American Society of Clinical Oncology (ASCO): Breast Cancer Symposium

SAN FRANCISCO – Women with early breast cancer who are treated with breast-conserving therapy have similar rates of freedom from locoregional recurrence whether chemotherapy is given before or after surgery, based on the experience of the University of Texas M.D. Anderson Cancer Center in Houston.

Investigators led by Dr. Elizabeth A. Mittendorf compared outcomes with these two approaches among nearly 3,000 women who had a segmental mastectomy plus whole-breast irradiation at the center in 1987-2005.

Results showed that with a median follow-up of 7-8 years, the rate of freedom from locoregional recurrence was high (90% or greater at 10 years) and did not differ significantly between the neoadjuvant and adjuvant chemotherapy groups after multiple potential confounders were taken into account.

"For appropriately selected patients, we can achieve high rates of locoregional control with breast-conserving therapy," Dr. Mittendorf, a surgical oncologist, commented, adding, "It is important to obtain a negative margin at the time of surgery."

"It appears that locoregional recurrence after breast-conserving therapy is driven primarily by [biological] factors and not by the timing of chemotherapy," she said.

However, discussant Dr. Barbara Fowble, a professor of clinical radiation oncology at the University of California San Francisco, said that the study was an example of "oversimplification of [a] complex issue ... especially in the era of personalized therapy."

She noted that factors such as breast cancer subtype (luminal A, luminal B, HER2 positive, or basal) can influence locoregional control after neoadjuvant chemotherapy with breast-conserving therapy.

"The identification of patients receiving neoadjuvant chemotherapy for whom mastectomy with or without radiation may result in a decreased risk of locoregional failure [when compared with breast-conserving therapy] is very important," commented Dr. Fowble. "Initial stage, molecular subtype, and response to therapy will impact on outcome."

Of the 2,984 women studied, 22% received neoadjuvant chemotherapy and 78% received adjuvant chemotherapy. Those in the former group were significantly more likely to have higher clinical stage and tumor grade, to have estrogen receptor–negative disease, and to have multifocal disease. Median durations of follow-up were 7.2 and 7.9 years.

In the neoadjuvant group, one-fifth of women had a pathological complete response, and there was a significant difference between the proportion having clinical stage II or III disease (93%) and the proportion having pathological stage II or III disease (46%) (P less than .001).

"Neoadjuvant chemotherapy downstages a significant number of patients with clinical stage II or III disease, presumably facilitating breast-conserving therapy," Dr. Mittendorf said.

In an unadjusted analysis, the rate of freedom from locoregional recurrence was lower with neoadjuvant chemotherapy than with adjuvant chemotherapy (P less than .001). For example, the 10-year rate was 90% with the former and 94% with the latter.

"Although the difference is statistically significant, I would suggest that these are excellent rates of locoregional control in our neoadjuvant chemotherapy patients, particularly considering that they presented with higher-stage disease, higher grade, and [more] ER-negative tumors," she maintained.

In a multivariate analysis that took into account clinical and disease factors, the timing of chemotherapy was no longer significantly associated with the risk of locoregional recurrence.

Eight factors conferred an elevated risk of such recurrence in this analysis: age younger than 50 years (hazard ratio, 1.9), clinical stage III disease (HR, 2.5), a grade 3 tumor (HR, 1.9), estrogen receptor–negative disease (HR, 2.4), multifocal disease (HR, 1.9), lymphovascular invasion (HR, 1.5), close or positive margins (HR, 2.5), and failure to receive hormone therapy in the context of estrogen receptor–positive disease (HR, 2.8).

When women were stratified according to the number of factors they had, there was still no significant difference in the rate of locoregional, recurrence–free survival between neoadjuvant and adjuvant chemotherapy, noted Dr. Mittendorf.

Dr. Mittendorf and Dr. Fowble reported no relevant conflicts of interest.

SAN FRANCISCO – Women with early breast cancer who are treated with breast-conserving therapy have similar rates of freedom from locoregional recurrence whether chemotherapy is given before or after surgery, based on the experience of the University of Texas M.D. Anderson Cancer Center in Houston.

Investigators led by Dr. Elizabeth A. Mittendorf compared outcomes with these two approaches among nearly 3,000 women who had a segmental mastectomy plus whole-breast irradiation at the center in 1987-2005.

Results showed that with a median follow-up of 7-8 years, the rate of freedom from locoregional recurrence was high (90% or greater at 10 years) and did not differ significantly between the neoadjuvant and adjuvant chemotherapy groups after multiple potential confounders were taken into account.

"For appropriately selected patients, we can achieve high rates of locoregional control with breast-conserving therapy," Dr. Mittendorf, a surgical oncologist, commented, adding, "It is important to obtain a negative margin at the time of surgery."

"It appears that locoregional recurrence after breast-conserving therapy is driven primarily by [biological] factors and not by the timing of chemotherapy," she said.

However, discussant Dr. Barbara Fowble, a professor of clinical radiation oncology at the University of California San Francisco, said that the study was an example of "oversimplification of [a] complex issue ... especially in the era of personalized therapy."

She noted that factors such as breast cancer subtype (luminal A, luminal B, HER2 positive, or basal) can influence locoregional control after neoadjuvant chemotherapy with breast-conserving therapy.

"The identification of patients receiving neoadjuvant chemotherapy for whom mastectomy with or without radiation may result in a decreased risk of locoregional failure [when compared with breast-conserving therapy] is very important," commented Dr. Fowble. "Initial stage, molecular subtype, and response to therapy will impact on outcome."

Of the 2,984 women studied, 22% received neoadjuvant chemotherapy and 78% received adjuvant chemotherapy. Those in the former group were significantly more likely to have higher clinical stage and tumor grade, to have estrogen receptor–negative disease, and to have multifocal disease. Median durations of follow-up were 7.2 and 7.9 years.

In the neoadjuvant group, one-fifth of women had a pathological complete response, and there was a significant difference between the proportion having clinical stage II or III disease (93%) and the proportion having pathological stage II or III disease (46%) (P less than .001).

"Neoadjuvant chemotherapy downstages a significant number of patients with clinical stage II or III disease, presumably facilitating breast-conserving therapy," Dr. Mittendorf said.

In an unadjusted analysis, the rate of freedom from locoregional recurrence was lower with neoadjuvant chemotherapy than with adjuvant chemotherapy (P less than .001). For example, the 10-year rate was 90% with the former and 94% with the latter.

"Although the difference is statistically significant, I would suggest that these are excellent rates of locoregional control in our neoadjuvant chemotherapy patients, particularly considering that they presented with higher-stage disease, higher grade, and [more] ER-negative tumors," she maintained.

In a multivariate analysis that took into account clinical and disease factors, the timing of chemotherapy was no longer significantly associated with the risk of locoregional recurrence.

Eight factors conferred an elevated risk of such recurrence in this analysis: age younger than 50 years (hazard ratio, 1.9), clinical stage III disease (HR, 2.5), a grade 3 tumor (HR, 1.9), estrogen receptor–negative disease (HR, 2.4), multifocal disease (HR, 1.9), lymphovascular invasion (HR, 1.5), close or positive margins (HR, 2.5), and failure to receive hormone therapy in the context of estrogen receptor–positive disease (HR, 2.8).

When women were stratified according to the number of factors they had, there was still no significant difference in the rate of locoregional, recurrence–free survival between neoadjuvant and adjuvant chemotherapy, noted Dr. Mittendorf.

Dr. Mittendorf and Dr. Fowble reported no relevant conflicts of interest.

SAN FRANCISCO – Women with early breast cancer who are treated with breast-conserving therapy have similar rates of freedom from locoregional recurrence whether chemotherapy is given before or after surgery, based on the experience of the University of Texas M.D. Anderson Cancer Center in Houston.

Investigators led by Dr. Elizabeth A. Mittendorf compared outcomes with these two approaches among nearly 3,000 women who had a segmental mastectomy plus whole-breast irradiation at the center in 1987-2005.

Results showed that with a median follow-up of 7-8 years, the rate of freedom from locoregional recurrence was high (90% or greater at 10 years) and did not differ significantly between the neoadjuvant and adjuvant chemotherapy groups after multiple potential confounders were taken into account.

"For appropriately selected patients, we can achieve high rates of locoregional control with breast-conserving therapy," Dr. Mittendorf, a surgical oncologist, commented, adding, "It is important to obtain a negative margin at the time of surgery."

"It appears that locoregional recurrence after breast-conserving therapy is driven primarily by [biological] factors and not by the timing of chemotherapy," she said.

However, discussant Dr. Barbara Fowble, a professor of clinical radiation oncology at the University of California San Francisco, said that the study was an example of "oversimplification of [a] complex issue ... especially in the era of personalized therapy."

She noted that factors such as breast cancer subtype (luminal A, luminal B, HER2 positive, or basal) can influence locoregional control after neoadjuvant chemotherapy with breast-conserving therapy.

"The identification of patients receiving neoadjuvant chemotherapy for whom mastectomy with or without radiation may result in a decreased risk of locoregional failure [when compared with breast-conserving therapy] is very important," commented Dr. Fowble. "Initial stage, molecular subtype, and response to therapy will impact on outcome."

Of the 2,984 women studied, 22% received neoadjuvant chemotherapy and 78% received adjuvant chemotherapy. Those in the former group were significantly more likely to have higher clinical stage and tumor grade, to have estrogen receptor–negative disease, and to have multifocal disease. Median durations of follow-up were 7.2 and 7.9 years.

In the neoadjuvant group, one-fifth of women had a pathological complete response, and there was a significant difference between the proportion having clinical stage II or III disease (93%) and the proportion having pathological stage II or III disease (46%) (P less than .001).

"Neoadjuvant chemotherapy downstages a significant number of patients with clinical stage II or III disease, presumably facilitating breast-conserving therapy," Dr. Mittendorf said.

In an unadjusted analysis, the rate of freedom from locoregional recurrence was lower with neoadjuvant chemotherapy than with adjuvant chemotherapy (P less than .001). For example, the 10-year rate was 90% with the former and 94% with the latter.

"Although the difference is statistically significant, I would suggest that these are excellent rates of locoregional control in our neoadjuvant chemotherapy patients, particularly considering that they presented with higher-stage disease, higher grade, and [more] ER-negative tumors," she maintained.

In a multivariate analysis that took into account clinical and disease factors, the timing of chemotherapy was no longer significantly associated with the risk of locoregional recurrence.

Eight factors conferred an elevated risk of such recurrence in this analysis: age younger than 50 years (hazard ratio, 1.9), clinical stage III disease (HR, 2.5), a grade 3 tumor (HR, 1.9), estrogen receptor–negative disease (HR, 2.4), multifocal disease (HR, 1.9), lymphovascular invasion (HR, 1.5), close or positive margins (HR, 2.5), and failure to receive hormone therapy in the context of estrogen receptor–positive disease (HR, 2.8).

When women were stratified according to the number of factors they had, there was still no significant difference in the rate of locoregional, recurrence–free survival between neoadjuvant and adjuvant chemotherapy, noted Dr. Mittendorf.

Dr. Mittendorf and Dr. Fowble reported no relevant conflicts of interest.

SAN FRANCISCO – A new gene-based biomarker assay may help to estimate prognosis and make decisions about extended endocrine therapy in women with estrogen receptor–positive early breast cancer, new data suggest.

Researchers tested the biomarker, the Breast Cancer Index (BCI), among 249 women with estrogen receptor–positive early breast cancer from the MA.17 trial, in which women received 5 years of adjuvant tamoxifen therapy and, if still disease free, were then randomized to an additional 5 years of either letrozole (Femara) or placebo.

Study results, reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology, showed that with each 5-unit increase in the 10-unit BCI score, women’s odds of late recurrence nearly tripled.

The index as a whole was not helpful in predicting the benefit of added letrozole therapy in reducing recurrence risk. But one of its components, called H/I, was helpful: Women having a high H/I were about half as likely to have a recurrence if they received letrozole instead of placebo.

In the future, these findings might be used to develop a management algorithm for women with estrogen receptor–positive breast cancer, according to lead investigator Dr. Dennis C. Sgroi, director of breast pathology at the Massachusetts General Hospital in Boston.

"If patients are disease free after 5 years of adjuvant endocrine therapy, we might be able to then test them with the BCI. If this assay identifies these patients to be at low risk, there will be no further therapy for these patients. However, if they are at high risk by BCI, we can then explore the H/I component," he explained.

"If they have high H/I, that indicates that these patients are likely to benefit from extended adjuvant therapy," he continued. "For patients who have low H/I, one might consider using extended adjuvant therapy, or these patients might be considered as a future focus for research in clinical trials."

The investigators identified 83 women from the MA.17 trial who had had a recurrence and had primary tumor tissue available. They then matched the women by age, N stage, T stage, and prior receipt of chemotherapy in a 1:2 ratio with 166 women who had not had a recurrence and had primary tumor tissue available. Tissue was analyzed by reverse transcriptase–polymerase chain reaction to determine the BCI.

The BCI has two components, Dr. Sgroi explained. The HOXB13/IL17BR (H/I) component is based on expression of two genes regulated by estradiol. The molecular grade index (MGI) component is based on five genes related to pathological grade.

"We have shown in the past that these two biomarkers are complementary, as the combination of the two biomarkers outperforms each individually," he noted. "In addition, we have shown that the combination biomarker outperforms standard clinicopathological parameters currently used to predict disease recurrence."

In a multivariate analysis, with each 5-unit increase in the BCI score, women’s odds of recurrence increased 2.91-fold (P = .014). The findings were similar when categories were used: Women with high or intermediate scores had 2.21-fold higher odds of recurrence than did their counterparts with low scores (P = .019).

The BCI as a whole did not predict the benefit of extended therapy with letrozole, but the H/I component did, Dr. Sgroi reported. In a multivariate analysis, women who had a high H/I had a 58% reduction in the odds of recurrence if they received letrozole instead of placebo (P = .037).

"Most notably, there was a statistically significant interaction between the H/I biomarker and treatment (P = .02), indicating that the magnitude of letrozole benefit depends on the expression level of H/I," he said. "These results suggest that patients with tumors expressing high H/I will benefit from extended endocrine therapy."

Dr. Sgroi reported receiving research funding from bioTheranostics Inc. The study was supported in part by Novartis, the manufacturer of letrozole.

SAN FRANCISCO – A new gene-based biomarker assay may help to estimate prognosis and make decisions about extended endocrine therapy in women with estrogen receptor–positive early breast cancer, new data suggest.

Researchers tested the biomarker, the Breast Cancer Index (BCI), among 249 women with estrogen receptor–positive early breast cancer from the MA.17 trial, in which women received 5 years of adjuvant tamoxifen therapy and, if still disease free, were then randomized to an additional 5 years of either letrozole (Femara) or placebo.

Study results, reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology, showed that with each 5-unit increase in the 10-unit BCI score, women’s odds of late recurrence nearly tripled.

The index as a whole was not helpful in predicting the benefit of added letrozole therapy in reducing recurrence risk. But one of its components, called H/I, was helpful: Women having a high H/I were about half as likely to have a recurrence if they received letrozole instead of placebo.

In the future, these findings might be used to develop a management algorithm for women with estrogen receptor–positive breast cancer, according to lead investigator Dr. Dennis C. Sgroi, director of breast pathology at the Massachusetts General Hospital in Boston.

"If patients are disease free after 5 years of adjuvant endocrine therapy, we might be able to then test them with the BCI. If this assay identifies these patients to be at low risk, there will be no further therapy for these patients. However, if they are at high risk by BCI, we can then explore the H/I component," he explained.

"If they have high H/I, that indicates that these patients are likely to benefit from extended adjuvant therapy," he continued. "For patients who have low H/I, one might consider using extended adjuvant therapy, or these patients might be considered as a future focus for research in clinical trials."

The investigators identified 83 women from the MA.17 trial who had had a recurrence and had primary tumor tissue available. They then matched the women by age, N stage, T stage, and prior receipt of chemotherapy in a 1:2 ratio with 166 women who had not had a recurrence and had primary tumor tissue available. Tissue was analyzed by reverse transcriptase–polymerase chain reaction to determine the BCI.

The BCI has two components, Dr. Sgroi explained. The HOXB13/IL17BR (H/I) component is based on expression of two genes regulated by estradiol. The molecular grade index (MGI) component is based on five genes related to pathological grade.

"We have shown in the past that these two biomarkers are complementary, as the combination of the two biomarkers outperforms each individually," he noted. "In addition, we have shown that the combination biomarker outperforms standard clinicopathological parameters currently used to predict disease recurrence."

In a multivariate analysis, with each 5-unit increase in the BCI score, women’s odds of recurrence increased 2.91-fold (P = .014). The findings were similar when categories were used: Women with high or intermediate scores had 2.21-fold higher odds of recurrence than did their counterparts with low scores (P = .019).

The BCI as a whole did not predict the benefit of extended therapy with letrozole, but the H/I component did, Dr. Sgroi reported. In a multivariate analysis, women who had a high H/I had a 58% reduction in the odds of recurrence if they received letrozole instead of placebo (P = .037).

"Most notably, there was a statistically significant interaction between the H/I biomarker and treatment (P = .02), indicating that the magnitude of letrozole benefit depends on the expression level of H/I," he said. "These results suggest that patients with tumors expressing high H/I will benefit from extended endocrine therapy."

Dr. Sgroi reported receiving research funding from bioTheranostics Inc. The study was supported in part by Novartis, the manufacturer of letrozole.

SAN FRANCISCO – A new gene-based biomarker assay may help to estimate prognosis and make decisions about extended endocrine therapy in women with estrogen receptor–positive early breast cancer, new data suggest.

Researchers tested the biomarker, the Breast Cancer Index (BCI), among 249 women with estrogen receptor–positive early breast cancer from the MA.17 trial, in which women received 5 years of adjuvant tamoxifen therapy and, if still disease free, were then randomized to an additional 5 years of either letrozole (Femara) or placebo.

Study results, reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology, showed that with each 5-unit increase in the 10-unit BCI score, women’s odds of late recurrence nearly tripled.

The index as a whole was not helpful in predicting the benefit of added letrozole therapy in reducing recurrence risk. But one of its components, called H/I, was helpful: Women having a high H/I were about half as likely to have a recurrence if they received letrozole instead of placebo.

In the future, these findings might be used to develop a management algorithm for women with estrogen receptor–positive breast cancer, according to lead investigator Dr. Dennis C. Sgroi, director of breast pathology at the Massachusetts General Hospital in Boston.

"If patients are disease free after 5 years of adjuvant endocrine therapy, we might be able to then test them with the BCI. If this assay identifies these patients to be at low risk, there will be no further therapy for these patients. However, if they are at high risk by BCI, we can then explore the H/I component," he explained.

"If they have high H/I, that indicates that these patients are likely to benefit from extended adjuvant therapy," he continued. "For patients who have low H/I, one might consider using extended adjuvant therapy, or these patients might be considered as a future focus for research in clinical trials."

The investigators identified 83 women from the MA.17 trial who had had a recurrence and had primary tumor tissue available. They then matched the women by age, N stage, T stage, and prior receipt of chemotherapy in a 1:2 ratio with 166 women who had not had a recurrence and had primary tumor tissue available. Tissue was analyzed by reverse transcriptase–polymerase chain reaction to determine the BCI.

The BCI has two components, Dr. Sgroi explained. The HOXB13/IL17BR (H/I) component is based on expression of two genes regulated by estradiol. The molecular grade index (MGI) component is based on five genes related to pathological grade.

"We have shown in the past that these two biomarkers are complementary, as the combination of the two biomarkers outperforms each individually," he noted. "In addition, we have shown that the combination biomarker outperforms standard clinicopathological parameters currently used to predict disease recurrence."

In a multivariate analysis, with each 5-unit increase in the BCI score, women’s odds of recurrence increased 2.91-fold (P = .014). The findings were similar when categories were used: Women with high or intermediate scores had 2.21-fold higher odds of recurrence than did their counterparts with low scores (P = .019).

The BCI as a whole did not predict the benefit of extended therapy with letrozole, but the H/I component did, Dr. Sgroi reported. In a multivariate analysis, women who had a high H/I had a 58% reduction in the odds of recurrence if they received letrozole instead of placebo (P = .037).

"Most notably, there was a statistically significant interaction between the H/I biomarker and treatment (P = .02), indicating that the magnitude of letrozole benefit depends on the expression level of H/I," he said. "These results suggest that patients with tumors expressing high H/I will benefit from extended endocrine therapy."

Dr. Sgroi reported receiving research funding from bioTheranostics Inc. The study was supported in part by Novartis, the manufacturer of letrozole.

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.

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.

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.

Many breast cancer patients would have more advanced disease at diagnosis and face harsher treatment if recently updated screening guidelines of the U.S. Preventive Services Task Force were widely adopted, suggests a retrospective cohort study of more than 5,000 women with breast cancer in Michigan.

Study results, being reported this week at a breast cancer symposium sponsored by the American Society of Clinical Oncology, show that nearly a third of the women’s cancers were detected by palpation. The guidelines do not advocate for self-exams at all and question the usefulness of clinical breast exams after age 40.

Additionally, nearly half of the cancers in women younger than 50 years were detected by mammography, while the guidelines now recommend against this practice in the 40- to 49-year age group.

Women with palpation-detected cancers had later-stage disease and were significantly more likely to undergo mastectomy and receive chemotherapy than were those with mammography-detected cancers.

"Annual screening mammograms and evaluation of palpable breast masses are important tools in breast cancer detection," second author Dr. Jamie Caughran said during a premeeting press briefing from the American Society of Clinical Oncology (ASCO).

She declined to say whether the study’s results contradict the U.S. Preventive Services Task Force (USPSTF) guidelines, as the investigators did not have adequate information on the women’s screening history.

But "we take this data to conclude that you’re better off if you can ... have your cancer detected by mammography – that you are more likely to have options and less likely to need aggressive treatment. So ... we would support the rest of the societies that continue to recommend annual screening mammography starting at age 40," she said.

Additionally, this study "highlights the still-significant number of women who present with a palpable mass that shouldn’t be overlooked by physicians even if they have a negative mammogram," pointed out Dr. Caughran, medical director of the Comprehensive Breast Center at the Lacks Cancer Center in Grand Rapids, Mich. "So it just continues to reinforce what we believe is inherently true."

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City, commented that the appropriate age for starting screening mammography remains controversial.

"A lot of the debate and focus regarding the utility of mammography have been on overall survival and breast cancer–specific survival, and I certainly think that is the most important end point," he said, noting that the study speaks to another important end point – reduced intensity of treatment.

"As a medical oncologist or chemotherapist, I think this is a very important gain, independent of any potential survival benefit," he said. "Having less disfiguring surgery and the ability to deliver less chemotherapy based on the stage at diagnosis are for me a step forward."

This newest study will not quell the debate, according to Dr. Seidman. "Undoubtedly, this area will continue to remain an area of controversy for some," he said. "But certainly, women in this age group would be well served to know about this data."

In the study, Dr. Caughran and her colleagues analyzed data from a statewide breast cancer registry managed by the Michigan Breast Oncology Quality Initiative, identifying 5,628 women who received a diagnosis of stage 0 to III breast cancer between 2006 and 2009. Their average age was 59.4 years.

In the cohort overall, 65.5% of breast cancers were detected by mammography, 29.8% by palpation, and 4.7% by other means.

Fully 90% of the cancers detected by palpation were detected by the patient herself, although "it’s unclear if the patients ... were practicing regular breast self-examination or if these were incidental findings," noted Dr. Caughran.

When analyses were restricted to women younger than 50 years of age, 48.3% of breast cancers were detected by mammography, 46.1% by palpation, and 5.6% by other means.

Palpation-detected cancers were of later stages (P less than .0001) – two-thirds were stage II or higher – and were more often treated with mastectomy (45.8% vs. 27.1%, P less than .0001) and with chemotherapy (22.7% vs. 15.7%, P less than .0001).

Dr. Caughran and Dr. Seidman reported that they had no relevant conflicts of interest.

Many breast cancer patients would have more advanced disease at diagnosis and face harsher treatment if recently updated screening guidelines of the U.S. Preventive Services Task Force were widely adopted, suggests a retrospective cohort study of more than 5,000 women with breast cancer in Michigan.

Study results, being reported this week at a breast cancer symposium sponsored by the American Society of Clinical Oncology, show that nearly a third of the women’s cancers were detected by palpation. The guidelines do not advocate for self-exams at all and question the usefulness of clinical breast exams after age 40.

Additionally, nearly half of the cancers in women younger than 50 years were detected by mammography, while the guidelines now recommend against this practice in the 40- to 49-year age group.

Women with palpation-detected cancers had later-stage disease and were significantly more likely to undergo mastectomy and receive chemotherapy than were those with mammography-detected cancers.

"Annual screening mammograms and evaluation of palpable breast masses are important tools in breast cancer detection," second author Dr. Jamie Caughran said during a premeeting press briefing from the American Society of Clinical Oncology (ASCO).

She declined to say whether the study’s results contradict the U.S. Preventive Services Task Force (USPSTF) guidelines, as the investigators did not have adequate information on the women’s screening history.

But "we take this data to conclude that you’re better off if you can ... have your cancer detected by mammography – that you are more likely to have options and less likely to need aggressive treatment. So ... we would support the rest of the societies that continue to recommend annual screening mammography starting at age 40," she said.

Additionally, this study "highlights the still-significant number of women who present with a palpable mass that shouldn’t be overlooked by physicians even if they have a negative mammogram," pointed out Dr. Caughran, medical director of the Comprehensive Breast Center at the Lacks Cancer Center in Grand Rapids, Mich. "So it just continues to reinforce what we believe is inherently true."

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City, commented that the appropriate age for starting screening mammography remains controversial.

"A lot of the debate and focus regarding the utility of mammography have been on overall survival and breast cancer–specific survival, and I certainly think that is the most important end point," he said, noting that the study speaks to another important end point – reduced intensity of treatment.

"As a medical oncologist or chemotherapist, I think this is a very important gain, independent of any potential survival benefit," he said. "Having less disfiguring surgery and the ability to deliver less chemotherapy based on the stage at diagnosis are for me a step forward."

This newest study will not quell the debate, according to Dr. Seidman. "Undoubtedly, this area will continue to remain an area of controversy for some," he said. "But certainly, women in this age group would be well served to know about this data."

In the study, Dr. Caughran and her colleagues analyzed data from a statewide breast cancer registry managed by the Michigan Breast Oncology Quality Initiative, identifying 5,628 women who received a diagnosis of stage 0 to III breast cancer between 2006 and 2009. Their average age was 59.4 years.

In the cohort overall, 65.5% of breast cancers were detected by mammography, 29.8% by palpation, and 4.7% by other means.

Fully 90% of the cancers detected by palpation were detected by the patient herself, although "it’s unclear if the patients ... were practicing regular breast self-examination or if these were incidental findings," noted Dr. Caughran.

When analyses were restricted to women younger than 50 years of age, 48.3% of breast cancers were detected by mammography, 46.1% by palpation, and 5.6% by other means.

Palpation-detected cancers were of later stages (P less than .0001) – two-thirds were stage II or higher – and were more often treated with mastectomy (45.8% vs. 27.1%, P less than .0001) and with chemotherapy (22.7% vs. 15.7%, P less than .0001).

Dr. Caughran and Dr. Seidman reported that they had no relevant conflicts of interest.

Many breast cancer patients would have more advanced disease at diagnosis and face harsher treatment if recently updated screening guidelines of the U.S. Preventive Services Task Force were widely adopted, suggests a retrospective cohort study of more than 5,000 women with breast cancer in Michigan.

Study results, being reported this week at a breast cancer symposium sponsored by the American Society of Clinical Oncology, show that nearly a third of the women’s cancers were detected by palpation. The guidelines do not advocate for self-exams at all and question the usefulness of clinical breast exams after age 40.

Additionally, nearly half of the cancers in women younger than 50 years were detected by mammography, while the guidelines now recommend against this practice in the 40- to 49-year age group.

Women with palpation-detected cancers had later-stage disease and were significantly more likely to undergo mastectomy and receive chemotherapy than were those with mammography-detected cancers.

"Annual screening mammograms and evaluation of palpable breast masses are important tools in breast cancer detection," second author Dr. Jamie Caughran said during a premeeting press briefing from the American Society of Clinical Oncology (ASCO).

She declined to say whether the study’s results contradict the U.S. Preventive Services Task Force (USPSTF) guidelines, as the investigators did not have adequate information on the women’s screening history.

But "we take this data to conclude that you’re better off if you can ... have your cancer detected by mammography – that you are more likely to have options and less likely to need aggressive treatment. So ... we would support the rest of the societies that continue to recommend annual screening mammography starting at age 40," she said.

Additionally, this study "highlights the still-significant number of women who present with a palpable mass that shouldn’t be overlooked by physicians even if they have a negative mammogram," pointed out Dr. Caughran, medical director of the Comprehensive Breast Center at the Lacks Cancer Center in Grand Rapids, Mich. "So it just continues to reinforce what we believe is inherently true."

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City, commented that the appropriate age for starting screening mammography remains controversial.

"A lot of the debate and focus regarding the utility of mammography have been on overall survival and breast cancer–specific survival, and I certainly think that is the most important end point," he said, noting that the study speaks to another important end point – reduced intensity of treatment.

"As a medical oncologist or chemotherapist, I think this is a very important gain, independent of any potential survival benefit," he said. "Having less disfiguring surgery and the ability to deliver less chemotherapy based on the stage at diagnosis are for me a step forward."

This newest study will not quell the debate, according to Dr. Seidman. "Undoubtedly, this area will continue to remain an area of controversy for some," he said. "But certainly, women in this age group would be well served to know about this data."

In the study, Dr. Caughran and her colleagues analyzed data from a statewide breast cancer registry managed by the Michigan Breast Oncology Quality Initiative, identifying 5,628 women who received a diagnosis of stage 0 to III breast cancer between 2006 and 2009. Their average age was 59.4 years.

In the cohort overall, 65.5% of breast cancers were detected by mammography, 29.8% by palpation, and 4.7% by other means.

Fully 90% of the cancers detected by palpation were detected by the patient herself, although "it’s unclear if the patients ... were practicing regular breast self-examination or if these were incidental findings," noted Dr. Caughran.

When analyses were restricted to women younger than 50 years of age, 48.3% of breast cancers were detected by mammography, 46.1% by palpation, and 5.6% by other means.

Palpation-detected cancers were of later stages (P less than .0001) – two-thirds were stage II or higher – and were more often treated with mastectomy (45.8% vs. 27.1%, P less than .0001) and with chemotherapy (22.7% vs. 15.7%, P less than .0001).

Dr. Caughran and Dr. Seidman reported that they had no relevant conflicts of interest.