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Hormone Receptor Status and TN Stage Influence the Locoregional Benefit From Trastuzumab in Patients With HER 2–Positive Breast Cancer After Adjuvant Radiation Therapy
S244
International Journal of Radiation Oncology Biology Physics
Cancer Institute, Boston, MA, 4Brigham & Women’s Hospital/ Massachusetts General Hospital/ Harvard Medical School Program, Boston, MA, 5Dana-Farber/Brigham & Women’s Cancer Center, Boston, MA, 6Dana-Farber Cancer Institute/Brigham & Women’s Hospital, Boston, MA
Cancer Center, Columbus, OH, 12Brigham & Women’s Hospital/DanaFarber Cancer Institute, Boston, MA
Purpose/Objective(s): ILC of the breast is more often multifocal in nature than invasive ductal carcinoma (IDC), with a higher rate of close or positive margins on excision. This histologic pattern raises questions about the efficacy of BCT for ILC. To address this concern, we assessed LR rates for patients with ILC treated with BCT. Materials/Methods: The study population included 998 patients who underwent BCT at our institution between 1998 and 2007. The median patient age was 55 years (range 23-87). All patients received tangential whole-breast radiation therapy (median dose 45 Gy) and 971 patients (97.1%) received a boost (median 16 Gy). 734 patients (74%) had IDC, 79 (8%) had ILC and 185 (18%) had cancers comprising both IDC and ILC (mixed). Biologic subtypes were approximated by receptor status and histologic grade: estrogen receptor (ER) positive or progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER 2) negative and moderately- or well-differentiated Z luminal A; ER+ or PR+, HER 2and poorly-differentiated Z luminal B; ER+ or PR+ and HER 2+ Z luminal-HER 2; ER-, PR- and HER 2+ Z HER 2; ER-, PR- and HER 2Z triple negative breast cancer. Fifty-two percent of patients with IDC, 91% with ILC, and 80% with mixed tumors had luminal A cancers. The Kaplan-Meier method was used to characterize time to LR. The log-rank test and Cox proportional hazards models were used to assess the effect of patient characteristics and disease factors on LR. Results: At a median follow-up of 103 months, 45 patients (4.5%) had a LR, 71 (7.1%) developed distant metastases, and 114 (11.4%) died. The rate of LR at 10 years was 5.5% for patients with IDC, 4.4% for patients with ILC, and 1.2% for patients with mixed cancers (p Z 0.08). For patients exclusively with luminal A disease, the rate of LR at 10 years was 2.6% for those with IDC, 3.4% for ILC, and 0% for mixed tumors (p Z 0.12). On multivariate analysis, IDC, ILC and mixed histology did not differ with regard to LR (p Z 0.60). Significant predictors of LR were younger age (p Z 0.04), subtype approximation (p Z 0.002), increasing tumor size (p Z 0.007) and increasing number of involved lymph nodes (p Z 0.04). Conclusions: In the era of modern mammographic imaging, detailed margin assessment and effective adjuvant systemic therapy, 10-year LR rates after BCT are similarly low for ILC, IDC, and mixed cancers despite the differences in histologic presentation and challenges of complete resection. This is true even when adjusted for biologic subtype. Author Disclosure: L.Z. Braunstein: None. J.E. Brock: None. Y. Chen: None. L. Truong: None. A.L. Russo: None. N.D. Arvold: None. J.R. Harris: None.
Purpose/Objective(s): Use of postmastectomy radiation (PMRT) for women with pathologic node-negative disease is controversial. We studied the effect of biological subtype on likelihood and timing of locoregional recurrence (LRR) among these women. Materials/Methods: We evaluated 3313 patients who presented to National Comprehensive Cancer Network (NCCN) centers with invasive breast carcinoma between 2000 and 2009. All patients received mastectomy and lymph node evaluation and were found to have pathologic nodenegative disease (pT1-T4N0). Biological subtypes were approximated by immunohistochemical staining of estrogen (ER), progesterone (PR), and HER 2 receptors: luminal A (ER+ and/or PR+, HER 2-), luminal B (ER+ and/or PR+, HER 2+), basal (ER-, PR-, HER 2-), and HER 2+ (ER-, PR-, HER 2+). Competing and Cox risk regression models were used to estimate hazard ratios (HR) for LRR among four patient groups defined by biological subtype and receipt of trastuzumab: luminal A/B, HER 2+ not treated with trastuzumab, HER 2+ treated with trastuzumab, and basal. A multivariate competing risk model was constructed using stepwise selection of various clinical, pathologic, and treatment variables. 5-year rates of LRR were estimated with a cumulative incidence function. Results: The majority of patients had luminal A (70%), followed by basal (13%), luminal B (10%), and HER 2+ (7%) subtypes. 41% were 50 years or younger and 71% had a primary tumor 2 cm or smaller. 47% received chemotherapy, 70% received hormonal therapy, and 7% received PMRT. Among those who were HER 2+, 87% received trastuzumab. With a median follow-up of 3.76 years, 67 have had LRR. No LRR occurred among HER 2+ patients treated with trastuzumab, and this group was excluded from the regression analysis. Both HER 2+ patients who did not receive trastuzumab (HR Z 3.19, 95% CI Z 1.42-7.17) and patients with basal subtype (HR Z 2.85, 95% CI Z 1.60-5.08) had a significantly shorter time to LRR on competing risk analysis; similar results were also obtained with a Cox regression model. The 5-year risk of LRR was 1.7% (luminal A/B), 0% (HER 2+ with trastuzumab), 5.3% (HER 2+ without trastuzumab), and 4.5% (basal). No other variables significantly predicted LRR on multivariate analysis. Conclusions: Biological subtype is associated with risk of LRR within this relatively favorable cohort of women who underwent mastectomy and had no pathologic involvement of lymph nodes, but the absolute risk of LRR is low. In the absence of trastuzumab, HER 2+ patients have a LRR risk similar to patients with basal subtype. The role of local therapy may vary by subtype and receipt of trastuzumab. Author Disclosure: Y.D. Tseng: None. H. Uno: None. M.E. Hughes: None. J.C. Niland: None. Y. Wong: None. R. Theriault: None. P.K. Marcom: None. B. Moy: None. T. Breslin: None. S.B. Edge: None. J.L. Wilson: None. R.S. Punglia: None.
2069 2068 Association Between Breast Cancer Biological Subtype and Risk of Locoregional Recurrence A Mastectomy in Node-Negative Patients Y.D. Tseng,1 H. Uno,2 M.E. Hughes,3 J.C. Niland,4 Y. Wong,5 R. Theriault,6 P.K. Marcom,7 B. Moy,8 T. Breslin,9 S.B. Edge,10 J.L. Wilson,11 and R.S. Punglia12; 1Harvard Radiation Oncology Program, Boston, MA, 2Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 4Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, 5 Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, 6Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC, 8Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, 9Department of Surgery, Division of Surgical Oncology, Northwestern Lake Forest Hospital, Lake Forest, IL, 10Baptist Cancer Center, Memphis, TN, 11The Ohio State University Comprehensive
Hormone Receptor Status and TN Stage Influence the Locoregional Benefit From Trastuzumab in Patients With HER 2ePositive Breast Cancer After Adjuvant Radiation Therapy L. Cao, G. Cai, X. Yu, J. Ma, Z. Yang, Z. Shao, X. Guo, and J. Chen; Fudan University Shanghai Cancer Center, Shanghai, China Purpose/Objective(s): Despite the established benefit of adjuvant trastuzumab in disease-free survival and overall survival for patients with HER 2-positive (HER 2+) breast cancers. Uncertainty remained concerning the effects of trastuzumab on locoregional control, especially in patients treated with adjuvant radiation therapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER 2+ breast cancer receiving adjuvant radiation therapy. Materials/Methods: Using single institutional database, we identified 337 patients with HER 2+ invasive breast cancer and who received adjuvant RT between January 2008 and July 2011. The percentage of stage I, II and III were 17.3%, 43.1%, and 39.6%, respectively. Median age at diagnosis was 48 years (24-78 years). Neo-adjuvant chemotherapy was given to 74 patients and adjuvant chemotherapy to 331 patients. Trastuzumab was
Volume 90 Number 1S Supplement 2014 started, with neo-adjuvant chemotherapy, with adjuvant chemotherapy, with RT and after RT in 29, 81, 30, and 26 patients, respectively. Patients were classified into HER 2+ (HR-/HER 2+, 160 pts) and Luminal B (HR+/ HER 2+, 177 pts) subtype. Locoregional recurrence was defined as any recurrence in the ipsilateral breast, chest wall, supraclavicular, internal mammary nodes or axillary nodes, and analyzed using Kaplan-Meier methods. The outcomes in the “no-trastuzumab” cohort and the “trastuzumab” cohort were compared using log-rank test. Results: The median follow-up was 38 months (3-67 months). Radiation therapy of 50 Gy/25F was delivered, postoperatively, to the chest wall in 213 patients or to the conserved breast in 124 patients with tumor bed boost of 10 Gy. Regional nodes irradiation was given in 231 patients. The 3-year locoregional recurrence free survival (LRFS) was 96.7% and 92.9% in the “trastuzumab” (n Z 166) and “no-trastuzumab” (n Z 171) cohort, respectively (P Z 0.085). In the subgroup of luminal B breast cancer, the 3-year LRFS was 100% and 94.5% in the “trastuzumab” cohort and “notrastuzumab” cohort, respectively (P Z 0.024). Both cohorts in this subgroup were balanced in age, tumor, nodal stage, hormone therapy, surgical types, and adjuvant chemotherapy. Patients with positive lymph nodes or pathological tumor size > 2 cm breast cancer were also found to benefit from trastuzumab in terms of 3-year LRFS (97% vs 91.2%, P Z 0.039; and 99% vs 92.7%, P Z 0.028, respectively). Conclusions: Trastuzumab did not appear to reduce risk of locoregional recurrence in all HER 2+ breast cancer patients after radiation therapy. However, hormone receptor status and TN (tumor and nodal) stage may help to identify the locoregional benefit of trastuzumab in these patients. Author Disclosure: L. Cao: None. G. Cai: None. X. Yu: None. J. Ma: None. Z. Yang: None. Z. Shao: None. X. Guo: None. J. Chen: None.
2070 Leptomeningeal Failure in Patients With Breast Cancer Receiving Stereotactic Radiosurgery for Brain Metastases B.R. Page,1 A.J. Huang,1 K.E. Huang,2 A.W. Laxton,3 S.B. Tatter,3 and M.D. Chan1; 1Wake Forest University Department of Radiation Oncology, Winston-Salem, NC, 2Wake Forest University, Winston-Salem, NC, 3Wake Forest University Department of Neurosurgery, Winston-Salem, NC Purpose/Objective(s): Prior studies suggest a higher incidence of leptomeningeal failure (LMF) in patients with breast cancer as compared to other histologies. We investigate variables affecting the probability of developing LMF after gamma knife radiosurgery (GKS) for brain metastases. Materials/Methods: Between 2000 and 2010, 149 patients with breast cancer were treated with GKS for brain metastases. Variables assessed include hormone and HER 2 receptor status, age, local and distant brain failure, prior craniotomy, and prior WBRT. The median follow-up period was 54 months (range, 0-106). Local and distant brain failure and LMF were determined on serial MRI. Neurologic death was defined as previously reported by Patchell et al. Breast cancer patients were compared with 658 historical controls with other histologies from our institution. Fisher’s exact test and Wilcoxon rank sum tests were used for categorical and continuous data comparisons, respectively. Survival distributions were compared using Log-Rank tests. Predictors of LMD were evaluated using Cox Proportional Hazard models. Results: Of 149 patients, 21 (14%) developed LMF at a median time of 11.9 months with an interquartile range (IQR) of 5.8-25.1 months after GKS. None of the following factors including HER 2 status (HR Z 0.49, p Z 0.16), hormone receptor status (HR Z 1.15, p Z 0.79), prior craniotomy (HR Z 1.58, p Z 0.42), nor prior WBRT (HR Z 1.36, p Z 0.55) were predictive of development of LMF. Breast cancer patients who had distant failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2, p Z 0.005); this included 15/65 (23%) patients who had distant failure and developed LMF. Median time to death for patients experiencing LMF was 6.1 months (IQR 3.4-7.8) from onset of LMF. Of 21 patients experiencing LMF, 12 (57%) also experienced neurologic death. Of the 106 patients that did not develop LMF, 43 (43.4%) had a
Poster Viewing Abstracts S245 neurologic death (p Z 0.34). Median survival was 14.2 months (IQR 4.9 to 24.4) and for patients who did not have LMF and 8.6 months (IQR 5.0 to 21.0) (p Z 0.48) for those who did. When compared to historical controls of other histologies in our institutional database, time from LMF diagnosis to death was much longer than in other histologies, with a median time to death of 6.1 months (IQR 3.4 to 7.8 months) compared to 1.7 months (IQR 1 to 4.4 months), p < 0.0003 for other histologies. Conclusions: Patients with distant failure after GKS were more likely to develop LMF at a later time. Breast cancer patients had a longer survival after diagnosis of LMF compared with other histologies. These patients may represent targets of future prospective studies. Author Disclosure: B.R. Page: None. A.J. Huang: None. K.E. Huang: None. A.W. Laxton: None. S.B. Tatter: None. M.D. Chan: None.
2071 Comparison of Clinical Treatment Effect Between SIB-IMRT and Late-Course Boost-IMRT for Early Breast Cancer After BreastConserving Surgery S. Wang, H. Xing, J. Li, Y. Zhang, M. Xu, and Y. Ding; Shandong Cancer Hospital, Jinan, China Purpose/Objective(s): To explore the difference on clinical observation of after breast conserving therapy for early breast cancer between the simultaneous integrated boost intensity modulated radiation therapy (SIBIMRT) and late-course boost intensity modulated radiation therapy (latecourse boost-IMRT). Materials/Methods: For this study, 353 female breast cancer patients (stages I-II), treated with breast-conserving surgery at our institute between November 2002 and February 2012, were retrospectively identified. Median age at diagnosis was 43 (range 20-67) years. Two hundred eighteen patients were treated with SIB-IMRT after breast conserving therapy and 135 patients were treated with late-course boost-IMRT. For the SIB-IMRT group, fractionation schemes used were 27-28 daily fractions of 1.8-1.9 Gray (Gy) to the whole breast PTV and 2.15-2.3 Gy to the boost PTVt. For the late-course boost-IMRT group, fractionation schemes used were 25 daily fractions of 2.0 Gy to the whole breast PTVb, then 5-8 daily fractions of 2.0 Gy to the boost PTVt only. Next to outcome, we estimated difference of the two group on the overall survival (OS), disease free survival (DFS), local control rate (LCR), locoregional recurrence rate (LRR) and distant metastasis rate (DMR) at 3, 5, 8 and 10-year by the Kaplan-Meier and c2 test. Results: Median follow-up was 62 (range 1-144) months. The two groups had comparability on age, TNM stages, histopathology, hormone receptor status, and postoperative chemotherapy (all P value > 0.05). For the SIBIMRT group, OS was 98.17%, 96.33%, 95.41% and 94.95% at 3, 5, 8, and 10-years, respectively. In addition, OS was 99.26%, 97.04%, 94.07% and 94.07% for the late-course boost-IMRT group. There were no significant differences between the groups on OS (all P value > 0.05). DFS was 95.87%, 92.20%, 90.83%, 90.37% and 94.81%, 88.89%, 85.93%, 85.93% at 3, 5, 8 and 10-years for the SIB-IMRT and late-course boost-IMRT groups, respectively. The differences were not significant for the two groups on DFS. For the LCR, it was 98.17%, 96.79%, 95.87%, 95.87% and 95.56%, 94.07%, 93.33%, 93.33% at 3, 5, 8 and 10-years for the SIBIMRT and late-course boost-IMRT group, respectively. Meanwhile, there was no significant difference between the groups on LCR (all P value > 0.05). The 3, 5, 8 and 10-year LRR were 1.83%, 3.21%, 4.13%, 4.13% and 4.44%, 5.93%, 6.67%, 6.67% for the SIB-IMRT and late-course boostIMRT group and there was also no significant differences between the groups (all P value > 0.05). There were no different for DMR of the two groups (all P value > 0.05). Conclusions: In conclusion, SIB-IMRT as part of breast cancer treatment had the same treatment effect in excellent OS, DFS, and LRC rates comparing with late-course boost-IMRT. Meanwhile, the LCR and DMR was the same as late-course boost-IMRT. Therefore, SIB-IMRT was worth to popularize in clinical treatment. Author Disclosure: S. Wang: None. H. Xing: None. J. Li: None. Y. Zhang: None. M. Xu: None. Y. Ding: None.
International Journal of Radiation Oncology Biology Physics
Cancer Institute, Boston, MA, 4Brigham & Women’s Hospital/ Massachusetts General Hospital/ Harvard Medical School Program, Boston, MA, 5Dana-Farber/Brigham & Women’s Cancer Center, Boston, MA, 6Dana-Farber Cancer Institute/Brigham & Women’s Hospital, Boston, MA
Cancer Center, Columbus, OH, 12Brigham & Women’s Hospital/DanaFarber Cancer Institute, Boston, MA
Purpose/Objective(s): ILC of the breast is more often multifocal in nature than invasive ductal carcinoma (IDC), with a higher rate of close or positive margins on excision. This histologic pattern raises questions about the efficacy of BCT for ILC. To address this concern, we assessed LR rates for patients with ILC treated with BCT. Materials/Methods: The study population included 998 patients who underwent BCT at our institution between 1998 and 2007. The median patient age was 55 years (range 23-87). All patients received tangential whole-breast radiation therapy (median dose 45 Gy) and 971 patients (97.1%) received a boost (median 16 Gy). 734 patients (74%) had IDC, 79 (8%) had ILC and 185 (18%) had cancers comprising both IDC and ILC (mixed). Biologic subtypes were approximated by receptor status and histologic grade: estrogen receptor (ER) positive or progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER 2) negative and moderately- or well-differentiated Z luminal A; ER+ or PR+, HER 2and poorly-differentiated Z luminal B; ER+ or PR+ and HER 2+ Z luminal-HER 2; ER-, PR- and HER 2+ Z HER 2; ER-, PR- and HER 2Z triple negative breast cancer. Fifty-two percent of patients with IDC, 91% with ILC, and 80% with mixed tumors had luminal A cancers. The Kaplan-Meier method was used to characterize time to LR. The log-rank test and Cox proportional hazards models were used to assess the effect of patient characteristics and disease factors on LR. Results: At a median follow-up of 103 months, 45 patients (4.5%) had a LR, 71 (7.1%) developed distant metastases, and 114 (11.4%) died. The rate of LR at 10 years was 5.5% for patients with IDC, 4.4% for patients with ILC, and 1.2% for patients with mixed cancers (p Z 0.08). For patients exclusively with luminal A disease, the rate of LR at 10 years was 2.6% for those with IDC, 3.4% for ILC, and 0% for mixed tumors (p Z 0.12). On multivariate analysis, IDC, ILC and mixed histology did not differ with regard to LR (p Z 0.60). Significant predictors of LR were younger age (p Z 0.04), subtype approximation (p Z 0.002), increasing tumor size (p Z 0.007) and increasing number of involved lymph nodes (p Z 0.04). Conclusions: In the era of modern mammographic imaging, detailed margin assessment and effective adjuvant systemic therapy, 10-year LR rates after BCT are similarly low for ILC, IDC, and mixed cancers despite the differences in histologic presentation and challenges of complete resection. This is true even when adjusted for biologic subtype. Author Disclosure: L.Z. Braunstein: None. J.E. Brock: None. Y. Chen: None. L. Truong: None. A.L. Russo: None. N.D. Arvold: None. J.R. Harris: None.
Purpose/Objective(s): Use of postmastectomy radiation (PMRT) for women with pathologic node-negative disease is controversial. We studied the effect of biological subtype on likelihood and timing of locoregional recurrence (LRR) among these women. Materials/Methods: We evaluated 3313 patients who presented to National Comprehensive Cancer Network (NCCN) centers with invasive breast carcinoma between 2000 and 2009. All patients received mastectomy and lymph node evaluation and were found to have pathologic nodenegative disease (pT1-T4N0). Biological subtypes were approximated by immunohistochemical staining of estrogen (ER), progesterone (PR), and HER 2 receptors: luminal A (ER+ and/or PR+, HER 2-), luminal B (ER+ and/or PR+, HER 2+), basal (ER-, PR-, HER 2-), and HER 2+ (ER-, PR-, HER 2+). Competing and Cox risk regression models were used to estimate hazard ratios (HR) for LRR among four patient groups defined by biological subtype and receipt of trastuzumab: luminal A/B, HER 2+ not treated with trastuzumab, HER 2+ treated with trastuzumab, and basal. A multivariate competing risk model was constructed using stepwise selection of various clinical, pathologic, and treatment variables. 5-year rates of LRR were estimated with a cumulative incidence function. Results: The majority of patients had luminal A (70%), followed by basal (13%), luminal B (10%), and HER 2+ (7%) subtypes. 41% were 50 years or younger and 71% had a primary tumor 2 cm or smaller. 47% received chemotherapy, 70% received hormonal therapy, and 7% received PMRT. Among those who were HER 2+, 87% received trastuzumab. With a median follow-up of 3.76 years, 67 have had LRR. No LRR occurred among HER 2+ patients treated with trastuzumab, and this group was excluded from the regression analysis. Both HER 2+ patients who did not receive trastuzumab (HR Z 3.19, 95% CI Z 1.42-7.17) and patients with basal subtype (HR Z 2.85, 95% CI Z 1.60-5.08) had a significantly shorter time to LRR on competing risk analysis; similar results were also obtained with a Cox regression model. The 5-year risk of LRR was 1.7% (luminal A/B), 0% (HER 2+ with trastuzumab), 5.3% (HER 2+ without trastuzumab), and 4.5% (basal). No other variables significantly predicted LRR on multivariate analysis. Conclusions: Biological subtype is associated with risk of LRR within this relatively favorable cohort of women who underwent mastectomy and had no pathologic involvement of lymph nodes, but the absolute risk of LRR is low. In the absence of trastuzumab, HER 2+ patients have a LRR risk similar to patients with basal subtype. The role of local therapy may vary by subtype and receipt of trastuzumab. Author Disclosure: Y.D. Tseng: None. H. Uno: None. M.E. Hughes: None. J.C. Niland: None. Y. Wong: None. R. Theriault: None. P.K. Marcom: None. B. Moy: None. T. Breslin: None. S.B. Edge: None. J.L. Wilson: None. R.S. Punglia: None.
2069 2068 Association Between Breast Cancer Biological Subtype and Risk of Locoregional Recurrence A Mastectomy in Node-Negative Patients Y.D. Tseng,1 H. Uno,2 M.E. Hughes,3 J.C. Niland,4 Y. Wong,5 R. Theriault,6 P.K. Marcom,7 B. Moy,8 T. Breslin,9 S.B. Edge,10 J.L. Wilson,11 and R.S. Punglia12; 1Harvard Radiation Oncology Program, Boston, MA, 2Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 4Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, 5 Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, 6Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC, 8Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, 9Department of Surgery, Division of Surgical Oncology, Northwestern Lake Forest Hospital, Lake Forest, IL, 10Baptist Cancer Center, Memphis, TN, 11The Ohio State University Comprehensive
Hormone Receptor Status and TN Stage Influence the Locoregional Benefit From Trastuzumab in Patients With HER 2ePositive Breast Cancer After Adjuvant Radiation Therapy L. Cao, G. Cai, X. Yu, J. Ma, Z. Yang, Z. Shao, X. Guo, and J. Chen; Fudan University Shanghai Cancer Center, Shanghai, China Purpose/Objective(s): Despite the established benefit of adjuvant trastuzumab in disease-free survival and overall survival for patients with HER 2-positive (HER 2+) breast cancers. Uncertainty remained concerning the effects of trastuzumab on locoregional control, especially in patients treated with adjuvant radiation therapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER 2+ breast cancer receiving adjuvant radiation therapy. Materials/Methods: Using single institutional database, we identified 337 patients with HER 2+ invasive breast cancer and who received adjuvant RT between January 2008 and July 2011. The percentage of stage I, II and III were 17.3%, 43.1%, and 39.6%, respectively. Median age at diagnosis was 48 years (24-78 years). Neo-adjuvant chemotherapy was given to 74 patients and adjuvant chemotherapy to 331 patients. Trastuzumab was
Volume 90 Number 1S Supplement 2014 started, with neo-adjuvant chemotherapy, with adjuvant chemotherapy, with RT and after RT in 29, 81, 30, and 26 patients, respectively. Patients were classified into HER 2+ (HR-/HER 2+, 160 pts) and Luminal B (HR+/ HER 2+, 177 pts) subtype. Locoregional recurrence was defined as any recurrence in the ipsilateral breast, chest wall, supraclavicular, internal mammary nodes or axillary nodes, and analyzed using Kaplan-Meier methods. The outcomes in the “no-trastuzumab” cohort and the “trastuzumab” cohort were compared using log-rank test. Results: The median follow-up was 38 months (3-67 months). Radiation therapy of 50 Gy/25F was delivered, postoperatively, to the chest wall in 213 patients or to the conserved breast in 124 patients with tumor bed boost of 10 Gy. Regional nodes irradiation was given in 231 patients. The 3-year locoregional recurrence free survival (LRFS) was 96.7% and 92.9% in the “trastuzumab” (n Z 166) and “no-trastuzumab” (n Z 171) cohort, respectively (P Z 0.085). In the subgroup of luminal B breast cancer, the 3-year LRFS was 100% and 94.5% in the “trastuzumab” cohort and “notrastuzumab” cohort, respectively (P Z 0.024). Both cohorts in this subgroup were balanced in age, tumor, nodal stage, hormone therapy, surgical types, and adjuvant chemotherapy. Patients with positive lymph nodes or pathological tumor size > 2 cm breast cancer were also found to benefit from trastuzumab in terms of 3-year LRFS (97% vs 91.2%, P Z 0.039; and 99% vs 92.7%, P Z 0.028, respectively). Conclusions: Trastuzumab did not appear to reduce risk of locoregional recurrence in all HER 2+ breast cancer patients after radiation therapy. However, hormone receptor status and TN (tumor and nodal) stage may help to identify the locoregional benefit of trastuzumab in these patients. Author Disclosure: L. Cao: None. G. Cai: None. X. Yu: None. J. Ma: None. Z. Yang: None. Z. Shao: None. X. Guo: None. J. Chen: None.
2070 Leptomeningeal Failure in Patients With Breast Cancer Receiving Stereotactic Radiosurgery for Brain Metastases B.R. Page,1 A.J. Huang,1 K.E. Huang,2 A.W. Laxton,3 S.B. Tatter,3 and M.D. Chan1; 1Wake Forest University Department of Radiation Oncology, Winston-Salem, NC, 2Wake Forest University, Winston-Salem, NC, 3Wake Forest University Department of Neurosurgery, Winston-Salem, NC Purpose/Objective(s): Prior studies suggest a higher incidence of leptomeningeal failure (LMF) in patients with breast cancer as compared to other histologies. We investigate variables affecting the probability of developing LMF after gamma knife radiosurgery (GKS) for brain metastases. Materials/Methods: Between 2000 and 2010, 149 patients with breast cancer were treated with GKS for brain metastases. Variables assessed include hormone and HER 2 receptor status, age, local and distant brain failure, prior craniotomy, and prior WBRT. The median follow-up period was 54 months (range, 0-106). Local and distant brain failure and LMF were determined on serial MRI. Neurologic death was defined as previously reported by Patchell et al. Breast cancer patients were compared with 658 historical controls with other histologies from our institution. Fisher’s exact test and Wilcoxon rank sum tests were used for categorical and continuous data comparisons, respectively. Survival distributions were compared using Log-Rank tests. Predictors of LMD were evaluated using Cox Proportional Hazard models. Results: Of 149 patients, 21 (14%) developed LMF at a median time of 11.9 months with an interquartile range (IQR) of 5.8-25.1 months after GKS. None of the following factors including HER 2 status (HR Z 0.49, p Z 0.16), hormone receptor status (HR Z 1.15, p Z 0.79), prior craniotomy (HR Z 1.58, p Z 0.42), nor prior WBRT (HR Z 1.36, p Z 0.55) were predictive of development of LMF. Breast cancer patients who had distant failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2, p Z 0.005); this included 15/65 (23%) patients who had distant failure and developed LMF. Median time to death for patients experiencing LMF was 6.1 months (IQR 3.4-7.8) from onset of LMF. Of 21 patients experiencing LMF, 12 (57%) also experienced neurologic death. Of the 106 patients that did not develop LMF, 43 (43.4%) had a
Poster Viewing Abstracts S245 neurologic death (p Z 0.34). Median survival was 14.2 months (IQR 4.9 to 24.4) and for patients who did not have LMF and 8.6 months (IQR 5.0 to 21.0) (p Z 0.48) for those who did. When compared to historical controls of other histologies in our institutional database, time from LMF diagnosis to death was much longer than in other histologies, with a median time to death of 6.1 months (IQR 3.4 to 7.8 months) compared to 1.7 months (IQR 1 to 4.4 months), p < 0.0003 for other histologies. Conclusions: Patients with distant failure after GKS were more likely to develop LMF at a later time. Breast cancer patients had a longer survival after diagnosis of LMF compared with other histologies. These patients may represent targets of future prospective studies. Author Disclosure: B.R. Page: None. A.J. Huang: None. K.E. Huang: None. A.W. Laxton: None. S.B. Tatter: None. M.D. Chan: None.
2071 Comparison of Clinical Treatment Effect Between SIB-IMRT and Late-Course Boost-IMRT for Early Breast Cancer After BreastConserving Surgery S. Wang, H. Xing, J. Li, Y. Zhang, M. Xu, and Y. Ding; Shandong Cancer Hospital, Jinan, China Purpose/Objective(s): To explore the difference on clinical observation of after breast conserving therapy for early breast cancer between the simultaneous integrated boost intensity modulated radiation therapy (SIBIMRT) and late-course boost intensity modulated radiation therapy (latecourse boost-IMRT). Materials/Methods: For this study, 353 female breast cancer patients (stages I-II), treated with breast-conserving surgery at our institute between November 2002 and February 2012, were retrospectively identified. Median age at diagnosis was 43 (range 20-67) years. Two hundred eighteen patients were treated with SIB-IMRT after breast conserving therapy and 135 patients were treated with late-course boost-IMRT. For the SIB-IMRT group, fractionation schemes used were 27-28 daily fractions of 1.8-1.9 Gray (Gy) to the whole breast PTV and 2.15-2.3 Gy to the boost PTVt. For the late-course boost-IMRT group, fractionation schemes used were 25 daily fractions of 2.0 Gy to the whole breast PTVb, then 5-8 daily fractions of 2.0 Gy to the boost PTVt only. Next to outcome, we estimated difference of the two group on the overall survival (OS), disease free survival (DFS), local control rate (LCR), locoregional recurrence rate (LRR) and distant metastasis rate (DMR) at 3, 5, 8 and 10-year by the Kaplan-Meier and c2 test. Results: Median follow-up was 62 (range 1-144) months. The two groups had comparability on age, TNM stages, histopathology, hormone receptor status, and postoperative chemotherapy (all P value > 0.05). For the SIBIMRT group, OS was 98.17%, 96.33%, 95.41% and 94.95% at 3, 5, 8, and 10-years, respectively. In addition, OS was 99.26%, 97.04%, 94.07% and 94.07% for the late-course boost-IMRT group. There were no significant differences between the groups on OS (all P value > 0.05). DFS was 95.87%, 92.20%, 90.83%, 90.37% and 94.81%, 88.89%, 85.93%, 85.93% at 3, 5, 8 and 10-years for the SIB-IMRT and late-course boost-IMRT groups, respectively. The differences were not significant for the two groups on DFS. For the LCR, it was 98.17%, 96.79%, 95.87%, 95.87% and 95.56%, 94.07%, 93.33%, 93.33% at 3, 5, 8 and 10-years for the SIBIMRT and late-course boost-IMRT group, respectively. Meanwhile, there was no significant difference between the groups on LCR (all P value > 0.05). The 3, 5, 8 and 10-year LRR were 1.83%, 3.21%, 4.13%, 4.13% and 4.44%, 5.93%, 6.67%, 6.67% for the SIB-IMRT and late-course boostIMRT group and there was also no significant differences between the groups (all P value > 0.05). There were no different for DMR of the two groups (all P value > 0.05). Conclusions: In conclusion, SIB-IMRT as part of breast cancer treatment had the same treatment effect in excellent OS, DFS, and LRC rates comparing with late-course boost-IMRT. Meanwhile, the LCR and DMR was the same as late-course boost-IMRT. Therefore, SIB-IMRT was worth to popularize in clinical treatment. Author Disclosure: S. Wang: None. H. Xing: None. J. Li: None. Y. Zhang: None. M. Xu: None. Y. Ding: None.