DCIS Score Independently Predicts Ipsilateral Breast Events

CHICAGO – The new DCIS score, an offshoot of the Oncotype DX recurrence score, independently predicts the risk of ipsilateral recurrence or invasive disease in patients with ductal carcinoma in situ, according to a subgroup analysis from the prospective validation study.

The score correlated only moderately, poorly, or not at all with measures such as menopausal status and histologic grade among 327 patients with ductal carcinoma in situ (DCIS) treated with wide local excision and without radiation therapy, investigators reported.

And even after such measures were taken into account, each 50-point increase in the 100-point score was significantly associated with more than a doubling of the 10-year risk of recurrence or invasive disease in the same breast.

"The DCIS score provides independent information on ipsilateral breast risk beyond clinical and pathologic variables," lead author Dr. Sunil S. Badve said at the annual meeting of the American Society of Clinical Oncology.

"One can use the DCIS score to select patients with ... a clinically good prognosis who may have a higher DCIS score and may have a slightly [greater] risk than one would have estimated by traditional criteria," added Dr. Badve, a professor in the department of pathology and laboratory medicine and the department of internal medicine, and director of the Translational Genomics Core at Indiana University, Indianapolis.

"So particularly for the subset with a clinically good prognosis, we may be able to dissect which patients really might have a better prognosis and which patients may need to be more cautious."

Discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C., called particular attention to the weak association between nuclear grade and DCIS Score.

"This is a very important point to make and a response to the criticism that’s often heard that the DCIS score or the Oncotype score may just be a surrogate – and a very expensive one – for proliferative index or Ki-67," she commented.

Next-generation sequencing and advances in epigenomics, proteomics, and molecular characterization of stroma are likely to make it possible to further risk-stratify DCIS in the future, according to Dr. Hwang.

"But none of this is important unless we can implement it into treatment of patients. So how this is implemented in our everyday practice will be very important to analyze – whether it impacts decision making, and whether it gives patients satisfaction with the decisions they make will also be very important to look at," she added.

"Finally, in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward," she noted.

Study analyses were based on a subset of women from the E5194 trial, a prospective study to validate the DCIS score, which contains 12 of the 21 genes included in the Oncotype DX recurrence score used in estrogen receptor–positive early-stage breast cancer.

All of the women had DCIS treated with wide local excision. They had a median age of 61 years and a median tumor size of 7 mm. Twenty-nine percent received tamoxifen. The median duration of follow-up was 8.8 years.

Results showed that the DCIS score was only moderately correlated with histologic grade (r = 0.41-0.46) and with the percentage of cells showing comedo necrosis (r = 0.49), and was poorly correlated with tumor size (r = 0.18), Dr. Badve reported. And there was no correlation with age, menopausal status, DCIS histologic pattern, or margin status.

In a multivariate analysis, each 50-point increase in DCIS score was associated with more than a doubling of the risk of a recurrence of DCIS or the occurrence of invasive disease in the ipsilateral breast (hazard ratio, 2.41; P = .02).

In addition, tumor size was an independent positive predictor of risk (HR for each 5-mm increase, 1.52; P = .01), and postmenopausal status was an independent negative predictor (HR, 0.49; P = .02).

Dr. Badve disclosed that he is a consultant to Genomic Health, which makes the assay. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO – The new DCIS score, an offshoot of the Oncotype DX recurrence score, independently predicts the risk of ipsilateral recurrence or invasive disease in patients with ductal carcinoma in situ, according to a subgroup analysis from the prospective validation study.

The score correlated only moderately, poorly, or not at all with measures such as menopausal status and histologic grade among 327 patients with ductal carcinoma in situ (DCIS) treated with wide local excision and without radiation therapy, investigators reported.

And even after such measures were taken into account, each 50-point increase in the 100-point score was significantly associated with more than a doubling of the 10-year risk of recurrence or invasive disease in the same breast.

"The DCIS score provides independent information on ipsilateral breast risk beyond clinical and pathologic variables," lead author Dr. Sunil S. Badve said at the annual meeting of the American Society of Clinical Oncology.

"One can use the DCIS score to select patients with ... a clinically good prognosis who may have a higher DCIS score and may have a slightly [greater] risk than one would have estimated by traditional criteria," added Dr. Badve, a professor in the department of pathology and laboratory medicine and the department of internal medicine, and director of the Translational Genomics Core at Indiana University, Indianapolis.

"So particularly for the subset with a clinically good prognosis, we may be able to dissect which patients really might have a better prognosis and which patients may need to be more cautious."

Discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C., called particular attention to the weak association between nuclear grade and DCIS Score.

"This is a very important point to make and a response to the criticism that’s often heard that the DCIS score or the Oncotype score may just be a surrogate – and a very expensive one – for proliferative index or Ki-67," she commented.

Next-generation sequencing and advances in epigenomics, proteomics, and molecular characterization of stroma are likely to make it possible to further risk-stratify DCIS in the future, according to Dr. Hwang.

"But none of this is important unless we can implement it into treatment of patients. So how this is implemented in our everyday practice will be very important to analyze – whether it impacts decision making, and whether it gives patients satisfaction with the decisions they make will also be very important to look at," she added.

"Finally, in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward," she noted.

Study analyses were based on a subset of women from the E5194 trial, a prospective study to validate the DCIS score, which contains 12 of the 21 genes included in the Oncotype DX recurrence score used in estrogen receptor–positive early-stage breast cancer.

All of the women had DCIS treated with wide local excision. They had a median age of 61 years and a median tumor size of 7 mm. Twenty-nine percent received tamoxifen. The median duration of follow-up was 8.8 years.

Results showed that the DCIS score was only moderately correlated with histologic grade (r = 0.41-0.46) and with the percentage of cells showing comedo necrosis (r = 0.49), and was poorly correlated with tumor size (r = 0.18), Dr. Badve reported. And there was no correlation with age, menopausal status, DCIS histologic pattern, or margin status.

In a multivariate analysis, each 50-point increase in DCIS score was associated with more than a doubling of the risk of a recurrence of DCIS or the occurrence of invasive disease in the ipsilateral breast (hazard ratio, 2.41; P = .02).

In addition, tumor size was an independent positive predictor of risk (HR for each 5-mm increase, 1.52; P = .01), and postmenopausal status was an independent negative predictor (HR, 0.49; P = .02).

Dr. Badve disclosed that he is a consultant to Genomic Health, which makes the assay. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.

CHICAGO – The new DCIS score, an offshoot of the Oncotype DX recurrence score, independently predicts the risk of ipsilateral recurrence or invasive disease in patients with ductal carcinoma in situ, according to a subgroup analysis from the prospective validation study.

The score correlated only moderately, poorly, or not at all with measures such as menopausal status and histologic grade among 327 patients with ductal carcinoma in situ (DCIS) treated with wide local excision and without radiation therapy, investigators reported.

And even after such measures were taken into account, each 50-point increase in the 100-point score was significantly associated with more than a doubling of the 10-year risk of recurrence or invasive disease in the same breast.

"The DCIS score provides independent information on ipsilateral breast risk beyond clinical and pathologic variables," lead author Dr. Sunil S. Badve said at the annual meeting of the American Society of Clinical Oncology.

"One can use the DCIS score to select patients with ... a clinically good prognosis who may have a higher DCIS score and may have a slightly [greater] risk than one would have estimated by traditional criteria," added Dr. Badve, a professor in the department of pathology and laboratory medicine and the department of internal medicine, and director of the Translational Genomics Core at Indiana University, Indianapolis.

"So particularly for the subset with a clinically good prognosis, we may be able to dissect which patients really might have a better prognosis and which patients may need to be more cautious."

Discussant Dr. Eun-Sil Shelley Hwang of Duke University Medical Center in Durham, N.C., called particular attention to the weak association between nuclear grade and DCIS Score.

"This is a very important point to make and a response to the criticism that’s often heard that the DCIS score or the Oncotype score may just be a surrogate – and a very expensive one – for proliferative index or Ki-67," she commented.

Next-generation sequencing and advances in epigenomics, proteomics, and molecular characterization of stroma are likely to make it possible to further risk-stratify DCIS in the future, according to Dr. Hwang.

"But none of this is important unless we can implement it into treatment of patients. So how this is implemented in our everyday practice will be very important to analyze – whether it impacts decision making, and whether it gives patients satisfaction with the decisions they make will also be very important to look at," she added.

"Finally, in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward," she noted.

Study analyses were based on a subset of women from the E5194 trial, a prospective study to validate the DCIS score, which contains 12 of the 21 genes included in the Oncotype DX recurrence score used in estrogen receptor–positive early-stage breast cancer.

All of the women had DCIS treated with wide local excision. They had a median age of 61 years and a median tumor size of 7 mm. Twenty-nine percent received tamoxifen. The median duration of follow-up was 8.8 years.

Results showed that the DCIS score was only moderately correlated with histologic grade (r = 0.41-0.46) and with the percentage of cells showing comedo necrosis (r = 0.49), and was poorly correlated with tumor size (r = 0.18), Dr. Badve reported. And there was no correlation with age, menopausal status, DCIS histologic pattern, or margin status.

In a multivariate analysis, each 50-point increase in DCIS score was associated with more than a doubling of the risk of a recurrence of DCIS or the occurrence of invasive disease in the ipsilateral breast (hazard ratio, 2.41; P = .02).

In addition, tumor size was an independent positive predictor of risk (HR for each 5-mm increase, 1.52; P = .01), and postmenopausal status was an independent negative predictor (HR, 0.49; P = .02).

Dr. Badve disclosed that he is a consultant to Genomic Health, which makes the assay. Dr. Hwang disclosed that she is a consultant to Genomic Health and receives research funding from Merck and Novartis.