Age, Tumor Characteristics Predict Locoregional Failure After Neoadjuvant Breast Cancer Therapy

NATIONAL HARBOR, Md. – Age 50 years or older, initial clinical tumor size greater than 5 cm, and pathologic tumor response to neoadjuvant chemotherapy were significant independent predictors of locoregional failure in women who underwent neoadjuvant chemotherapy in two large breast cancer trials.

Investigators presented these results from a 10-year follow-up study of 2,961 patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 and NSABP B-27 trials at the 2010 Breast Cancer Symposium.

Dr. Eleftherios P. Mamounas of Aultman Hospital in Canton, Ohio, and his colleagues reported the 10-year incidence of local or regional failure based on type of surgery was 12.3% in patients who had mastectomies and 10.3% in those who had lumpectomies plus chemotherapy. The incidence of local failure was 8.9% in the mastectomy group and 8.1% in the lumpectomy plus chemotherapy group. The incidence of regional failure was 3.4% and 2.2%, respectively.

In a multivariate analysis based on 318 locoregional failure events in all 2,961 patients, the overall significant predictors of locoregional failure included age 50 years or older (hazard ratio 0.79, P = .04), clinical tumor size greater than 5 cm (HR 1.52, P = .0005), and positive clinical nodal status (HR 1.64, P less than .0001). In addition, being node negative without pathologic complete response (HR 1.65, P less than .001) or node positive with pathologic complete response (HR 2.77, P less than 0.001) were significant predictors as well.

The lack of data on predictors of locoregional failure after neoadjuvant chemotherapy has raised questions about whether to use radiation therapy and when to perform sentinel node biopsies in these patients, said Dr. Mamounas.

He also presented data on locoregional failure in lumpectomy patients and mastectomy patients separately, for the purpose of developing separate treatment nomograms for each procedure. A majority of the locoregional failures in the lumpectomy patients were in-breast recurrences. In mastectomy patients, rates of chest wall recurrence were inversely correlated to pathologic nodal response, Dr. Mamounas said.

“The effect of age (in lumpectomy patients), clinical tumor size (in mastectomy patients), and clinical nodal status at locoregional failure appears to diminish with increasing pathologic response in the breast and axillary nodes,” said Dr. Mamounas.

The neoadjuvant chemotherapy regimens were one of two: doxorubicin (Adriamycin) and cyclophosphamide (AC) for four cycles, or the AC regimen for four cycles followed by four cycles of neoadjuvant/adjuvant docetaxel (Taxotere). Patients in the B-27 trial received tamoxifen in addition to their neoadjuvant chemotherapy. Lumpectomy patients were treated with radiation, but mastectomy patients were not.

The independent predictors were incorporated into two nomograms: one for mastectomy and one for lumpectomy plus breast radiation, Dr. Mamounas explained. Additional studies are planned to include treatment effects in the development and validation of the nomograms, he said.

Disclosures: Dr. Mamounas disclosed serving as a consultant for Eli Lilly & Co. and receiving honoraria from AstraZeneca and Sanofi-Aventis.

NATIONAL HARBOR, Md. – Age 50 years or older, initial clinical tumor size greater than 5 cm, and pathologic tumor response to neoadjuvant chemotherapy were significant independent predictors of locoregional failure in women who underwent neoadjuvant chemotherapy in two large breast cancer trials.

Investigators presented these results from a 10-year follow-up study of 2,961 patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 and NSABP B-27 trials at the 2010 Breast Cancer Symposium.

Dr. Eleftherios P. Mamounas of Aultman Hospital in Canton, Ohio, and his colleagues reported the 10-year incidence of local or regional failure based on type of surgery was 12.3% in patients who had mastectomies and 10.3% in those who had lumpectomies plus chemotherapy. The incidence of local failure was 8.9% in the mastectomy group and 8.1% in the lumpectomy plus chemotherapy group. The incidence of regional failure was 3.4% and 2.2%, respectively.

In a multivariate analysis based on 318 locoregional failure events in all 2,961 patients, the overall significant predictors of locoregional failure included age 50 years or older (hazard ratio 0.79, P = .04), clinical tumor size greater than 5 cm (HR 1.52, P = .0005), and positive clinical nodal status (HR 1.64, P less than .0001). In addition, being node negative without pathologic complete response (HR 1.65, P less than .001) or node positive with pathologic complete response (HR 2.77, P less than 0.001) were significant predictors as well.

The lack of data on predictors of locoregional failure after neoadjuvant chemotherapy has raised questions about whether to use radiation therapy and when to perform sentinel node biopsies in these patients, said Dr. Mamounas.

He also presented data on locoregional failure in lumpectomy patients and mastectomy patients separately, for the purpose of developing separate treatment nomograms for each procedure. A majority of the locoregional failures in the lumpectomy patients were in-breast recurrences. In mastectomy patients, rates of chest wall recurrence were inversely correlated to pathologic nodal response, Dr. Mamounas said.

“The effect of age (in lumpectomy patients), clinical tumor size (in mastectomy patients), and clinical nodal status at locoregional failure appears to diminish with increasing pathologic response in the breast and axillary nodes,” said Dr. Mamounas.

The neoadjuvant chemotherapy regimens were one of two: doxorubicin (Adriamycin) and cyclophosphamide (AC) for four cycles, or the AC regimen for four cycles followed by four cycles of neoadjuvant/adjuvant docetaxel (Taxotere). Patients in the B-27 trial received tamoxifen in addition to their neoadjuvant chemotherapy. Lumpectomy patients were treated with radiation, but mastectomy patients were not.

The independent predictors were incorporated into two nomograms: one for mastectomy and one for lumpectomy plus breast radiation, Dr. Mamounas explained. Additional studies are planned to include treatment effects in the development and validation of the nomograms, he said.

Disclosures: Dr. Mamounas disclosed serving as a consultant for Eli Lilly & Co. and receiving honoraria from AstraZeneca and Sanofi-Aventis.

NATIONAL HARBOR, Md. – Age 50 years or older, initial clinical tumor size greater than 5 cm, and pathologic tumor response to neoadjuvant chemotherapy were significant independent predictors of locoregional failure in women who underwent neoadjuvant chemotherapy in two large breast cancer trials.

Investigators presented these results from a 10-year follow-up study of 2,961 patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 and NSABP B-27 trials at the 2010 Breast Cancer Symposium.

Dr. Eleftherios P. Mamounas of Aultman Hospital in Canton, Ohio, and his colleagues reported the 10-year incidence of local or regional failure based on type of surgery was 12.3% in patients who had mastectomies and 10.3% in those who had lumpectomies plus chemotherapy. The incidence of local failure was 8.9% in the mastectomy group and 8.1% in the lumpectomy plus chemotherapy group. The incidence of regional failure was 3.4% and 2.2%, respectively.

In a multivariate analysis based on 318 locoregional failure events in all 2,961 patients, the overall significant predictors of locoregional failure included age 50 years or older (hazard ratio 0.79, P = .04), clinical tumor size greater than 5 cm (HR 1.52, P = .0005), and positive clinical nodal status (HR 1.64, P less than .0001). In addition, being node negative without pathologic complete response (HR 1.65, P less than .001) or node positive with pathologic complete response (HR 2.77, P less than 0.001) were significant predictors as well.

The lack of data on predictors of locoregional failure after neoadjuvant chemotherapy has raised questions about whether to use radiation therapy and when to perform sentinel node biopsies in these patients, said Dr. Mamounas.

He also presented data on locoregional failure in lumpectomy patients and mastectomy patients separately, for the purpose of developing separate treatment nomograms for each procedure. A majority of the locoregional failures in the lumpectomy patients were in-breast recurrences. In mastectomy patients, rates of chest wall recurrence were inversely correlated to pathologic nodal response, Dr. Mamounas said.

“The effect of age (in lumpectomy patients), clinical tumor size (in mastectomy patients), and clinical nodal status at locoregional failure appears to diminish with increasing pathologic response in the breast and axillary nodes,” said Dr. Mamounas.

The neoadjuvant chemotherapy regimens were one of two: doxorubicin (Adriamycin) and cyclophosphamide (AC) for four cycles, or the AC regimen for four cycles followed by four cycles of neoadjuvant/adjuvant docetaxel (Taxotere). Patients in the B-27 trial received tamoxifen in addition to their neoadjuvant chemotherapy. Lumpectomy patients were treated with radiation, but mastectomy patients were not.

The independent predictors were incorporated into two nomograms: one for mastectomy and one for lumpectomy plus breast radiation, Dr. Mamounas explained. Additional studies are planned to include treatment effects in the development and validation of the nomograms, he said.

Disclosures: Dr. Mamounas disclosed serving as a consultant for Eli Lilly & Co. and receiving honoraria from AstraZeneca and Sanofi-Aventis.