Neil Osterweil

CHICAGO – Carboplatin or cisplatin monotherapy has significant activity as a first- or second-line treatment against metastatic triple-negative breast cancer, according to Dr. Steven J. Isakoff.

The overall response rate to therapy with one of the platinum compounds was 30.2% – 4.7% complete responses and 25.6% partial responses, Dr. Isakoff of Massachusetts General Hospital cancer center, Boston, and his colleagues in the Translational Breast Cancer Research Consortium found.

Subgroup analyses of the multicenter single-arm trial suggested a higher response rate with cisplatin (37%) than with carboplatin (23%), but this was not a head-to-head study, and the results should be interpreted with caution because physicians were allowed to choose one of the two agents at their own discretion, which could introduce bias into the results, Dr. Isakoff said at the meeting.

The drugs were generally well tolerated with manageable toxicities; some patients have received as many as 23 cycles, he said in an interview.

The investigators also looked at the utility of two members of the p53 family of oncogenic transcription factors, p63 and p73, for predicting response to platinum agents in triple-negative breast cancer (tumors lacking receptors for estrogen, progesterone, or HER2/neu that are targeted by other forms of therapy).

"As information about the activity of platinum in BRCA carriers has become recognized, people are thinking about it more in triple-negative breast cancer," Dr. Isakoff said. "We still don’t know whether triple-negative breast cancer is particularly sensitive to platinum or is just sensitive to chemotherapy, and I think it’s going to take some of the randomized studies that are going on now in Europe, such as the TNT trial comparing carboplatin to docetaxel, to see whether there’s something special about triple negative and platinum."

The TBCRC009 study enrolled 86 patients with triple-negative breast cancer. The patients were assigned on the treating physician’s choice to receive either cisplatin at 75mg/m² IV every 3 weeks, or carboplatin to an area under the curve of 6 every 3 weeks.

In addition to the overall response rates noted here, the authors calculated a clinical benefit rate (a combination of complete and partial response and stable disease) of 34%.

Median progression-free survival (PFS) was 89 days. Thirty-three percent of patients had a PFS of less than 6 weeks, and another 33% had a PFS longer than 6 months. Among responders, a median PFS was 242 days. Responders had a median of nine chemotherapy cycles.

In subgroup analyses, platinum compounds were associated with a 33% response rate when used as first-line agents, and 17% when used in the second line. Only 17 patients received platinum as a second-line therapy, however.

The patients generally tolerated the drugs well. There was one case each of grade 4 neutropenia and hypertension. Grade 3 events included nine cases of fatigue, six of neutropenia, five of anemia, and four of hyponatremia.

"In general, it was well tolerated. We didn’t see unexpected toxicities with platinum, and we modified things with dose reductions as appropriate. It was not a common event to come off therapy due to toxicity," Dr. Isakoff said.

The investigators continue to collect data to determine whether p63/p73 expression can be a biomarker for response to platinum agents. The authors are also conducting BRCA mutation, molecular subtype, and circulating tumor cell analyses.

"This study was well designed with prospective powering for the p63/p73 correlative end point," said Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia, in Vancouver, the invited discussant.

The rationale for investigating p63/p73 as a predictive biomarker is sound because these markers can be found in about 35%-40% of triple-negative breast cancers, he said. Questions that need to be addressed include whether there is a change in expression of the markers in metastatic relapse, and whether the heterogeneous group of triple-negative breast cancers can be further refined through molecular subtyping.

The study was funded by the AVON Foundation, Breast Cancer Research Foundation, Susan D. Komen for the Cure, Golfers Against Cancer, the Tracey Davis Breast Cancer Research Fund, and investigator awards from the NCI-AVON Partners for Progress, Harvard-MIT, and the Dana-Farber/Harvard Cancer Center. The authors said they had no other relevant financial disclosures.

CHICAGO – Carboplatin or cisplatin monotherapy has significant activity as a first- or second-line treatment against metastatic triple-negative breast cancer, according to Dr. Steven J. Isakoff.

The overall response rate to therapy with one of the platinum compounds was 30.2% – 4.7% complete responses and 25.6% partial responses, Dr. Isakoff of Massachusetts General Hospital cancer center, Boston, and his colleagues in the Translational Breast Cancer Research Consortium found.

Subgroup analyses of the multicenter single-arm trial suggested a higher response rate with cisplatin (37%) than with carboplatin (23%), but this was not a head-to-head study, and the results should be interpreted with caution because physicians were allowed to choose one of the two agents at their own discretion, which could introduce bias into the results, Dr. Isakoff said at the meeting.

The drugs were generally well tolerated with manageable toxicities; some patients have received as many as 23 cycles, he said in an interview.

The investigators also looked at the utility of two members of the p53 family of oncogenic transcription factors, p63 and p73, for predicting response to platinum agents in triple-negative breast cancer (tumors lacking receptors for estrogen, progesterone, or HER2/neu that are targeted by other forms of therapy).

"As information about the activity of platinum in BRCA carriers has become recognized, people are thinking about it more in triple-negative breast cancer," Dr. Isakoff said. "We still don’t know whether triple-negative breast cancer is particularly sensitive to platinum or is just sensitive to chemotherapy, and I think it’s going to take some of the randomized studies that are going on now in Europe, such as the TNT trial comparing carboplatin to docetaxel, to see whether there’s something special about triple negative and platinum."

The TBCRC009 study enrolled 86 patients with triple-negative breast cancer. The patients were assigned on the treating physician’s choice to receive either cisplatin at 75mg/m² IV every 3 weeks, or carboplatin to an area under the curve of 6 every 3 weeks.

In addition to the overall response rates noted here, the authors calculated a clinical benefit rate (a combination of complete and partial response and stable disease) of 34%.

Median progression-free survival (PFS) was 89 days. Thirty-three percent of patients had a PFS of less than 6 weeks, and another 33% had a PFS longer than 6 months. Among responders, a median PFS was 242 days. Responders had a median of nine chemotherapy cycles.

In subgroup analyses, platinum compounds were associated with a 33% response rate when used as first-line agents, and 17% when used in the second line. Only 17 patients received platinum as a second-line therapy, however.

The patients generally tolerated the drugs well. There was one case each of grade 4 neutropenia and hypertension. Grade 3 events included nine cases of fatigue, six of neutropenia, five of anemia, and four of hyponatremia.

"In general, it was well tolerated. We didn’t see unexpected toxicities with platinum, and we modified things with dose reductions as appropriate. It was not a common event to come off therapy due to toxicity," Dr. Isakoff said.

The investigators continue to collect data to determine whether p63/p73 expression can be a biomarker for response to platinum agents. The authors are also conducting BRCA mutation, molecular subtype, and circulating tumor cell analyses.

"This study was well designed with prospective powering for the p63/p73 correlative end point," said Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia, in Vancouver, the invited discussant.

The rationale for investigating p63/p73 as a predictive biomarker is sound because these markers can be found in about 35%-40% of triple-negative breast cancers, he said. Questions that need to be addressed include whether there is a change in expression of the markers in metastatic relapse, and whether the heterogeneous group of triple-negative breast cancers can be further refined through molecular subtyping.

The study was funded by the AVON Foundation, Breast Cancer Research Foundation, Susan D. Komen for the Cure, Golfers Against Cancer, the Tracey Davis Breast Cancer Research Fund, and investigator awards from the NCI-AVON Partners for Progress, Harvard-MIT, and the Dana-Farber/Harvard Cancer Center. The authors said they had no other relevant financial disclosures.

CHICAGO – Carboplatin or cisplatin monotherapy has significant activity as a first- or second-line treatment against metastatic triple-negative breast cancer, according to Dr. Steven J. Isakoff.

The overall response rate to therapy with one of the platinum compounds was 30.2% – 4.7% complete responses and 25.6% partial responses, Dr. Isakoff of Massachusetts General Hospital cancer center, Boston, and his colleagues in the Translational Breast Cancer Research Consortium found.

Subgroup analyses of the multicenter single-arm trial suggested a higher response rate with cisplatin (37%) than with carboplatin (23%), but this was not a head-to-head study, and the results should be interpreted with caution because physicians were allowed to choose one of the two agents at their own discretion, which could introduce bias into the results, Dr. Isakoff said at the meeting.

The drugs were generally well tolerated with manageable toxicities; some patients have received as many as 23 cycles, he said in an interview.

The investigators also looked at the utility of two members of the p53 family of oncogenic transcription factors, p63 and p73, for predicting response to platinum agents in triple-negative breast cancer (tumors lacking receptors for estrogen, progesterone, or HER2/neu that are targeted by other forms of therapy).

"As information about the activity of platinum in BRCA carriers has become recognized, people are thinking about it more in triple-negative breast cancer," Dr. Isakoff said. "We still don’t know whether triple-negative breast cancer is particularly sensitive to platinum or is just sensitive to chemotherapy, and I think it’s going to take some of the randomized studies that are going on now in Europe, such as the TNT trial comparing carboplatin to docetaxel, to see whether there’s something special about triple negative and platinum."

The TBCRC009 study enrolled 86 patients with triple-negative breast cancer. The patients were assigned on the treating physician’s choice to receive either cisplatin at 75mg/m² IV every 3 weeks, or carboplatin to an area under the curve of 6 every 3 weeks.

In addition to the overall response rates noted here, the authors calculated a clinical benefit rate (a combination of complete and partial response and stable disease) of 34%.

Median progression-free survival (PFS) was 89 days. Thirty-three percent of patients had a PFS of less than 6 weeks, and another 33% had a PFS longer than 6 months. Among responders, a median PFS was 242 days. Responders had a median of nine chemotherapy cycles.

In subgroup analyses, platinum compounds were associated with a 33% response rate when used as first-line agents, and 17% when used in the second line. Only 17 patients received platinum as a second-line therapy, however.

The patients generally tolerated the drugs well. There was one case each of grade 4 neutropenia and hypertension. Grade 3 events included nine cases of fatigue, six of neutropenia, five of anemia, and four of hyponatremia.

"In general, it was well tolerated. We didn’t see unexpected toxicities with platinum, and we modified things with dose reductions as appropriate. It was not a common event to come off therapy due to toxicity," Dr. Isakoff said.

The investigators continue to collect data to determine whether p63/p73 expression can be a biomarker for response to platinum agents. The authors are also conducting BRCA mutation, molecular subtype, and circulating tumor cell analyses.

"This study was well designed with prospective powering for the p63/p73 correlative end point," said Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia, in Vancouver, the invited discussant.

The rationale for investigating p63/p73 as a predictive biomarker is sound because these markers can be found in about 35%-40% of triple-negative breast cancers, he said. Questions that need to be addressed include whether there is a change in expression of the markers in metastatic relapse, and whether the heterogeneous group of triple-negative breast cancers can be further refined through molecular subtyping.

The study was funded by the AVON Foundation, Breast Cancer Research Foundation, Susan D. Komen for the Cure, Golfers Against Cancer, the Tracey Davis Breast Cancer Research Fund, and investigator awards from the NCI-AVON Partners for Progress, Harvard-MIT, and the Dana-Farber/Harvard Cancer Center. The authors said they had no other relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – Topoisomerase II-alpha protein, which is frequently overexpressed in breast cancers, appears to be an independent predictor of response to anthracycline-based chemotherapy and a marker for rapidly proliferating disease, investigators reported at the annual meeting of the American Society of Clinical Oncology.

By testing 171 samples from a series of primary breast tumors and validating the results in an additional 2,630 samples from women with both primary and locally advanced cancers, Dr. Stephen Chan and his colleagues from the University of Nottingham (England) found that topoisomerase II-alpha (TOP2A) protein expression predicted pathologically confirmed complete responses, independent of HER2 status.

The TOP2A gene is coamplified in about a third of breast cancers in which the HER2 gene is amplified, leading some researchers to propose coamplification of the genes as a possible explanation for the relationship between TOP2A levels and breast cancer. Others, however, have suggested that levels of TOP2A protein, the expression product, may be a better marker than gene amplification for tumor aggressiveness and/or sensitivity to anthracyclines, the investigators noted.

To test the latter hypothesis, the authors looked for changes in the number of gene copies, and measured TOP2A messenger RNA (mRNA) levels and protein expression in a series of 171 unselected breast cancers.

They then sought to validate their results in samples from 2,000 consecutive cases of primary breast cancer that was treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil and/or hormonal therapies; 240 locally advanced primary breast cancers treated with neoadjuvant anthracycline-based regimens with or without a taxane; 245 breast cancers treated with adjuvant anthracycline-based chemotherapy; and 145 primary breast tumors overexpressing HER2 that were treated with sequential adjuvant anthracycline-based therapy (the FEC regimen, consisting of 5-fluorouracil, epirubicin, and cyclophosphamide) plus trastuzumab (Herceptin).

They found a statistically significant correlation between TOP2A mRNA levels and gene copy number changes (Pearson correlation = .6817; adjusted P = .00001). Additionally, TOP2A mRNA was significantly overexpressed when the gene was amplified (adjusted P = .002). Protein overexpression poorly correlated with copy number changes, however, suggesting that overexpression is independent of gene amplification.

Looking at the relationship between TOP2A protein expression and clinical outcomes, they found that among patients with tumors that were positive for TOP2A protein expression, the pathological complete response rate was 27%-30%, regardless of whether TOP2A or HER2 genes were amplified. In contrast, when TOP2A protein expression was absent, only 2%-10% of patients had a pathological complete response.

"The authors have done a nice job to correlate [TOP2A] mRNA with amplification and mitotic index, but not protein expression, which brings into play [the question,] Is it an analytical variable?" commented Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia in Vancouver. Dr. Chia was the invited discussant.

He said that the results could not be used to assess for predictive effect because the study lacked adequate power and an interaction test, and that the authors did not have data from randomized, controlled trials.

Dr. Chia noted that in a recent Canadian trial in which 477 of 710 patients had tumor samples tested for TOP2A and other biomarkers, TOP2A was – as the U.K. investigators also found – predictive of a benefit from anthracyclines, "but so was gene amplification and HER2 over-expression," which calls into question the value of TOP2A as a stand-alone marker, he said.

The study was supported by Breakthrough Breast Cancer, a U.K. charity. Neither the authors nor Dr. Chia had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – One of the hardest things about having a newly diagnosed advanced cancer may be getting in to see an oncologist, investigators reported at the annual meeting of the American Society of Clinical Oncology.

When volunteers posed as patients with a new diagnosis of inoperable hepatocellular carcinoma (HCC), they were able to secure a new patient appointment only 23% of the time in 432 attempts, reported Dr. Keerthi Gogineni and Dr. Katrina Armstrong of the University of Pennsylvania in Philadelphia.

Contrary to expectations, insurance appeared to be a barrier rather than a boon: Some 29% of volunteers who reported being uninsured were able to get a new-patient appointment, compared with 22% of those who said they were privately insured and 17% who said they were on Medicaid, the investigators found.

The most frequent reason (39% of cases) that the "patients" couldn’t get a first appointment was an expectation on the part of the hospital or oncology practice that patients would have all of their medical records in hand at the time of scheduling.

"That’s a lot to ask of someone who has just gotten a frightening diagnosis. Their records may be in lots of different places, and you have to be pretty savvy to say ‘I’m going to get my doctor’s notes from here, my scans from here, my labs from here, and pathology from here, and have all of that ready by the time you call them and ask for an appointment," Dr. Gogineni said in an interview.

Other grounds for refusal to schedule an appointment included inability to reach the scheduler (24% overall), referral requirements (18%), refusal to see uninsured patients (4%), need to go through a new-patient coordinator (3%), insurance type not accepted (2%), and need to talk to a financial counselor.

"It’s a huge problem right now," commented Dr. David P. Ryan, clinical director of the cancer center at Massachusetts General Hospital in Boston.

His hospital found that it has to have one phone number for new cancer patients, and that the calls need to be directed quickly to access nurses on call for each disease center, he said in an interview. The nurses talk to patients to help determine the best referral.

"What we realized very quickly is that a nonclinical person [answering the phone] just doesn’t have the right clinical expertise to find the right disease center, particularly in a big academic medical center, where everybody is subspecialized," Dr. Ryan said.

The finding that National Cancer Institute–designated centers were less likely to grant a new-patient appointment highlights the fact that many physicians at such centers are paid by salary, and may not have incentives to see additional patients above their current caseload, Dr. Ryan suggested. The study reported that appointment rates were lower at NCI-designated sites than at non-NCI sites (16% vs. 25%).

The investigators modeled their study on a paired-testing design similar to the type used to root out housing discrimination. Research assistants were instructed in how to simulate a patient with newly diagnosed inoperable HCC, and with varying insurance statuses. The study sampled 160 clinical sites, including NCI centers, hospitals caring for a disproportionate share of low-income patients, and academic medical centers in 25 of the largest metropolitan areas in the United States.

The authors recommended that "more socially nuanced and medically informed intakes may improve access to new cancer patients. Access to patient navigators at the earliest point of contact could increase access to new appointments for vulnerable patients."

The study was internally funded. Neither the authors nor Dr. Ryan had relevant financial disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.

CHICAGO – Adding carboplatin to standard chemotherapy for patients with basal-like breast cancer neither increased toxicity of the regimen nor improved its efficacy, reported investigators at the annual meeting of the American Society of Clinical Oncology.

Patients who were randomized to receive epirubicin and cyclophosphamide followed by docetaxel (Taxotere) and carboplatin had a pathologically confirmed complete response (pCR) rate of 30%, compared with 35% for patients who were assigned to a similar regimen without the platinum compound (P = .6064).

Mastectomy rates were also similar between the groups, at 28% and 33%, respectively, reported Dr. Emilio Alba from Hospital Universitario Virgen de la Victoria in Malaga, Spain, and colleagues in the Spanish Breast Cancer Research Group (GEICAM).

The rationale for adding carboplatin to a standard chemotherapy regimen is that basal-like breast cancer and the genetically similar triple-negative breast cancer subtypes are known to be sensitive to DNA-damaging agents such as alkylators, anthracyclines, and – theoretically – platinum compounds. But the patients in the study had already been exposed to an anthracycline (epirubicin), which may explain the lack of efficacy of a second DNA-damaging agent, the investigators speculated.

"Do we know whether a platinum compound is necessary for the efficacy? There are many other potential agents under investigation, including a PARP [poly (ADP [adenosine diphosphate]–ribose) polymerase] inhibitor, and we don’t really know what the molecular signature is to predict the benefit of adding another toxin," said Dr. George Somlo of the City of Hope Cancer Center in Duarte, Calif., who commented on the study in a poster discussion session.

He added that there are data to suggest that paclitaxel may be a better partner than docetaxel in this population.

The GEICAM investigators enrolled women with tumors 2 cm in diameter or greater (smaller tumors were allowed if axillary nodes were positive) and basal-like disease by immunophenotype (negative for the estrogen receptor, progesterone receptor, and HER2, but positive for cytokeratin 5/6 and/or epidermal growth factor receptor).

The patients were randomly assigned to receive either epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² for four cycles, followed by either docetaxel 100 mg/m² for four cycles, or docetaxel 75 mg/m² plus carboplatin to an area-under-the-curve dose of 6 mL/min for four cycles. In all, 46 patients were assigned to standard therapy, and 47 to the carboplatin arm.

The primary end point was pCR measured by Miller and Payne criteria. Secondary end points included clinical response, toxicity, type of surgery, and axillary status at surgery.

In an intention-to-treat analysis, the overall response rate was 72% in the standard arm and 79% in the carboplatin arm. The pCRs in the breast and axilla combined were 30% in each arm.

Grade 3/4 toxicities were generally similar between the treatment groups, with neutropenia, febrile neutropenia, fatigue, infection, and vomiting more frequent in the standard therapy arm; and hemoglobinemia, leukocytopenia, nausea and syncope more frequent in the carboplatin group.

The authors recommend that "the findings from this trial should be taken into account in the future development of PARP inhibitors."

The study was supported by the GEICAM. The authors had no disclosures.