRANCISCO – The more metabolically active a woman’s bone metastases of breast cancer are on imaging, the greater her risk of death, researchers reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In a retrospective cohort study of 269 women with newly diagnosed metastatic breast cancer, those whose bone metastases were "hotter" on a PET/CT – as assessed from maximum standardized uptake value (SUV-max) – had poorer overall survival.

Compared with their counterparts with values in the bottom tertile of SUV-max values, women with values in the middle and top tertiles were roughly two to three times more likely to die after other prognostic factors were taken into account.

"To our understanding, this is the first large retrospective series to correlate SUV-max at metastatic breast cancer diagnosis with overall survival," said lead author Dr. Komal Jhaveri of Memorial Sloan-Kettering Cancer Center, New York.

The risk of death also rose with increasing tertile of SUV-max in liver, lung, and lymph node metastases, but those associations were not significant. Their nonsignificance may have been due to the smaller numbers of patients having metastases in those sites, she said.

Session chair Dr. Robert R. Kuske, a radiation oncologist with Arizona Breast Cancer Specialists in Scottsdale, noted that SUV-max is a surrogate for how rapidly the tumor cells are proliferating and, hence, the tumor’s aggressiveness. "So there should be a strong correlation between this SUV on the PET and the Ki-67 [histologic proliferation index]," he said.

"This gives us another tool in our tool chest to evaluate how patients are going to do," he commented. "Now [oncologists] can look at a metastasis on PET, measure the SUV, and get a handle on what the future of that patient is going to be – is it going to be a rapid slide to death, or is it going to be a very slow, indolent progression maybe over 10 or 15 years. And they can tailor the therapy based on the aggressiveness of the disease."

The PET/CT is usually done to determine whether the patient has metastases, so this additional prognostic information "is a little something extra you get from the test."

Will these new findings be practice changing? "I’ll start looking at SUV values in my patients with newly diagnosed metastasis," said Dr. Kuske. "Yes, it will change my practice."

In the study, Dr. Jhaveri and her coinvestigators reviewed records for women with metastatic breast cancer diagnosed between 2001 and 2008 who had a PET/CT scan performed within 60 days of the detection of metastases; had at least one avid metastasis in bone, liver, lung, or lymph node; and had not received chemotherapy in the month before the scan. Prior or current hormonal therapy was permitted.

The investigators determined the SUV-max for individual metastatic sites. They compared values only within a given site because of known variation across sites such as liver and lung, Dr. Jhaveri explained.

The women had a median age of 58 years. The median time elapsed between primary breast cancer diagnosis and PET/CT was 2.3 years. A fifth each had triple-negative disease and HER2-positive disease.

The median duration of follow-up was 40 months. In a multivariate analysis that included other prognostic factors (grade, tumor phenotype, and visceral metastases), overall survival differed across tertiles of SUV-max for bone metastases (P = .006). Women with values in the middle and top tertiles were 1.87 and 2.67 times more likely to die, respectively, than their counterparts with values in the bottom tertile.

"Given the variation in SUV and the differential impact on survival by site, it is possible that SUV-max may not be the most optimal PET variable," Dr. Jhaveri commented. She proposed that an alternate variable, called total lesion glycolysis (TLG), which incorporates tumor lesion size, might perform better and be more informative.

"Ultimately, prospective studies are required to further delineate the role of PET/CT as a prognostic tool in metastatic breast cancer," she concluded.

Dr. Jhaveri and Dr. Kuske reported having no relevant conflicts of interest.

Young women with early breast cancer need not have a mastectomy instead of a breast-conserving therapy if the rationale is based solely on their age, investigators concluded in a pair of retrospective cohort studies being reported at the ASCO Breast Cancer Symposium.

In the studies, conducted among more than 15,000 women aged 40 years or younger having median follow-up of about 6 years, rates of locoregional recurrence, overall survival, and breast cancer–specific survival were statistically indistinguishable from those who had breast conservation and their counterparts who had mastectomy, according to data presented in a premeeting press briefing.

Collectively, the results suggest that contemporary management of breast cancer has helped to offset the poorer outcomes historically associated with younger age at diagnosis, commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York.

"This is an important revisitation of the conventional wisdom that young women who have breast cancer really need to have mastectomy," he said. "There certainly are differences in the biology of the disease in young women, compared to older women."

He suggested these new findings likely reflect changing influences on breast cancer management, such as use of genetic testing to better identify women with deleterious mutations and possibly breast MRI.

"It’s reassuring to younger women that simply young age alone does not seem to mandate the need for mastectomy, and one needs to look at other variables independent of age," Dr. Seidman said. Those variables will include factors like multicentricity or multifocality, BRCA mutations, family history, and, not least, women’s concerns about recurrence and second cancers.

Additionally, research is identifying biological subtypes of breast cancer that may be useful here, he noted. For example, among women with luminal type A breast cancer, emerging data suggest that Oncotype DX recurrence score may help assess risk of local relapse.

The bottom line, he stressed, is that "if a woman is told, you need to have mastectomy because you are young, the discussion needs to go beyond that," and individualized decision making is essential.

In the first study, Dr. Julliette M. Buckley and her colleagues at Massachusetts General Hospital in Boston reviewed the medical records of 628 women aged 40 years or younger who received a diagnosis of breast cancer up to stage III between 1996 and 2008 and were treated at their institution.

The women had a median age of 37 years. Overall, 71% had breast-conserving therapy, according to Dr. Buckley.

With a median follow-up of 72 months, the women had statistically indistinguishable rates of locoregional recurrence with breast conserving–therapy vs. mastectomy. Rates of locoregional and distant recurrence were 5.6% and 12% at 5 years, respectively, and 13% and 19% at 10 years. Rates of disease-free survival and overall survival were 82.5% and 93% at 5 years, respectively, and 87% and 68.5% at 10 years.

The findings suggest "that lumpectomy is indeed a safe option for young women," concluded Dr. Buckley, a breast surgery fellow.

"We believe that awareness of the genetic risk of breast cancer, advances in the screening for breast cancer, and improvements in systemic and radiation therapy have contributed to the longer overall survival for young women with breast cancer that we have demonstrated in this study," she said. "We feel that these results ... will give young women with breast cancer some reassurance if they choose to have a lumpectomy."

In the second study, investigators led by Dr. Usama Mahmood of the University of Texas M.D. Anderson Cancer Center in Houston analyzed data from the Surveillance, Epidemiology, and End Results database for 14,764 women 20-39 years old who received a diagnosis of early breast cancer between 1990 and 2007. Overall, 45% received breast-conserving therapy. The median duration of follow-up was 5.7 years.

In multivariate analyses that adjusted for potential confounders (including year of diagnosis, age, race/ethnicity, histology, grade, one vs. multiple regions of involvement, tumor size, number of positive lymph nodes, number of examined lymph nodes, estrogen receptor status, and progesterone receptor status), women treated with breast-conserving therapy did not differ significantly from their counterparts treated with mastectomy in terms of either overall survival (hazard ratio, 0.93; P = .16) or breast cancer–specific survival (hazard ratio, 0.93; P = .26).

The findings were similar in an additional analysis of a subset of 4,644 women from the two groups who were matched for patient and tumor characteristics, according to Dr. Mahmood, a fellow in radiation oncology, who did much of her search while at the University of Maryland’s Greenebaum Cancer Center in Baltimore. In this analysis, women treated with breast-conserving therapy and their counterparts treated with mastectomy again had similar 10-year overall survival (83.5% vs. 83.6%, P = .99) and breast cancer–specific survival (85.5% vs. 85.5%, P = .88).

"We found similar survival with either breast-conserving therapy or mastectomy in the treatment of young women with early-stage breast cancer," Dr. Mahmood concluded. "This just serves as a reminder that women should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on an assumption of improved survival."

Dr. Seidman, Dr. Buckley, and Dr. Mahmood reported that they had no relevant conflicts of interest.

Young women with early breast cancer need not have a mastectomy instead of a breast-conserving therapy if the rationale is based solely on their age, investigators concluded in a pair of retrospective cohort studies being reported at the ASCO Breast Cancer Symposium.

In the studies, conducted among more than 15,000 women aged 40 years or younger having median follow-up of about 6 years, rates of locoregional recurrence, overall survival, and breast cancer–specific survival were statistically indistinguishable from those who had breast conservation and their counterparts who had mastectomy, according to data presented in a premeeting press briefing.

Collectively, the results suggest that contemporary management of breast cancer has helped to offset the poorer outcomes historically associated with younger age at diagnosis, commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York.

"This is an important revisitation of the conventional wisdom that young women who have breast cancer really need to have mastectomy," he said. "There certainly are differences in the biology of the disease in young women, compared to older women."

He suggested these new findings likely reflect changing influences on breast cancer management, such as use of genetic testing to better identify women with deleterious mutations and possibly breast MRI.

"It’s reassuring to younger women that simply young age alone does not seem to mandate the need for mastectomy, and one needs to look at other variables independent of age," Dr. Seidman said. Those variables will include factors like multicentricity or multifocality, BRCA mutations, family history, and, not least, women’s concerns about recurrence and second cancers.

Additionally, research is identifying biological subtypes of breast cancer that may be useful here, he noted. For example, among women with luminal type A breast cancer, emerging data suggest that Oncotype DX recurrence score may help assess risk of local relapse.

The bottom line, he stressed, is that "if a woman is told, you need to have mastectomy because you are young, the discussion needs to go beyond that," and individualized decision making is essential.

In the first study, Dr. Julliette M. Buckley and her colleagues at Massachusetts General Hospital in Boston reviewed the medical records of 628 women aged 40 years or younger who received a diagnosis of breast cancer up to stage III between 1996 and 2008 and were treated at their institution.

The women had a median age of 37 years. Overall, 71% had breast-conserving therapy, according to Dr. Buckley.

With a median follow-up of 72 months, the women had statistically indistinguishable rates of locoregional recurrence with breast conserving–therapy vs. mastectomy. Rates of locoregional and distant recurrence were 5.6% and 12% at 5 years, respectively, and 13% and 19% at 10 years. Rates of disease-free survival and overall survival were 82.5% and 93% at 5 years, respectively, and 87% and 68.5% at 10 years.

The findings suggest "that lumpectomy is indeed a safe option for young women," concluded Dr. Buckley, a breast surgery fellow.

"We believe that awareness of the genetic risk of breast cancer, advances in the screening for breast cancer, and improvements in systemic and radiation therapy have contributed to the longer overall survival for young women with breast cancer that we have demonstrated in this study," she said. "We feel that these results ... will give young women with breast cancer some reassurance if they choose to have a lumpectomy."

In the second study, investigators led by Dr. Usama Mahmood of the University of Texas M.D. Anderson Cancer Center in Houston analyzed data from the Surveillance, Epidemiology, and End Results database for 14,764 women 20-39 years old who received a diagnosis of early breast cancer between 1990 and 2007. Overall, 45% received breast-conserving therapy. The median duration of follow-up was 5.7 years.

In multivariate analyses that adjusted for potential confounders (including year of diagnosis, age, race/ethnicity, histology, grade, one vs. multiple regions of involvement, tumor size, number of positive lymph nodes, number of examined lymph nodes, estrogen receptor status, and progesterone receptor status), women treated with breast-conserving therapy did not differ significantly from their counterparts treated with mastectomy in terms of either overall survival (hazard ratio, 0.93; P = .16) or breast cancer–specific survival (hazard ratio, 0.93; P = .26).

The findings were similar in an additional analysis of a subset of 4,644 women from the two groups who were matched for patient and tumor characteristics, according to Dr. Mahmood, a fellow in radiation oncology, who did much of her search while at the University of Maryland’s Greenebaum Cancer Center in Baltimore. In this analysis, women treated with breast-conserving therapy and their counterparts treated with mastectomy again had similar 10-year overall survival (83.5% vs. 83.6%, P = .99) and breast cancer–specific survival (85.5% vs. 85.5%, P = .88).

"We found similar survival with either breast-conserving therapy or mastectomy in the treatment of young women with early-stage breast cancer," Dr. Mahmood concluded. "This just serves as a reminder that women should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on an assumption of improved survival."

Dr. Seidman, Dr. Buckley, and Dr. Mahmood reported that they had no relevant conflicts of interest.

Young women with early breast cancer need not have a mastectomy instead of a breast-conserving therapy if the rationale is based solely on their age, investigators concluded in a pair of retrospective cohort studies being reported at the ASCO Breast Cancer Symposium.

In the studies, conducted among more than 15,000 women aged 40 years or younger having median follow-up of about 6 years, rates of locoregional recurrence, overall survival, and breast cancer–specific survival were statistically indistinguishable from those who had breast conservation and their counterparts who had mastectomy, according to data presented in a premeeting press briefing.

Collectively, the results suggest that contemporary management of breast cancer has helped to offset the poorer outcomes historically associated with younger age at diagnosis, commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York.

"This is an important revisitation of the conventional wisdom that young women who have breast cancer really need to have mastectomy," he said. "There certainly are differences in the biology of the disease in young women, compared to older women."

He suggested these new findings likely reflect changing influences on breast cancer management, such as use of genetic testing to better identify women with deleterious mutations and possibly breast MRI.

"It’s reassuring to younger women that simply young age alone does not seem to mandate the need for mastectomy, and one needs to look at other variables independent of age," Dr. Seidman said. Those variables will include factors like multicentricity or multifocality, BRCA mutations, family history, and, not least, women’s concerns about recurrence and second cancers.

Additionally, research is identifying biological subtypes of breast cancer that may be useful here, he noted. For example, among women with luminal type A breast cancer, emerging data suggest that Oncotype DX recurrence score may help assess risk of local relapse.

The bottom line, he stressed, is that "if a woman is told, you need to have mastectomy because you are young, the discussion needs to go beyond that," and individualized decision making is essential.

In the first study, Dr. Julliette M. Buckley and her colleagues at Massachusetts General Hospital in Boston reviewed the medical records of 628 women aged 40 years or younger who received a diagnosis of breast cancer up to stage III between 1996 and 2008 and were treated at their institution.

The women had a median age of 37 years. Overall, 71% had breast-conserving therapy, according to Dr. Buckley.

With a median follow-up of 72 months, the women had statistically indistinguishable rates of locoregional recurrence with breast conserving–therapy vs. mastectomy. Rates of locoregional and distant recurrence were 5.6% and 12% at 5 years, respectively, and 13% and 19% at 10 years. Rates of disease-free survival and overall survival were 82.5% and 93% at 5 years, respectively, and 87% and 68.5% at 10 years.

The findings suggest "that lumpectomy is indeed a safe option for young women," concluded Dr. Buckley, a breast surgery fellow.

"We believe that awareness of the genetic risk of breast cancer, advances in the screening for breast cancer, and improvements in systemic and radiation therapy have contributed to the longer overall survival for young women with breast cancer that we have demonstrated in this study," she said. "We feel that these results ... will give young women with breast cancer some reassurance if they choose to have a lumpectomy."

In the second study, investigators led by Dr. Usama Mahmood of the University of Texas M.D. Anderson Cancer Center in Houston analyzed data from the Surveillance, Epidemiology, and End Results database for 14,764 women 20-39 years old who received a diagnosis of early breast cancer between 1990 and 2007. Overall, 45% received breast-conserving therapy. The median duration of follow-up was 5.7 years.

In multivariate analyses that adjusted for potential confounders (including year of diagnosis, age, race/ethnicity, histology, grade, one vs. multiple regions of involvement, tumor size, number of positive lymph nodes, number of examined lymph nodes, estrogen receptor status, and progesterone receptor status), women treated with breast-conserving therapy did not differ significantly from their counterparts treated with mastectomy in terms of either overall survival (hazard ratio, 0.93; P = .16) or breast cancer–specific survival (hazard ratio, 0.93; P = .26).

The findings were similar in an additional analysis of a subset of 4,644 women from the two groups who were matched for patient and tumor characteristics, according to Dr. Mahmood, a fellow in radiation oncology, who did much of her search while at the University of Maryland’s Greenebaum Cancer Center in Baltimore. In this analysis, women treated with breast-conserving therapy and their counterparts treated with mastectomy again had similar 10-year overall survival (83.5% vs. 83.6%, P = .99) and breast cancer–specific survival (85.5% vs. 85.5%, P = .88).

"We found similar survival with either breast-conserving therapy or mastectomy in the treatment of young women with early-stage breast cancer," Dr. Mahmood concluded. "This just serves as a reminder that women should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on an assumption of improved survival."

Dr. Seidman, Dr. Buckley, and Dr. Mahmood reported that they had no relevant conflicts of interest.

A new set of nomograms based on easily assessed risk factors accurately predicts a woman’s likelihood of developing lymphedema after axillary lymph node dissection for breast cancer, researchers are reporting at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The nomograms, which enable risk assessment throughout the course of treatment using data available at the time, had accuracy exceeding 70%, according to results presented in a press briefing before the meeting.

"The accuracy is the same as mammography to detect breast cancer. ... So that’s a very good statistical tool," said lead author Dr. Jose Bevilacqua, a surgical oncologist at the Hospital Sirio-Libanês in São Paulo, Brazil.

Being able to identify high-risk patients has several potential applications, he added. They could be monitored more closely and offered interventions that might prevent or reduce the severity of lymphedema, such as use of compression sleeves. "The earlier you detect [it], the better is the outcome," Dr. Bevilacqua said.

Additionally, high-risk patients with a positive sentinel lymph node could be counseled about the risk of further surgery. Thus, "you have physicians who make closer follow-up and [have] a better discussion with the patients."

Finally, the nomograms could be applied in clinical research. "These tools might help [ongoing] or new studies to select high-risk patients in order to avoid exposing the low-risk patients to unproven therapies," he explained.

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, commended the investigators for a study that "has real practical implications for patients."

"It allows us to identify patients who then can be appropriately triaged for early intervention and perhaps for clinical trials aimed at preventing what many consider inevitable, and that is the development of lymphedema."

The effectiveness of early interventions is controversial, according to Dr. Seidman, who did not report any relevant conflicts of interest. "There are believers and there are nonbelievers," he commented. "What I think this nomogram does is [allow] us in a scientific way to segregate out patients in terms of their risk, and by doing that, we can have more uniform cohorts for which early intervention can be studied more rigorously."

The researchers prospectively followed 1,054 women with unilateral breast cancer who underwent breast-conserving surgery or mastectomy with an axillary lymph node dissection in 2001-2002. Median follow-up was 41 months.

"As far as we know, we have established the largest prospective cohort specifically established to study the incidence and factors associated with lymphedema after axillary node dissection for breast cancer," commented Dr. Bevilacqua.

Using Data to Predict Lymphedema

The women had serial arm volume measurements starting before surgery. To facilitate this process, the researchers created a tool that is now available free online (www.armvolume.com).

They then developed and internally validated three multivariate nomograms (or statistical models) for predicting lymphedema using data available at various time points.

The first model, to be used preoperatively, incorporated age, body mass index, and number of cycles of neoadjuvant chemotherapy infusions in the ipsilateral arm.

The second model, to be used within the first 6 months after surgery, incorporated all the factors from the first plus the extent of axillary dissection, the location of radiation therapy field, and the number of cycles of adjuvant chemotherapy infusions in the ipsilateral arm.

The third model, to be used 6 months or later after surgery, incorporated all the factors from the second, plus the development of postoperative seroma and development of early edema.

Study results showed that within 5 years of axillary lymph node dissection, 30.3% of the women developed lymphedema (defined as a difference in volume of at least 200 mL between arms at 6 months or later after surgery).

All of the risk factors used in the models were significantly associated with the development of lymphedema, Dr. Bevilacqua reported.

"One of the novelties of our study is the [finding] that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema," he pointed out. "This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of this fact."

For predicting the 5-year risk of lymphedema, the first, second, and third models had accuracy of 70.6%, 72.9%, and 73.6%, respectively. The investigators have converted the models into free, user-friendly calculators that are available online (www.lymphedemarisk.com) during the ASCO Breast Cancer Symposium (Sept. 8-10), but will be taken off line until the manuscript is published, after which they are to become available again.

Dr. Bevilacqua reported that he had no relevant conflicts of interest.

A new set of nomograms based on easily assessed risk factors accurately predicts a woman’s likelihood of developing lymphedema after axillary lymph node dissection for breast cancer, researchers are reporting at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The nomograms, which enable risk assessment throughout the course of treatment using data available at the time, had accuracy exceeding 70%, according to results presented in a press briefing before the meeting.

"The accuracy is the same as mammography to detect breast cancer. ... So that’s a very good statistical tool," said lead author Dr. Jose Bevilacqua, a surgical oncologist at the Hospital Sirio-Libanês in São Paulo, Brazil.

Being able to identify high-risk patients has several potential applications, he added. They could be monitored more closely and offered interventions that might prevent or reduce the severity of lymphedema, such as use of compression sleeves. "The earlier you detect [it], the better is the outcome," Dr. Bevilacqua said.

Additionally, high-risk patients with a positive sentinel lymph node could be counseled about the risk of further surgery. Thus, "you have physicians who make closer follow-up and [have] a better discussion with the patients."

Finally, the nomograms could be applied in clinical research. "These tools might help [ongoing] or new studies to select high-risk patients in order to avoid exposing the low-risk patients to unproven therapies," he explained.

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, commended the investigators for a study that "has real practical implications for patients."

"It allows us to identify patients who then can be appropriately triaged for early intervention and perhaps for clinical trials aimed at preventing what many consider inevitable, and that is the development of lymphedema."

The effectiveness of early interventions is controversial, according to Dr. Seidman, who did not report any relevant conflicts of interest. "There are believers and there are nonbelievers," he commented. "What I think this nomogram does is [allow] us in a scientific way to segregate out patients in terms of their risk, and by doing that, we can have more uniform cohorts for which early intervention can be studied more rigorously."

The researchers prospectively followed 1,054 women with unilateral breast cancer who underwent breast-conserving surgery or mastectomy with an axillary lymph node dissection in 2001-2002. Median follow-up was 41 months.

"As far as we know, we have established the largest prospective cohort specifically established to study the incidence and factors associated with lymphedema after axillary node dissection for breast cancer," commented Dr. Bevilacqua.

Using Data to Predict Lymphedema

The women had serial arm volume measurements starting before surgery. To facilitate this process, the researchers created a tool that is now available free online (www.armvolume.com).

They then developed and internally validated three multivariate nomograms (or statistical models) for predicting lymphedema using data available at various time points.

The first model, to be used preoperatively, incorporated age, body mass index, and number of cycles of neoadjuvant chemotherapy infusions in the ipsilateral arm.

The second model, to be used within the first 6 months after surgery, incorporated all the factors from the first plus the extent of axillary dissection, the location of radiation therapy field, and the number of cycles of adjuvant chemotherapy infusions in the ipsilateral arm.

The third model, to be used 6 months or later after surgery, incorporated all the factors from the second, plus the development of postoperative seroma and development of early edema.

Study results showed that within 5 years of axillary lymph node dissection, 30.3% of the women developed lymphedema (defined as a difference in volume of at least 200 mL between arms at 6 months or later after surgery).

All of the risk factors used in the models were significantly associated with the development of lymphedema, Dr. Bevilacqua reported.

"One of the novelties of our study is the [finding] that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema," he pointed out. "This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of this fact."

For predicting the 5-year risk of lymphedema, the first, second, and third models had accuracy of 70.6%, 72.9%, and 73.6%, respectively. The investigators have converted the models into free, user-friendly calculators that are available online (www.lymphedemarisk.com) during the ASCO Breast Cancer Symposium (Sept. 8-10), but will be taken off line until the manuscript is published, after which they are to become available again.

Dr. Bevilacqua reported that he had no relevant conflicts of interest.

A new set of nomograms based on easily assessed risk factors accurately predicts a woman’s likelihood of developing lymphedema after axillary lymph node dissection for breast cancer, researchers are reporting at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The nomograms, which enable risk assessment throughout the course of treatment using data available at the time, had accuracy exceeding 70%, according to results presented in a press briefing before the meeting.

"The accuracy is the same as mammography to detect breast cancer. ... So that’s a very good statistical tool," said lead author Dr. Jose Bevilacqua, a surgical oncologist at the Hospital Sirio-Libanês in São Paulo, Brazil.

Being able to identify high-risk patients has several potential applications, he added. They could be monitored more closely and offered interventions that might prevent or reduce the severity of lymphedema, such as use of compression sleeves. "The earlier you detect [it], the better is the outcome," Dr. Bevilacqua said.

Additionally, high-risk patients with a positive sentinel lymph node could be counseled about the risk of further surgery. Thus, "you have physicians who make closer follow-up and [have] a better discussion with the patients."

Finally, the nomograms could be applied in clinical research. "These tools might help [ongoing] or new studies to select high-risk patients in order to avoid exposing the low-risk patients to unproven therapies," he explained.

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, commended the investigators for a study that "has real practical implications for patients."

"It allows us to identify patients who then can be appropriately triaged for early intervention and perhaps for clinical trials aimed at preventing what many consider inevitable, and that is the development of lymphedema."

The effectiveness of early interventions is controversial, according to Dr. Seidman, who did not report any relevant conflicts of interest. "There are believers and there are nonbelievers," he commented. "What I think this nomogram does is [allow] us in a scientific way to segregate out patients in terms of their risk, and by doing that, we can have more uniform cohorts for which early intervention can be studied more rigorously."

The researchers prospectively followed 1,054 women with unilateral breast cancer who underwent breast-conserving surgery or mastectomy with an axillary lymph node dissection in 2001-2002. Median follow-up was 41 months.

"As far as we know, we have established the largest prospective cohort specifically established to study the incidence and factors associated with lymphedema after axillary node dissection for breast cancer," commented Dr. Bevilacqua.

Using Data to Predict Lymphedema

The women had serial arm volume measurements starting before surgery. To facilitate this process, the researchers created a tool that is now available free online (www.armvolume.com).

They then developed and internally validated three multivariate nomograms (or statistical models) for predicting lymphedema using data available at various time points.

The first model, to be used preoperatively, incorporated age, body mass index, and number of cycles of neoadjuvant chemotherapy infusions in the ipsilateral arm.

The second model, to be used within the first 6 months after surgery, incorporated all the factors from the first plus the extent of axillary dissection, the location of radiation therapy field, and the number of cycles of adjuvant chemotherapy infusions in the ipsilateral arm.

The third model, to be used 6 months or later after surgery, incorporated all the factors from the second, plus the development of postoperative seroma and development of early edema.

Study results showed that within 5 years of axillary lymph node dissection, 30.3% of the women developed lymphedema (defined as a difference in volume of at least 200 mL between arms at 6 months or later after surgery).

All of the risk factors used in the models were significantly associated with the development of lymphedema, Dr. Bevilacqua reported.

"One of the novelties of our study is the [finding] that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema," he pointed out. "This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of this fact."

For predicting the 5-year risk of lymphedema, the first, second, and third models had accuracy of 70.6%, 72.9%, and 73.6%, respectively. The investigators have converted the models into free, user-friendly calculators that are available online (www.lymphedemarisk.com) during the ASCO Breast Cancer Symposium (Sept. 8-10), but will be taken off line until the manuscript is published, after which they are to become available again.

Dr. Bevilacqua reported that he had no relevant conflicts of interest.