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Pathologic Features Predicting for High Rates of Local-Regional Recurrence after Neoadjuvant Chemotherapy and Radiation Therapy for Breast Cancer
Proceedings of the 52nd Annual ASTRO Meeting
207
Pathologic Features Predicting for High Rates of Local-Regional Recurrence after Neoadjuvant Chemotherapy and Radiation Therapy for Breast Cancer
K. E. Hoffman, W. F. Symmans, J. Oh, W. Tereffe, T. K. Yu, G. H. Perkins, E. A. Strom, A. M. Gonzalez-Angulo, T. A. Buchholz, W. A. Woodward The University of Texas M. D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): Identifying women with an elevated risk of local failure despite good local breast cancer therapy is important to determine if there is a group of women who may benefit from more aggressive local therapy. We evaluated the combined impact of lymphovascular space invasion (LVSI), estrogen receptor (ER) status, and residual cancer burden (RCB) on local regional recurrence (LRR) after definitive treatment with neoadjuvant chemotherapy, surgical resection, and radiation therapy. Materials/Methods: We evaluated 381 women with Stages I-III breast cancer treated with neoadjuvant fluorouracil, doxorubicin, cyclophosphamide (FAC) and paclitaxel chemotherapy and either breast conservation therapy with whole breast radiation (BCT, n = 215) or mastectomy with post-mastectomy radiation therapy (PMRT, n = 166). RCB was assessed by combining pathological measurements of the primary tumor bed, the proportion that contained residual invasive carcinoma, the number of involved axillary lymph nodes and the size of the largest lymph node. LVSI was categorized as present, absent or unknown and ER status was categorized as positive, negative, or unknown. Kaplan-Meier and log-rank tests were calculated to compare LRR. Results: Median age at treatment was 48 years (Inter-quartile range (IQR) 42 to 57) and median follow-up was 72 months (IQR 48 to 94). Five-year LRR was 4.5% overall, 4.1% in women treated with BCT and 5.0% in women treated with PMRT. LRR did not vary by age (p = 0.857). Women with ER-negative disease had higher 5-year LRR (8.2%) than women with ER-positive disease (1.7%) or unknown ER status (4.9%), (p = 0.007). Women with LVSI had higher 5year LRR (9.6%) than women without LVSI (2.2%) or unknown LVSI status (4.9%), (p = 0.025). Women with RCB score less than 2 (pathologic complete response or near complete response) had lower 5-year LRR (2.8%) than women with RCB score of 2 or greater (11.8%), (p = 0.004). Among women with ER-positive disease and no LVSI (n = 98), RCB did not predict 5-year LRR (1.2% vs. 0%, p = 0.707). Among women with either LVSI-positive or ER-negative disease (n = 206) RCB predicted for increased LRR (p = 0.007). Among women with either ER-negative or LVSI-positive disease, 5-year LRR was 20.6% for women with RCB score greater than or equal to 2 and 4% for women with RCB score less than 2. Conclusions: Women with breast cancer that is ER-negative or LVSI-positive who have at least a modest residual cancer burden after neoadjuvant chemotherapy are at markedly increased risk of LRR after surgical resection and local radiation therapy. These women should be considered for enrollment in clinical trials investigating ways to enhance local control, such as trials evaluating concurrent radiosensitizing agents. Author Disclosure: K.E. Hoffman, None; W.F. Symmans, None; J. Oh, None; W. Tereffe, None; T.K. Yu, None; G.H. Perkins, None; E.A. Strom, None; A.M. Gonzalez-Angulo, None; T.A. Buchholz, None; W.A. Woodward, None.
208
Relationship between Nodal Stage, Post Mastectomy Radiation Field Selection, and Clinical Outcome after Neoadjuvant Chemotherapy for Breast Cancer
J. L. Wright, I. Reis, W. Zhao, V. Gunaseelan, M. Moller, C. Takita, J. Hurley University of Miami, Miami, FL Purpose/Objective(s): Post mastectomy radiation (PMRT) field selection may vary with extent of nodal disease, and there are no clear guidelines for field selection after neoadjuvant chemotherapy (NACT). We evaluated the relationships between nodal stage, PMRT field selection, and locoregional recurrence (LRR) in patients receiving NACT. Materials/Methods: We reviewed records of 481 patients treated from 1/1999 to 12/2009 to obtain data on patient demographics, disease and treatment characteristics and outcome. Rate of locoregional recurrence (LRR) was estimated by the method of cumulative incidence allowing for competing risks and the effect of prognostic factors was examined by Gray’s test. Results: Patient demographics: 25% African descent, 68% Hispanic, and 52% age #50. Clinical stage: 31% II, 69% III, 14% inflammatory; 31% were cN0, and 69% cN1-3; mean clinical tumor size was 7.3 cm. Receptor status: 10% ER+HER2+, 42% ER+HER2-, 15% ER-HER2+, and 33% ER-HER2-. Treatment: There was no pathologic evaluation of nodes prior to NACT. Chemotherapy was 43% platinum-based, 20% anthracycline/taxane-based, 21% trastuzumab based, 16% other; all patients had mastectomy, 99% with axillary node dissection, 1% with SLNBx. Overall, 20% had a complete response (pCR) in breast + axilla, and 46% were pN0 after NACT. of those who were cN0 at diagnosis, 56% were also found to be pN0 after NACT, but 44% were pN+. In the entire cohort, 21% received RT to the chest wall (CW) only, and 79% to CW + supraclavicular nodes (SCV). Field selection varied with nodal stage. For clinical N-stage, RT was delivered to CW only in 36% of cN0 patients and 14% of cN+ patients (p \ 0.001). For final pathologic stage, RT was delivered to CW only in 31% of pN0 patients, 20% of those with p1-3 nodes+, and 6% of those with p$4 nodes+ (p \ 0.001). Nearly half (49%) of patients who were both cN0 and pN0 received RT to CW only. Outcome: 5-year cumulative incidence of LRR as first site of failure was 6.3% (CI 4.19.1). LRR increased with nodal stage. For clinical N-stage, LRR was 1.9% (CI 0.4-6.1) for cN0, and 8.4% (CI 5.4-12.3) for cN1-3 (p = 0.009), and for pathologic N- stage, LRR was 2.1% (CI 0.6-5.6) for pN0, 6.8% (CI 2.9-12.8%) for p1-3 nodes+, and 11.9% (CI 6.7-18.6%) for p$4 nodes+ (p = 0.002). Treatment of the SCV field was not associated with risk of LRR in the entire cohort or in any subset. Conclusions: Despite omission of the SCV field in selected patients, the risk of LRR was low in both clinically and pathologically node-negative patients. Treatment of the SCV field was not associated with risk of LRR. Omission of the SCV field may result in acceptably low LRR in selected node-negative patients treated with NACT, and this should be studied prospectively. Author Disclosure: J.L. Wright, None; I. Reis, None; W. Zhao, None; V. Gunaseelan, None; M. Moller, None; C. Takita, None; J. Hurley, None.
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207
Pathologic Features Predicting for High Rates of Local-Regional Recurrence after Neoadjuvant Chemotherapy and Radiation Therapy for Breast Cancer
K. E. Hoffman, W. F. Symmans, J. Oh, W. Tereffe, T. K. Yu, G. H. Perkins, E. A. Strom, A. M. Gonzalez-Angulo, T. A. Buchholz, W. A. Woodward The University of Texas M. D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): Identifying women with an elevated risk of local failure despite good local breast cancer therapy is important to determine if there is a group of women who may benefit from more aggressive local therapy. We evaluated the combined impact of lymphovascular space invasion (LVSI), estrogen receptor (ER) status, and residual cancer burden (RCB) on local regional recurrence (LRR) after definitive treatment with neoadjuvant chemotherapy, surgical resection, and radiation therapy. Materials/Methods: We evaluated 381 women with Stages I-III breast cancer treated with neoadjuvant fluorouracil, doxorubicin, cyclophosphamide (FAC) and paclitaxel chemotherapy and either breast conservation therapy with whole breast radiation (BCT, n = 215) or mastectomy with post-mastectomy radiation therapy (PMRT, n = 166). RCB was assessed by combining pathological measurements of the primary tumor bed, the proportion that contained residual invasive carcinoma, the number of involved axillary lymph nodes and the size of the largest lymph node. LVSI was categorized as present, absent or unknown and ER status was categorized as positive, negative, or unknown. Kaplan-Meier and log-rank tests were calculated to compare LRR. Results: Median age at treatment was 48 years (Inter-quartile range (IQR) 42 to 57) and median follow-up was 72 months (IQR 48 to 94). Five-year LRR was 4.5% overall, 4.1% in women treated with BCT and 5.0% in women treated with PMRT. LRR did not vary by age (p = 0.857). Women with ER-negative disease had higher 5-year LRR (8.2%) than women with ER-positive disease (1.7%) or unknown ER status (4.9%), (p = 0.007). Women with LVSI had higher 5year LRR (9.6%) than women without LVSI (2.2%) or unknown LVSI status (4.9%), (p = 0.025). Women with RCB score less than 2 (pathologic complete response or near complete response) had lower 5-year LRR (2.8%) than women with RCB score of 2 or greater (11.8%), (p = 0.004). Among women with ER-positive disease and no LVSI (n = 98), RCB did not predict 5-year LRR (1.2% vs. 0%, p = 0.707). Among women with either LVSI-positive or ER-negative disease (n = 206) RCB predicted for increased LRR (p = 0.007). Among women with either ER-negative or LVSI-positive disease, 5-year LRR was 20.6% for women with RCB score greater than or equal to 2 and 4% for women with RCB score less than 2. Conclusions: Women with breast cancer that is ER-negative or LVSI-positive who have at least a modest residual cancer burden after neoadjuvant chemotherapy are at markedly increased risk of LRR after surgical resection and local radiation therapy. These women should be considered for enrollment in clinical trials investigating ways to enhance local control, such as trials evaluating concurrent radiosensitizing agents. Author Disclosure: K.E. Hoffman, None; W.F. Symmans, None; J. Oh, None; W. Tereffe, None; T.K. Yu, None; G.H. Perkins, None; E.A. Strom, None; A.M. Gonzalez-Angulo, None; T.A. Buchholz, None; W.A. Woodward, None.
208
Relationship between Nodal Stage, Post Mastectomy Radiation Field Selection, and Clinical Outcome after Neoadjuvant Chemotherapy for Breast Cancer
J. L. Wright, I. Reis, W. Zhao, V. Gunaseelan, M. Moller, C. Takita, J. Hurley University of Miami, Miami, FL Purpose/Objective(s): Post mastectomy radiation (PMRT) field selection may vary with extent of nodal disease, and there are no clear guidelines for field selection after neoadjuvant chemotherapy (NACT). We evaluated the relationships between nodal stage, PMRT field selection, and locoregional recurrence (LRR) in patients receiving NACT. Materials/Methods: We reviewed records of 481 patients treated from 1/1999 to 12/2009 to obtain data on patient demographics, disease and treatment characteristics and outcome. Rate of locoregional recurrence (LRR) was estimated by the method of cumulative incidence allowing for competing risks and the effect of prognostic factors was examined by Gray’s test. Results: Patient demographics: 25% African descent, 68% Hispanic, and 52% age #50. Clinical stage: 31% II, 69% III, 14% inflammatory; 31% were cN0, and 69% cN1-3; mean clinical tumor size was 7.3 cm. Receptor status: 10% ER+HER2+, 42% ER+HER2-, 15% ER-HER2+, and 33% ER-HER2-. Treatment: There was no pathologic evaluation of nodes prior to NACT. Chemotherapy was 43% platinum-based, 20% anthracycline/taxane-based, 21% trastuzumab based, 16% other; all patients had mastectomy, 99% with axillary node dissection, 1% with SLNBx. Overall, 20% had a complete response (pCR) in breast + axilla, and 46% were pN0 after NACT. of those who were cN0 at diagnosis, 56% were also found to be pN0 after NACT, but 44% were pN+. In the entire cohort, 21% received RT to the chest wall (CW) only, and 79% to CW + supraclavicular nodes (SCV). Field selection varied with nodal stage. For clinical N-stage, RT was delivered to CW only in 36% of cN0 patients and 14% of cN+ patients (p \ 0.001). For final pathologic stage, RT was delivered to CW only in 31% of pN0 patients, 20% of those with p1-3 nodes+, and 6% of those with p$4 nodes+ (p \ 0.001). Nearly half (49%) of patients who were both cN0 and pN0 received RT to CW only. Outcome: 5-year cumulative incidence of LRR as first site of failure was 6.3% (CI 4.19.1). LRR increased with nodal stage. For clinical N-stage, LRR was 1.9% (CI 0.4-6.1) for cN0, and 8.4% (CI 5.4-12.3) for cN1-3 (p = 0.009), and for pathologic N- stage, LRR was 2.1% (CI 0.6-5.6) for pN0, 6.8% (CI 2.9-12.8%) for p1-3 nodes+, and 11.9% (CI 6.7-18.6%) for p$4 nodes+ (p = 0.002). Treatment of the SCV field was not associated with risk of LRR in the entire cohort or in any subset. Conclusions: Despite omission of the SCV field in selected patients, the risk of LRR was low in both clinically and pathologically node-negative patients. Treatment of the SCV field was not associated with risk of LRR. Omission of the SCV field may result in acceptably low LRR in selected node-negative patients treated with NACT, and this should be studied prospectively. Author Disclosure: J.L. Wright, None; I. Reis, None; W. Zhao, None; V. Gunaseelan, None; M. Moller, None; C. Takita, None; J. Hurley, None.
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